Ajog aj 2017

Page 1

Volume 1, Number 2, April-June 2017

ISSN 0971-8788 Case Report

Asian Journal of

Obstetrics &

Gynaecology Practice In this Issue Maternal and Perinatal Outcome in Antepartum Hemorrhage in a Tertiary Care Center: An Observational Study A Retrospective Study of Prevalence of Hepatitis B, Hepatitis C and HIV in Pregnant Women and Their Perinatal Outcome A Comparative Study Between Oral Iron, Intravenous Iron Sucrose and Ferric Carboxymaltose in the Management of Postpartum Anemia Conservative Surgical Techniques in Management of Morbidly Adherent Placenta: A 5-year Study Intrapartum HELLP Syndrome Associated with Mild Pre-eclampsia

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 2, April-June 2017

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Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 2, April-June 2017


Asian Journal of

Online Submission

Volume 1, Number 2, April-June 2017

An IJCP Group Publication Corporate Panel Dr Sanjiv Chopra Prof. of Medicine and Faculty Dean Harvard Medical School Group Consultant Editor Dr Deepak Chopra Chief Editorial Advisor

Contents from the issue editor

High Cesarean Section Rates in the Country

5

Alka Kriplani

Dr KK Aggarwal Group Editor-in-Chief IJCP Group, eMedinewS and eMediNexus Dr Veena Aggarwal MD, Group Executive Editor AJOG Specialty Panel Dr Alka Kriplani Editor Consultant Editor Dr Urmil Sharma Assistant Editors Dr Nutan Agarwal (Delhi) Dr Neera Aggarwal (Delhi) Dr A Biswas (Singapore) Dr CS Dawn (Kolkata) Dr Gauri (Delhi) Dr Suneeta Mittal (Delhi) Dr S Mehra (Delhi) Dr Prashant Mangeshikar (Mumbai) Dr Prakash Trivedi (Mumbai) Dr Gita Ganguly

Mukherjee (Kolkata) Dr (Mrs) Prabha Arora (Delhi) Dr Hema Divakar (Bangalore) Dr Kamini A Rao (Bangalore) Dr Deepti Goswami (Delhi) Dr Neerja Bhatla (Delhi) Dr Bhawna Malhotra (Delhi) Dr Biswas Nicholas (Australia) Dr Sudhaa Sharma (Jammu) Dr Jaibhagwan Sharma (Delhi) Dr Veena Mathur (Agra) Dr Garima Kachhawa

Editorial Board

Obstetrics and Gynaecology Dr Alka Kriplani Dr Thankam Verma Dr Kamala Selvaraj

Cardiology Dr Praveen Chandra Dr SK Parashar Paediatrics Dr Swati Y Bhave Diabetology Dr CR Anand Moses Dr Sidhartha Das Dr A Ramachandran Dr Samith A Shetty Dr Vijay Viswanathan Dr V Mohan Dr V Seshiah Dr Vijayakumar ENT Dr Jasveer Singh Dr Chanchal Pal

Dentistry Dr KMK Masthan Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar Dr Rajiv Khosla Dr JS Rajkumar Dermatology Dr Hasmukh J Shroff Dr Pasricha Dr Koushik Lahiri Dr Jayakar Thomas Nephrology Dr Georgi Abraham Neurology Dr V Nagarajan Dr Vineet Suri Dr AV Srinivasan

FROM THE DESK OF the GROUP EDITOR-IN-CHIEF

Family Physicians are the Need of the Hour

6

KK Aggarwal

Clinical Study

Maternal and Perinatal Outcome in Antepartum Hemorrhage in a Tertiary Care Center: An Observational Study

7

Ruby Bhatia, Parmjit Kaur, Gurdip Kaur, Satinder Kaur, Aman Dev, Santosh Kumari

A Retrospective Study of Prevalence of Hepatitis B, Hepatitis C and HIV in Pregnant Women and Their Perinatal Outcome 12 Navneet Kaur, Parneet Kaur

Oncology Dr V Shanta Orthopedics Dr J Maheshwari

Anand Gopal Bhatnagar Editorial Anchor Advisory Body Heart Care Foundation of India Non-Resident Indians Chamber of Commerce and Industry World Fellowship of Religions

A Comparative Study Between Oral Iron, Intravenous Iron Sucrose and Ferric Carboxymaltose in the Management of Postpartum Anemia 17 Divya Yadav Sharma, Saroj Singh, Abhilasha Yadav, Asha Nigam, Deepti Tandon, Alok Sharma


Asian Journal of Volume 1, Number 2, April-June 2017

Contents

Published, Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Ltd. and Published at E-219, Greater Kailash, Part-1 New Delhi-110 048 E-mail: editorial@ijcp.com

Clinical Study

Conservative Surgical Techniques in Management of Morbidly Adherent Placenta: A 5-year Study 21

Printed at New Edge Communications Pvt. Ltd., New Delhi E-mail: edgecommunication@gmail.com

Rekha Rani, Shikha Singh, Ruchika Garg, Urvashi Verma, Sangeeta Sahu, Saroj Singh, Surendra Kumar, Himani Goyel

Copyright 2017 IJCP Publications Ltd. All rights reserved. The copyright for all the editorial material contained in journal, in the form of layout, content including images and design, is held by IJCP Publications Ltd. No part of this publication may be published in any form whatsoever without the prior written permission of the publisher.

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Case Report

Intrapartum HELLP Syndrome Associated with Mild Pre-eclampsia

29

Jaya Kundan Gedam, Minal Bhalerao, Utkarsh

AROUND THE GLOBE

News and Views

32

Note: Asian Journal of Obs and Gynae Practice does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature in this issue.

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from the issue editor

High Cesarean Section Rates in the Country

Dr Alka Kriplani

Professor and Head of Unit II Dept. of Obstetrics and Gynecology AIIMS, New Delhi

The rates of cesarean section deliveries are increasing in the country and there is a perception amongst the public that many of these are unnecessary cesarean sections. According to a World Health Organization (WHO) report published in 2010, the cesarean section rate in India was 8.5%. The percentage of cesarean section deliveries in the country is 17.2% as per the National Family Health Survey (NFHS)-4 (2015-16) released earlier this year (Press Information Bureau, Ministry of Health and Family Welfare, March 28, 2017). This latest figure is apparently higher than the “ideal” rate between 10% and 15% as that recommended by the WHO in 1985. The high cesarean rates in the country, as a number, cannot be viewed in isolation. There are several reasons why a cesarean section delivery may be chosen over a vaginal birth. There are the medical indications, the absolute and relative indications, because of which a doctor may recommend an elective cesarean section. At times, in conditions such as obstructed labor or other obstetrical emergencies, a cesarean section is done as an emergency procedure, where it is lifesaving for both the mother and the child. Then there are the nonmedical reasons. The decision to perform a cesarean section is not solely in the hands of the doctor. Patient preferences or cesarean on maternal request also play a part. Anxiety about vaginal birth, fear of vaginal birth (tocophobia), precious child are some factors which influence the choice of cesarean section by the expectant mother as a mode of delivery, in the absence of any medical or obstetrical contraindication to vaginal birth. Some women want to deliver on an auspicious date or even time. This is another reason why they opt for an elective cesarean. Cesarean section rates are higher in tertiary institutes or super speciality hospitals. Similar is the case with senior and experienced doctors, who may not do routine vaginal deliveries. If you take informed consent, then

again the cesarean section rates may be higher. All these nonmedical factors contribute to the increase in cesarean section rates. And, while they are not the sole cause, they do need to be taken into account. Then again it is important to evaluate the correlation between cesarean section rates and the infant mortality rate (IMR) and maternal mortality rate (MMR). Data from NFHS-4 showed that private hospitals carried out 40.9% cesarean sections, while this rate in government hospitals was 11.9%. The two cannot be compared. It is important to assess the corresponding IMR and MMR. Many women doctors may choose to have a cesarean section instead of vaginal birth, which also needs to be computed. Unless it can be proved that the cesarean rate in doctors and VIPs is low compared to the general population, it cannot be said that the cesarean rates are unnecessarily high. This is not so. Cesarean section is a surgical procedure, with potential complications for both the mother and the child. An informed consent needs to be taken before proceeding with the procedure. The decision of the United Kingdom (UK) Supreme Court in the case of Montgomery v Lanarkshire Health Board was a landmark judgement, which made the patient an active partner in decision making as far as his/her treatment is concerned. It ruled that the doctor has a duty “to ensure that the patient is aware of any material risks involved in any recommended treatment, and of any reasonable alternative or variant treatments”. The doctor has to inform the patient of all possible risks, even though rare and let the patient take a decision. The patient should be informed that even elective cesarean section is not risk-free and carries serious risks for mother and child. An audit of deliveries cesarean sections, in the private as well as public health facilities, is needed to find out the reasons for the decision to perform each cesarean section before judging that economics and not medicine, influence a doctor’s decision to do a cesarean delivery.

