SAJOG Vol 24, No 1 (2018)

ISSN 2305-8862

May 2018 Vol. 24 No. 2

• Prenatal screening for congenital toxoplasmosis • In utero transmission of influenza A H1N1 • Indications for caesarean sections at Chris Hani Baragwanath Hospital • Gestational outcomes after invasive prenatal testing for spinal muscular atrophy • Use of a visual aid to improve estimation of blood loss in obstetrics • Guideline: Thromboprophylaxis in obstetrics and gynaecology

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

EDITORIAL

Vulvovaginal conditions remain difficult and unresolved Vulvovaginal disease is often difficult and problematic. Standard information is often lacking, as may be the knowledge of the individual gynaecologist, who is required to make diagnoses and decide on a management course.

Difficulties associated with vulvar and vaginal conditions may not be as commonplace for the practising gynaecologist as the dilemma of an uncomplicated pregnancy at 40 weeks, or how to perform a challenging caesarean section or how to manage painful and heavy menstruation, but the average gynaecologist must be aware that many patients with vulvar and vaginal conditions are not adequately treated, and that the classification of some conditions often seems incomplete and confusing.

The simplest and yet most complex of these conditions is vulvar thrush, or candidiasis, ‘Candida albicans’. Many gynaecologists know that Candida is the genus and Candida albicans a species, one of a multitude of Candida spp., which leads to a difficulty – the common treatment of candidiasis, imidazoles, treats primarily the pseudohyphae-forming C. albicans and not its relatives. A patient affected by recurrent thrush will describe how ineffective imidazoles can be. Perhaps this failure of imidazole treatment should be attributed as much to the cyclical or recurring alteration of the vaginal environment, such as pH, as to deficiencies in therapy.

Every student can explain that this changing environment may be caused by loss of the vaginal Lactobacillus spp., which may occur menstrually, with antibiotic use, pregnancy, or hormone treatments. However, this knowledge does not resolve the problem of a person with recurrent thrush who remains affected.

Perhaps it is important to look beyond the Candida genus. Tinea spp. and many other fungi may infect the vulva, as they favour a naturally damp environment. Some are responsive to imidazoles. If feet are a possible source of these fungi, perhaps simple washing of feet last may prevent certain cases of recurring candidiasis that are otherwise inexplicable?

Our understanding of pathogens in the vagina is lacking. Our understanding of the infinitely complex normal vaginal bacterial environment is also deficient: what are the normal organisms of the vagina and vulva?

Mycoplasma spp. have been associated with many conditions, including bacterial vaginosis and pelvic inflammatory disease (PID), which is presumably a condition in which pathogenic organisms ascend from the vagina in association with sexual intercourse and pass into the uterus and adnexa. Mycoplasma and other species have been associated with PID, and yet further reading will show that their behaviour as pathogens is open to considerable debate and that they may also be commensals, found in circumstances where there is no pathology. There are many other organisms, including anaerobic streptococci, for which this is true. And so perhaps it is not the organism itself that is the ratelimiting step in creating a pathological state, but, as with Candida spp., some other factor that stimulates pathogenic behaviour.

This uncertainty of identification of the normal vaginal flora may seem theoretical and academic, but this inability to identify the normal vaginal flora makes it difficult to isolate and identify the abnormal.

A patient with a recurrent or persistent vaginal discharge, with a distressing odour, may respond to metronidazole at first. But then the distressing discharge with no apparent cause, returns, leaving both the patient and gynaecologist frustrated.

The uncertain dilemma of pathogenic/commensal behaviour is well illustrated by bacterial vaginosis, which may or may not be associated with a discharge. Bacterial vaginosis is a condition known to every medical student, having recognised criteria which are easily asked in local and national exams. Yet, bacterial vaginosis may be described as a purely incidental finding on a Pap smear. On questioning, the patient may say that the key component of the discharge is absent, as is any associated local discomfort. This incidental finding of asymptomatic bacterial vaginosis (though it may have obstetric implications, which are also contested) may lead the gynaecologist to prescribe metronidazole – a substance that is unpleasant, may have no benefit, and may even initiate a previously non-existent disturbance of the vaginal flora.

Attempting to find an infective agent has confused the understanding of another condition that has many names and often no recognisable cure – vulvodynia, vulvar vestibulitis, the dysaesthetic vulva – the names can be changed or refined, but the absence of a cure remains. It is difficult to understand how one nomenclature can represent cases without an obvious cure when the majority of cases do. Certain instances may be associated with a recognisable allergic stimulus, a dermatosis or an underlying psychological difficulty, but many are not. They occur in seemingly well individuals in whom an exhaustive search for an allergen or predisposition is fruitless. The condition can remain baffling and frustrating to the patient and to the assisting gynaecologist. Human papilloma virus (HPV) was a favourite cause temporarily, but studies showed identical rates in sufferers and controls, and this association remained nothing more than a case of applying a current focus of research to a condition, without obvious logic or benefit.

Molluscum contagiosum is a condition of the vulva which is virally associated, where small raised lesions exist but do not coalesce to form warty growths. It may be reassuring to know that there are no significant sequelae or that in this case, a simple viral cause may be implicated, but ineffective treatment and recurrence may continue to hamper the patient and physician.

A lack of significant sequelae or association seems not to be the case for Paget’s disease of the vulva. The excellent and distinguished American gynaecological oncologist Philip Disaia, co-editor of the current 9th edition of a standard oncology textbook, co-authored a paper in 1989 which identified no patients with vulvar Paget’s disease as having an underlying carcinoma during a 10-year follow-up.[1] Studies by himself have since given a different emphasis, and a study published by the MD Anderson Cancer Center in 2017 showed that, of 89 patients who were followed up over 44 years, 46% had a synchronous or metachronous underlying carcinoma supporting the current recommended management of colonoscopy and cystoscopy on diagnosis, and stringent follow-up.[2] This represents an about-face on a condition fairly recently considered less significant than the more well-known Paget’s disease of the breast.

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EDITORIAL The classification of intra-epithelial vulvar disease has been a minefield of misunderstanding and correction. The International Society for the Study of Vulvar Disease (ISSVD) has reclassified vulvar disease multiple times over the last 40 years. Terms have come into the classification and disappeared. The current version notes the collaboration of dermatologists, anal specialists, general physicians, pathologists and other interested parties. Perhaps this divergence of skills has contributed to the shifting sea of terms and conditions, and may even have contributed to misunderstanding.

Perhaps, if lichen sclerosus (LS) had kept its original name of lichen sclerosus et atrophicus (it is frequently not atrophic), a recent discovery of a patient who was accidentally on maintenance high-strength topical steroids – likely to cause iatrogenic atrophy and accidental harm – would not have been made. The initial high-strength treatment is better followed by low-strength maintenance treatment, a protocol known to many. Sometimes, even inadvertently, there may be a certain logic to a nomenclature that has been forgotten.

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The vulva and vagina may seem the source of a simple understanding of simple conditions, but scrutiny shows that that understanding is changing constantly, and that many fundamental deficiencies in that understanding still exist.

William Edridge

Editor william.edridge@gmail.com

S Afr J Obstet Gynaecol 2018;24(1):2-3. DOI:10.7196/SAJOG.2018.v24i1.1362

1. Bergen S, DiSaia PJ, Liao SY, Berman ML. Conservative management of extramammary Paget’s disease of the vulva. Gynecol Oncol 1989;33(2):151-156. https://doi.org/10.1016/00908258(89)90541-6 2. Onaiwu CO, Salcedo MP, Pessini SA, et al. Paget’s disease of the vulva: A review of 89 cases.

Gynecol Oncol Rep 2017;19:46-49. https://doi.org/10.1016/j.gore.2016.12.010

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COMMENTARY

Prenatal screening for congenital toxoplasmosis Toxoplasma gondii is a parasitic protozoan and is mainly transmitted to humans by eating undercooked contaminated meat or during clearing cat litters. Acute T. gondii infection causes mild symptoms, such as fever, fatigue, and lymphadenopathy in immunocompetent pregnant women, or may be completely asymptomatic. Women infected by this agent prior to conception rarely transmit the infection to the fetus.

However, mothers infected acutely during the pregnancy are likely to transmit the protozoan through the placenta to the fetus, with an overall risk of 20 - 50%.

The transmission risk is higher when the mother becomes infected during the third trimester (transmission rate 60 - 90%) in comparison to infections occurring during the first trimester (transmission rate 10 25%); but, similar to most other TORCH agents, early infections usually result in a poorer fetal outcome, with the majority of first-trimester infections leading to miscarriage. The survivors of prenatally acquired toxoplasmosis during the second trimester present with major brain abnormalities and severe chorioretinitis; while infections acquired during the third trimester present with less severe findings, such as brain calcifications, mild chorioretinitis, and hepatosplenomegaly.

The principal fetal abnormalities in congenital toxoplasmosis (CTX) are classically described as the triad of chorioretinitis, intracranial calcifications, and hydrocephalus. However, it is estimated that only 1 out of 6 infected fetuses shows two or three findings of this classic triad. About 80% of infants are asymptomatic at birth, but they may present the complications during late childhood or adolescence. Therefore, making an early correct diagnosis and initiating the appropriate treatment is of paramount importance. In the regions of active parasitic transmission, maternal serologic screening should be offered to all pregnant women, and diagnostic fetal testing (i.e. amniotic fluid polymerase chain reaction) should be suggested to the confirmed cases of recent acute infection (Fig. 1).[1-4] In developing countries, however, serologic screening of all pregnant women may not be possible, but upon prenatal ultrasound findings, one may suspect CTX

and initiate appropriate anti-protozoa treatment after confirming the diagnosis by serologic and molecular testing on the maternal serum and amniotic fluid.

The main fetal neurosonographic findings suggestive of CTX include parenchymal calcifications and hydrocephalus (Fig. 2A). These findings may be appreciated in the affected fetuses from 18 - 22 weeks᾽ gestation onwards (depending on the time of infection).

Parenchymal calcifications in CTX are seen as foci of hyperechogenicity, with or without posterior shadowing, that are randomly distributed throughout the brain. This finding has been described as a fairly characteristic feature for CTX compared with the mostly periventricular calcifications in congenital cytomegalovirus (CMV) and Zika virus (ZIKV) infections. Microcephaly, i.e.

a head circumference that measures 2 standard deviations below the mean for the gestational age, is another possible finding but its prevalence in CTX is much less than in congenital CMV and ZIKV infections. Malformations of cortical development (such as underopercularisation), as well as dysplasia of the corpus callosum, which are commonly seen in congenital ZIKV infection and with a lower prevalence in congenital CMV infection, have been rarely described in CTX. Parenchymal cystic changes secondary to abscess formation is another uncommon feature in CTX. Non-neurologic findings (Figs 2B and 2C) such as hepatosplenomegaly, intrahepatic echogenicities, peritoneal calcification, and evidences of hydrops fetalis (e.g. ascites, pleural effusion, and pericardial effusion), as well as placental

Maternal serologic screening for toxoplasmosis

IgG – IgM –

IgG + IgM –

IgG + IgM +

No evidence of life-time infection

Evidence of remote infection

Evidence of suspected recent infection*

Monthly serologic screening (in the case of ongoing active exposure)

No further evaluation or therapy is recommended

Re-test after 2 - 3 weeks (at least a fourfold increase in the IgG level)

–

False-positive IgM

+

1. Initiate spiramycin† 2. Amniotic fluid PCR for Toxoplasma gondii

–

Spiramycin prophylaxis until delivery

+

Initiate anti-toxoplasma treatment‡

Fig. 1. Recommended algorithm for prenatal screening for congenital toxoplasmosis.

(Ig = immunoglobulin; PCR = polymerase chain reaction; BD = twice per day). *A false-positive IgM occurs commonly and a positive result should be confirmed by further evaluation. † Spiramycin is generally used if the gestational age is less than 18 weeks. ‡ Anti-toxoplasma treatment with sulfadiazine (50 mg/kg BD), pyrimethamine (2 mg/kg/day for 2 days, then 1 mg/kg 3 times a week for the rest of the treatment period), and folinic acid (10 mg 3 times a week). The medical treatment should continue for a minimum of 12 months.

Anti-toxoplasma treatment is recommended if gestational age is >18 weeks. Pyrimethamine should be avoided during the first trimester due to its teratogenic effects.

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COMMENTARY of 89 fetuses were normal in a study by Hohlfeld et al. in 1991), but there is still the risk of late complications in these fetuses, which may be prevented partially by initiating early treatment. Therefore, maternal serologic screening is the method of choice that should be offered to pregnant women, and ultrasound may detect only a proportion of more severely affected fetuses. In addition, it has been revealed that the infected fetuses with neuroimaging abnormalities have a poorer prognosis in comparison with those who have normal prenatal neuroimaging results.[9]

Mohammad Zare Mehrjardi

Department of Radiology, Shohada Tajrish Hospital, Shahid Beheshti University of Medical Siences, Tehran, Iran; and Section of Fetal Imaging, Division of Clinical Research, Climax Radiology Education Foundation, Tehran, Iran zare@sbmu.ac.ir Fig. 2. Possible prenatal ultrasonographic findings in congenital toxoplasmosis (CTX). (A) Head ultrasound of a 23-week fetus with CTX showing lateral ventriculomegaly (bidirectional arrow), as well as periventricular and scattered parenchymal brain echogenic foci representing calcification (arrows); (B) axial abdominal ultrasound of the same fetus demonstrating hepatomegaly and intrahepatic hyperechogenicities (arrows); (C) axial abdominal ultrasound of a 25-week fetus showing multiple echogenic foci on the peritoneal surface representing areas of calcification; (D) an enlarged placenta containing hypoechogenic areas (asterisk) representing placental infarct and intervillous thrombi. changes (Fig. 2D) such as a thick placenta with hyperechoic and/or necrotic foci are also possible in CTX. Fetal brain magnetic resonance imaging (MRI) may be used as a complementary study in suspected cases, which can delineate the abnormalities better due its inherent higher soft-tissue resolution in comparison with ultrasound. However, parenchymal calcifications may be undetectable on MRI.[5-8] It should be emphasised that a large proportion of infected fetuses may be completely normal on prenatal ultrasound (57 out

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S Afr J Obstet Gynaecol 2018;24(1):4-5. DOI:10.7196/SAJOG.2018. v24i1.1216

1. Jones JL, Lopez A, Wilson M, Schulkin J, Gibbs R. Congenital toxoplasmosis: A review. Obstet Gynecol Surv 2001;56:296-305.

2. Jones J, Lopez A, Wilson M. Congenital toxoplasmosis. Am Fam Physician 2003;67:2131-2138.

3. Kieffer F, Wallon M. Congenital toxoplasmosis. Handb Clin Neurol 2013;112:1099-1101. https:// doi.org/10.1016/B978-0-444-52910-7.00028-3 4. Hampton MM. Congenital toxoplasmosis: A review. Neonatal Netw 2015;34:274-278. https://doi. org/10.1891/0730-0832.34.5.274 5. Malinger G, Werner H, Rodriguez Leonel JC, et al. Prenatal brain imaging in congenital toxoplasmosis. Prenat Diagn 2011;31:881-886. https://doi.org/10.1002/pd.2795 6. Antsaklis A, Daskalakis G, Papantoniou N, Mentis A, Michalas S. Prenatal diagnosis of congenital toxoplasmosis. Prenat Diagnosis 2002;22:1107-1111.

7. Zare Mehrjardi M, Keshavarz E, Poretti A, Hazin AN. Neuroimaging findings of Zika virus infection: A review article. Jap J Radiol 2016;34:765-770. https://doi.org/10.1007/s11604-0160588-5 8. Villena I, Bory JP, Chemla C, Hornoy P, Pinon JM. Congenital toxoplasmosis: Necessity of clinical and ultrasound follow-up despite negative amniocentesis. Prenat Diagnosis 2003;23:1098-1069. https://doi.org/doi:10.1002/pd.754 9. Hohlfeld P, MacAleese J, Capella-Pavlovski M, et al. Fetal toxoplasmosis: Ultrasonographic signs. Ultrasound Obstet Gynecol 1991;1:241-244. https//doi.org/10.1046/j.14690705.1991.01040241.x

Accepted 17 April 2018.

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CASE REPORT

In utero transmission of influenza A H1N1 A Bezzine,1 MD; E Ben Hamida,1 PhD; B Rabii,1 MD; A Slim,2 PhD; Z Marrakchi,1 PhD 1 2

Neonatology Department, Charles Nicolle Hospital, Tunis-El Manar University, Tunis, Tunisia Microbiology Department, Charles Nicolle Hospital, Tunis-El Manar University, Tunis, Tunisia

Corresponding author: A Bezzine (ahbezzine@gmail.com) The influenza A pandemic H1N1 was first detected in the USA in April 2009. It is associated with a high risk of complications in pregnant women and children. Transplacental infection of influenza A is rare. We report a case of in utero transmission of influenza A H1N1 infection in a newborn whose mother was seriously ill with influenza A H1N1 during the perinatal period. Our patient was probably infected in utero because he was delivered by caesarean section and was never exposed to his mother, who required intensive cardiopulmonary support at the time of delivery.

S Afr J Obstet Gynaecol 2018;24(1):6-7. DOI:10.7196/SAJOG.2018.v24i1.1295

Influenza A H1N1 infection is a very serious condition, especially in pregnant women and children.[1] Vertical transmission of influenza A H1N1 virus has been suspected in some cases but definitive evidence was not available.[2] We report a case of in utero transmission of influenza A H1N1 infection.

Case

A preterm baby was born by emergency cesarean section at 34 weeks’ gestation, to a 38-year-old mother with dilated cardiomyopathy complicated by an arrhythmia and who consulted for acute distress respiratory syndrome (ADRS). The diagnosis of influenza A H1N1 was immediately suspected and confirmed by multiplex reverse transcription polymerase chain reaction (RT-PCR) of the throat swab specimen. The episode occurred during the Tunisian influenza season and the mother had nasopharyngeal symptoms suggestive of influenza A1 H1N1 infection. The newborn’s Apgar scores were 7 and 8 at 1 and 5 minutes, respectively. He was small for his gestational age, with a weight of 1 880 g, and had a head circumference of 29 cm. Based on the perinatal history, the newborn was admitted to the neonatal intensive care unit and isolated from other babies in an incubator.