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 2, April-June 2017

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FROM THE DESK OF the GROUP EDITOR-IN-CHIEF

Family Physicians are the Need of the Hour

Dr KK Aggarwal

Group Editor-in-Chief IJCP Group, eMedinewS and eMediNexus

With a population of more than a billion (~1.32 billion), India is facing a shortage of doctors, establishment and beds. Presently, India has one doctor for every 1,700 people against the WHO recommended norm of 1 doctor for every 1,000 people. There are not enough doctors to take care of the health needs of all. This is the time to bring back the age-old concept of ‘Family physician’. Unlike a General Practitioner, a family physician looked after all the health needs of a family, even many generations of a family, regardless of his/her specialization. They not only treat, but also provide preventive healthcare to the family being aware of the family history and was the link between the patient and the specialist. Considered a part of the family, he was an integral part of all important family functions and events. All in all, he was a ‘friend, philosopher and guide’ of the family. For good health outcomes, a physician has to be aware of the social determinants of health i.e. the conditions in which people are born, grow, work, live, and age, and the wider set of forces and systems shaping the conditions of daily life. It is important to know the socioeconomic circumstances of a patient, because

these influence outcomes. Family physicians address the social determinants of health. Family physicians also offer several advantages; most important are familiarity, trust and ease of communication due to a long-lasting relationship. As a result, patient is more likely to open up about his problems and adhere to the treatment prescribed. Family physicians provide a continuum of care at all levels of care, including emergency care. Medicine has become highly specialized today leading to isolation among different specialties as well as from patients. Lack of communication has fostered distrust among patients becoming evident as rising litigations or often as violence against doctors. Hence, instead of destroying the family physician system, reintroducing the ‘traditional concept’ of family physician is the need of the hour. They are the first link in healthcare delivery for the population and play a pivotal role in preventive health, early diagnosis and timely referral including maintaining health details of all family members. Their services can be used on a retainership basis.

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Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 2, April-June 2017


Clinical Study

Maternal and Perinatal Outcome in Antepartum Hemorrhage in a Tertiary Care Center: An Observational Study Ruby Bhatia*, Parmjit Kaur†, Gurdip Kaur*, Satinder Kaur‡, Aman Dev#, Santosh Kumari¥

Abstract Antepartum hemorrhage (APH) complicates 2-5% of all pregnancies. Placenta previa and placental abruptio remain the most common causes of APH. Any pregnancy with APH remains at increased risk for an adverse outcome even though bleeding has stopped and placenta previa has been excluded sonographically. An observational study was carried out in high dependency unit of obstetrics at Govt. Medical College and Rajindra Hospital, Patiala to study maternal and perinatal outcome in APH complicating pregnancy. Keywords: Antepartum hemorrhage, placenta previa, abruptio placenta

H

emorrhage is the single most important cause of maternal death worldwide and is responsible for half of all postpartum deaths in developing countries.1 Antepartum hemorrhage (APH) is defined as any bleeding from female genital tract between fetal viability and delivery of the fetus.2 APH complicates 2-5% of all pregnancies.1 Obstetric hemorrhage remains the most important cause of maternal and perinatal morbidity and mortality in developing countries. APH and postpartum hemorrhage (PPH) are the leading causes for maternal mortality followed by sepsis and eclampsia in India. Placenta previa and placental abruptio remain the most common causes of APH. Any pregnancy with APH remains at increased risk for an adverse outcome even though bleeding has stopped and placenta previa has been excluded sonographically. Hence, to study maternal and fetal outcomes and various risk factors associated with APH is the need of the hour, so as to improve maternal

*Associate Professor † Professor ‡ Assistant Professor Dept. of Obstetrics and Gynecology # Civil Surgeon Dept. of PSM ¥ Postgraduate Student Dept. of Obstetrics and Gynecology Govt. Medical College and Rajindra Hospital, Patiala, Punjab Address for correspondence Dr Ruby Bhatia D-8, Medical College Campus, Patiala - 147 001, Punjab E-mail:drrubybhatia@yahoo.com

and perinatal morbidity and mortality by providing efficient emergency services. Aims and Objectives zz To determine incidence and the type of APH. zz Associated risk factors for APH. zz To study maternal and perinatal outcome in APH complicating pregnancy. Material and Methods It was an observational study carried out in high dependency unit of obstetrics at Govt. Medical College and Rajindra Hospital, Patiala for a period of 6 months with effect from November 2015 to May 2016. Antenatal women with chief complaint of bleeding per vaginum after the period of viability (≥24 weeks of gestation) admitted to high dependency unit were included in the study. A detailed history, thorough clinical examination with special reference to abdominal examination, laboratory test and ultrasound examination of pelvis for fetal well-being, placental localization, any evidence of placenta accreta and retroplacental hemorrhage, carried out in all the cases. Immediate resuscitative measures in the form of two wide bore 16 gauge cannulas for transfusion of crystalloids and colloid were taken in all the cases of APH. Adequate quantity of blood was arranged and transfused in all the cases of APH. Sociodemographic characteristics were noted. Patients were grouped as placenta previa, abruptio placenta, combined (placenta previa and abruptio placenta both), local cause and indeterminate cause. Risk factors such as age, parity,

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 2, April-June 2017

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clinical study pre-eclampsia, malpresentation, polyhydramnios, multiple pregnancy and smoking in present pregnancy were recorded. Past history of scarred uterus (previous cesarean one, two or more, myomectomy, check curettage, medical termination of pregnancy), placenta previa, abruptio placenta or any other risk factors were evaluated. Maternal complications in the form of anemia, hypovolemic shock, intrapartum hemorrhage, need for blood transfusion, need of cesarean section, PPH, peripartum hysterectomy, acute renal injury, disseminated intravascular coagulation (DIC) and maternal death were recorded. Perinatal outcome was evaluated in relation to prematurity, fetal growth restriction, low birth weight, low Apgar score at 1 and 5 minutes, admission to neonatal intensive care unit (NICU) and stillbirth. Observations A total of 2,040 births occurred during the study period with effect from 1st November 2015 to 31st May 2015.

Prevalence of APH was found to be 4.55% with a total of 93 cases. Abruptio placenta was encountered in 52 patients (2.54%), while placenta previa (1.81%) in 37 cases (Table 1). Only three cases were due to indeterminate causes (0.14%), while only one case had combined placenta previa as well as abruptio placenta. Majority of the patients with APH were unbooked (82.76%) and reported as emergency admission in our high dependency unit. Only 16 patients with APH were booked with complete antenatal care (Table 2). It was observed that 77.41% of the women with APH were in the age group of 20-30 years. The elderly gravida (>35 years) were encountered in 19.35% of the women with APH with equal distribution among placenta previa and abruptio placenta (Table 2). Majority of the women in the study group (49.46%) were gravida 2-3, but 21.50% of the patients with APH were grand multipara, which was significantly high in abruptio placenta (12.90%) as compared to placenta previa (8.60%) (Table 2). Majority of the patients were from low socioeconomic status (80.64%) and 61.29% were

Table 1. Incidence of Antepartum Hemorrhage (Total 93 = 100%) Total births

Total APH

Abruptio placenta

Placenta previa

Combined

Indeterminate causes

Local cause

2,040

93

52

37

1

3

0

100

4.55

2.54

1.81

0.04

0.14

0

No. Percentage (%)

Table 2. Sociodemographic Characteristics in Antepartum Hemorrhage (Total 93 = 100%) Sociodemographic factors

No. of APH cases

% among APH cases

Booked

NN 17

% 18.27

N 8

% 8.60

N 8

% 8.60

N 1

% 1.07

N 0

% 0

Unbooked

76

81.72

44

47.311

29

31.18

2

2.15

1

1.07

Age <20 20-30 >30 Parity

3 72 18

3.22 77.41 19.35

3 40 9

3.22 43.01 9.67

0 29 8

0 31.18 8.60

0 2 1

0 2.15 1.07

0 1 0

0 1.07 0

27 46 20

29.03 49.46 21.50

14 26 12

15.05 27.95 12.90

11 18 8

11.82 19.35 8.60

1 2 0

1.07 2.15 0

1 0 0

1.07 0 0

75 14 4

80.64 15.05 4.30

44 6 2

47.31 6.45 2.15

28 7 2

30.10 7.52 2.15

2 1 0

2.15 1.07 0

1 0 0

1.07 0 0

57 36

61.29 38.70

32 20

34.40 21.50

22 15

23.65 16.12

2 1

2.15 1.07

1 0

1.07 0

Primi gravida Gravida 2-3 Grand multipara (gravida >4) Socioeconomic status Lower Middle Upper Residence Rural Urban

8

Abruptio placenta

Placenta previa

Indeterminate cause

Combined

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 2, April-June 2017


clinical study from rural areas (Table 2). Out of 37 patients of placenta previa, major degree placenta previa was encountered in 29 cases (78.37%), while two cases of major degree placenta previa had placenta accreta (5.4%) (Table 3). Grand multipara was found to be the major risk factor and was encountered in 21.50% of the patients with APH, the incidence was higher in abruptio placenta (12.90%) than placenta previa (8.60%) (Table 4). The second most important risk factor was association with severe pre-eclampsia and eclampsia seen in 20.43% of the patients with APH. A significantly higher incidence of severe pre-eclampsia and eclampsia Table 3. Distribution According to the Type of Placenta Previa (Total 37 =1 00%) Types of placenta previa

No.

Percentage (%)

Type I

3

8.10

Type II

3

8.10

Type III

2

5.40

Type IV

29

78.37

Placenta accreta in type IV

2

5.40

was observed in association with abruptio placenta (16.12%) as compared to placenta previa (4.30%) (Table 4). In 6.45% of the patients with APH, malpresentation was seen. The incidence of malpresentation was double in placenta previa (4.30%) than abruptio placenta (2.15%). Abruptio placenta was associated in 2.15% of the women each with polyhydramnios and premature rupture of membranes (PPROM). The prevalence of placenta previa was 13.97% in the women with previous one or more cesarean delivery, which was significantly higher than in abruptio placenta with previous cesarean delivery (4.30%) (Table 4). History of manual removal of the placenta (MROP) in previous pregnancy could not be ascertained. Two patients with major degree placenta previa with previous two cesarean sections were diagnosed placenta accreta on color Doppler. The most dreaded maternal outcome associated with APH was anemia encountered in 34.40% of the patients, which indirectly increased the maternal morbidity and higher need for blood transfusion to

Table 4. Risk Factors for Antepartum Hemorrhage (Total 93 = 100%) Risk factors

No. of APH cases

% among APH cases

Abruptio placenta

Placenta previa

Unknown cause

Combined

N

%

N

%

N

%

N

%

N

%

Grand multipara

20

21.50

12

12.90

8

8.60

0

0

0

0

Severe pre-eclampsia/ eclampsia

19

20.43

15

16.12

4

4.30

0

0

0

0

Maternal age (>35)

8

8.60

4

4.30

3

3.22

1

1.07

0

0

Malpresentation

6

6.45

2

2.15

4

4.30

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Present pregnancy

Polyhydramnios

2

2.15

2

2.15

PROM

2

2.15

2

2.15

Trauma

0

0

0

0

0

0

0

0

0

0

Smoking/drug misuse

0

0

0

0

0

0

0

0

0

0

First trimester bleeding

1

1.07

0

0

1

1.70

0

0

0

0

H/o previous LSCS

18

19.34

4

4.30

13

13.97

1

1.07

0

0

Previous 1 LSCS

13

13.97

4

4.30

8

8.60

1

1.07

0

0

Past history

0

Previous 2 LSCS

4

4.30

0

0

4

4.30

0

0

0

0

Previous 3 LSCS

1

1.07

0

0

1

1.07

0

0

0

0

H/o previous MTP/check curettage

10

10.75

3

3.22

6

6.45

1

1.07

0

0

H/o abruptio placenta

2

2.15

2

2.15

0

0

0

0

0

0

H/o placenta previa

4

4.30

0

0

4

4.30

0

0

0

0

H/o previous MROP

0

0

0

0

0

0

0

0

0

0

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 2, April-June 2017

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clinical study 34.40% of the patient with APH (Table 5). Also, 11.82% of the cases with APH had atonic PPH, which were managed by uterine massage, uterotonics and balloon tamponade along with resuscitative measures. Peripartum hysterectomy had to be performed in three (3.22%) patients of atonic PPH as a lifesaving measures (Table 5). One of the patient with abruptio placenta required MROP. DIC and acute renal injury was encountered in 2.15% of the cases each (Table 5). One of the patient with APH, with major degree

placenta previa and placenta accreta with previous two lower segment cesarean section (LSCS) was lost due to intractable atonic PPH during cesarean delivery in spite of best efforts. Premature termination of pregnancy before 37 weeks was required in 65.58% cases to manage APH; 23.65% babies required NICU admission. Almost quarter of the patients with APH had stillbirth with a higher incidence (17.20%) in abruptio placenta (Table 6).

Table 5. Maternal Outcome in Antepartum Hemorrhage (Total 93 = 100%) Maternal outcome

APH

Abruptio placenta

Placenta previa

Indeterminate cause

Combined

N

%

N

%

N

%

N

%

N

%

32

34.40

18

19.35

14

15.05

0

0

0

0

Nil

61

65.59

34

36.55

23

24.73

3

3.22

1

1.07

1-4

27

29.03

15

16.12

12

12.90

0

0

0

0

Severe anemia (<7 g%) Units of blood transfused

5-10

5

5.37

3

3.22

2

2.15

0

0

0

0

PPH

11

11.82

6

6.45

5

5.37

0

0

0

0

Intrapartum hemorrhage

3

3.22

2

2.15

1

1.07

0

0

0

0

Peripartum hysterectomy

3

3.22

2

2.15

1

1.07

0

0

0

0

DIC

2

2.15

1

1.07

1

1.07

0

0

0

0

Acute renal injury

2

2.15

1

1.07

1

1.07

0

0

0

0

MROP

1

1.07

1

1.07

0

0

0

0

0

0

Maternal mortality

1

1.07

0

0

1

1.07

0

0

0

0

Table 6. Perinatal Outcome in Antepartum Hemorrhage (Total 93 = 100%) Perinatal outcome

APH

Abruptio placenta

Placenta previa N

%

Indeterminate causes N

%

Combined

N

%

N

%

N

%

<34 weeks

14

15.05

10

10.75

3

3.22

1

1.07

0

0

34-36+6 weeks

47

50.53

19

20.43

26

27.95

1

1.07

1

1.07

32

34.40

23

24.73

8

8.60

1

1.07

0

0

14

15.05

09

9.67

4

4.30

1

1.07

0

0

Maturity Preterm

Term >37 weeks Birth weight <1.5 kg 1.5-2.5 kg

46

49.46

22

23.65

23

24.73

1

1.07

0

0

>2.5 kg

33

35.48

21

22.58

10

10.75

1

1.07

1

1.07

10

10.75

8

8.60

2

2.15

0

Apgar in 1 and 5 minutes <7

10

7-9

10

10.75

3

3.22

6

6.45

1

1.07

>9

49

52.68

17

18.27

29

31.18

2

2.15

1

1.07

NICU admission

22

23.65

12

12.90

9

9.67

1

1.07

0

0

Stillbirth

23

24.73

16

17.20

7

7.52

0

0

0

0

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 2, April-June 2017


clinical study Discussion

Conclusion

Antepartum hemorrhage was an important cause for maternal and perinatal morbidity and mortality. APH complicates 2-5% of all pregnancies.2 Incidence in our study is 4.55%, comparable to an incidence of 3% in studies conducted by Maurya et al3 and Singhal et al.4 In our study, 81.72% of cases were unbooked and 80.64% belonged to poor socioeconomic status. Majority were in the age group 20-30 years (77.41%) with 49.46% being multiparous, which is similar to Maurya et al, Singhal et al and Das et al;5 grand multiparity is a significant risk factor for APH as 21.50% patients were grand multipara. Incidence was higher in abruptio placenta 12.90% compared to 8.6% in placenta previa. In our study, 20.43% of cases had severe pre-eclampsia and eclampsia; Singhal et al also reported hypertension in 22% of the cases in their study. Incidence of placenta previa in our study was 1.81% with a total of 37 cases. Previous one or more cesarean delivery was a risk factor in 19.34% cases with APH correlated with the study of Serella et al.6 Eight cases of placenta previa had one previous section and four had previous two sections with an incidence of 8.60% and 4.30%, respectively, which is similar as reported by Pandey et al.7 Six cases of placenta previa (6.45%) had previous history of curettage; 4.30% cases had placenta previa in previous pregnancy also (Table 4).

Prevalence of APH in our institute, which is a tertiary care center was 4.55%. Incidence of abruptio placenta (2.54%) is higher than placenta previa (1.81%). Grand multiparity, severe pre-eclampsia, increased maternal age and polyhydramnios were significant risk factors for abruptio placenta, while previous one or two cesarean delivery and previous curettage were major risk factors for placenta previa. All women with APH heavier than spotting or ongoing bleeding per vaginum should be assessed by consultant led care at tertiary hospitals, advised admission till bleeding stops and to establish the need for urgent intervention to manage maternal and fetal compromise. Prompt resuscitation of hypovolemia and blood administration is an absolute requirement for acceptable obstetric care. Good perinatal outcome is anticipated with early referral to tertiary care center, early cesarean section, liberal availability of blood products and timely neonatal resuscitation.