He presented with a transient tachypnoea during the first two hours of life. Procalcitonin and C-reactive protein (CRP) assays were negative. Blood culture was negative. The specimen obtained from the throat swab was positive for influenza A H1N1 virus by realtime RT-PCR. Therefore, 4 mg oseltamivir was administered to our patient every 12 hours (1.5 mg/kg/12h). The infant was probably infected in utero because he was delivered by cesarean section and was never exposed to his mother, who required intensive cardiopulmonary support at the time of delivery. The mother died from respiratory failure 10 days after the caesarean section.

The outcome for our patient was favourable. The newborn was discharged from hospital on day 13 of life.

Discussion

Our newborn’s mother was critically ill and she died on day 10 after delivery. Pregnant women are one of the highest risk groups

for influenza A infection and influenza-associated complications, including increased maternal and perinatal illness and death rates.[3] Severely ill or perimortal women, defined as women who are admitted to an intensive care unit or who ultimately die, have an increased risk of adverse infant outcomes.[4] Our patient was born prematurely; he was small for gestational age and remained asymptomatic, other than transient tachypnoea of the newborn, until discharge. Among reported cases of infants born to women who have delivered while hospitalised for 2009 H1N1 illness, 63.6% (95% confidence interval (CI) 51.8 - 74.3) were born preterm (compared with 12.3% of all USA births), 69.4% (95% CI 57.5 - 79.8) were admitted to a neonatal intensive care unit (compared with 6.1% of all USA births), and 29.2% (95% CI 19.1 - 41.1) had 5-minute Apgar scores that were ≤6 (compared with 1.6% of all USA births).[5] Infants born to women who had been hospitalised for respiratory illness during the influenza season at any time during pregnancy were more likely to be small for gestational age than infants born to women who were not hospitalised.[5] Viraemia is more frequent and more extensive in pregnant women due to depressed cell-mediated immune response during the pregnancy.[6] When pregnant women are infected by influenza A H1N1 during the perinatal period, newborns can be infected by respiratory droplets after birth or, more rarely, transplacentally during maternal viraemia,[7] although there have been few case reports in this regard.[1] Our patient was delivered by an emergency caesarean section and he was never exposed to his mother, who required intensive cardiopulmonary support at the time of delivery. Therefore, we presume that the transmission was transplacental. Oseltamivir was administered to our patient with a dose of 3 mg/kg/day.

The outcome for our patient was favourable. The newborn was discharged from hospital on day 13 of life. This suggests that early treatment with oseltamivir can prevent severe illness in newborns with perinatal influenza A H1N1. The World Health Organization issued a statement allowing the use of oseltamivir in newborns <14 days old for the treatment of suspected or confirmed influenza, at a dose of 3 mg/kg/day.[8] Influenza vaccination during pregnancy

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CASE REPORT is a key strategy to prevent influenza and influenza-related complications in pregnant women and their infants. Indeed, it has been established that influenza vaccination during pregnancy decreases the frequency of influenza or its complications in infants up to 6 months old.[5]

Conclusion

The prenatal transmission of influenza A H1N1 should be considered in infected pregnant women. Thus, preventive treatment should be prescribed to avoid neonatal complication.

Acknowledgements. None.

Author contributions. AB: author; BR, EBH, ZM: data collection; AS: performed multiplex RT-PCR. Funding. None.

Conflicts of interest. None.

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1. Jamieson DJ, Honein MA, Rasmussen SA, Williams JL, et al. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet 2009;374:451-458.

2. Dulyachai W, Makkoch J, Rianthavorn P, et al. Perinatal pandemic (H1N1) 2009 infection, Thailand. Emerg Infect Dis 2010;16:343-344. https://doi.org/10.3201/eid1602.091733 3. Irving WL, James DK, Stephenson T, et al. Influenza virus infection in the second and third trimesters of pregnancy: A clinical and seroepidemiological study. BJOG 2000;107:1282-1289. https://doi.org/10.1111/j.1471-0528.2000.tb11621.x 4. Mosby LG, Rasmussen SA, Jamieson DJ. 2009 Pandemic influenza A (H1N1) in pregnancy: A systematic review of the literature. Am J ObstetGynecol 2011;205:10-18. https://doi.org/10.1016/j. ajog.2010.12.033 5. Centers for Disease Control and Prevention. Prevention and control of influenza with vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2011. Morb Mortal Week Rep 2011;60:1128-1132.

6. Purtilo DT, Hallgren HM, Yunis EJ. Depressed maternal lymphocyte response to phytohaemagglutinin in human pregnancy. Lancet 1972;299(7754):769-771. https://doi. org/10.1016/s0140-6736(72)90522-3 7. Kanmaz HG, Erdeve O, Ogz SS, et al. Placental transmission of novel pandemic influenza A virus.

Fetal Pediatr Pathol 2011;30:280-285. https://doi.org/10.3109/15513815.2011.572956 8. European Medicines Agency (EMA). Assessment Report for Tamiflu, International Nonproprietary Name: Oseltamivir.

London: EMA; 2009. http://www.ema. e u r o p a . e u / d o c s / e n _ G B / d o c u m e n t _ l i b r a r y / E PA R _ - _ A s s e s s m e n t _ R e p o r t Variation/human/000402/WC500033109.pdf (accessed 25 May 2011).

Accepted 31 May 2018.

SAJOG â&#x20AC;˘ May 2018, Vol. 24, No. 1

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RESEARCH

Lactic acid as an adjuvant marker in pregnancy-associated sepsis R Agarwal,1 MS (O&G); R K Yadav,1 MBBS; S Garg,1 MD (Biochem); H Srivastava,1MS (O&G); G Radhakrishnan,2 MS (O&G); A Tiwari,1 MS (O&G) 1 2

Department of Obstetrics & Gynaecology, University College of Medical Sciences & Guru Teg Bahadur, Delhi, India Department of Obstetrics & Gynaecology, University College of Medical Sciences & Guru Teg Bahadur, Delhi, India

Corresponding author: R Agarwal (rachna_anila@yahoo.co.in)

Background. Lactic acid level is one index which is currently actively researched for its role in pregnancy-associated sepsis (PAS). We aimed to quantify the severity of PAS using lactic acid levels.

Methods. All pregnant, post-abortal (2 weeks) and postpartum women (up to 6 weeks) with clinical sepsis were enrolled as per systemic inflammatory response syndrome criteria, and lactic acid levels were estimated at admission. Severe PAS was defined as one or more organ dysfunctions due to sepsis. The severity of obstetric sepsis was graded according to number of organ failures.

Results. There were 42 patients with non-severe PAS, and 58 with severe PAS. The ≥4 mmol/L lactic acid threshold had 88.10% specificity and 37.93% sensitivity for detection of severe PAS. A significant difference (p=0.006) was found between lactic acid levels (mean (standard deviation (SD)) in cases with single OF (n=24; 3.02 (0.92) mmol/L) v. multi-organ failure (n=34; 3.70 (0.81) mmol/L). The mean (SD) lactic acid levels (3.76 (0.97) mmol/L) with any type of culture-positive PAS cases (n=35) were significantly higher than in culture-negative PAS cases (2.95 (0.98); p=0.0001).

Conclusions. Lactic acid level ≥4 mmol/L had reasonable specificity for severity and culture positivity in PAS. A serum lactic acid level ≥3 mmol/L was associated with more number of organ failures.

S Afr J Obstet Gynaecol 2018;24(1):8-10. DOI:10.7196/SAJOG.2018.v24i1.1219

Lactic acid is one of the products of anaerobic metabolism related to hypovolemia and hypoxia. Following the recognition of lactic acid importance in critical care management of sepsis in general, its use was extended to pregnancy-associated sepsis (PAS).[1] The existing evidence on the subject is still scanty.[2-5] The only focused study of lactic acid measurements in obstetric sepsis indicated it as a marker of severe infection, associated with positive blood cultures, increased risk of intensive care unit ICU and telemetry unit admission and longer hospital stays.[2] Presently, the lactic acid estimations have been included in the diagnostic criteria of the Sepsis Obstetrics Score (SOS) and Surviving Sepsis Campaign care bundles.[3,6] Low-income countries have high burdens of morbidity and mortality related to PAS. The increasing severity of PAS worsens the maternal prognosis, and therefore there is a strong need to develop parameters for its identification to optimise outcomes. Lactic acid level is one index that is currently being researched for its role in PAS. We therefore conducted this study with the aim of quantifying the severity of PAS using lactic acid levels. We also compared the culture positivity in obstetrics sepsis with lactic acid levels, to try to find a possible association between them.

Methods

Ethics clearance was obtained from the Institutional Ethical Committee and prior consent was obtained from all patients. All pregnant, post-abortal (2 weeks) and postpartum women (up to 6 weeks) with clinical sepsis were investigated using systemic inflammatory response syndrome criteria: mean arterial blood pressure <65 mmHg; systolic blood pressure ≤90 mmHg; heart rate ≥110/min; respiratory rate ≥22/min; temperature ≥38°C or ≤36°C; and leukocyte count ≥14 000/µL or <4 000/µL.[3] Patients meeting ≥2

of these criteria were classified as having PAS and enrolled as cases for our study.

Detailed clinical, pertinent laboratory and imaging tests were performed for all enrolled patients. Blood, high vaginal swab and pus (if present) swabs were sent for bacterial cultures and sensitivity.

Specimens were considered culture-positive if single microbial growth was isolated in any of the above samples. Venous lactic acid levels were obtained, along with other haematological investigations, at admission. For organ failure assessment, the key body systems were assessed and monitored: respiratory, cardiac, kidney and liver.

The important criteria representing organ failure used were: altered mental status; arterial hypoxaemia (the ratio of partial pressure of arterial oxygen and the fraction of inspired oxygen (PaO2/ FiO2)<300); acute oliguria (urine output <0.5 mL/kg/h for at least 2 hours); creatinine increase >0.5 mg/dL; coagulation abnormalities (INR >1.5 or a PTT >60 s); thrombocytopenia (platelet count <100 000/mL); hyperbilirubinaemia (plasma total bilirubin >4 mg/dL).[7] Severe sepsis was defined as an infectionrelated to ≥1 organ dysfunction within 24 hours of admission.[7] Patients were further managed as per the hospital protocol and the patient’s condition.

Lactic acid estimations were associated with severity of sepsis and culture positivity using parametric and non-parametric statistical methods (SPSS software version 20 (IBM Corp., USA)).

Results

There were 42 patients with non-severe PAS and 58 with severe PAS. The common causes of PAS were urinary tract infection (80%), followed by chorioamnionitis (10%), endometritis (5%) and peritonitis, along with pyoperitoneum (5%). The two groups were

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RESEARCH similar in age, BMI and socioeconomic characteristics. The mean (standard deviation (SD)) lactic acid level in our cohort was 3.23 (0.98) mmol/L (range 1.2 - 5.4 mmol/L). The statistical comparison between mean lactic acid levels in non-severe (2.97 (1.02) mmol/L; range 1.2 - 5.4 mmol/L) v. severe PAS (3.42 (0.91) mmol/L; range 1.3 - 4.6 mmol/L) was not significant (p=0.197). When a lactic acid level of 4 mmol/L was considered as a threshold, a statistically significant difference (p=0.000) was found between non-severe and severe PAS (Table 1). The ≥4 mmol/L threshold had a positive predictive value of 81.48% (specificity 88.10% and sensitivity 37.93%) for PAS severity. The best lactic acid diagnostics were seen at cutoff levels of 3.2 mmol/L (specificity 50%; sensitivity 71%). The statistical analysis established the high specificity (nearly 90%) of lactic acid levels ≥4 mmol/L for severe sepsis prediction. Moreover, there was a steady increase in lactic acid level at admission with the highest number of organ failures in subjects with severe sepsis. The mean (SD) lactic acid (mmol/L) was 3.02 (0.92) in a single organ failure (OF) (n=24), and it increased to 4.01 (0.43) in those with ≥4 OF (n=12). The mean values for 2 and 3 OFs (n=11 each) were 3.25 (0.92) and 3.89 (0.80) mmol/L, respectively. A significant difference (p=0.006) was found in lactic acid levels for single (3.02 (0.92) mmol/L; range 1.3 - 4.45 mmol/L) and multi-organ failure (OF ≥2; n=34) (3.70 (0.81) mmol/L; range 1.4 - 4.6 mmol/L).

The lactic acid levels were also found to be associated with positive cultures. The lactic acid levels (3.76 (0.97) mmol/L) in patients with any type of positive culture (n=35) were significantly higher than in those with negative cultures (2.95 (0.98); p=0.0001).

At the critical threshold of 4 mmol/L, there were significant differences between culture-negative and culture-positive cohorts (Table 1). The lactic acid levels ≥4 mmol/L had a positive predictive value of 70.4% and negative predictive value of 78.08% with a specificity of 87.7% for a positive bacterial culture in PAS patients.

Discussion

A product of anaerobic metabolism related to hypovolaemia and hypoxia, serum lactic acid levels is a known parameter for the early identification of sepsis in general.[1] A review of 15 studies using lactic acid as a sepsis marker in adult populations suggested a higher specificity compared with sensitivity in indicating sepsisrelated prognosis and mortality.[1] Lactic acid was an indicator of poor perfusion, and higher levels of lactate were consistent with a more compromised circulatory system. The above review identified lactic acid levels >4 mmol/L as necessitating critical care in sepsis; however, there were limitations of evidence levels and biases in various studies included in the review.[1] Table 1. Lactic acid levels in PAS subjects: Association with severity and culture results.

Lactic acid (mmol/L) <4 ≥4

<4 ≥4

Severity of PAS Non-severe sepsis Severe sepsis (N=42), n (%) (N=58), n (%) 37 (50.7) 36 (49.3) 5 (18.5) 22 (81) Culture results Negative (N=65), Positive n (%) (N=35), n (%) 57 (87.7) 16 (45.7) 8 (12.3) 19 (54.3)

p-value* 0.000

0.000

*χ2 test. The result is significant at p<0.05.

9

The evidence for the role of lactic acid as a potential marker for critical care in PAS is still scanty.[2-5] In pregnant patients, lactic acid levels >2mmol/L indicate tissue hypoxia and >4 mmol/L is associated with severe tissue hypoxia.[4] It is also considered to be one of the reasons for metabolic acidosis.[4] Notably, a study of 159 pregnant women showed that increased lactic acid levels were associated with adverse maternal and perinatal outcomes, such as the need for critical care, positive blood cultures, preterm delivery and prolonged hospital admission.[2] The mean lactic concentration was higher in patients admitted to the intensive care unit (2.6 v. 1.6 mmol/L; p=0.04) and in those with positive blood cultures (2.2 v. 1.6; p<0.01).[2] With growing evidence in support of the importance of evaluating lactic acid levels when making clinical decisions, a popular scoring system for identification of sepsis in pregnant and postpartum women, the SOS, now considers lactic acid measurement as a standard practice when evaluating the possibly septic obstetric patient.[3] Lactic acid levels form a key part of the Surviving Sepsis Campaign Care bundle and are used as a guide to determine the degree of organ hypoxia, as well as whether organ perfusion improves with volume replacement.[4]

Study limitations and strengths The main limitation of our study was the lack of a control group without sepsis. We could not perform serial lactic acid estimations to establish lactic acid as a monitoring tool in PAS for logistic and financial reasons. The lactic acid therefore formed part of the initial care bundle of the patients. Study strengths included it being the first of its kind to investigate lactic acid levels in an obstetric population in a low-income setting. Another strength was that we employed a robust sample size. The importance of the study is further indicated by looking at the high burden of maternal sepsisassociated morbidity and mortality in low-income countries, and the urgent need to develop cheaper diagnostic tools with wide availability.

Conclusion

Our study demonstrated reasonable specificity of lactic acid level ≥4 mmol/L for severe PAS in our population. A serum lactic acid level >3 mmol/L at admission had considerable association with the occurrence of organ failure. Thus, lactic acid estimations can be used as a useful guide for triaging PAS patients for severity and timely critical care. Further, our prospective study revealed that the lactic acid level of ≥4 mmol/L had significant statistical association with positive cultures. We strongly believe that if lactic acid levels are elevated, microbial identification and prompt antibiotic administration should be considered.

Overall, our study highlights the fact that lactic acid levels have a role to play in detecting the severity of PAS, similar to that played with non-pregnant adults with PAS. There is a strong need to develop multicentre case control evidence for better quantification of the role of lactic acid in PAS.

Acknowledgements. None.

Author contributions. All authors contributed equally to the preparation of the manuscript.

Funding. None.

Conflicts of interest. None.

SAJOG • May 2018, Vol. 24, No. 1

RESEARCH 1. National Guideline Centre. Sepsis: Recognition, Assessment and Early Management. London: National Institute for Health and Care Excellence, 2016. https://www.ncbi.nlm.nih.gov/pubmedhealth/ PMH0088862/ (accessed 14 May 2017).

2. Albright CM, Ali TN, Lopes V, Rouse DJ, Anderson BL. Lactic acid measurement to identify risk of morbidity from sepsis in pregnancy. Am J Perinatol 2015;32(5):481-486. https://doi. org/10.1055/s-0034-1395477 3. Albright CM, Mehta ND, Rouse DJ, Hughes BL. Sepsis in pregnancy: Identification and management. J Perinat Neonatal Nurs 2016;30(2):95-105. https://doi.org/10.1097/JPN.0000000000000159 4. Brown KN, Arafeh JM. Obstetric sepsis: Focus on the 3-hour bundle. J Perinat Neonatal Nurs 2015;29(3):213-221. https://doi.org/10.1097/JPN.0000000000000115 5. Galvão A, Braga AC, Gonçalves DR, Guimarães JM, Braga J. Sepsis during pregnancy or the postpartum period. J Obstet Gynaecol 2016;36(6):735-743. https://doi.org/10.3109/01443615.2016.1148679

6. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign. International guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 2017;43(3):304-377. https://doi. org/10.1007/s00134-017-4683-6 7. Oud L. Pregnancy associated severe sepsis. Curr Opin Obstet Gynecol 2016;28(2):73-78. https://doi. org/10.1097/GCO.0000000000000250

Accepted 16 February 2018.