Malpresentation was seen in 6.45% cases, which is comparatively lesser than found in study conducted by Serella et al (18.03%).6 Perinatal mortality was as high as 24.73% in our study with maternal mortality of 1.07%, which is comparable to Singhal et al study with 23% perinatal mortality and maternal mortality of 2%. Arora et al and Khosla et al reported very high perinatal mortality of 61.5% and 53.5%, respectively.8,9 This difference may be due to better NICU care in our institute. Mean birth weight in our study was 2.4 kg comparable to Singhal et al.4 High neonatal morbidity was due to low birth weight related to preterm birth in (65.58%) and NICU admission in (23.65%). DIC and acute renal injury developed in 2.15% each in our study compared to 7% in Singhal et al4 study requiring blood products transfusion; 11.82% of cases had PPH managed with uterotonics, B-Lynch, bilateral uterine artery ligation while three cases required peripartum hysterectomy. This is comparable to Singhal et al study,4 which had three women requiring peripartum cesarean hysterectomy.

References 1. Lalonde A, Daviss BA, Acosta A, Herschderfer K. Postpartum hemorrhage today: ICM/FIGO initiative 2004-2006. Int J Gynaecol Obstet. 2006;94(3):243-53. 2. Caric V, Bhide A. Antepartum hemorrhage (Chap 10). In: Arias F, Bhide A, Kaizad AS, Daftary DS. Arias’ Practical Guide to High Risk Pregnancy and Delivery, 4th Edition, Elsevier, India; 2014. 3. Maurya A, Arya S. Study of antepartum hemorrhage and its maternal and perinatal outcome. Int J Sci Res Pub. 2014;4(2):1-8. 4. Singhal S, Nymphaea, Nanda S. Maternal and perinatal outcome in antepartum hemorrhage: a study at a tertiary care referral institute. Int J Gynecol Obstet. 2007;9(2):1-4. 5. Das B. Antepartum hemorrhage in three decades. J Obstet Gynaecol India. 1975,25:636-7. 6. Sarella L, Chinta A. A study on maternal and perinatal outcome in placenta previa. Sch J App Med Sci. 2014;2(5A):1555-8. 7. Pandey VP, Pandey M. Study of antepartum haemorrhage and its maternal and perinatal outcome. Ann Int Med Den Res. 2016;2(1):384-9. 8. Arora R, Devi U, Majumdar R. Perinatal morbidity and mortality in antepartum hemorrhage. J Obstet Gynaecol India. 2001;51(3):102-4. 9. Khosla A, Dahiya V, Sangwan K, Rathore S. Perinatal outcome in antepartum hemorrhage. J Obstet Gynaecol India. 1989;9:71-3.

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Clinical Study

A Retrospective Study of Prevalence of Hepatitis B, Hepatitis C and HIV in Pregnant Women and Their Perinatal Outcome Navneet Kaur*, Parneet Kaurâ€

Abstract Background: The incidence of hepatitis B, hepatitis C and human immunodeficiency virus (HIV) is increasing day by day and majority of transmission of these viruses occurs vertically from an infected carrier mother to the neonate. Up to 90% babies born to carrier mothers may also become carriers and are at high risk of developing chronic liver diseases at a younger age. Objectives: The present study was done to know the prevalence, maternal and neonatal outcome in the hepatitis B, hepatitis C and HIV positive pregnant women. Material and methods: This retrospective study was done based on review of records of 2,194 pregnant women who came to the labor room of Dept. of Obstetrics and Gynecology, Govt. Medical College and Rajindra Hospital, Patiala, Punjab from 1st August 2015 to 31st March 2016 for delivery. Results: Amongst 2,194 pregnant women, 106 (4.83%) were either hepatitis B, hepatitis C or HIV positive and 2,088 (95.17%) were negative for any viral marker. Out of 106 women, 30 (28.30%), 43 (40.56%) and 31 (29.25%) women were positive for HIV, hepatitis C and hepatitis B, and the prevalence was 1.36%, 1.95% and 1.41%, respectively. Seventy-one (66.98%) women had vaginal delivery and 35 (33.01%) had cesarean section. Babies born with ≤2,500 g; 2,600-3,000 g and >3,000 g in weight were 41 (37.61%), 46 (42.20%) and 22 (20.18%), respectively. Conclusion: Screening of all the pregnant women for HIV, hepatitis B and hepatitis C is necessary in order to identify those neonates at risk of transmission. Women who are tested positive should be treated properly and health education should be given to such women during antenatal visits and complications should be dealt with carefully. Keywords: Human immunodeficiency virus, hepatitis B, hepatitis C, pregnancy, prevalence

H

epatitis is the inflammation of liver characterized by presence of inflammatory cells in the tissue of the organ. Hepatitis is acute when it lasts less than 6 months and chronic when it persists longer. Hepatitis B virus (HBV) is a member of the Hepadnaviridae family; it is a DNA virus with partially double-stranded DNA and a core antigen surrounded by a shell containing hepatitis B surface antigen (HBsAg).1 According to the World Health Organization (WHO), HBV infection affects more than 2 billion people worldwide and about 350 million of these remain infected chronically. Over 20 million people are infected annually with this virus.2

*Senior Resident †Professor Dept. of Obstetrics and Gynecology Govt. Medical College and Rajindra Hospital, Patiala, Punjab Address for correspondence Dr Navneet Kaur 267, SST Nagar/Sunder Nagar Near Guru Harkrishan Public School, Patiala - 147 001, Punjab E-mail: nav_neetu8@yahoo.in

12

Hepatitis C virus (HCV) infection is a globally prevalent pathogen and a leading cause of death and morbidity. WHO estimates that 3% of the world population are chronically infected with HCV and almost 50% of all cases become chronic carriers and are at risk of liver cirrhosis and liver cancer.3 Both HBV and HCV are transmitted by sexual, parenteral and vertical route and leads to serious sequelae like chronic active hepatitis, cirrhosis and hepatocellular carcinoma.4 Viral hepatitis during pregnancy can lead to coagulation defects, postpartum hemorrhage (PPH), organ failure and is associated with high risk of maternal and fetal complications.5 There is a high rate of vertical transmission causing fetal and neonatal hepatitis leading to impaired physical and mental health later in life. Maternal rupture of membranes more than 6 hours increase the risk of mother-to-child transmission of HCV and HBV.6 Ideally, all pregnant women should be screened both for hepatitis B and hepatitis C. The HIV is a retrovirus which is transmitted by sexual, parenteral route and it has quite a high vertical transmission rate of about 30%, which is highest during

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 2, April-June 2017


clinical study the labor (40-80%). It attacks the CD4 helper cells and leads to an immunosuppressive state with progressive decrease in capacity to fight against infections. In 2014, an estimated 36.9 million people were living with HIV (including 2.6 million children) - a global HIV prevalence of 0.8% and in the same year 1.2 million died of acquired immune deficiency syndrome (AIDS)-related illnesses.7 The biological interaction between HIV and pregnancy is not well-understood. It is said that pregnancy may accelerate HIV progression as pregnancy is associated with suppressed immune system independent of HIV status. However, the epidemiological evidence supporting this hypothesis is weak. A review investigating the effects of pregnancy on HIV progression found no evidence that pregnancy increased progression to an HIV-related illness or fall in CD4 count to fewer than 200 cells per cubic milliliter.8 People at high risk of HIV are also likely to be at risk for hepatitis B or hepatitis C co-infection and are thus associated with reduced survival and increased risk of progression to severe liver disease.9 However, highly active antiretroviral therapy (HAART) should be started immediately after the detection of virus and various protective measures should be taken to avoid transmission of any of three viruses. These days prevalence of viral infections is on the rise and we are getting more and more pregnant females with these infections when tested during pregnancy. The concern remains the effect of infections on pregnant females health and risk of vertical transmission. Because of a significant increase in the number of positive pregnant cases, we decided to conduct a study to see the incidence of hepatitis B, hepatitis C and HIV, and correlation of various maternal parameters to positive status and to view maternal and fetal outcome.