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

RESEARCH

An evaluation of the indications for caesarean sections at Chris Hani Baragwanath Academic Hospital Y Adam,1,2 BSc, MB BCh, FCOG(SA), MSc (Epid/Stat); J Mwinyoglee,1,2 MB ChB, DTM&H, DCH, Dip (Obstet), MMed, FCOG (SA), MPH; B Masuku, 1,2 MB ChB, FCOG (SA), MMed; E Nicolaou, 1,2 MD, FCOG (SA), Dip Fet Med (UK) 1 2

Maternity Hospital, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa Department of Obstetrics and Gynaecology, Chris Hani Baragwanath Academic Hospital and University of the Witwatersrand, Johannesburg, South Africa

Corresponding author: Y Adam (yasminadam@gmail.com)

Background. A systematic review concluded that a caesarean section (CS) performed for medical indications will save lives; however, it is associated with short- and long-term complications. The CS rate at Chris Hani Baragwanath Academic Hospital (CHBAH) was 39.78% in 2015.

Objectives. To evaluate the indications for CSs at CHBAH. Methods. This was a cross-sectional study conducted on the data collected in the week of 23 June to 29 June 2015. Each file was evaluated for the correctness of the decision by at least two researchers. Each reviewer could state that he/she absolutely agreed, partially agreed, did not agree or could not make an assessment.

Results. The mean (standard deviation (SD)) age of the women was 27.01 (6.35) (range 15 - 44) years. The median (interquartile range (IQR)) parity was 1 (0 - 2) (range 0 - 4). No co-morbidities were found in 13.6% (n=20) of the reviewed cases. Complications were found to have occurred in 17% (n=25) of women who gave birth over the week reviewed. The median (IQR) gestational age at delivery was 38.14 (36.39 - 40.14) (range 28.0 - 42.4) weeks. The median (IQR) Apgar (5 minutes) was 10 (9 - 10) (range 0 - 10). The median (IQR) birth weight was 3 040 (2 530 - 3 440) (range 825 - 4 575) g. The most common indications were fetal distress (n=73; 49.66%) and dystocia (n=42; 28.57%). There was absolute agreement between the two reviewers in the following: retained second twin, antepartum haemorrhage (APH) of unknown origin, placenta previa, severe intrauterine growth restriction, multiple pregnancy, abnormal presentation, eclampsia and two previous CSs. When the indication was fetal distress, dystocia, second-stage CS, or one previous CS, the absolute agreement was between 73.85% and 90.24%.

Conclusion. There were few absolute disagreements with the indication cited. Methods used to diagnose fetal distress and dystocia must be evaluated.

S Afr J Obstet Gynaecol 2018;24(1):11-14. DOI:10.7196/SAJOG.2018.v24i1.1226

In 2015, the World Health Organization (WHO) statement on caesarean section (CS) rates stated that ‘Every effort should be made to provide a caesarean section to women in need, rather than striving to achieve a specific rate’.[1] A CS should be undertaken when it is medically necessary and efforts should focus on providing a CS to all women in need. However, defining a woman ‘in need’ can only be ascertained by the healthcare providers caring for the woman on a case-by-case basis.

While the need for a CS is important in addressing the care for every individual woman, every CS contributes to an increase in the CS rate. WHO used country-level data to show that, at a population level, maternal and neonatal mortality is not reduced any further when the CS rate increases above 10%.[1] Delivery by CS in South Africa (SA) is associated with severe complications and maternal deaths. In the Saving Mothers Report (2011 - 2013), the institutional maternal mortality ratio (iMMR) was 66.6/100 000 live births for vaginal delivery v. an iMMR of 185.8/100 000 live births for delivery

by CS in SA.[2] While it is difficult to separate the risk associated with indications for the CSs, the continued increase in the CS rate in SA is what prompted the study on indications.[3] A study in the United States of America (USA) noted that subjective indications such as arrest of dilation and non-reassuring

fetal heart tracings are documented with more frequency, while more objectively defined medical indications, such as maternal, fetal or obstetric conditions, have remained stable.[4] Other reasons which are thought to contribute to the increasing rate is the increase in obstetric malpractice claims.[5] The Robson Ten Group Classification System (RTGC) is a classification system that may assist with the main determinants of the CS rate.[6] This classification is based on four obstetric concepts which classify women into 10 groups. These groups are mutually exclusive, totally inclusive, clinically relevant and prospectively identifiable. The RTGC is useful in that it may assist in allocating resources; moreover, it is useful for public health purposes, but it will not assist with determining the correctness of the indication for CS. The CS rate at Chris Hani Baragwanath Academic Hospital (CHBAH) has increased from 27.12% in 2008 to 39.80% in 2015 (departmental statistics). In the week of 23 June to 29 June 2015, the rate was 49%. This week was chosen arbitrarily to investigate the indications and correctness of CSs in any given week.

Methods

CHBAH is a secondary/tertiary hospital which serves pregnant women in southern Gauteng. Women are referred from four

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RESEARCH midwife obstetrics units (MOUs), one district hospital and three regional hospitals according to criteria defined in the Maternity Care Guidelines.[7] Thus, there is a case mix which includes low-, intermediate- and high-risk women. Risk assessment is determined in the antenatal period, in labour or postpartum. Women who are classified as ‘low risk’ will have their antenatal care administered by a midwife and deliver at a MOU. Women who are classified as ‘intermediate risk’ will have their antenatal care administered by a midwife and will deliver in a hospital. Women who are classified as ‘high risk’ will have their antenatal care and delivery in a hospital.

All women who had a CS in the specified week had their medical notes retrieved. This was a retrospective cross-sectional study.

Demographic information, co-morbidities, indication for CS (as recorded in the file), Robson’s classification, intra-operative findings, immediate neonatal outcomes and immediate maternal outcomes were recorded on a datasheet by one of the researchers.

At least two of the researchers reviewed the indication for correctness according to the departmental protocol. The reviewers had been specialists from between 3 to 20 years. They were all attached to an academic hospital and actively involved in postgraduate teaching. One reviewer (EN) is a maternal fetal subspecialist. Each reviewer could absolutely agree, absolutely disagree, partially agree, or state that it was not possible to assess the correctness of the indication. ‘Partially agree’ was when there was more than one indication and where the reviewer only agreed with one of the indications recorded. The reviewer also reviewed the quality of notes. This was an overall subjective assessment of between 0% (incomplete) and 100% (complete). This assessment was not validated.

The information was exported to a database (REDCap Software version 6.11.5, Vanderbilt University) hosted at the University of the Witwatersrand and then exported to STATA 14.2 (StataCorp, USA) for analysis. Categorical variables were described using frequencies and percentages and continuous variables using means (SD) and medians (IQR).

Ethics approval for the study was obtained from the Human Research Ethics Committee at the University of the Witwatersrand (ref. no. M150869) and permission to conduct the study was also obtained from the CEO of the hospital.

Results

CHBAH delivered 20 324 women in 2015. A total of 147 CSs were performed in the week of 23 to 29 June 2015. The mean (SD) age of the women was 27.01 (6.35) (range 15 - 44) years. The median (IQR) parity was 1 (0 - 2) (range 0 - 4). The median (IQR) gravidity was 2 (1 - 3) (range 1 - 6). The median (IQR) BMI was 27.30 (22.67 - 32.350) (range 17.88 - 50.50). The median (IQR) gestational age at booking was 20 (16 - 23) (range 5.0 - 35) weeks. There was a wide range of haemoglobin measured at the booking visit of between 5.1 15.5 g/dL, with a mean (SD) of 11.34 (1.92) g/dL. Only 20 (13.61%) of the women had no co-morbidities during the antenatal period. The co-morbidities were HIV infection (n=33; 22.45%), hypertension (n=26; 17.69%), any previous CS (n=34; 20.56%), anaemia (n=25; 17.01%), pre-eclampsia/eclampsia (n=20; 13.61%), referral for postdates (n=14; 9.52%), previous abdominal surgery (n=4; 2.72%), multiple pregnancy (n=3; 2.04%), poor obstetric history (n=3; 2.04%), diabetes (n=2; 1.36%) and intrauterine growth restriction (IUGR) (n=1; 0.68%). Of those

12

who were HIV-infected, the median (IQR) CD4 cell count was 309 (72 - 422) (range 53 - 952) cells/µL and 30 (90.91%) were on antiretroviral therapy.

The decision to perform a CS was made by a consultant in 29 (19.73%) cases, by a registrar in 87 (59.18%) cases, by an intern in 5 (3.40%) cases and it was unknown who made the decision in 26 (17.69%) cases. The quality of notes scored out of 10 was assessed by at least two reviewers and the mean (SD) scores were 6.55 (1.73) (range 3 - 9) and 6.63 (1.61) (range 3 - 9). None of the prescription charts noted the number of doses of antibiotics to be given and the fluid charts were incomplete from a nursing perspective.

A spinal anaesthetic was performed in 119 (82.99%) women, a general anaesthetic in 21 (14.29%) women, an epidural in 2 (1.36%) women, and the spinal anaesthetic was converted to a general anaesthetic in 5 (3.40%) women.

In 2 (1.36%) women a classical CS was performed, and the rest had transverse lower uterine segment CSs. The median (IQR) blood loss recorded by the surgeon was 500 (450 - 800) (range 200 - 2 000) mL. The median (IQR) blood loss recorded by the anaesthetist was 500 (400 - 750) (range 200 - 2 780) mL. The blood loss was recorded in only 51 (34.69%) cases by the anaesthetist and in 135 (91.84%) cases by the attending obstetrician.

There were 25 (17.01%) women who had one or more complications at CS. Postpartum haemorrhage (>1 000 mL) occurred in 12 (8.16%) women, 2 (1.36%) needed a substantial blood transfusion and 4 (2.72%) needed a B-Lynch suture. Three (2.04%) required ventilation not for anaesthetic purposes, 1 (0.68%) had an anaesthetic-related complication (spinal headache) and 11 (7.48%) were admitted to the maternity high care unit. There were no women who required a hysterectomy or who were admitted to the intensive care unit.

The median (IQR) gestational age at delivery was 38.14 (36.39 - 40.14) weeks. There was 1 (0.68%) stillbirth. The median (IQR) Apgar at 5 minutes was 10 (9 - 10) (range 0 - 10); the mean (SD) was 9.47 (1.33). The median (IQR) birth weight was 3 040 (2 530 - 3 440) (range 825 - 4 575) g.

The frequency of indications (Fig. 1) illustrate that some women had more than one indication. Transverse lie (n=1), oblique lie

Retaind 2nd twin

0.68% (n=1)

APH (unknown origin)

1.36% (n=2)

Placenta previa

1.36% (n=2)

Severe IUGR

2.04% (n=3)

Multiple pregnancy

2.72% (n=4)

Abnormal presentation

3.40% (n=5)

2nd stage

4.08% (n=6)

Abruptio placentae

6.80% (n=10)

Pre-eclampsia/eclampsia

14.29% (n=21)

Any previous C/S

23.13% (n=34)

CPD/dystocia

28.57% (n=42)

Fetal distress

49.66% (n=73) 0

20

40

60

80

100

Fig. 1. A description of the indications for caesarean section.

(APH = antepartum haemorrhage; IUGR = intrauterine growth restriction; C/S = caesarean section; CPD = cephalopelvic disproportion.)

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RESEARCH (n=1), and breech (n=3) were grouped into abnormal presentation.

There were 3 women with eclampsia and 18 with pre-eclampsia.

Women who had 1 previous CS (n=27) were grouped with women who had 2 previous CSs (n=9).

There was absolute agreement between the 2 reviewers that a CS was indicated in the following indications (Table 1): retained second twin, APH of unknown origin, placenta previa, severe IUGR, multiple pregnancy, oblique lie, transverse lie, breech presentation, eclampsia and 2 previous CSs. There was absolute agreement with the recorded indication in 73.85% to 90.24% for the other indications. The primary reasons for disagreement were that the notes recorded were inadequate Table 1. An explanation of the agreement with indications for CS Indication (n (%) CS in second stage (n=6; 4.08%)

Abruptio placentae (n=10; 6.80%) Pre-eclampsia (n=18; 12.24%) CPD/dystocia (n=42; 28.57%) One previous CS (n=27;18.37%) Fetal distress (n=73; 49.66%)

Explanation 0 - absolute disagreement* 2 - cannot assess† (no note of level of engagement, and no repeat examination before the CS) 1 - absolute disagreement (3 reviewers); 6 - partially agree;‡ had other indications as well (1 of these was a ruptured uterus) 1 - absolute disagreement (1 reviewer) 1 - partially agree 2 - absolute disagreement (2 reviewers); 8 - partially agree 4 - cannot assess insufficient information 0 - absolute disagreements 6 - partially agree 2 - absolute disagreement (2 reviewers) 15 - partially agree 4 - cannot assess

CS = caesarean section; CPD = cephalopelvic disproportion *Absolute disagreement - agree with the indication completely. † Cannot assess - insufficient notes (mainly no cardiotocograph). ‡ Partially agree - do not agree with the recorded indication, but with a second indication.

Using Robson’s classification, the following concepts are reflected: (i) category of pregnancy (singleton v. multiple); (ii) past obstetric history; (iii) course of pregnancy (spontaneous, pre-labour CS or induction of labour); and (iv) gestational age at delivery. The CSs were then related to the various categories (Table 2).

Discussion

A CS for fetal distress was the most common indication, followed by dystocia and then previous CS. These three indications also appear to be important drivers responsible for increasing the CS rate in both developed and developing countries.[4,8,9] There were no women where the indication was ‘maternal request’ in this group.

Fetal distress is diagnosed using cardiotocography (CTG) at CHBAH. Several studies have shown that the sensitivity of CTG for fetal hypoxia is high, but that the specificity is low. Inter-observer interpretation of fetal distress has been shown to be moderate[10] at best, and the sensitivity and specificity are also affected by the guideline that is used. In the present study we used the NICE guideline to categorise CTGs.[10] Agreement between treating doctor and the reviewer was good. The ‘absolute disagreements’ in the diagnosis of fetal distress were very few. Among women where there was ‘partial agreement’, it was thought that the CS was still indicated because of the second indication.

Another study on evaluation of indications has shown that the most common disagreement was in interpreting fetal heart rate tracings. [8] All women at CHBAH are monitored in labour using a partogram.

Dystocia is diagnosed when the labour does not progress for 4 hours in the active phase of labour. At this stage, a decision is made to either initiate a syntocinon infusion or perform a CS. There were two absolute disagreements where the reviewers were of the opinion that the woman should have had a trial of syntocinon. The South African Maternity Guidelines now advocate a 2-hour gap between the alert line and the action line.[7] This may increase the proportion of women in whom labour intervention is instituted. The diagnosis of dystocia has

Table 2. The percentage of caesarean sections grouped according to Robson’s Classification Group 1 (21.71%) Nulliparous Single cephalic pregnancy ≥37 weeks gestation Spontaneous labour Group 2 (9.30%) Nulliparous Single cephalic pregnancy ≥37 weeks᾽ gestation Labour induced or delivery by CS before labour Group 3 (10.08%) Multiparous No previous uterine scar Singleton cephalic pregnancy ≥37 weeks᾽ gestation Spontaneous labour Group 4 (6.98%) Multiparous No previous uterine scar Singleton cephalic pregnancy ≥37 weeks᾽ gestation Labour induced or delivered by CS before labour Group 5 (20.16%) Multiparous At least one previous uterine scar Singleton cephalic pregnancy ≥37 weeks᾽ gestation

Group 6 (0.78%) Nulliparous Single breech pregnancy

Group 7 (3.10%) Multiparous Single breech pregnancy Including women with previous uterine scars Group 8 (3.88%) All women with multiple pregnancies Including women with previous uterine scars

Group 9 (1.55%) All women with a singleton pregnancy Transverse or oblique lie Including women with previous uterine scars

Group 10 (22.48%) All women with a singleton cephalic pregnancy ≤36 weeks᾽ gestation Including women with previous scars

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RESEARCH also been shown to be one of the drivers of the primary CS.[4,10] Recent data provide a better understanding of the active phase of labour where they infer that the active phase of labour only begins when the cervix is 6 cm dilated.[11-13] This concept of individualising labour management would have to be discussed nationally in SA, rather than be instituted at one facility.

One-quarter of the previous CSs were because of having had two CSs previously, which is an indication for a repeat CS at CHBAH. One previous CS was shown to be an important contributor in this study and will probably continue to impact the CS rate until the rate for the primary CS is addressed.

We did not look at indications within each of the Robson’s classes, but Group 1 and Group 3 reflect primary CS that is mainly driven by non-reassuring fetal heart rate patterns and dystocia. Women in Group 3 were those who had had a singleton pregnancy, with a cephalic presentation and in spontaneous labour, and who had not had a previous CS – these women should contribute the least to the number of CSs. This category contributed 1% to Robson’s classes in the National Maternity Hospital in Dublin in 2006[14] and 3.7% in the Royal Women’s Hospital in Melbourne in 2005.[15] In the present study, Robson’s Group 1 contributed to 10.8% of the CSs. The CS rate has increased over the last 50 years,[16] with a dramatic rise in the last decade. The CS rate has also increased steadily at CHBAH, with a rate of 28.4% (2005), 34.4% (2010) and 39.8% (2015) (departmental statistics). The rate at CHBAH is much higher than the overall rate in SA which was reported as 23.2% for 2011 - 2013 in the Saving Mothers Report.[2] The rate is expected to be higher in this high-risk population with only 13.61% with no antenatal co-morbidities. The rate reported in the USA in 2013 was 16.2% for low-risk women v. 76.1% for non-low-risk women.[4] We did not look at the rates separately for different risk categories. Rates are important for healthcare planning and allocation of funds, but the indications for every CS are important in making institutional changes regarding protocols and training.

Clinical recommendations in this institution would be to obtain a senior opinion on CTGs that are deemed to have non-reassuring heart rate tracings (NRHRTs). The use of fetal blood sampling may be another possibility in women who are not HIV-infected.

Introducing a ST segment analysis monitoring programme which has its own guidelines may be of assistance, but whether it will assist in better selection of women for operative delivery in this setting will have to be tested. We suggest ongoing audit of indications in conjunction with categorisation using Robson’s criteria.