booked status, referred, education status, positive status (HIV/hepatitis B/hepatitis C). The maternal and fetal outcome was then noticed in form of vaginal delivery/ cesarean section, birth weight and Apgar of baby. If the patient had a cesarean section done, its indication was also taken into account. The study included all the positive pregnant women irrespective of twin gestation who had crossed the period of viability and had come for delivery. After the delivery of baby, any postpartum complications were also noted down. The study was done basically to see the prevalence of all three viral infections in pregnant women and to correlate them to the maternal parameters and fetal outcome. Results During the study, total number of subjects who delivered in the labor room from 1st August 2015 to 31st March 2016 were 2,194 and out of them 106 (4.83%) were either hepatitis B, hepatitis C or HIV positive and 2,088 (95.17%) were negative for any viral marker (Fig. 1). All pregnant women delivered at ≼28 weeks of gestation. Out of the 106 positive cases, 30 (28.30%) women were HIV positive, 43 (40.56%) were detected positive for hepatitis C and 31 (29.25%) were hepatitis B positive. Two (1.88%) cases were double positive i.e., one was positive for HIV and hepatitis B and the other was HIV and hepatitis C positive (Table 1). The prevalence of the hepatitis B was 1.41%, hepatitis C was 1.95% and HIV was 1.36% thus indicating high incidence and prevalence for hepatitis C followed by hepatitis B and HIV. Twenty-five HIV positive women Total

Positive

Negative

Material and Methods This retrospective study was conducted to see the prevalence of the HIV, hepatitis B and hepatitis C in all the pregnant women who came to the labor room of Dept. of Obstetrics and Gynecology, Govt. Medical College and Rajindra Hospital, Patiala, Punjab from 1st August 2015 to 31st March 2016 for delivery. The study was conducted in 2,194 pregnant women and out of them, 106 women were positive for any of three markers and all the data were collected retrospectively. The maternal parameters taken were age, unbooked/

2,088 (95.17%)

2,194 (100%)

106 (4.83%)

Figure 1. Total number of pregnant women and percentage of hepatitis B, hepatitis C and HIV positive women.

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clinical study Table 1. Prevalence of Hepatitis B, Hepatitis C and HIV Positive Pregnant Women Viral markers Prevalence

HIV

Hepatitis B

Hepatitis C

Double positive

Total = 2,194

30 (1.36%)

31 (1.41%)

43 (1.95%)

2 (0.09%)

106 (4.83%)

Table 2. No. of Hepatitis B, Hepatitis C and HIV Positive Pregnant Women at Different Ages and Gestation Period Age (years)

≤25

26-30

>30

Total 19-40 (years)

No. Period of gestation (weeks) No.

59 (55.67%)

38 (35.84%)

106 (100%)

≤34

34-40

>40

32-41 (weeks)

5 (4.72%)

86 (81.13%)

15 (14.15%)

106 (100%)

were already on ART and treatment was started in five pregnant women after the investigations. Forty-four women were primigravida who came to the labor room for delivery. Of the total 106 pregnant women who delivered, it was found that 54 (50.94%) were booked. They were booked either in our institution or somewhere else. Fifty-two (49.05%) women came totally uninvestigated and were unbooked. Eighty-one (76.42%) pregnant women were referred to our tertiary care hospital from outside (either Govt. or Private center) for either obstetrical or fetal indication. The education status of the pregnant women who came to our institution was also calculated and it was found that 36 (33.96%) were illiterate, 36 (33.96%) were educated up to school level and 10 (9.43%) were graduate. The criteria of age of women was also taken in the study and it was found that there were 59 (55.67%) women of age ≤25 years, 38 (35.85%) women were of 26-30 years of age and 9 (8.49%) women were >30 years of age. If we take the period of gestation of women, there were only 5 (4.72%) women with gestation ≤34 weeks. A large number of women 86 (81.13%) were 34-40 weeks of gestation and 15 (14.15%) women were >40 weeks of gestation (Table 2); 39.62% positive pregnant women had anemia. Regarding the outcome of all the positive pregnant women, out of 106, 71 (66.98%) had vaginal delivery and 35 (33.01%) had cesarean section (Fig. 2). The cesarean section were done for obstetrical indications only and cesarean sections done for fetal distress were only four and babies born to them were healthy with good Apgar score. Twelve women had cesarean due to previous cesarean section, in 3 women it was done 14

9 (8.49%)

due to oligohydramnios and restricted fetal growth, in 7 women due to cephalopelvic disproportion and it was done due to primi with breech in 5 women. There were only 14.15% preterm vaginal deliveries, which were all unbooked and were referred from other centers and their babies had good Apgar scores. Three women came with a twin pregnancy, out of which two had a vaginal delivery and one had a cesarean section due to previous cesarean section. All twins had a good Apgar score. We had a favorable neonatal outcome in our study. Babies born with ≤2,500 g weight were 41 (37.61%), 46 (42.21%) babies were 2,600-3,000 g in weight and 22 (20.18%) were >3,000 g in weight (Fig. 3). The Apgar score of the newborn babies was very good except two babies who had Apgar of 2/5/6 and 3/6/9 and out of these two, one woman was HIV positive and other was HCV positive and both of these women had vaginal deliveries at term gestation and were referred from other centers with premature rupture of membranes (PROM). Baby with low Apgar score died after 1 hour and other baby remained in nursery ICU for some time and survived. 70

66.98%

60 50 40

33.01%

30 20 10 0 Vaginal delivery

Cesarean section

Figure 2. Maternal outcome of hepatitis B, hepatitis C and HIV positive pregnant women.

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clinical study

50

42.21%

40

37.61%

30 20.18%

20 10 0 ≤2,500 g

≤2,600-3,000 g

≥3,000 g

Figure 3. Birth weight of the newborn babies delivered to hepatitis B, hepatitis C and HIV positive pregnant women.

We had three women who came with intrauterine death (IUD) at ≥35 weeks of gestation and one had a cesarean section done due to nonprogress of labor with scar tenderness in previous cesarean section in labor. The other two delivered vaginally and one of them came with pregnancy-induced hypertension (PIH). All the three cases were unbooked and were referred from other centers at term gestation. We had 27 (25.47%) women who had PPH after delivery and it was managed conservatively. Rest of the women had no postpartum complications due to good and optimum care of the mother after admission. Discussion Both viral hepatitis and HIV are a global health problem. The prevalence of hepatitis B and hepatitis C in our study was 1.41% and 1.95% as compared to Khakhkhar et al10 and Goyal et al,11 which showed a higher prevalence of 3.07% and 2.8%. The higher prevalence may be because they both did a 3-year study and we did a study of only 8 months. A study by Dwivedi et al12 showed the prevalence of 0.9% of hepatitis B who took 4,000 women and it was almost double than our study and the prevalence was 3.03% in the study by Khokhar et al,13 because they also screened syphilis along with hepatitis B, hepatitis C and HIV. In the study by Gupta et al,14 prevalence of HIV was 0.88% and in our study it was 1.36%. In our study, two pregnant women had co-infection of HIV with hepatitis B and hepatitis C with no woman with co-infection with hepatitis B and hepatitis C was found as compared to one study by Bansal et al15 in which one woman had co-infection of HIV with hepatitis B and 4 had combined infection with hepatitis B and hepatitis C. The primigravida in our study were 41.50%

which was similar to the study conducted by Shukla et al5 (41%) and incidence of the hepatitis B and hepatitis C was 37% and 4% concluding that hepatitis B was more common than hepatitis C, whereas in our study hepatitis C was more common than hepatitis B (40.57% and 29.25%). It was seen that 2.69% and 0.41% women in age groups 21-25 years and 31-35 years, respectively were positive for hepatitis B as compared to Khakhkhar et al10 in which the corresponding incidence was 4.20% and 1.37% which is higher than our study which may be because we screened three viral markers and they only screened hepatitis B in all the women in their study of the HIV positive women, we had 53.33%, 16.66% and 10% women in the age groups 20-24 years, 30-34 years and ≥35 years, respectively as compared to a study by Gupta et al14 who had 34.6%, 17.7% and 4.2% in the same age groups. This difference may be because they enrolled large number of women in their study (3,529) and did only HIV screening in their women. We had 71.69% women with less than secondary level of education and a similar study by Elsheikh et al3 had 40% women who had the same level of education. In our study, 39.62% women had anemia as compared to (29.3%) in the study by Maiques et al,16 which was less as compared to our study as they involved very less number of women in their study (2,194 vs. 480). In the study by Safir et al17 who just screened hepatitis B and C, 15.8% pregnant women had PROM as compared to our study in which only 9.43% had PROM. There were 14.15% preterm vaginal deliveries and 2.83% intrauterine deaths in our study as compared to study by Shukla et al5 who had 17% preterm vaginal deliveries and 6% IUDs. In the study by Ryoo et al,18 12.6% had PPH in women who were hepatitis B positive and it was 25.47% in our study, which was almost double. The sample size was large in their study as compared to ours. They had one woman with twin pregnancy with hepatitis B and we had three twins with hepatitis B positivity in one woman. In our study, 7 women came with PIH and there was no woman with PIH in their study. We had a 33.01% cesarean section rate in our study and it was almost similar to the study by Safir et al17 (32.2%). The incidence of low birth weight (<2,500 g)

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clinical study was 24.53% in our study as compared to 18.2% in their study and it was because we screened all the three parameters in our study. We had 97.24% live births and fetal mortality was seen in just 0.94%, whereas in the study by Karegoudar et el19 among the 53.85% of live births, fetal mortality was seen in 4.76%.

writing this topic. This paper has been possible due to joint effort of my co-author as well. I really appreciate the work of juniors who helped me in this topic a lot. This study has been conducted retrospectively, so no harm has been inflicted upon the patients involved in the study.

Conclusion

1. Cunningham FG, Lenovo KJ, Bloom SL, Spong CY, Dashe JS, Hoffman BL, et al. Williams Obstetrics. 24th Edition, McGraw Hill; 2014. pp. 1090-2.

Viral hepatitis and HIV are becoming a global health problem. In conclusion, prevalence of women who were positive either for hepatitis B, hepatitis C or HIV who came to our tertiary care center for delivery was 4.83%. A high number of HCV positive pregnant women 43 (40.56%) came for delivery compared to HBsAg positive 31 (29.24%) and HIV 30 (28.30%) positive women and their prevalence in decreasing order was (1.95%, 1.41%, 1.36%), respectively. Being a tertiary care center, lot of patients are referred to this center. Also, large number of women who came for delivery were referred from other nearby centers 81 (76.42%). Almost 50% women were unbooked with no antenatal check-ups and were on no treatment from anywhere else. Quite a large number of uneducated positive pregnant women 36 (33.96%) came to our center in this study. Only two babies had poor Apgar score and the postpartum complications were also less in number (25.47%). We had no maternal death and just one neonatal death in the study. Hence to conclude, proper antenatal screening should be done in all the pregnant women who are coming to antenatal clinics. Women who are diagnosed to be either of hepatitis B, hepatitis C or HIV positive should be investigated for any other associated risk factors and treated properly. Husband should also be screened and should be put on medication. All the required precautions should be taken in the positive women to prevent further transmission of the disease especially during delivery. Cesarean sections should be done in the women with ruptured membranes more than 6 hours and for obstetrical indications only and all the maternal and fetal complications should be dealt with vigilantly. Acknowledgment I am highly thankful to all my teachers and my family who encouraged me in every aspect of my life. I am thankful to Dr Parneet Kaur who helped me in collecting the material and

16

References

2. Ugbebor O, Aigbirior M, Osazuwa F, Enabudoso E, Zabayo O. The prevalence of hepatitis B and C viral infections among pregnant women. N Am J Med Sci. 2011;3(5):238-41. 3. Elsheikh RM, Daak AA, Elsheikh MA, Karsany MS, Adam I. Hepatitis B virus and hepatitis C virus in pregnant Sudanese women. Virol J. 2007;4:104. 4. Sharma JB. Textbook of Obstetrics. 2014;1:550-4. 5. Shukla S, Mehta G, Jais M, Singh A. A prospective study on acute viral hepatitis in pregnancy; seroprevalence and fetomaternal outcome in 100 cases. J Biosci Tech. 2011;2(3):279-86. 6. Dunkelberg JC, Berkley EM, Thiel KW, Leslie KK. Hepatitis B and C in pregnancy: a review and recommendations for care. J Perinatol. 2014;34(12):882-91. 7. UNAIDS (2015). "How AIDS changed everything" UNAIDS (2015), Fact Sheet. 2014. 8. Calvert C, Ronsmans C. HIV and the risk of direct obstetric complications: a systematic review and meta-analysis. PLoS One. 2013;8(10):e74848. 9. Floreani A. Hepatitis C and pregnancy. World J Gastroenterol. 2013;19(40):6714-20. 10. Khakhkhar VM, Bhuva PJ, Bhuva SP, Patel CP, Cholera MS. Seroprevalence of hepatitis B amongst pregnant women attending the antenatal clinic of tertiary care hospital, Jamnagar (Gujarat). Natl J Med Res. 2012;2(3):362-5. 11. Goyal LD, Kaur S, Jindal N, Kaur H. HCV and pregnancy: prevalence, risk factors, and pregnancy outcome in north Indian population: a case-control study. J Obstet Gynaecol India. 2014;64(5):332-6. 12. Dwivedi M, Misra SP, Misra V, Pandey A, Pant S, Singh R, et al. Seroprevalence of hepatitis B infection during pregnancy and risk of perinatal transmission. Indian J Gastroenterol. 2011;30(2):66-71. 13. Khokhar N, Jethwa D, Lunagaria R, Panchal N, Badrakiya S, Badrakiya G. Seroprevalence of hepatitis B, hepatitis C, syphilis and HIV in pregnant women in a tertiary care hospital, Gujarat, India. Int J Curr Microbiol App Sci. 2015;4(9):188-94.

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Clinical Study

A Comparative Study Between Oral Iron, Intravenous Iron Sucrose and Ferric Carboxymaltose in the Management of Postpartum Anemia Divya Yadav Sharma*, Saroj Singh†, Abhilasha Yadav, Asha Nigam, Deepti Tandon, Alok Sharma

Abstract Introduction: Parenteral iron helps to restore iron stores faster and more effectively than oral iron. Intravenous (IV) iron sucrose is safe, effective and economical in comparison to oral iron. IV ferric carboxymaltose (FCM) has a neutral pH, physiological osmolarity, is dextran free, which makes it possible to administer its higher single doses over shorter time periods. Material and methods: A total of 90 postnatal women were randomly categorized in three groups of 30 each to receive oral iron (ferrous sulfate) equivalent to elemental iron 100 mg daily (Group I), IV iron sucrose (Group II) or IV FCM (Group III) after calculating their doses. Changes in hemoglobin (Hb) and serum ferritin levels after 1 week and after 4 weeks of treatment were measured. Results: In our study, an increase in 0.8 g/dL was achieved in 4 weeks of oral iron therapy; an increase of 1.4 and 2.1 g/dL was seen at the end of 1 week and 4 weeks, respectively of IV iron sucrose, which was significant (p < 0.0001); an increase of 2.5 g/dL and 4.9 g/dL was observed after 1 week and 4 weeks of IV FCM, which was again significant (p < 0.0001). Conclusion: Intravenously administered iron elevates serum Hb and restores iron stores better that oral iron (ferrous sulfate). Both drugs are effective and offer a rapid normalization of Hb after delivery. The single administration of FCM shows advantages of lower incidence of side effects at the injection site, a shorter treatment period and better patient compliance. Keywords: Ferric carboxymaltose, iron sucrose, intravenous, postpartum anemia

T

he World Health Organization (WHO) has defined postpartum anemia (PPA) as hemoglobin (Hb) <10 g/dL in postpartum period. PPA may aggravate puerperal sepsis, thromboembolic complications and lead to subinvolution of uterus, delayed wound healing and failure of lactation. It is associated with an impaired quality-of-life, lactation failure, reduced cognitive abilities, emotional instability and depression. Oral iron therapy was conventionally the treatment of choice but it has disadvantages. Parenteral iron helps to restore iron stores faster and more effectively than oral iron. Intravenous (IV) iron sucrose is safe, effective and economic in comparison to oral and repeated, painful intramuscular iron injections; however, multiple doses and hospital visits are typically required. IV ferric carboxymaltose (FCM) has a neutral pH, physiological osmolarity, is dextran

*Lecturer †Professor and Head (Principal) Dept. of Obstetrics and Gynecology SN Medical College, Agra, Uttar Pradesh Address for correspondence Dr Divya Yadav Sharma Lecturer SN Medical College, Agra, Uttar Pradesh

free, which makes it possible to administer its higher single doses over shorter time periods. Iron is released slowly thereby reducing toxicity and oxidative stress. The objective of the present study was to compare the safety and efficacy of FCM, and IV iron sucrose in the treatment of PPA. Material and Methods This randomized control trial was carried out in the Dept. of Obstetrics and Gynecology, SN Medical College, Agra from July 2015 to February 2016. After informed, written consent and attaining permission from Ethical Committee, a total of 90 postnatal women, diagnosed as cases of iron deficiency anemia (IDA) (Hb <8 g/dL), were randomly categorized in three groups of 30 each to receive oral iron (ferrous sulfate) equivalent to elemental iron 100 mg daily (Group I), IV iron sucrose (Group II) or IV FCM (Group III). Patients with types of anemia other than IDA and known hypersensitivity to iron were excluded from the study. Detailed history of age, parity, socioeconomic status, type of delivery, obstetric complications like pregnancy-induced hypertension (PIH), postpartum hemorrhage (PPH), history of blood transfusions, etc. were obtained. Patients were examined in detail and