The limitations of the study are its retrospective nature and the problem of not having clear notes. The method of assessment of ‘agreement’ and the ‘completion’ of notes was not validated. An ongoing random audit over the year may produce more generalisable

14

results. An audit over a week looks at practice by a small group of healthcare practitioners as this setting has a rapid turnover of staff.

Conclusion

It is reassuring that the indications for CS were assessed as correct in more than two-thirds of the reviewed cases. Fetal blood sampling could assist in better management of women with fetal heart rate abnormalities and selecting those that require a caesarean delivery.

Acknowledgements. The authors would like to thank the Records Department at Chris Hani Baragwanath Academic Hospital for making the records available.

Author contributions. All authors were involved in conceptualising the study.

All of the authors contributed equally to the data collection. YA performed the statistical calculations and wrote the first draft. All authors contributed to the final write-up.

Funding. None.

Conflict of interests. None.

1. World Health Organization (WHO). WHO statement on caesarean section rates 2015. http://apps. who.int/iris/bitstream/10665/161442/1/WHO_RHR_15.02_eng.pdf?ua=1 (accessed 12 June 2017).

2. Moodley J, National committee on confidential enquiries into maternal deaths. Saving mothers 2011-2013: Sixth report on confidential enquiries into maternal deaths in South Africa. Short report.

Pretoria: National Department of Health, 2016. http://www.kznhealth.gov.za/mcwh/Maternal/ Saving-Mothers-2011-2013-short-report.pdf. (accessed 26 December 2012).

3. Nathan R, Rautenbach P. Differences in the average caesarean section rate across levels of hospital care in Gauteng, South Africa. S Afr J Infect Dis 2014;29(4):147-150.

4. Barber EL, Lundsberg LS, Belanger K, et al. Indications contributing to the increasing cesarean delivery rate. Obstet Gynecol 2011;118(1):29-38. https://doi.org/10.1097/aog.0b013e31821e5f65 5. Schifrin B, Cohen W. The effect of malpractice claims on the use of caesarean section. Best Pract Res Clin Obstet Gynaecol 2013;27:269-228. https://doi.org/10.1016/j.bpobgyn.2012.10.004 6. Robson M. The Ten Group Classification System (TGCS) – a common starting point for more detailed analysis. BJOG 2015;122(5):701. https://doi.org/10.1111/1471-0528.13267 7. National Department of Health (NDoH). Guidelines for Maternity Care in South Africa. A Manual for Clinics, Community Health Centres and District Hospitals. Pretoria: NDoH, 2014. https://www. health-e.org.za/wp-content/uploads/2015/11/Maternal-Care-Guidelines-2015_FINAL-21.7.15.pdf (accessed 2 July 2017).

8. Pillai SA, Vaidyanathan G, Al-Shukri M, et al. Decisions to perform emergency caesarean sections at a university hospital: Do obstetricians agree? Sultan Qaboos Univ Med J 2016;16(1):e42-e46. https:// doi.org/10.18295/squmj.2016.16.01.008 9. Wang X, Hellerstein S, Hou L, et al. Caesarean deliveries in China. BMC Preg Childbirth 2017;17(1):1233-1238. https://doi.org/10.1186/s12884-017-1233-8 10. Garabedian C, Butruille L, Drumez E, et al. Inter-observer reliability of 4 fetal heart rate classifications. J Gynecol Obstet Hum Reprod 2017;46(2):131-135. https://doi.org/10.1016/j. jogoh.2016.11.002 11. Mistry K, Fingar KR, Elixhauser A. Variation in the Rate of Caesarean Section across U.S. Hospitals, 2013: Statistical Brief #211. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs.

Rockville: Agency for Healthcare Research and Quality, 2006. http://www.hcup-us.ahrq.gov/ reports/statbriefs/sb211-HospitalVariation-C-sections-2013.pdf. (accessed 14 June 2017).

12. Zhang J, Troendle J, Reddy UM, et al. Contemporary caesarean delivery practice in the United States. Am J Obstet Gynecol 2010;203(4):326. https://doi.org/10.1016/j.ajog.2010.06.0581 13. Zhang J, Landy HJ, Branch DW, et al. Contemporary patterns of spontaneous labor with normal neonatal outcomes. Obstet Gynecol 2010;116(6):1281-1287. https://doi.org/10.1097/ ogx.0b013e31821685d0 14. Robson M. National Maternity Hospital Dublin. Clinical report for the year 2006 Dublin. National Maternity Hospital, 2007.

15. McCarthy FP, Rigg L, Cady L, Cullinane F. A new way of looking at caesarean section births. Aust N Z J Obstet Gynaecol 2007;47(4):316-320. https://doi.org/10.1111/j.1479-828x.2007.00753.x 16. National Institutes of Health state-of-the-science conference statement: Caesarean delivery on maternal request. Obstet Gynecol 2006;107:1386-97. https://doi.org/10.1097/00006250-20060600000027

Accepted 16 February 2018.

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

RESEARCH

Gestational outcomes of pregnant women who have had invasive prenatal testing for the prenatal diagnosis of spinal muscular atrophy M S Beksac,1 PhD; H Yurter,2 PhD; A Tanacan,1 PhD; B Soyak B,1 PhD; G Orgul G,1 PhD; D A Hakli,3 PhD; T Celik,4 PhD; G Bora,2 PhD; A N Cakar,5 PhD; H Topaloglu,6 PhD Division of Perinatalogy, Department of Obstetrics and Gynecology, Haçettepe University Hospital, Ankara, Turkey Department of Medical Biology, Haçettepe University Hospital, Ankara, Turkey 3 Department of Biostatistics, Haçettepe University Hospital, Ankara, Turkey 4 Division of Neonatology, Department of Pediatrics, Haçettepe University Hospital, Ankara, Turkey 5 Department of Histology and Embryology, TOBB ETU University Medical Faculty, Ankara, Turkey 6 Division of Neurology, Department of Pediatrics, Haçettepe University Medical Faculty, Ankara, Turkey 1 2

Corresponding author: A Tanacan (atakantanacan@yahoo.com)

Background. Spinal muscular atrophy (SMA) is a neurodegenerative disease which is characterised by progressive degeneration of motor neurons in the anterior horns of the spinal cord. It is a mainly chromosome 5-linked genetic disorder, with recessive inheritance and it can be diagnosed prenatally.

Objective. To communicate the importance of prenatal diagnosis of spinal muscular atrophy (SMA) and to demonstrate the gestational outcomes of disease carrier pregnant women who have had invasive prenatal testing (IPT).

Methods. We retrospectively evaluated 113 pregnancies of 76 patients who were referred to the Division of Perinatal Medicine at Haçettepe University in Ankara, Turkey for the prenatal diagnosis of SMA between 2000 and 2015. We evaluated the screening results and gestational outcomes of the patients. The pregnancy outcomes were compared with a control group of 179 patients. The Beksac Obstetrics Index (BOI) was used for the comparison of obstetrical histories/backgrounds of the study and control groups.

Results. Chorionic villus sampling (CVS) and amniocentesis (AC) were performed in 83 (73.5%) and 30 (26.5%) cases, respectively. In 24 cases (21.2%), the fetuses were found to be disease-positive and 23 of them were terminated. The median gestational day at birth (p<0.001), median birthweights (p=0.002) and median BOI (p=0.001) of the study and control groups were compared and the differences were statistically significant.

Conclusion. Prenatal diagnosis of SMA is very important and a nationwide special antenatal care programme must be established for better diagnosis and eradication of this genetic disorder.

S Afr J Obstet Gynaecol 2018;24(1):15-17. DOI:10.7196/SAJOG.2018.v24i1.1270

Spinal muscular atrophy (SMA) is a neurodegenerative disease which is characterised by progressive degeneration of motor neurons in the anterior horns of the spinal cord; the prevalence of SMA is 1 in 6 000 heterozygotes and 1 in 40 homozygotes.[1] SMA is a mainly chromosome 5-linked genetic disorder, with recessive inheritance which results from genetic mutations in the survival motor neuron (SMN) genes.[2] Telomeric and duplicated centromeric genes (SMN1 and SMN2, respectively) play a role in the occurrence of SMA types 1 to 4 . There are also autosomal dominant (chromosome 14-linked) and X-linked forms of SMA.[3] SMA is associated with a wide spectrum of symptoms in terms of the age of onset and severity. The amount of functional SMN protein is critical to the extent of the symptoms, including hypotonia, muscle atrophy, paralysis and even death.[4] Normally, SMN1 genes produce fully functional SMN protein but this production is insufficient in the case of SMA. SMN2 genes also produce SMN protein but in different forms, and only a small percentage of this production is functional. Thus, the level of impaired SMN1 gene production and the contribution of the SMN2 gene determine the severity and progress of the disease.[5]

As mentioned above, SMA has a wide spectrum of variability in phenotype with subtypes depending on the age of onset and clinical severity:[5,6] SMA type 0 fetuses are inactive in utero, the infant has little ability to move and the prognosis is poor; SMA type 1, or Werdnig-Hoffmann disease, is the severe variant which represents 50 - 70%[7] of childhood onset cases (age of onset between birth and 6 months) – these individuals may not sit and usually die within 2 years; SMA type 2 is the intermediate variant and usually begins between 6 and 18 months of age – children with this variant may be able to sit but never stand, and death usually occurs after 2 years of age;[8] SMA type 3 is a mild variant with onset at ~18 months of age, most patients eventually require use of a wheelchair and death occurs in adulthood; and SMA type 4 is the adult variant and presents during the second or third decade – individuals walk during adulthood and death occurs in adult life.[9] SMA is a disease that most often presents with protracted difficulties for affected individuals, their families and for health systems. For this reason, prenatal diagnosis (PD) is very important, especially in severe forms.[4] A polymerase chain reaction-restriction

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RESEARCH fragment length polymorphism (PCR-RFLP) assay has been established for the diagnosis of SMA and it distinguishes the base differences in exons 7 and 8 SMN1 from SMN2 and is used to define homozygous deletions of SMN1 exon 7 and 8.[10] Deletions of the exons 7 and 8 of SMN1 is the most common form; however, point mutations and compound heterozygous cases have also been reported.

Chorion villus sampling (CVS) and amniocentesis (AC) are invasive prenatal tests (IPTs) used for the prenatal diagnosis of SMA.[10] Due to the recessive inheritance of types 1 to 4 SMA cases, up to 25% of prenatal diagnoses are expected to be SMA and pregnancies are terminated. The other important issue is the follow-up of the remaining pregnancies on whom IPT has been performed.

In this study, we have reported PD results and evaluated the gestational outcomes of the remaining pregnant women who gave birth at our medical centre.

Methods

We retrospectively evaluated 113 pregnancies of 76 patients who were referred to the Division of Perinatal Medicine at Haçettepe University in Ankara, Turkey, for the PD of SMA between 2000 and 2015. Prenatal diagnosis was performed on couples who were both carriers of the disease or had at least one child with SMA in their families. Fetuses with a homozygous SMN1 deletion were terminated after genetic counselling with ethical and legal support.

The study protocol was approved by the institutional ethics committee of Haçettepe University (ref. no. GO 16/690) and written informed consent was obtained from the patients.

In the second step of the study, we evaluated the gestational outcomes of the remaining pregnant women whose fetuses were normal or heterozygous for SMN1 deletion and who gave birth at our institution. Patients who gave birth at other hospitals and patients with missing data were excluded from the second step of the study. The pregnancy outcomes were compared with a control group of 179 patients which was randomly chosen from the Antenatal Care Program patients who gave birth to their babies at our hospital between January 2000 and December 2015, without any history suggestive of SMA.

Results

Table 1. Demographical features of the patients Age (years) Gravida Parity APGAR 1 BOI Prenatal test week

CV specimens were dissected under a microscope to remove maternal tissue and were transferred to the Department of Medical Biology for molecular genetic analysis. Fetal DNA was extracted from uncultured CV and amniotic fluid by the phenol-chloroform method. Deletion analysis of the SMN1 gene was performed

by PCR-RFLP as previously described. Briefly, exons 7 and 8 of SMN1 were amplified with PCR using specific primers to the corresponding exons through 35 cycles at the following conditions: 94°C for 1 minute, 55°C for 1 minute and 72°C for 1 minute. Exon 7 and 8 deletions were analysed via overnight digestion of the amplicons at 37°C with DraI and DdeI restriction endonucleases, respectively. Digestion products were electrophoresed in ethidium bromide-stained 4% agarose gel and the results were evaluated according to the digestion pattern. Genomic DNA of the mother was extracted from peripheral blood and multiple polymorphic markers were used in both maternal and fetal samples to rule out the risk of maternal cell contamination.

Tables 1 and 2 show the personal/clinical characteristics of the patients, Beksac Obstetric Index (BOI) scores and the PD data together with pregnancy outcomes. BOI is an obstetric index for the assessment of risk levels by using the following formula: number of alive children + π/10/gravida.[11] Chorionic villus sampling (CVS) or amniocentesis was performed in 83 (73.5%) and 30 (26.5%) cases, respectively.

Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) software version 22 (IBM Corp., USA). The variables were investigated using visual (histograms and probability plots) and analytical methods (Shapiro-Wilk’s test) to determine whether they were normally distributed. Descriptive analyses were presented using medians and minimum-maximum values for the non-normally distributed and ordinal variables. Since the age, gestational day at birth, BOI, and first-minute APGAR values were not normally distributed, nonparametric tests were conducted to compare these parameters, as well as to compare ordinal variables.

The Mann-Whitney U-test was used to compare age, gestational day at birth, BOI, and APGAR 5 values between the groups. A p-value <0.05 was considered to show statistical significance.

In this retrospective study, 113 pregnancies of 76 patients, who had undergone PDs, were evaluated for the risk of SMA. Among the 113 pregnancies, 24 (21.2%) of the fetuses were found to be disease-positive. Twenty-three of the 113 fetuses were found to have both exon 7 and 8 deletions and one was found to have only exon 7 deletion in the SMN1 gene. Twenty-three of the cases underwent termination of pregnancy. The remaining patient delivered prematurely at 26 weeks’ gestation and the fetus died on the first day.

Mean (SD) 29.65 (5.19) 3.50 (1.67) 1.65 (0.94) 8.26 (1.44) 0.15 (0.04) 13.2 (2.45)

SD = standard deviation; BOI = Beksac Obstetrics Index.

Table 2. The results of pregnancy outcomes of prenatally healthy and carrier fetuses Gestation (days), median (range) Birthweight (grams), median (range) APGAR 1, median (range) C/S, n Vaginal birth, n BOI (median)

Study group (n=49) 267 (231 - 281) 3 000 (1 670 - 3 800) 9 (6 - 9) 38 11 0.15 (0.06 - 0.31)

Control group (n=179) 272 (189 - 294) 3245 (600 - 4 500) 9 (4 - 10) 66 113 0.20 (0.01 - 0.41)

C/S = caesarean section; BOI = Beksac Obstetrics Index.

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p-value <0.001 0.02 <0.001

0.001

RESEARCH We also evaluated the frequency of consanguinous marriages and found that 96 of the cases had consanguinous marriages (85%). Eighty patients had a family history of SMA type 1 (70.8%), 28 patients had an SMA type 2 history (24.8%) and 5 patients had an SMA type 3 history (4.4%). There were 69 (61%) male and 44 female (39%) fetuses in our cohort. Among them, 20.2% of the male and 22.7% of the female fetuses had a deletion in the SMN1 gene.

Forty pregnancies who were delivered at other medical institutions or for which there were missing data were excluded from the study and the pregnancy outcomes of the remaining 49 pregnancies whose fetuses were found to be healthy or carriers in terms of SMA and delivered at our hospital were compared with the control group which consisted of 179 patients. Table 2 shows the results of pregnancy outcomes of prenatally diagnosed deletion-negative fetuses (n=49).

The median (range) maternal age of the study group was 30 (17 - 42) years, while the median (range) maternal age of the control group was 28 (19 - 44) years. Maternal age was not statistically significantly different between the study and the control groups (p=0.297).

The median (range) gestational day at birth of the study and control groups were 267 (231 - 281) and 272 (189 - 294) days, respectively, and the difference was statistically significant (p<0.001). The median (range) birthweights of the study and control groups were 3 000 and (1 670 - 3 800 ) and 3 245 (600 - 4 500) g, respectively, and the difference was also statistically significant (p=0.002). The median (range) BOIs of the study and control groups were found to be 0.15 (0.06 - 0.31) and 0.2 (0.01 - 0.41), respectively (p=0.001). Thus, gestational day at birth, birthweight and BOI were lower in the study group and the results were statistically significant. The median (range) APGAR 5 scores of the 2 groups were 9 (6 - 9) and 9 (4 - 10) (p<0.001).

Discussion

Our study consisted of 113 pregnancies of 76 patients and was retrospective. Multicentre-based studies with greater numbers of patients may reveal more information about gestational outcomes of women who had IPT for SMA. The study was limited by large amounts of missing data from obstetric follow-ups and therefore only limited conclusions could be drawn from existing data for a condition which presents in infancy or beyond.

SMA is a disease with social consequences for the families and the societies in which they live.[12,13] Prenatal diagnosis of SMA is critical for couples who are heterozygous for SMN1 gene deletion, although screening must be limited to families who already have children with SMA (or SMA presence in the extended family). We must remember that there is a significant de novo mutation rate (1.7%).[3,14] The American College of Obstetricians and Gynecologists does not recommend general screening and offers screening only for patients who had preconception or antenatal genetic counselling.[15] Furthermore, the screening tests show if there are homozygous deletions of the telomeric exons 7 and 8 of the SMN1 gene but they cannot distinguish the different types of the disease. The other important issue is the ethical issue, especially for type 4 SMA as individuals can reach middle age by the help of supportive therapies.[4] In this study, we have demonstrated that the obstetric histories of the pregnant women who had undergone the PD of SMA were more problematic compared with the control group, but the exact reason for this remains unclear.

We have shown that birthweights and gestational age at delivery were statistically significantly lower in pregnancies which had undergone IPT for the PD of SMA and were delivered at our hospital, but remained within normal/acceptable ranges.

The median gestational age at birth was 38 weeks and 1 day and the median (range) birthweight of the neonates was 3 000 (1 670 - 3 800).

Study limitation As previously stated, the study is limited, particularly in the interpretation of obstetric outcomes, by a considerable amount of missing data.