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clinical study initial Hb, serum ferritin, iron studies and peripheral smear to diagnose the type of anemia was done in all patients. Changes in Hb and serum ferritin levels after 1 week and after 4 weeks of treatment were measured. The adverse effects to drugs in the three groups were noted and treated. The cumulative dose required for Hb restoration and repletion of iron stores was calculated by Ganzoni formula: Cumulative iron deficit (mg) = 2.4 × W × D + 500, Where W= body weight in kg, D = Target Hb - Actual Hb. 2.4 derived from blood volume, which is 7% of body weight and iron content of Hb, which is 0.34%. 0.07 × 0.0034 × 100 = 2.4 (conversion from g/dL to mg). zz In patients receiving iron sucrose, 200 mg of elemental iron diluted in 100 mL saline, was the maximum dose given in 30 minutes period, on alternate days, when necessary. zz In patients receiving FCM, maximum single dose of 1,000 mg (20 mL), diluted in 250 mL saline, infused in 15 minutes, not more than once a week. Observations and Results The mean age and body mass index (BMI) in the three groups were comparable i.e., 24.5 years, 23.6 years, 24.9 years and mean BMI was 21.3, 22.3, 23.1 in the

oral iron, iron sucrose and FCM group, respectively. All the patients belonged to Class III socioeconomic status, according to BJ Prasad Classification. The mean parity was 2.6, 3.1 and 2.9 in the three groups. Antenatal anemia was present in 68% patients in Group I, 69% cases in Group II and 67.9% cases in Group III. The percentage of cesarean section was 20%, 17.7% and 18.8% in Group I, Group II and Group III, respectively. Thirty-one percent patients in Group I, 33% cases in Group II and 36% cases in Group III had history of PPH of any cause in this delivery. Twenty-eight percent patients in Group I, 32% patients in Group II and 27% patients in Group III had a history of PIH (Table 1). Table 2 shows the comparison of initial Hb and rise of Hb after 1 week and after 4 weeks. The mean initial Hb was similar in all the three groups i.e., 7.1 g/dL, 7.1 g/dL and 7 g/dL in Group I, Group II and Group III, respectively. After 1 week of treatment, the Hb rose to 7.2 g/dL, 8.5 g/dL and 9.4 g/dL in Group I, II and III, respectively. After 4 weeks, the Hb rose to 7.9 g/dL, 10.6 g/dL and 11.9 g/dL in Group I, Group II and Group III, respectively. Table 3 shows the mean difference of Hb. The mean difference of Hb from initial to 1 week was 0.1 g/dL, 1.4 g/dL and 2.4 g/dL in Group I, Group II and Group III, respectively. The difference of Hb from 1 week to 4 weeks of treatment was 0.7 g/dL, 2.1 g/dL and

Table 1. Patient Profile Parameters

Oral iron (Group I)

Iron sucrose (Group II)

FCM (Group III)

Mean age (years)

24.5

23.6

24.9

Mean BMI

21.3

22.3

23.1

Class III

Class III

Class III

Mean parity

2.6

3.1

2.9

Presence of antenatal anemia (%)

68

69

67.9

Percentage of LSCS (%)

20

17.7

18.8

History of PPH (%)

31

33

36

PIH (%)

28

32

27

Socioeconomic status

BMI = Body mass index; LSCS = Lower segment cesarean section; PPH = Postpartum hemorrhage; PIH = Pregnancy-induced hypertension.

Table 2. Comparison of Mean Hemoglobin with Different Iron Preparations

18

Time period

Oral iron (Group I)

Iron sucrose (Group II)

FCM (Group III)

Day 0 (g/dL)

7.1

7.1

7

After 1 week (g/dL)

7.2

8.5

9.4

After 4 weeks (g/dL)

7.9

10.6

11.9

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clinical study 2.5 g/dL in Group I, Group II and Group III, respectively. After 4 weeks, the difference of Hb from initial level (i.e., 0-4 weeks) was 0.8 g/dL, 3.5 g/dL and 4.9 g/dL in Group I, Group II and Group III, respectively. Table 4 shows the comparison of mean initial ferritin levels and rise of ferritin after 1 week and after 4 weeks. The mean initial ferritin was similar in all the three groups i.e., 35 ng/mL, 36 ng/mL and 35 ng/mL in Group I, Group II and Group III, respectively. After 1 week of treatment, the ferritin levels rose to 43 ng/mL, 122 ng/mL and 143 ng/mL in Group I, Group II and Group III, respectively. After 4 weeks, the ferritin levels rose to 52 ng/mL, 156 ng/mL and 164 ng/mL in Group I, Group II and Group III, respectively. Table 5 shows the side effect profile of the different iron preparations. It was observed that most common Table 3. Comparison of Rise in Mean Hb Difference of Hb at

Oral iron (Group I)

Iron sucrose (Group II)

FCM (Group III)

0-1 week (g/dL)

0.1

1.4

2.4

1-4 weeks (g/dL)

0.7

2.1

2.5

0-4 weeks (g/dL)

0.8

3.5

4.9

Table 4. Mean Ferritin Levels Time period

Oral iron Iron sucrose FCM (Group I) (Group II) (Group III)

Day 0 (ng/mL)

35

36

35

After 1 week (ng/mL)

43

122

143

After 4 weeks (ng/mL)

52

146

164

Table 5. Side Effects of Different Iron Preparations Drug-related adverse effects Adverse effects

Oral iron (n= 30)

Iron sucrose (n = 30)

FCM (n = 30)

0

9

10

Headache

2

3

2

Nausea/vomiting

13

3

1

Constipation

12

1

1

Sensation of heat

0

2

1

Shivering

1

2

1

Diarrhea

8

1

0

Abdominal pain

6

2

1

Joint pain

2

6

2

Tingling sensation

2

7

5

Injection site pain

side effect with oral iron was constipation, nausea and vomiting. Eight had diarrhea and 6 had abdominal pain; while few patients (2 each) had headache, joint pain and tingling sensation. In the patients receiving iron sucrose, maximum patients i.e., 9 had injection site pain, 7 had tingling sensation, 6 had joint pain, 3 had headache, nausea/vomiting and 2 each had shivering of heat sensation and abdominal pain. Those receiving FCM, maximum patients i.e., 10 had injection site pain, 5 had tingling sensation, 2 each had joint pain and headache. Discussion Postpartum anemia imposes a substantial disease burden during a critical period of maternal-infant interaction and may give rise to lasting developmental deficits in infants of the affected mothers. IDA is the most common cause of anemia world-wide. Each mL blood loss results in loss of 0.5 mg of iron. This study was conducted to compare the safety and efficacy of IV FCM, IV iron sucrose and oral iron in the treatment of PPA. This comparative study was conducted in SN Medical College, Agra on 90 patients of PPA. Patients were equally divided in three groups and were given 100 mg oral iron daily or IV iron sucrose or FCM after calculating their dose. It was observed that maximum patients in the study were parous and belonged to Class III socioeconomic status because anemia mainly affects low income parous women. More than half of the patients were already anemic in their antenatal period because antenatal anemia is a risk factor of PPA. Other risk factors of PPA are PPH and PIH, which was present in many patients in our study. The initial Hb was comparable in all the three groups. Various studies had reported increase of Hb level by 2-3 g/dL within 4-12 weeks of oral iron therapy (Table 6). In our study, an increase of 0.8 g/dL was achieved in 4 weeks of oral iron. Giannoulis et al reported an increase of Hb by 4-6 g/dL in patients receiving iron sucrose, whereas in our study an increase of 1.4 and 2.1 g/dL is seen at the end of 1 week and 4 weeks, respectively, which was significant (p < 0.0001). Rathod et al reported an increase of Hb 2.4 g/dL and 3.4 g/dL after 2 weeks and 6 weeks of iron sucrose, respectively. Van Wyck et al reported an increase of Hb by 2 g/dL in 7 days and 3 g/dL

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clinical study Table 6. Comparison of Our Study with Various Other Studies Done in the Past Study

Time (weeks) period

Rise of Hb (g/dL) Iron sucrose

FCM

Rise in serum ferritin by FCM (ng/mL)