Conclusion

We believe that PD of SMA is critical and a nationwide special antenatal care programme must be run for better diagnosis and eradication of this genetic disorder. In our study, almost all families whose fetuses were found to be homozygous for the SMN1 gene deletion accepted termination of the pregnancy. Nationwide programmes will enable relevant institutions to spend and invest more money in this field.

The very high incidence of consanguinity in the study undoubtedly contributed to the prevalence of SMA. Social and cultural factors in Turkey contribute to the high incidence of marriage between first and second cousins.

Acknowledgements. Special thanks to healthcare staff at our institution for their contribution to the study.

Author contributions. MSB took part in manuscript writing, interpretation of the data and review of the literature. HY took part in manuscript writing and genetic analysis of the specimens. AT took part in manuscript writing, statistical analysis, review of the literature and data collection. BS took part in data collection and manuscript writing. GO took part in manuscript writing. DAH took part in statistical analysis and manuscript writing. TC took part in manuscript writing. GB took part in manuscript writing and genetic analysis of the specimens. ANC took part in manuscript writing. HT took part in manuscript writing and study design.

Funding. None.

Conflicts of interest. None.

1. Mostacciuolo M, Danieli G, Trevisan C, Müller E, Angelini C. Epidemiology of spinal muscular atrophies in a sample of the Italian population. Neuroepidemiology 1992;11(1):34-38. https://doi. org/10.1159/000110905 2. Frugier T, Nicole S, Cifuentes-Diaz C, Melki J. The molecular bases of spinal muscular atrophy. Curr Opin Genet Dev 2002;12(3):294-298.

3. Khaniani MS, Derakhshan SM, Abasalizadeh S. Prenatal diagnosis of spinal muscular atrophy: Clinical experience and molecular genetics of SMN gene analysis in 36 cases. J Prenat Med 2013;7(3):32-34.

4. Lefebvre S, Burlet P, Liu Q, et al. Correlation between severity and SMN protein level in spinal muscular atrophy. Nat Genet 1997;16(3):265-269. https://doi.org/10.1038/ng0797-265 5. Monani UR. Spinal muscular atrophy: A deficiency in a ubiquitous protein; a motor neuron-specific disease. Neuron 2005;48(6):885-895. https://doi.org/10.1016/j.neuron.2005.12.001 6. Monani UR, Lorson CL, Parsons DW, et al. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Gen 1999;8(7):1177-1183.

7. Pearn JH. The gene frequency of acute Werdnig-Hoffmann disease (SMA type 1). A total population survey in North-East England. J Med Gen 1973;10(3):260-265.

8. Kaufmann P, McDermott MP, Darras BT, et al. Observational study of spinal muscular atrophy type 2 and 3: Functional outcomes over 1 year. Arch Neurol 2011;68(6):779-786. https://doi.org/10.1001/ archneurol.2010.373 9. Antonellis A, Ellsworth RE, Sambuughin N, et al. Glycyl tRNA synthetase mutations in CharcotMarie-Tooth disease type 2D and distal spinal muscular atrophy type V. Am J Hum Genet 2003;72(5):1293-1299. https://doi.org/10.1086/375039 10. Cifuentes-Diaz C, Frugier T, Tiziano FD, et al. Deletion of murine SMN exon 7 directed to skeletal muscle leads to severe muscular dystrophy. J Cell Biol 2001;152(5):1107-1114.

11. Beksaç MS, Aydın E, Turğal M, Karaağaoğlu E. An obstetrics index for the assessment of risk levels of ῾high risk pregnancy᾽ groups. Gynecol Obstet Reprod Med 2015;21(1):10-13.

12. Sugarman EA, Nagan N, Zhu H, et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: Clinical laboratory analysis of >72 400 specimens. Eur J Hum Genet 2012;20(1):27-32. https://doi.org/10.1038/ejhg.2011.134 13. Arnold WD, Kassar D, Kissel JT. Spinal muscular atrophy: Diagnosis and management in a new therapeutic era. Muscle Nerve 2015;51(2):157-167. https://doi.org/10.1002/mus.24497 14. Cuscó I, Barceló M, Soler C, Parra J, Baiget M, Tizzano E. Prenatal diagnosis for risk of spinal muscular atrophy. Br J Obstet Gynaecol 2002;109(11):1244-1249.

15. ACOG Committee on Genetics. ACOG Committee Opinion No. 432: Spinal Muscular Atrophy.

Obstet Gynecol 2009;113(5):1194-1196. https://doi.org/10.1097/AOG.0b013e3181a6d03a

Accepted 27 April 2018.

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

RESEARCH

Use of a visual aid to improve estimation of blood loss in obstetrics N Makhubo,1 BSc (Physiology), MB BCh; J D Makin,2 MB BCh, BSc Hon (Epidemiol Biostat); S Adam,1 MB ChB, FCOG (SA), MMed (UP), Cert Mat Fetal Med (SA), PhD (UP) 1 2

Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa Medical Research Unit for Maternal and Infant Health Care Strategies, University of Pretoria

Corresponding author: S Adam (sumaiya.adam@up.ac.za)

Background. Postpartum haemorrhage (PPH) remains one of the most significant causes of maternal morbidity and mortality. In South Africa (SA) it is the second leading cause of maternal death. Educational programmes, such as visual aids, can improve the estimation of blood loss and subsequently improve clinical judgement and intervention.

Objective. To assess any improvement in blood loss estimation after the introduction of a visual aid.

Methods. We conducted an intervention study at the University of Pretoria Academic Complex and included the Departments of Obstetrics and Gynaecology and Anaesthesiology. The visual aid was created using surgical materials and expired blood from the SA National Blood Services. A pre-intervention objective structured clinical examination (OSCE) was conducted with various blood volumes. Thereafter, the visual aid was made available to all study participants. Nine months later, a second OSCE was conducted.

Results. Eighty-two participants were recruited and 21 were lost to follow-up. Sixty-one participants were included in the analysis.

The overall score from the initial OSCE improved from 4.7500 to 5.6393 on the second OSCE (p=0.003). Participants tended to move from underestimation to either overestimation or accurate estimation of blood loss. The consultant group of participants were the most accurate in estimating blood loss (p=0.450).

Conclusion. The use of a visual aid can improve the estimation of blood loss by healthcare professionals, thus potentially improving resuscitation, and impacting positively on maternal morbidity and mortality associated with PPH, while improving the use of resources.

S Afr J Obstet Gynaecol 2018;24(1):18-21. DOI:10.7196/SAJOG.2018.v24i1.1282

Postpartum haemorrhage (PPH) remains one of the most significant causes of maternal morbidity in both developing and developed countries, with a global prevalence of 6%. It is also a significant cause of maternal deaths in developing countries, with Africa and Asia accounting for 30% of cases of PPH-related deaths globally.[1-4] In South Africa (SA), the 2013 Saving Mothers Report reported that PPH was the second leading cause of maternal death after sepsis.

The main challenge contributing to the high incidence of PPH was the delayed referral from the primary level of care to tertiary institutions; approximately 80% of deaths were thought to have been preventable.[2,3] Prevention of PPH and early intervention for cases of PPH are the most effective measures to combat this problem. One challenge in attaining the second goal is that, prior to an intervention occurring, a correct estimation of blood loss needs to be made.

Visual estimation is the main method used to estimate blood loss in obstetrics leading to interventions such as blood transfusion.

Studies have demonstrated that the visual estimation of blood loss is inaccurate. Visual estimation can underestimate blood loss by up to 33 - 50%.[5-7] In studies comparing the assessment of different specialities, surgeons generally underestimated blood loss while anaesthetists tended to overestimate; also, small blood volumes, e.g. <50 mL, were more likely to be overestimated while large blood volumes, e.g. >1 000 mL were often underestimated.[5-7] Underestimation of blood loss results in a delay in the implementation of the necessary intervention, while overestimation will often lead to wastage of scarce resources, especially in under-resourced settings.

Studies have shown that education programmes, be they web-based or using interventions like a visual aid, can improve the estimation of blood loss and subsequently improve clinical judgement and intervention. These education programmes are institution-based and not easily transferrable, hence the need for the study in each institution.[5]

Objective The aim of our study was to assess if there would be any improvement in blood loss estimation after the introduction of a visual aid.

Methods

We conducted an intervention study at the hospitals in the University of Pretoria Academic Complex, which includes the Kalafong Tertiary Academic and Steve Biko Academic Hospitals, in the Departments of Obstetrics and Gynaecology and Anaesthesiology. The intervention was a visual aid that was created using materials commonly used in a labour ward and expired blood from the SA National Blood Services (SANBS). Images were then taken to create the visual aid (Fig. 1).

Participants included in the study were consultants, registrars, interns and midwives who worked in these departments and were involved in the management of obstetric patients. Second-year interns and final-year registrars who would not be available for the duration of the study were excluded.

The study was conducted using two objective structured clinical examinations (OSCEs). The first OSCE was conducted prior

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RESEARCH

50 mL - Sanitary pad

500 mL - Full kidney dish

100 mL - Soaked pad

200 mL Soaked surgical swab

1 500 mL - PPH

Fig.1. Visual aid with known blood volumes. (PPH = postpartum haemorrhage.) to introduction of the intervention in November 2015. This OSCE had 5 stations with the following volumes of blood: • Station 1: Pad with 30 mL of blood • Station 2: Soaked pad with 80 mL of blood • Station 3: Half-soaked swab with 100 mL of blood • Station 4: Kidney dish with 350 mL of blood • Station 5: Picture with 1 500 mL of blood on the bed and the floor.

Participants completed a questionnaire with demographic information and their estimation of blood loss at each station.

Participants were not informed about the outcome of the OSCE. Thereafter, posters of the visual aid were put up in all labour rooms and obstetric theatres at both hospitals. In addition, all participants were provided with a pocket-sized version of the visual aid (Fig. 1). The second OSCE was conducted in August 2016, 9 months after introduction of the visual aid.

Nine months later, the same individuals were asked to participate in a second OSCE with the following blood volumes. Of note is that these volumes were not identical to the volumes used in OSCE 1: • Station 1: Pad soaked with 20 mL blood • Station 2: Pad soaked with 40 mL of blood • Station 3: Swab soaked with 100 mL of blood • Station 4: Kidney dish with 100 mL of blood • Station 5: PPH image depicting 1 200 mL blood loss

A study number was allocated to each candidate and the same number was used to identify participants in both OSCEs. No new candidates were included in the second OSCE. Participants who did not complete the second OSCE were excluded from the

study as paired data were not available for comparison.

Data were entered into an Excel spreadsheet, corrected for inaccuracies and exported to SPSS version 23.0 (IBM Corp., USA) for analysis. The answers to all the OSCEs were classified as follows: accurate if the estimation was between -20% and +20% of the actual blood volume; overestimation if it was >20% of the blood volume; and underestimation if it was <20% of the correct blood volume. This classification follows that used by Zuckerwise et al.[8] Frequencies and proportions were used to describe the levels of inaccuracy of blood loss estimation by clinicians and at what levels of blood loss difficulties exist. We compared the OSCE results to ascertain whether there was any difference in estimations, pre- and post-intervention in terms of estimation, by means of cross tabulation. A score was created by assigning points to the categories of estimation, i.e. 0 - underestimation, 1 - overestimation, and 2 - accurate.

The reasoning behind this was that overestimation was deemed ‘safer’ than underestimation. The pre- and post-test OSCE scores were compared by means of a paired t-test.

The effect of years of experience, category of the healthcare worker and department (obstetrics and gynaecology v. anaesthesiology) were assessed by means of Pearson correlations, one-way analysis of variance (ANOVA), and independent sample t-tests as appropriate. These variables were then entered into a repeated measures mixed linear analysis to assess whether they had a significant independent effect on the score as a whole. A p-value <0.05 was considered significant.

Ethical approval for the study was obtained from the University of Pretoria,

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Faculty of Health Sciences Ethics Committee (ref. no. 292/2015) and from the SANBS Ethics Committee. Informed consent was obtained from the participants prior to inclusion into the study.

Results

There were 82 participants in the first OSCE. Twenty-one (25.6%) participants were lost to follow-up. Sixty-one (74.4%) participants were included in the analysis.

Fifty-three (86.9%) participants were from the Department of Obstetrics and Gynaecology and 8 (13.1%) participants were from the Department of Anaesthesiology. There were 13 (21.35%) consultants, 18 registrars (29.5%), 11 interns (18%) and 19 midwives (31.1%).

Thirty-nine (63.9%) participants had between 1 - 5 years of experience, with a range of between 1 and 40 years of experience (median 4 years) (Fig. 3).

Table 1 illustrates the comparison of the pre- and post-intervention OSCE. Initially with a small blood volume (Station 1), most participants (n=40; 65%) overestimated the blood loss, while 14 (22.9%) underestimated blood volume.

Only 6 (9.8%) participants were accurate.

Post-intervention we found that 52 (85.2%) participants now overestimated blood loss, 6 (9.8%) remained accurate, and only 3 (4.9%) participants underestimated blood loss.

In Station 2 initially, 35 (57.4%) participants overestimated blood volume, 20 (32.8%) underestimated blood loss and 6 (9.8%) were accurate in their estimation. Post-exposure, 57 (93.4%) of the participants overestimated, 3 (4.9%) were accurate and only 1 (1.6%) underestimated blood volume.

For the estimation of moderate blood loss (Station 3), pre-intervention, 47

RESEARCH (77%) participants overestimated, 12 (19.7%) were accurate and 2 (3.3%) underestimated. Post-intervention, 42 (68.9%) participants overestimated, 18 (29.5%) were accurate, and 1 (1.6%) underestimated blood volume.

In Station 4, most participants (n=35; 57.4%) underestimated blood loss initially, 15 (24.6%) overestimated, while 11 (18%) were accurate. Post-intervention, 48 (78.7%) participants overestimated, while 11 (18%) were accurate and only 1 (1.6%) underestimated blood volume at this station.

In the case of massive blood loss (Station 5), 31 (50.8%) participants underestimated, 18 (29.5%) overestimated, and 11 (18%) were accurate. Post-intervention, 42 (68.9%) overestimated, 13 (21.3%) were now accurate and only 6 (9.8%) underestimated blood loss.

On analysis, the overall score from the initial OSCE (4.7500) improved to 5.6393 on the second OSCE (p=0.003). Participants tended to move from underesimation to either overestimation or accurate estimation of blood loss (Table 2).

It was found that blood loss estimation was inversely related to the number of years of experience; that is, the more experience a participant had, the less accurate was the blood estimation (p=0.006).

However, of note is that the years of experience includes all the categories, from midwives to consultants.

When assessing categories separately in both departments, it was noted that the consultant group (including Department of Obstetrics and Gynaecology and Anaesthesiology) was the most accurate

Years of experience

30 25 20 15 10 5 0 1 2

3 4 5

6 8 10 11 12 13 15 17 18 19 21 22 40 Number of participants

Fig. 2. Years of experience of participants.

Table 2. Score improvement (N=61) Frequency, n (%) 19 (31.1) 13 (21.3) 29 (47.5)

Worse Stayed the same Improved

group in visually estimating blood loss. These values were, however, not statistically significant (p=0.450). Comparison between the two departments showed that the Department of Anaesthesia (95% CI 0.341 - 1.940) was more accurate in visual estimation of blood loss than the Department of Obstetrics and Gynaecology (mean (SD) difference 1.141 (0.399); 95% CI 0.341 - 1.940; p=0.006).

Discussion

Visual blood loss estimation has been reported to be very inaccurate in numerous studies. Most studies demonstrated that there is a tendency to underestimate large blood volumes, i.e. more than a 1 000 mL, and a tendency to overestimate volumes that are less than 50 mL.[4,5] This is similar to the findings in our study. Since small blood volumes were used in both OSCEs it was noted that there was a tendency to overestimate blood loss as noted in most of our stations. The tendency to overestimate was more evident in the second OSCE, in which most participants who had initially underestimated, were now overestimating blood loss.

For practical purposes, underestimating blood loss is worse than overestimating blood loss, since the former results in less reaction, or delayed reaction to postpartum haemorrhage, and thus underresuscitation of the bleeding patient. Whilst overestimating is not as desirable as accuracy, it is safer, since it leads to over-resuscitation, which can decrease mortality as well as morbidity. Therefore, this means the intervention has sensitised most of our participants to err on the side of caution and react quicker to acute blood loss. This, however, does have undesirable consequences such as unnecessary expenditure, especially when scarce commodities such as blood products are consumed.

Studies have demonstrated that the visual aid or other educational programmes results in an improvement in blood loss estimation.[5-8] This was also seen in our study group. The overall scoring in all stations demonstrated an improvement in estimation of blood loss, when comparing the two OSCEs. In our study, the constant exposure to the visual aid in labour ward and theatre may have contributed to the improved blood loss estimation. This gave our midwives, registrars and interns an opportunity to educate themselves each time they were working in the labour ward or the obstetric theatre. The long duration of exposure, i.e. nine months, is a lengthy period for education and remediation. The provision of a pocket visual aid to our participants probably contributed to the improvement as well, since they had it available as an easy reference throughout the 9-month period.

Some studies noted there was no difference in the accuracy of blood loss estimation when comparing years of experience.[7-10] In our study there was a statistically significant difference noted in estimating blood loss, with an inverse relationship when comparing

Table 1. Overall comparisons of the estimations of the first and second OSCE results (N=61)

Station number 1 2 3 4* 5*

Overestimation, n (%) 40 (65.6) 35 (57.4) 47 (77.0) 15 (24.6) 31 (50.8)

OSCE 1 Underestimation, n (%) 14 (23) 20 (32.8) 2 (3.3) 35 (57.4) 18 (29.5)

Accurate, n (%) 7 (11.5) 6 (9.8) 12 (19.7) 11 (18.0) 11 (18.0)

Overestimation, n (%) 52 (85.2) 57 (93.4) 42 (68.9) 48 (78.7) 42 (68.9)

OSCE = objective structured clinical examination. *Only 60 participants completed Station 4 in the post-exposure OSCE (i.e. OSCE 2) and Station 5 in the pre-exposure OSCE (i.e. OSCE 1).

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OSCE 2 Underestimation, n (%) 3 (4.9) 1 (1.6) 1 (1.6) 1 (1.6) 6 (9.8)

Accurate, n (%) 6 (9.8) 3 (4.9) 18 (29.5) 11 (18.0) 13 (21.3)

RESEARCH years of experience with accurate estimation of blood loss. However, the group with more years of experience, that is, more than five yearsâ&#x20AC;&#x2122; experience, were mainly midwives. When comparing categories exclusively, it was noted that the consultant category had the highest score; however, the result was not statistically significant. We would theoretically expect this group to estimate more accurately, since practically speaking, they have more experience. It needs to be noted however, that that the consultant group also included consultants from both departments (Obstetrics and Gynaecology and Anaesthesiology).

The literature reports that surgeons tend to underestimate blood loss as opposed to anaesthetists who usually overestimate blood loss.[7,8] In our setting, the anaesthetists had a significantly higher overall score compared with the Department of Obstetrics and Gynaecology. This may be attributed to the anaesthetists working with a variety of surgeons and estimating various volumes of blood loss on a daily basis, or the surgeons preferring a lower documented blood loss, to the detriment of the patient. The smaller number of anaesthetists in our study and the inclusion of midwives in the obstetric group may have influenced this outcome.

In our study, we are uncertain regarding whether the visual aid pocket card or the charts had a greater impact. The charts were posted in labour ward and in theatre. This was advantageous as these are the sites where blood loss is estimated. The advantage of the pocket-sized chart was that it was always with the individual.

It is of interest, yet not surprising, that most of our participants shifted from under- to overestimation, since we used small volumes in both our OSCEs due to practical considerations. There is a shortage of blood products and we could only secure a limited amount of expired blood per OSCE. Health professionals tend to overestimate small blood volumes (<50 mL) and underestimate large volumes (>1 000 mL).[5-8] Hence, it was not surprising that most of the volumes were overestimated, and that there was a shift from underestimation to overestimation post-intervention. This shift is particularly important because overestimation as opposed to underestimation is preferable, since morbidity and mortality can be prevented int the event of an overestimation of blood loss.

Overall, our study is in keeping with findings in previous studies that teaching programmes, be it a visual aid, as in our case, or computer programmes, can lead to improvement in the estimation of blood loss. However, what needs to be remembered is that education is institution-dependent and ongoing.

The strength of our study is that we included a range of healthcare workers, including midwives, with varying levels of experience. We also used human blood rather than artificial blood or its equivalent in our OSCEs and visual aids.

Study limitations Limited matched data were available for analysis, owing to the significant loss to follow-up. This could be due to the long period

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between the two OSCEs. The other limitation was the type of blood used. As whole blood is expensive and a scarce resource, we used expired red cell concentrate which is concentrated compared with whole blood which also includes plasma.

We also noted that 31% of participants did not improve in this study, though 47% did. This suggests that the visual aid intervention still needs improvement; this might be either by using a greater range of blood loss images (we have already acknowledged that there were a number of images with limited blood loss due to the limited amount of expired blood available), or perhaps by some other adjustment of the intervention.

Conclusion

The use of a visual aid can improve the estimation of blood loss by healthcare professionals. We have demonstrated that a visual aid can be developed for each institution. This holds the potential to improve resuscitation and thus decrease maternal morbidity and mortality associated with PPH underestimation, and to decrease unnecessary intervention and the use of scarce resources by overestimation.

Acknowledgements. We would like to thank the Department of Obstetrics and Gynaecology and Anaesthesiology at the University of Pretoria, and the SANBS for their assistance in this project.

Author contributions. NM was responsible for the research protocol, data collection and compilation of the article. JDM was responsible for the statistics analysis. SA was responsible for conceptualisation of the study, protocol development and compilation of the article.

Funding. None.

Conflicts of interest. None.

1. Fawcus S, Moodley JA. Management of post-partum haemorrhage. S Afr J Obstet Gynaecol 2011;17(2):26-27.

2. National Department of Health. A Monograph of the Management of Post-Partum Haemorrhage.

National Committee on Confidential Enquiries into Maternal Deaths in South Africa. Pretoria: NDOH, 2010.

3. National Committee for Confidential Enquiries into Maternal Deaths. Saving Mothers 2011 - 2013: Sixth Report on Confidential Enquiries into Maternal Deaths in South Africa. Pretoria: NCCEMD, 2014. http://www.kznhealth.gov.za/mcwh/Maternal/Saving-Mothers-2011-2013-short-report.pdf (accessed 23 November 2017).

4. Fawole B, Awolude OA, Adeniji AO, Onafuwokan O. WHO Recommendations for the Prevention of Postpartum Haemorrhage: RHL Guideline. Geneva: World Health Organization, 2010.

5. Toledo P, McCarthy RJ, Burke CA, Goetz K, Wong CA, Grobman WA. The effect of live and webbased education on the accuracy of blood loss estimation in simulated obstetric scenarios. Am J Obstet Gynecol 2010;202(4):400)e.1-5. https://doi.org/10.1016/j.ajog.2009.10.881 6. Stafford I, Dildy G, Clark S, Belfort M. Visually estimated and calculated blood loss in vaginal and caesarean delivery. Am J Obstet Gynecol 2008;199(5):519.e1-7 https://doi.org/10.1016/j. ajog.2008.04.049 7. Wong C. Accuracy of blood loss estimation after vaginal delivery. http//www.clinicaltrials.gov (accessed 25 October 2017).

8. Zuckerwise LC, Pettker CM, Illuzzi J, Raab CR, Lipkind HS. Use of a novel visual aid to improve estimation of obstetric blood loss. Obstet Gynecol 2014;123(5):982-986. https://doi.org/10.1097/ AOG.0000000000000233 9. Yoong W, Karavolos S, Damodaram M, et al. Observer accuracy and reproducibility of visual estimation of blood loss in obstetrics: How accurate and consistent are health-care professionals?

Arch Gynecol Obstet 2010;281:207. https://doi.org/10.1007/s00404-009-1099-8 10. Patel A, Walia R, Patel D. Accuracy of visual estimation of blood loss. Int J Gynaecol Obstet 2006;3:220-224.

Accepted 29 April 2018.

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

RESEARCH

Barriers to cervical cancer screening uptake among rural women in South West Nigeria: A qualitative study A O C Onyenwenyi, BSc Nursing, MPH; G G Mchunu, B Soc Sci Nursing, MN, PhD School of Nursing and Public Health, Howard College, University of KwaZulu-Natal, Durban, South Africa Corresponding author: A O C Onyenwenyi (oguoguo2001@yahoo.com)

Background. Diverse barriers influence cervical cancer screening uptake among rural women. The study explored barriers related to the uptake of cervical cancer screening among rural men and women in 14 communities of Ado-Odo Ota, Ogun State, Nigeria.

Objective. To inform the development of a cervical cancer screening model for use by rural women.

Methods. A qualitative exploratory research design was used. Qualitative information was collected from purposively sampled 28 individuals (13 rural men and 15 rural women) using focus group discussions and in-depth interviews. Data were analysed thematically.

Results. Five categorical barrier themes were identified including hospital-related, economic, geographical, educational and psychosocial barriers.

Conclusion. To address the identified barriers, the involvement of spouses and religious and cultural leaders in the planning and implementation of cervical cancer screening intervention is recommended. Cervical cancer screening services should be integrated into the services of primary healthcare centres. The government should consider providing subsidised or free screening programmes for rural women.

S Afr J Obstet Gynaecol 2018;24(1):22-26. DOI:10.7196/SAJOG.2018.v24i1.1290

Deaths related to cervical cancer in developed countries have drastically declined over the past three decades due to successfully organised population-based cervical cancer screening programmes.[1,2] Similar programmes are generally lacking in sub-Saharan Africa and other low- and middle-income countries (LMICs).[3,4] Barriers to screening uptake have been widely documented. A study in the UK identified barriers to cervical cancer screening, including not wishing to know the result of the test, belief that the test was not necessary in asymptomatic women, not trusting the health services and inconvenient appointment times.[3] A Canadian study reported inconvenient clinic hours, procedural barriers and travel distance to screening services.[5] Among Asian-American women, psychosocial factors, religious beliefs, lack of knowledge and poor access to healthcare were identified.[6] Chidyaonga-Masek et al.[7] reviewed contributing factors for underutilisation of cervical cancer prevention services in LMICs. They identified three categorical barriers at individual, community and health systems levels. The individual barriers were knowledge and awareness about risk factors, while stigma related to discussion of reproductive issues was a limiting factor at the community level, and inadequate financial resources and infrastructure as well as poorly-trained personnel were health system-related barriers.

In sub-Saharan Africa, notable barriers to cervical screening have been attributed to widespread poverty and lack of awareness of such programmes.[1,8] Other factors include psychosocial and cultural contexts, and limited family support.[3] Earlier studies attributed poor screening uptake to the presence of competing healthcare priorities, burdens of diseases other than cancers, and reduced public budgets resulting in failure to establish cervical cancer screening programmes.[9] In Nigeria, healthcare

services have traditionally been based on curative interventions rather than preventive healthcare. War and civil strife have had consequences on the existing healthcare infrastructure.[10] The principal barriers associated with cervical cancer screening uptake reported in the literature for developing countries such as Nigeria are mainly a low level of awareness, widespread poverty, and lack of the requisite human and material resources to support cytology-based programmes and poverty.[3,11,12] Isa-Modibbo et al.[4] explored the religious and cultural barriers to cervical screening in two hospitals, from the South West and North Central regions of Nigeria. The study reported that barriers to cervical cancer screening vary by religious affiliation.

Most of the previous studies that examined barriers to screening uptake among women were institutional or hospital-based. The present study focused on understanding the barriers among rural community men and women. As the heads of households/families, men are increasingly involved in reproductive issues. Our study aimed to identify the current barriers against uptake of cervical cancer screening by rural men and women. The aim of the study was to inform the development of a community-based cervical cancer screening model for the Sango community in South West Nigeria.

Methods Study site

The study was conducted in 14 catchment communities of Sango Primary Health Center (PHC) located in Ado-Odo/Ota Local Government Area (LGA) of Ogun state, South West Nigeria. AdoOdo/Ota LGA has an estimated population of 527 242, of whom 261 523 are male and 265 719 are female,[13] in ~450 towns, villages and settlements. The LGA has 16 constitutional wards and Sango is one of them.

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RESEARCH

Study design selection, description of participants’ data collection

Ethical approval

An exploratory qualitative study design was used. Data were collected through in-depth interviews and focus group discussion (FGD) sessions from 28 purposively sampled participants that included rural dwellers (13 men and 15 women). Purposive sampling was used to identify subjects for in-depth investigation that enabled the researcher to gain a deeper understanding of the issue of enquiry.[14] Traditional, religious and opinion leaders were considered most appropriate to provide responses that would help to answer the research questions.

The inclusion criteria were rural men and women residing in the catchment communities of Sango PHC, men aged ≥30 years, and women aged 23 to 65 years, which is the recommended screening age range. The head of the community, village development committee chairmen, religious leaders (pastor, imam, priest, traditional religion) were included in the study as key informants.

Three FGD sessions were held with groups comprising 7 males and 8 females. The FGD guide assessed participants’ demographics, their experiences or opinions about cervical cancer screening, and what could prevent community women from accessing screening services. Thirteen interview sessions were conducted using a semistructured interview guide (6 males and 7 females). The interview guide assessed participants’ demographics, screening experience (personal for the female and spouses among male respondents) and perceived barriers to screening uptake.

Data were collected by trained research assistants fluent in the local languages. All interview sessions were audio recorded and transcribed verbatim with participants’ permission. Confidentiality of information and anonymity of participants were maintained and assurances on these were given to the participants during the process. Credibility was developed through earlier familiarity with the participants from preliminary visits before the first data collection commenced. Prolonged investigation strategies were used to establish trust.

Data analysis All interviews were audio recorded, transcribed verbatim and translated into English. Validity was ensured by checking back transcripts against original audio recordings for accuracy, thereby confirming the semantic equivalence of the data.[15] The transcripts were prepared for coding by providing adequate space at the margin for comments. Using highlighters, potential patterns were marked as follows: (i) notes on the text were analysed with highlights; (ii) codes were identified and matched with extracted data; (iii) codes were collated together on a board; (iv) the different codes were sorted into potential themes, grouping relevant coded data extracted within the identified themes in tabular form with names of code and the meaning identified and described; (v) using an iterative process, a thematic map was generated from the FGD and in-depth interview sessions; (vi) themes were defined and redefined; the themes involved identifying what was important in answering the research questions.

Codes generated from the data and the responses were organised into key thematic areas, from which a report was produced with verbatim quotes from participants to support each theme. The data collection process lasted 16 weeks (13 July to 30 November 2016).

Observational field notes and responses from rural men and women (different sources) were triangulated to provide multiple perspectives of the information, as well as validate the data.

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Ethical approval and permission to conduct this study were obtained from: (i) the Biomedical Research Ethics Committee (BREC) at the University of KwaZulu-Natal (ref. no. BFC505/15), (ii) the Ethics and Research Committee of the Federal Medical Centre, Abeokuta, Nigeria, (ref. no. NREC/06/21/2010-15); (iii) the Ado-Odo Ota LGA; and (iv) the Sango Joint Community Development Association. All participants were given an information sheet indicating the research aim, purpose, and meaning of their participation and their right to withdraw from the study at any time. Thereafter, each participant signed a consent form.

Results

Sociodemographics of study participants The mean (range) age of the participants was 49 (36 - 60) years.

Of the 28 participants interviewed, 15 were women and 13 men.

A higher proportion of 18 were Christians and 10 were Muslim.

Twenty-six were married and from the Yoruba ethnic group.

Ten had technical and tertiary education, and 8 had no formal education. The participants’ occupations included petty trading, technicians, faith leaders and retired civil servants.

Barriers to screening uptake Five broad themes emerged that described the barriers to cervical cancer screening uptake: hospital-related barriers, economic, geographical, educational and psychosocial barriers (Fig. 1).

Hospital-related barriers Complaints were expressed about long clinic waiting hours, often resulting in loss of business or earnings, and excessive hospital fees. Other issues cited included the painful screening procedure, an inconvenient screening time, and lack of trust of the healthcare workers. Some prominent comments associated with screening time are given below: ῾ ...when I come for hospital, the doctor cannot come in time and check us so I can’t go to the market... that’s why I don’t want to come, because of my market.᾽ (ID1 p4; female) ῾ …but the money they are collecting for the test is too much, they [referring to rural women] cannot afford it.' (IDIp5, female) ῾ ...Patience on the part of the community health workers; they should not be harsh on the women. They should explain it vividly and tell them the whole truth about it.᾽ (IDIp6, male)

Geographical barriers Geographical barriers are related to hospital-related barriers.

Distance to screening centres, not knowing where the screening centres are located and travel costs to healthcare services discourage cervical cancer screening uptake, especially for women who do not have an adequate source of income. Distance to screening centre was cited as centres are located in tertiary health institutions located in a town of a neighbouring state. Some of the concerns raised are captured in the quotes below: ῾ Because I want to do cervical test I have to go to Lagos University Teaching Hospital or Lagos State University Teaching Hospital … no money even for transport and it is not near us …᾽ (IDIp5, female). ῾Well, the lack of availability of screening centres is also a critical issue. ᾽ (FGD3P3, male).

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RESEARCH

Hospitalrelated

Long hospital waiting time Cost of screening expensive Insufficient financial resources

Economic

Barriers

Geographical Educational

Time loss for market and business

Lack of transport fare to go for screening Lack of money to pay for screening test

High cost of living

Little money reserved for health expenses

Location of the screening site in urban areas

Screening places situated too far

Illiteracy

No awareness of the screening Women fail to interact with others

Religious

Psychosocial

Cultural

Psychological

Prefer herbs to orthodox medicine Fear of the test results Low self-esteem Consent from husband

Partner/or spouse-related

Husbands do not want wives to be seen by males

Refusal to go for test for fear of outcome Decision regarding screening is made by husband

Fig. 1. Categories of barriers to cervical cancer screening among rural women.

Economic/financial barriers Financial constraints that were cited included cost of travel to distant screening centres and charges for screening and treatment.

These difficulties were compounded by the prevailing high cost of living and the economic recession, as well as high levels of unemployment in Nigeria, were noted by participants in comments such as the following: ῾ Some women are just ordinary house wives. Yes, they are unemployed. So…if the husband doesn’t give her any money, she cannot go to the hospital. And some of them, their husband will be jobless, the wife jobless… will not be able to be affording the test.᾽ (IDIp10, female).

Educational barriers Illiteracy, especially of husbands, was noted as a barrier to cervical cancer screening uptake. This was in relation to lack of appropriate health information concerning the disease among community men and women. Women’s responses showed that when they experienced symptoms, they preferred herbs to orthodox medications.

The women perceived no need for healthy women to visit hospitals for a check-up of any form; the perception was that hospital visits were for sick people only, not for those in good health. If you were healthy looking, you were assumed to be healthy. This poor

health maintenance behaviour is reflected in the following response: ῾...Illiteracy is the major problem that

may…if the husbands are illiterate, because they will say ‘why? Why are you going, don’t say that you have it’...when somebody is an illiterate they may not see the need to go for screening (IDIp3, male).

Psychosocial barriers In relation to psychological, religious, cultural or partner-related, a few of the respondents cited cultural and religious barriers. The findings indicate linkage between partner/ spousal approvals and religious beliefs. The female respondents mentioned spousal approval before undergoing screening.

Community beliefs in traditional medicine could constitute a barrier to using orthodox medicine. Major reasons for non-utilization of orthodox medicine were the negative belief that not all forms of ailment require orthodox medical intervention. There was a negative perception that some illnesses, one of which was cervical cancer, should not be treated by orthodox medicine. An FGD participant made the following comment: ῾The community may say, that type of sickness you are having is not the one they treat in the…..they use medical treatment for, it might be done locally and they continue to apply local medicine.’ (FGD3P2, male)

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Other responses conveyed similar perceptions: ‘Cultural reasons too can affect because there are...some people who have never left their village. They believe that they don’t have business with the Oyinbo medicine (orthodox medicine). So, they don’t want to even hear anything about white man, their own is their root and their herbs, and will not agree to go for screening.’ (IDIp7, female) ‘...like we the Hausa’s, it is not every man that will allow his wife to go to the hospital.

In fact, it is not every man that will even allow his wife to go outside the house. not to talk of going to the hospital. Some men will say “Ha their wives, their mothers, did they go to the hospital before giving birth to them?” Some will say that the practices in the hospital doesn’t tally with what they have in the culture so they will not go to the hospital.’ (IDIp10, female) Fear was a very frequently used word in describing barriers to screening uptake by rural men and women: fear of a positive result and its implication; issues related to the disclosure of results to the spouse; fear of embarrassment following disclosure of positive test results; and fear of what the spouse would say or do on learning about a positive result, since it could lead to a broken home. A woman could potentially be forced to leave the husband’s house because she had a sexually transmitted infection and is assumed to be unfaithful. Shame was especially associated with disclosure of cervical cancer-related symptoms as it is a disease of the female reproductive system.

The situation would be worse if the woman was young and unmarried. The following responses reflect these perceptions: ‘It depends on the age these things occur, if it is much younger family or is not married you know, sometimes they have the tendency to hide such things. Like a woman who is raped, if she doesn’t want people to know what happened to her and if she has such sickness, she might not even tell her family.’ (FGD3P3, male) ‘In a situation where the husband is not the understandable type, such woman can even lose her home. The process of saying how did you get this thing and the thinking that she is cheating on the husband that is why she caught the cervical problem.’ (FGD3P3, male)

RESEARCH

Dependency on spouse for decision-making Spousal approval is needed for women to undertake cervical cancer screening; this could constitute a barrier if the husband delayed the decision, providing funds for the screening or giving approval to undertake the service. The extract below supports this information: ‘I have to seek the permission of my husband, if he permits me to go, then I can go.’ (IDIp8, female).

‘Some husband can delay their wife not to go, because of what?

Because of money. Maybe the woman is not doing anything to buy matches from another woman only her husband. So, all these things can disturb them not to come for the screening.’ (FGDp2, female)

Religious and gender barriers Religious beliefs and practices can constitute a barrier among Christians and Muslims. Some Muslim women would not allow male screeners to attend to them in the hospital, which is a potential barrier to uptake of cervical cancer screening. In our cohort, most women respondents preferred female health workers to attend to them as indicated in the quotes below: ‘Alfa’s wife may not want her private part to be seen by another person other than her husband.’ (FGD2P5, female) ‘...some categories of Muslim women that will not allow men to examine them, so they will not go for the screening. The husbands won’t allow other men to see their womb...so they may not be permitted to come for screening.’ (FGD3P3, male) ‘Some religious belief don’t go to hospital like the Jehovah Witness.

They do not believe in hospital services Christians and Muslim alike.’

(ID1p1, female) Stigma/shame was an associated barrier, as indicated in the quote below: ‘So again, if it is a tight community, the ideas of not being seen can also restrain the person…everybody knows each other and err what is wrong with her?...maybe can prevent or cause hiding the sickness.’

(FGD3P3, female)

Discussion

The aim of this study was to explore the perceptions of rural community men and women on barriers to cervical cancer screening uptake. The findings informed designing a culture-sensitive model of care for use by rural women. Hospital-associated factors, such as poor access due to high screening costs, location, unprofessional attitude and gender of healthcare workers, emerged as key barriers that need to be addressed. These findings are similar to the reports from other LMICs. Chidyaonga-Maseko et al.[7] reported that underutilisation of cervical cancer screening services was associated with health system-related barriers, infrastructure, and lack of trained personnel.

The rural women in our study saw no need for healthy women to undergo any kind of hospital check-ups. Cues to seek hospital care were having obvious symptoms and having tried herbal remedies without a desired result. This leads women to present at an advanced stage of the disease.

In our study, screening uptake was influenced by psychological, religious and cultural barriers, such as spousal approval. Similar findings have been documented elsewhere.[9,12] Further barriers of significant concern are erroneous cultural beliefs that cervical cancer is not among the diseases that require orthodox medical

25

intervention, and the high preference given to the use of herbs in the management of most diseases.

In Nigeria, poor access to screening services was compounded by poverty, which had a negative influence on screening uptake.

Similar findings were documented in other LMICs,[7,8] where rural women reported poor access to screening services as a result of transportation costs.

Fears expressed by the women studied were associated more with an anticipated reaction from spouses/partners and community members rather than with the health implications of a positive test result. Women feared the negative consequences such as separation and abandonment. Drawing on the lessons of the HIV/AIDS epidemic, male involvement through couples’ counselling and education for cervical cancer uptake can ease such fears. Shame was associated with disclosure of cervical cancer-related symptoms and screening results because it is a disease of the female reproductive system. Isa-Modibbo et al.[4] also reported fear of disclosure of results and lack of awareness among the barriers to uptake of screening.

Study limitation Limited funding restricted the study to a single geopolitical region in Nigeria. The findings of this study may not be generalisable to other regions due to diverse cultures and religions.

Conclusions and recommendations

Hospital-related barriers, poverty, ignorance and psycho-social barriers (cultural and religious) negatively influenced screening uptake. To address the identified barriers in cervical cancer prevention interventions, we recommend the following: (i) male involvement, including spouses, and religious and cultural leaders; (ii) cervical cancer screening services should be integrated into primary healthcare centres as a strategy to improve screening access; and (iii) the government should consider providing free or subsided cervical cancer screening for rural women. Further exploration of the roles of culture and religion in promoting cervical cancer prevention programmes would be useful.

Acknowledgements. We gratefully acknowledge the Sango community for their participation. We wish to thank Professor Moses Chimbari and his team of consultants for reviewing the manuscript and for their support.

Author contributions. AOC was the principal investigator, conceived the study, carried out the data collection and analysis and prepared the manuscript. GG guided the development of the protocol to completion, verified data, edited and revised the manuscript for intellectual content and approved the version for submission. Both authors approved the final version to be published.

Funding. This research study was funded through scholarship support for the principal investigator from the School of Nursing and Public health, University of KwaZulu-Natal, Durban, South Africa.

Conflicts of interest. None.

1. World Health Organization (WHO). Comprehensive Cervical Cancer Control: A Guide to Essential Practice. 2nd ed. Geneva: WHO, 2014.

2. Cunningham MS, Skrastins E, Fitzpatrick R, et al. 2015. Cervical cancer screening and HPV vaccine acceptability among rural and urban women in Kilimanjaro Region, Tanzania. BMJ 2015;5(3):e005828. https://doi.org/ 10.1136/bmjopen-2014-005828.

3. Marlow LVA, Waller J, Wardle J. Barriers to cervical cancer screening among ethnic minority women: A qualitative study. J Fam Plann Reprod Health Care 2015;41(4):248-54. https://doi. org/10.1136/jfprhc-2014-101082.

4. Isa-Modibbo FI, Dareng E, Bamisaye P, et al. Qualitative study of barriers to cervical cancer screening among Nigerian women. BMJ 2016 Jan 11;6(1):e008533. doi:10.1136/bmjopen-2015-008533.

5. Racey SC, Gesink C. Barriers and facilitator to cervical cancer screening among women in rural Ontario, Canada: The role of self-collecting HPV testing. J Rural Health 2015;32(2):136-145. https:// doi.org/10.1111/jrh.12136. Epub 2015 Aug 12.

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RESEARCH 6. Fang CY, Ma GX, Tan Y. Overcoming barriers to cervical cancer screening among Asian-American women. Nam J Med Sci 2011;4(2),77-83.

7. Chidyaonga-Maseko F, Chirwa ML, Muula AS. Underutilization of cervical cancer prevention services in low and middle-income countries: a review of contributing factors. Pan Afr Med J 2015;21, 231. https://doi.org/10.11604/pamj.2015.21.231.6350.

8. Denny L, Quinn M, Sankaranarayanan R. Screening for cervical cancer in developing countries.

Vaccine 2006;24(Suppl 3):S71-S77. https://doi.org10.1016/j.vaccine.2006.05.121 9. Compaore S, Ouedraogo CMR, Koanda S, Haynatzki G, Chamberlain RM, Soliman AS. Barriers to cervical cancer screening in Burkina Faso: Needs for patient and professional education. J Cancer Educ 2016;31(4):760-766. https://doi.org/10.1007/s13187-015-0898-9 10. Dodo AM, Sykes P, Powell C. Exploring the barriers to breast and cervical cancer screening in Nigeria: A narrative review. Afr J Reprod Health 2016;20(4):89-98.

11. Al Meer FM, Aseel MT, Al Khalaf J, Al Kuwari MG, Ismail MFS. Knowledge, attitude and practices regarding cervical cancer and screening among women visiting primary healthcare in Qatar. Eastern Mediterranean Health J 2011;(17)11:855-861.

12. Chigbu CO, Onyebuchi AK, Ajah LO, Onwudiwe EN. Motivations and preferences of rural Nigerian women undergoing cervical cancer screening via visual inspection with acetic acid. Int J Gynecol Obstet 2013;120(3):262-265. https://doi.org/10.1016/j.ijgo.2012.10.011 13. Chigbu CO, Aniebue U. Why southeastern Nigerian women who are aware of cervical cancer screening do not go for cervical cancer screening. Int J Gynecol Cancer 2011;21(7):1282-1286. https://doi.org/10.1097/IGC.0b013e31822bd139.

14. National Population Commission (NPC). Population Distribution by Sex, State, LGAs and Senatorial Districts: 2006 Census Priority Tables Volume III. Lagos: NPC, 2010. http://catalog.ihsn. org/index.php/catalog/3340/download/48521 (accessed 4 September 2017).

15. Chen HY, Boore JZ. Translation and back â&#x20AC;&#x201C; translation in qualitative Nursing research: Methodological review. J Clin Nurs 2010;19(1-2):234-239. https://doi.org/10.1111/j.13652702.2009.02896.x

Accepted 29 April 2018.

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

RESEARCH

Recommendations for thromboprophylaxis in obstetrics and gynaecology E Schapkaitz,1 FCPath (Haem), MMed (Haem); P R de Jong,2 MMed, FRCOG (London), FCOG; B F Jacobson,3 FRCS (Glasgow), PhD; H R BĂźller,4 MD, PhD Department of Molecular Medicine and Haematology, National Health Laboratory Service and University of Witwatersrand, Johannesburg, South Africa 2 Dept of Obstetrics and Gynaecology, University of Cape Town and Christiaan Barnard Memorial Hospital, Cape Town, South Africa 3 Department of Molecular Medicine and Haematology, National Health Laboratory Service and University of Witwatersrand, Johannesburg, South Africa 4 Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands 1

Corresponding author: E Schapkaitz (elise.schapkaitz@nhls.ac.za)

Background. Venous thromboembolism (VTE) is associated with considerable morbidity and mortality in the absence of thromboprophylaxis.

Method. The Southern African Society of Thrombosis and Haemostasis reviewed the available literature and comprehensive evidencebased guidelines on the prevention of VTE in obstetrics and gynaecology. A draft document was produced and revised by consensus agreement by a panel of professionals from various specialties. The recommendations were adjudicated by an independent international expert to avoid local bias.

Results and conclusion. We present concise, practical thromboprophylaxis guidelines for the clinical management of patients in obstetrics and gynaecology. Recommendations reflect current best practice, which it is hoped will lead to improved anticoagulation practice in this group of patients.

S Afr J Obstet Gynaecol 2018;24(1):27-31. DOI:10.7196/SAJOG.2018.v24i1.1312

Venous thromboembolism (VTE) is associated with considerable morbidity, and mortality in the absence of thromboprophylaxis.

Pulmonary embolism (PE) is the leading cause of maternal death worldwide.[1] Further, PE is the cause of ~20% of deaths following hysterectomy.[2] The prevalence of deep vein thrombosis (DVT) in patients having major gynaecologic surgery ranges between 15% and 40%.[3] There are a few randomised trials to guide the management of this group of patients. Recommendations in this guideline therefore reflect current best practice. Management should be individualised according to the risk-benefit ratio and cost.

Methods

On behalf of the Southern African Society of Thrombosis and Haemostasis, a representative guideline panel of professionals from various specialities reviewed the available literature on the prevention of VTE in obstetrics and gynaecology.

Recommendations presented are in accordance with the more comprehensive evidence-based guidelines namely the 9th edition of the American College of Chest Physicians (ACCP),[4] the Green Top guidelines of the Royal College of Obstetricians and Gynaecologists (RCOG),[5] the American College of Obstetricians and Gynecologists (ACOG),[6] the Society of Obstetricians and Gynaecologists of Canada (SOGC),[7] Society of Obstetric Medicine of Australia and New Zealand (SOMANZ)[8] and the European Society of Regional Anaesthesia (ESRA) Guidelines on Anticoagulation and Regional Anaesthesia.[9] Many of these recommendations are formulated in

the absence of strong evidence and the guidelines were also prepared in conjunction with systematic reviews and observational studies. A draft document was produced and revised by consensus agreement.

The guidelines were adjudicated and co-authored by an independent international expert to avoid local bias.

VTE in gynaecology

Oestrogen and VTE risk Oestrogen use increases the risk of VTE as a class effect which is dose dependant.[10] The risk of VTE is dependent on the route of administration. There is lower associated risk with transdermal and intra-uterine hormonal therapy as well as the progesterone-only oral contraceptive.[11,12]

Gynaecological surgery and VTE risk Table 1 provides a practical risk assessment for VTE in patients undergoing gynaecological surgery. Patient- and procedure-related risk factors should be considered when assessing the risk of VTE. Patient-related risk factors include: age >60 years, prior history and family history of VTE, immobility, dehydration, sepsis, underlying malignancy, pregnancy, oestrogen therapy, obesity, hereditary thrombophilia, inflammatory bowel disease, human immunodeficiency virus infection, and autoimmune diseases including antiphospholipid syndrome.

Procedure-related risk factors include: duration of the procedure; degree of tissue damage; degree of immobility following surgery;

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Table 1. Risk categories for gynaecological surgical patients Risk Category High Risk Major surgery, age >60 years with malignancy or history of VTE Major surgery, age 40 - 60 years with malignancy Major surgery with additional risk factors such as obesity (BMI >30 kg/m2), hereditary thrombophilia, HIV, autoimmune disease, oestrogen therapy Moderate Risk Major surgery for benign condition without other risk factors Minor or laparoscopic surgery with additional risk factors such as obesity, hereditary thrombophilia, HIV, autoimmune disease, oestrogen therapy Low Risk Minor or laparoscopic surgery without other risk factors

and nature of the surgical procedure. The post-operative risk of VTE in patients on the combined oral contraceptive (COC) increases from 0.5% to 1%.[13] The risk of VTE needs to be balanced against the risk of stopping the COC prior to surgery. There is insufficient evidence at this time to recommend discontinuation of the COC prior to surgery or immobilisation. Hormonal therapy does not need to be stopped prior to surgery if appropriate thromboprophylaxis is used.[5]

Thromboprophylaxis following gynaecological surgery • Low-molecular-weight heparin (LMWH) is the anticoagulant of choice: • Enoxaparin 40 mg subcutaneous (sc) once daily • Dalteparin 5 000 units sc once daily • Nadroparin 2 850 units sc once daily.

• It is recommended to use weight-adjusted LMWH dosing in patients at extremes of weight.

• It is recommended to start LMWH 6 - 12 hours after surgery, provided there is no active bleeding.

• In patients at high risk of bleeding or undergoing neuraxial anaesthesia, it is recommended to start LMWH a minimum of 12 hours postoperatively.

• LMWH prophylaxis should be continued until the patient is fully mobile.

• For major cancer surgery, 5 weeks of thromboprophylaxis is recommended.

• For major surgery, in patients with additional risk factors, at least 7 - 10 days of thromboprophylaxis is indicated.

• Avoid additional antiplatelet drugs for analgesia during anticoagulation.

• In patients at high risk of bleeding, use of mechanical prophylaxis such as intermittent pneumatic compression (IPC) should be considered.[14] There is, however, limited evidence for graduated compression stockings.

VTE in obstetrics

The risk of VTE is increased five- to tenfold in pregnancy.[15] The hypercoagulability of pregnancy persists for several weeks after delivery and the greatest risk for VTE is in the early postpartum period.[16] The recent decline in maternal deaths from VTE can be attributed to the use of thromboprophylaxis in high-risk women.[1] There are multiple risk factors which increase the risk of VTE. Several guidelines have proposed a risk assessment score. In the absence of randomised controlled trials, there is no evidence for

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Recommendation Thromboprophylaxis Thromboprophylaxis Thromboprophylaxis

Consider thromboprophylaxis Consider thromboprophylaxis

Early mobilisation

a complex clinical score.[17] The appropriate use of prophylaxis depends on identification of patients who are at high risk of VTE. • Risk assessment is recommended early during pregnancy and in the postpartum period (Tables 2 and 3).

• Risk factors include previous VTE, family history of VTE, hereditary thrombophilia, antiphospholipid syndrome (APS), medical comorbidities, significant pregnancy complications, caesarean delivery (CD) prolonged antepartum immobilisation and clinical risk factors such as increased body mass index (BMI), age >35 years and parity ≥3.

• High-risk patients should be managed in conjunction with a haematologist. Further, women with APS should be managed in conjunction with a haematologist and rheumatologist.

• Antepartum and postpartum thromboprophylaxis with LMWH and low-dose aspirin is recommended in women with APS and previous VTE. Higher doses of LMWH may be required.[18]

Caesarean delivery and VTE risk Caesarean delivery (CD) is an important independent risk factor for VTE in the postpartum period.[20] The risk of VTE after an emergency CD is twice greater than after an elective CD. • In hospital, thromboprophylaxis should be considered in all women who have undergone an elective CD.[21] • Additional risk factors for VTE post CD include: multiple pregnancy, BMI ≥30 kg/m2, severe pre-eclampsia, re-operation, prolonged immobilisation and placenta praevia.[1]

Antepartum and postpartum thromboprophylaxis The ideal anticoagulant in pregnancy should be one that does not cross the placenta and can be easily reversed.

• The oral direct thrombin and factor Xa inhibitors should not be used in pregnancy as the molecules are small and cross the placenta.

• Warfarin is associated with a teratogenic effect, especially between 6 and 12 weeks’ gestation. In addition, there is an increased risk of miscarriage, prematurity and fetal bleeding (including intracranial haemorrhage resulting in brain damage) at any time during pregnancy.

• The preferred anticoagulant is LMWH. • Allergic skin reactions can occur with LMWH but are uncommon.

In pregnant women with severe allergic skin reactions, an alternative LMWH should be used.

• It is recommended that the platelet count be monitored one week after initiation of LMWH and at regular follow-ups thereafter.

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RESEARCH Table 2. Obstetric antepartum thromboprophylaxis risk assessment[4-8] Risk Category High Risk Previous unprovoked or pregnancy or oestrogen-related VTE High-risk hereditary thrombophilia (compound heterozygous or homozygous for Factor V Leiden or prothrombin gene mutation and some deficiencies of antithrombin)[19] and a positive family history of VTE* Anti-phospholipid syndrome and previous VTE Intermediate Risk Single VTE related to a transient risk factor (not related to pregnancy or oestrogen use) Low and intermediate risk hereditary thrombophilia (some antithrombin deficiencies, Protein S deficiency, Protein C deficiency; heterozygous for Factor V Leiden or prothrombin gene mutation) [19] and a positive family history of VTE* High risk hereditary thrombophilia and no positive family history of VTE Antiphospholipid syndrome Non-obstetric surgery during pregnancy Medical co-morbidities, e.g. cancer, heart failure, peripartum cardiomyopathy, active systemic lupus erythematosus, inflammatory polyarthropathy or inflammatory bowel disease; nephrotic syndrome; type 1 diabetes mellitus with nephropathy, sickle cell disease, current intravenous drug user Ovarian hyperstimulation syndrome (3 months after resolution) Low Risk Age >35 years BMI ≥30 kg/m2† Parity ≥3 Smoker (at least 10 cigarettes per day) Family history of unprovoked or oestrogen-related VTE in first-degree relative Low-risk thrombophilia Gross varicose veins‡ Current systemic infection or peri-operative infection Immobility, e.g. paraplegia, long-distance travel (>8 hours), strict bedrest ≥7 days Pre-eclampsia with intrauterine growth restriction Multiple pregnancy In vitro fertilisation Dehydration/hyperemesis

Recommendation Antepartum Thromboprophylaxis indicated

Clinical monitoring indicated Consider thromboprophylaxis

Early mobilisation and avoid dehydration Thromboprophylaxis if multiple (≥4) risk factors are present

*A positive family history of VTE is associated with a two- to fourfold increase in the risk of VTE. † The patient’s BMI is based on the booking weight. ‡ Gross varicose veins are by definition symptomatic, above the knee or associated with phlebitis or oedema or skin changes.

• Fondaparinux may be considered in consultation with a haematologist.[22] • Antepartum prophylaxis should be initiated early in pregnancy.

• Postpartum thromboprophylaxis should be continued for 6 weeks in high-risk women, for 10 days in intermediate-risk women and at least until discharge from hospital in low-risk women.

• In the presence of ongoing risk factors, e.g. prolonged hospital admission, wound infection, surgery extended thromboprophylaxis until the risk factor is no longer present should be considered.

• The use of mechanical prophylaxis, such as IPC, can be considered in patients at high risk of bleeding.

LMWH dose • Fixed doses of LMWH, e.g. dalteparin 5 000 units daily or nadroparin 2 850 units daily or enoxaparin 40 mg daily are recommended. This is practical and covers most of the obstetric population.

• There is an increased dose requirement of LMWH during pregnancy because of increased volume of distribution and renal clearance.

Therefore, regular anti-Xa monitoring is suggested.

• Dose adjustments (increase or decrease by 10 mg) to achieve a target anti-Xa level of 0.3 - 0.5 units/mL in conjunction with a haematologist is suggested.

• It is recommended to use weight-adjusted LMWH dosing with antiXa monitoring in patients at extremes of weight (Table 4).[4,5] • Anti-Xa monitoring is also indicated in renal disease and severe pre-eclampsia.[23]

Delivery • It is recommended that all pregnant women receiving antepartum thromboprophylaxis have a delivery plan.

• The mode of delivery is determined by the obstetric indication. A planned CD is often indicated.

• Prophylactic LMWH should be discontinued at least 12 hours prior to the expected time of epidural analgesia or delivery.

• Patients should be advised to discontinue thromboprophylaxis upon the onset of spontaneous labour.

Spinal and epidural anaesthesia • The catheter should not be placed within 12 hours of the last dose of LMWH. • LMWH should be started at least 6 hours after removal of the catheter.[9] • LMWH should be delayed at least 24 hours if there is blood in the needle or neuraxial catheter during needle insertion.

• Neurological monitoring is mandatory for a minimum of 12 hours and ideally for 72 hours after neuraxial blockade.

• Extreme caution should be exercised in patients on other agents such as aspirin, clopidogrel and non-steroidal anti-inflammatories that may interfere with normal haemostasis.

Postpartum • Assess for major bleeding postpartum (resulting in a drop in the haemoglobin concentration ≥2 g/dL or bleeding requiring transfusion of at least 2 units of packed red blood cells).

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RESEARCH Table 3. Obstetric postpartum thromboprophylaxis risk assessment[4-8] Risk Category High Risk Anyone requiring antenatal LMWH Previous VTE High-risk hereditary thrombophilia (compound heterozygous or homozygous for Factor V Leiden or prothrombin gene mutation or some deficiencies of antithrombin) Low- and intermediate-risk (some antithrombin deficiencies, Protein S deficiency, Protein C deficiency, heterozygous for Factor V Leiden or prothrombin gene mutation) hereditary thrombophilia and positive family history of VTE* Antiphospholipid syndrome Intermediate Risk Caesarean delivery in labour Readmission or prolonged admission (≥ 3 days) postpartum Surgery in the puerperium (except immediate repair of the perineum) Medical co-morbidities e.g. cancer, heart failure, peripartum cardiomyopathy, active systemic lupus erythematosus, inflammatory polyarthropathy or inflammatory bowel disease, nephrotic syndrome, type 1 diabetes mellitus with nephropathy, sickle cell disease, current intravenous drug user BMI ≥40 kg/m2† Low Risk Age >35 years BMI ≥30 kg/m2 Parity ≥3 Smoker Elective caesarean delivery Family history of VTE Low-risk thrombophilia Gross varicose veins‡ Current systemic infection Immobility, e.g. paraplegia, long-distance travel (>8 hours) Multiple pregnancy Preterm delivery in this pregnancy (<37 weeks) Stillbirth in this pregnancy Mid-cavity or rotational operative delivery Prolonged labour (>24 hours) Postpartum haemorrhage (> 1 L or blood transfusion requiring re-operation)

Recommendation Postpartum thromboprophylaxis indicated for at least 6 weeks

Postpartum thromboprophylaxis indicated for at least 7 - 10 days If risk factors persist or multiple (≥2) risk factors are present, consider extending thromboprophylaxis

Early mobilisation, mechanical prophylaxis§ and avoid dehydration Postpartum thromboprophylaxis at least until discharge from hospital if multiple (≥ 2) risk factors

*A positive family history of VTE is associated with a two- to fourfold increase in the risk of VTE. † The patient’s BMI is based on the booking weight. ‡ Gross varicose veins are by definition symptomatic, above the knee or associated with phlebitis or oedema or skin changes. § Mechanical prophylaxis includes intermittent pneumatic compression which is preferable to graduated compression stockings.

Table 4. Recommended dosages of LMWH thromboprophylaxis[5] Weight (kg) <50 50 - 90

91 - 130 131 - 170 >170

Dosage Enoxaparin 20 mg once daily Dalteparin 2 500 units daily Enoxaparin 40 mg once daily Dalteparin 5 000 units daily Nadroparin 2 850 units daily Enoxaparin 60 mg once daily Dalteparin 7500 units daily Enoxaparin 80 mg once daily Dalteparin 10 000 units daily Enoxaparin 0.6 mg/kg once daily Dalteparin 75 units/kg once daily

Table 5. Interpretation of anti-Xa levels in patients on LMWH Target anti-Xa levels Low anti-Xa level

High anti-Xa level

0.3 - 0.5 anti-Xa units/mL Inadequate dosing Delayed specimen draw Dose of LMWH omitted Weight gain Gestation (volume of distribution of LMWH changes) Excessive dosing Weight loss Renal dysfunction Reduced creatinine clearance (end of the third trimester)

Anti-Xa = anti-factor Xa ; LMWH = low-molecular-weight heparin.

LMWH = low-molecular-weight heparin.

• Every woman should have a repeat VTE risk assessment after delivery.

• Prophylactic LMWH may be started/restarted 6 - 12 hours post delivery or should be delayed if there is any evidence of bleeding from the surgical site.

• Warfarin, LMWH, fondaparinux and UFH are safe to use in breastfeeding mothers. The oral direct thrombin and factor Xa inhibitors should be avoided.

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Acknowledgements. None.

Author contributions. ES and PRD: authors; BFJ and HRB: critical review.

Funding. None.

Conflicts of interest. Prof. H R Büller reports that he has served as a scientific advisory board member for Sanofi-Aventis, Bayer HealthCare, Bristol-Myers Squibb, Daichi-Sankyo, GlaxoSmithKline, Pfizer, Roche, Isis and Thrombogenics and has received honoraria from Sanofi-Aventis, Bayer HealthCare,

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RESEARCH Bristol-Myers Squibb, Daichi-Sankyo, GlaxoSmithKline, Pfizer, Roche, Isis and Thrombogenics. Prof. BF Jacobson has received honoraria from Bayer HealthCare, Boehringer, Aspen and Sanofi-Aventis. Drs P de Jong and E Schapkaitz have declared no conflicts of interest with respect to the authorship and/or publication of this article.

1. Wilkinson H. Medical, Saving mothersâ&#x20AC;&#x2122; lives. Reviewing maternal deaths to make motherhood safer: 2006 - 2008. BJOG 2011;118(11):1402-1403. https://doi.org/10.1111/j.1471-0528.2011.03097.x 2. Greer IA. Epidemiology, risk factors and prophylaxis of venous thrombo-embolism in obstetrics and gynaecology. Baillieres Clin Obstet Gynaecol 1997;11(3):403-430. https://doi.org/10.1016/ s0950-3552(97)80019-3 3. Clarke-Pearson DL, Coleman RE, Synan IS, Hinshaw, W, Creasman WT. Venous thromboembolism prophylaxis in gynecologic oncology: A prospective, controlled trial of low-dose heparin. Am J Obstet Gynecol 1983;145(5):606-613. https://doi.org/10.1016/0002-9378(83)91205-x 4. Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e691S-736S. 5. Royal College of Obstetricians and Gynaecologists (RCOG). Green-top Guideline No. 37a: Reducing the Risk of Thrombosis and Embolism during Pregnancy and the Puerperium.

London: RCOG, 2015. https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg37a/ (accessed 26 October 2017).

6. James A. Committee on Practice, practice bulletin no. 123: Thromboembolism in pregnancy. Obstet Gynecol 2011;118(3):718-729. https://doi.org/10.1097/aog.0b013e3182310c4c 7. Chan WS, Rey E, Kent NE, et al. Venous thromboembolism and antithrombotic therapy in pregnancy.

J Obstet Gynaecol Can 2014;36(6):527-553. https://doi.org/10.1016/s1701-2163(15)30569-7 8. McLintock C, Brighton T, Chunilal S, et al. Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism in pregnancy and the postpartum period. Aust N Z J Obstet Gynaecol 2012;52(1):14-22. https://doi.org/10.1111/j.1479-828x.2011.01361.x 9. Ducloy-Bouthors AS, Baldini A, Abdul-Kadir R, Nizard J. ESA VTE Guidelines Task Force.

European guidelines on perioperative venous thromboembolism prophylaxis: Surgery during pregnancy and the immediate postpartum period. Eur J Anaesthesiol 2018;35(2):130-133. https://doi. org/10.1097/eja.0000000000000704 10. Stegeman BH, de Bastos M, Rosendaal FR, et al. Different combined oral contraceptives and the risk of venous thrombosis: Systematic review and network meta-analysis. BMJ 2013;347:f5298. https://doi. org/10.1136/bmj.f5298

11. Van Hylckama Vlieg A, Helmerhorst FM, Rosendaal FR. The risk of deep venous thrombosis associated with injectable depot-medroxyprogesterone acetate contraceptives or a levonorgestrel intrauterine device. Arterioscler Thromb Vasc Biol 2010;30(11):2297-2300. https://doi.org/10.1161/ atvbaha.110.211482 12. Sweetland S, Beral V, Balkwill A, et al. Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study. J Thromb Haemost 2012;10(11):2277-2286. https://doi.org/10.1111/j.1538-7836.2012.04919.x 13. Vessey MP, Doll R, Fairbairn AS, Glober G. Postoperative thromboembolism and the use of oral contraceptives. Br Med J 1970;3(5715):123-126. https://doi.org/10.1136/bmj.3.5715.123 14. Ho KM, Tan JA. Stratified meta-analysis of intermittent pneumatic compression of the lower limbs to prevent venous thromboembolism in hospitalized patients. Circulation 2013;128(9):1003-1020. https://doi.org/10.1161/circulationaha.113.002690 15. Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: A 30-year population-based study.

Ann Intern Med 2005;143(10):697-706. https://doi.org/10.7326/0003-4819-143-10-200511150-00006 16. Kamel H, Navi BB, Sriram N, Hovsepian DA, Devereux RB, Elkind MS. Risk of a thrombotic event after the 6-week postpartum period. N Engl J Med 2014;370(14):1307-1315. https://doi.org/10.1056/ nejmoa1311485 17. Bain E, Wilson A, Tooher R, Gates S, Davies LJ, Middleton P. Prophylaxis for venous thromboembolic disease in pregnancy and the early postnatal period. Cochrane Datab Syst Rev 2014;2:CD001689. https://doi.org/10.1002/14651858.cd001689.pub3 18. Committee on Practice Bulletins - Obstetrics, American College of Obstetricians and Gynecologists.

Practice Bulletin No. 132: Antiphospholipid syndrome. Obstet Gynecol 2012;120(6):1514-1521. https://doi.org/10.1097/01.aog.0000423816.39542.0f 19. Gerhardt A, Scharf RE, Greer IA, Zotz RB. Hereditary risk factors for thrombophilia and probability of venous thromboembolism during pregnancy and the puerperium. Blood 2016;128(19):2343-2349.

20. Sultan AA, Tata LJ, West, J, et al. Risk factors for first venous thromboembolism around pregnancy: A population-based cohort study from the United Kingdom. Blood 2013;121(19):3953-3961. https://doi. org/10.1182/blood-2012-11-469551 21. Blondon M, Casini A, Hoppe KK, Boehlen F, Righini M, Smith NL. Risks of venous thromboembolism after cesarean sections: A meta-analysis. Chest 2016;150(3):572-596. https://doi.org/10.1016/j. chest.2016.05.021 22. Knol HM, Schultinge L, Erwich JJ, Meijer K. Fondaparinux as an alternative anticoagulant therapy during pregnancy. J Thromb Haemost 2010;8(8):1876-1879. https://doi.org/10.1111/j.15387836.2010.03926.x 23. Lim W, Dentali F, Eikelboom JW, Crowther MA. Meta-analysis: Low-molecular-weight heparin and bleeding in patients with severe renal insufficiency. Ann Intern Med 2006;144(9):673-684. https://doi. org/10.7326/0003-4819-144-9-200605020-00011

Accepted date 30 April 2018.

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CPD

True (A) or false (B): Prenatal screening for congenital toxoplasmosis (CTG) 1. Adult infection with Toxoplasma gondii is never asymptomatic.

2. The overall risk of transmission to the fetus in utero is 20 - 50%, but this may rise to 60 - 90% in the third trimester.

3. The classic triad of lesions associated with CTG is chorioretinitis, intracerebral calcifications and hydrocephalus, although only 1 in 6 fetuses may show 2 out of 3.

4. Calcification seen throughout the brain in T. gondii infection, visible from 18 - 20 weeks onwards, may differ from the periventricular distribution of calcification seen in cytomegalovirus or Zika virus infection.

5. Microcephaly is defined as a head circumference that measures 3 standard deviations below the mean for gestation.

6. In congenital T. gondii infection, parenchymal calcification may not be visible on MRI. Visual aids to improve estimation of blood loss 7.

According to quoted published literature, surgeons tend to underestimate blood loss, whereas anaesthetists tend to overestimate blood loss.

8. In the study presented, the accuracy of blood-loss estimation was associated with years of experience – the greater the experience of the healthcare professional, the greater the accuracy of bloodloss estimation.

Outcomes of patients who have had invasive testing for spinal muscular atrophy (SMA) 9. SMA exists in four forms of variable degrees of severity.

10. Werdnig-Hoffman disease, SMA Type 1, represents 10 - 20% of childhood cases. These children cannot sit and most die within 2 years of birth.

11. SMA is inherited as an X-linked recessive disease.

Lactic acid as an adjuvant marker in pregnancy-associated sepsis 12. In the study presented a lactic acid level of >4 had a positive predictive value of 70% and a negative predictive value of 78%, with a specificity of 88% for positive bacterial culture in pregnancy-associated sepsis.

An evaluation of indications for caesarean section (CS) 13.

In 2015, the World Health Organization (WHO) issued a statement that ‘Every effort should be made to provide a CS to women in need rather than striving to achieve a specific rate’.

14. The CS rate at the South African (SA) teaching hospital studied was 39.8% in 2015, up from 28.4% in 2005.

15. The national CS rate in SA in the of was quoted as 28% in the 2011 - 2013 Saving Mothers Report.

Recommendations for thromboprophylaxis in obstetrics and gynaecology 16. The percentage of deaths attributable to pulmonary embolus following hysterectomy may be as high as 20%.

17.

Venous thrombosis may be demonstrable, although not clinically apparent, in 15 - 40% of cases of major gynaecological surgery.

18. Pre-eclampsia is not a risk factor for venous thromboembolism (VTE).

19.

Following major cancer surgery, venous thromboprophylaxis should continue for as long as 5 weeks postoperatively.

20. HIV infection is a risk factor for VTE.

The CPD programme for SAJOG is administered by Medical Practice Consulting: CPD questionnaires must be completed online at www.mpconsulting.co.za A maximum of 3 CEUs will be awarded per correctly completed test.

Accreditation number: MDB015/032/01/2018 (Clinical)

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