Van Wyck et al

1

2

-

Seid et al

4 6

-

3 3

238

Rathod et al

2

2.4

3.2

6

3.4

4.4

Breymann et al

1

568

Giannoulis et al

4

4-6

Our Study

1

1.4

2.4

143

4

3.5

4.9

184

in 2-4 weeks, while Rathod et al reported an increase of Hb 3.2 g/dL and 4.4 g/dL after 2 weeks and 6 weeks, respectively in patients receiving FCM. Similarly, in our study, an increase of 2.5 g/dL and 4.9 g/dL was observed after 1 week and 4 weeks of FCM, which was again significant (p < 0.0001). Seid et al reported that ferritin levels replenished in 42 days in FCM group but not in oral iron group, similar to our study in which there is only minimal rise of ferritin in oral iron group. Adverse reactions do occur with various iron therapies. Gastrointestinal disorders are the most common with various oral iron preparations. This led to poor compliance among these patients. The incidence of adverse effects reported by various studies is between 6.8% and 24.2%. The adverse drug reactions were least in the parenteral preparations (p < 0.0001). Few patients (9 in Group II and 10 in Group III), had injection site pain, which subsided by itself after discontinuation of the drug. Some patients in IV iron group had joint pain, tingling sensation, which too subsided by itself. Patient satisfaction and general well-being was highest in subjects treated with FCM followed by iron sucrose and lastly with oral iron. The incidence of adverse effects reported by various studies is between 6.8% and 24.2%. Aggarwal reported fever, arthritis, dysgeusia and anaphylaxis Grade I in patients receiving iron sucrose therapy. In our study, 30% had injection site pain and 20% had tingling sensation in patients receiving iron sucrose and FCM. All patients made an uneventful recovery after receiving treatment in the form of analgesics. 20

Conclusion The prophylaxis of PPA should begin early in pregnancy in order to ensure a good iron status prior to delivery and preventing further PPA. In India, 36% of total maternal deaths are attributable to PPH or anemia. IV FCM is as safe as iron sucrose in the management of postpartum IDA despite five times of higher dosage. Both iron sucrose and FCM are a safe and effective treatment option for PPA, but the ability to administer 1,000 mg doses in a single sitting, fewer adverse reactions and better compliance makes FCM, the first-line drug in the management of postpartum IDA, causing a faster and higher replenishment of iron stores and correction of Hb levels. So, we conclude that, intravenously administered iron elevates serum Hb and restores iron stores better than oral iron (ferrous sulfate). Both drugs are effective and offer a rapid normalization of Hb after delivery. The single application of FCM shows advantages of lower incidence of side effects at the injection site, a shorter treatment period and better patient compliance. Out of the two different IV iron preparations used in this study, FCM proved to be statistically better than iron sucrose. Suggested Reading 1. Sutherland T, Bishai DM. Cost-effectiveness of misoprostol and prenatal iron supplementation as maternal mortality interventions in home births in rural India. Int J Gynaecol Obstet. 2009;104(3):189-93. 2. Giannoulis C, Daniilidis A, Tantanasis T, Dinas K, Tzafettas J. Intravenous administration of iron sucrose for treating anemia in postpartum women. Hippokratia. 2009;13(1):38-40. 3. Van Wyck DB, Martens MG, Seid MH, Baker JB, Mangione A. Intravenous ferric carboxymaltose compared with oral iron in the treatment of postpartum anemia: a randomized controlled trial. Obstet Gynecol. 2007;110(2 Pt 1):267-78. 4. Seid MH, Derman RJ, Baker JB, Banach W, Goldberg C, Rogers R. Ferric carboxymaltose injection in the treatment of postpartum iron deficiency anemia: a randomized controlled clinical trial. Am J Obstet Gynecol. 2008;199(4):435.e1-7. 5. Aggarwal RS, Mishra VV, Panchal NA, Patel NH, Deshchougule VV, Jasani AF. Comparison of oral iron and IV iron sucrose for treatment of anemia in postpartum Indian Woman. Natl J Commun Med. 2012;3(1):48-54. 6. Rathod S, Samal SK, Mahapatra PC, Samal S. Ferric carboxymaltose: A revolution in the treatment of postpartum anemia in Indian women. Int J Appl Basic Med Res. 2015;5(1):25-30.

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Clinical Study

Conservative Surgical Techniques in Management of Morbidly Adherent Placenta: A 5-year Study Rekha Rani*, Shikha Singh†, Ruchika Garg*, Urvashi Verma*, Sangeeta Sahu‡, Saroj Singh#, Surendra Kumar¥, Himani Goyel$

Abstract Objectives: To evaluate the role of various conservative surgical techniques in management of morbidly adherent placenta. To estimate the fertility and pregnancy outcomes after successful conservative surgical treatment for placenta accreta. Material and methods: This retrospective study included women with a history of conservative management for placenta accreta. The study was conducted in SN Medical College, Agra from December 2010 to November 2015 (5 years review) on 131 patients. The aim of our study was to estimate the postoperative and future reproductive outcomes after performing various successful conservative surgical techniques in management of morbidly adherent placenta. Results: Compressive sutures, intrauterine packing and vessel embolization, etc. may be considered life-saving procedures by achieving the best hemostatic efficacy. Data on restoration of menses and pregnancy rates after these procedures are limited by short-term follow-up and by the paucity of studies, especially for vascular ligation. Conclusion: Successful conservative treatment for placenta accreta does not appear to compromise the patients’ subsequent fertility or obstetrical outcome. Keywords: Placenta accreta, pelvic vessel embolization, compressive sutures, fertility

P

lacenta accreta/percreta is a leading cause of third trimester hemorrhage and postpartum maternal death. The current treatment for third trimester hemorrhage due to placenta accreta/percreta is cesarean hysterectomy, which may be complicated by large volume blood loss. The incidence of placenta accreta is increasing parallel with the increase in cesarean delivery. Aim and Objectives zz To evaluate the role of various conservative surgical techniques in management of morbidly adherent placenta.

zz

Material and Methods Type of Study zz

zz zz zz

*Assistant Professor † Associate Professor ‡ Lecturer # Professor and Head ¥ Consultant Anesthesia $ 3rd Year Junior Resident Dept. of Obstetrics and Gynecology, SN Medical College, Agra, Uttar Pradesh Address for correspondence Dr Rekha Rani Assistant Professor Dept. of Obstetrics and Gynecology, SN Medical College, Agra - 282 003, Uttar Pradesh E-mail: drrekha.gynae@gmail.com

To estimate the fertility and pregnancy outcomes after successful conservative surgical treatment for placenta accreta.

zz zz

This retrospective study was conducted in SN Medical College, Agra from December 2010 to November 2015 (5 years review) on 131 patients. The present study was undertaken among all pregnant patients attending OPD and labor room. Success of conservative treatment was defined by uterine preservation. Data were retrieved from medical files and telephone interviews. An informed consent was taken from all women included in the study. Thorough history taking, physical examination and investigations were done in all patients.

Inclusion Criteria

Reproductive age group (21-35 years). zz Parity (≤4). zz Elective cesarean cases. zz All pregnant patients with placenta previa in previous one or more than one cesarean section. zz

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clinical study Women with a history of conservative management for placenta accreta. zz Patients booked in antenatal period. zz Hemoglobin ≥11 g/dL in elective cases. zz

Exclusion Criteria zz zz zz zz

zz

Age more than 35 years. Grand multipara more than 4 children. Patients undergoing emergency cesarean section. Patients with previous history of scar rupture or dehiscence in which repair of uterus or hysterotomy done. Any medical and coagulation disorders (diabetes, epilepsy, heart diseases), history of bronchial asthma.

zz zz

B-Lynch and Cho sutures Methotrexate adjuvant treatment to hasten the placental resolution.

Whatever the option chosen, when placenta accreta is suspected before delivery in a woman with an anterior placenta previa, it is recommended to perform a vertical fundal uterine incision to avoid the placenta and reduce the risk of massive postpartum hemorrhage (PPH) (Fig. 4). Cesarean Section Hysterectomy Performing a hysterectomy after the birth of the child without attempting removal of the placenta when placenta accreta is strongly suspected antenatally or after an attempted placental removal when the diagnosis of placenta accreta is not made until during delivery.

Diagnosis

For diagnosis, high resolution ultrasound with color Doppler findings at gestational Week 29 consistent with placenta accreta, included irregularly shaped placental lacunae (vascular spaces) within the placenta, thinning of the myometrium overlying the placenta, loss of the retroplacental ‘clear space’, protrusion of the placenta into the bladder, increased vascularity of the uterine serosa - bladder interface and turbulent blood flow through the lacunae on Doppler ultrasonography (Fig. 1). Uterine findings during laparotomy included cesarean section scar at uterine fundus and bulging isthmic part with placenta accreta/percreta (Fig. 2). In addition, placenta accreta was seen involving the urinary bladder (Fig. 3 a and b) .

Placenta

Storm flow

Figure 1. High resolution ultrasound with color Doppler findings at gestational Week 29 consistent with placenta accreta.

Procedures

There are some basic options for management of placenta accreta: zz The cesarean hysterectomy zz Conservative treatment zz Localized packing of thinned placental site with absorbable gel (Abgel) followed by compression sutures zz Ligation of individual vessels in the placental bed - Simple or box stitches where continuous oozing is present zz Temporarily packing of uterine segment. zz The stepwise surgical approach if preservation of fertility is desired 22

Caesarean section scar

Prominent isthmic portion of uterus

Figure 2. Uterine findings during laparotomy. Note cesarean section scar at uterine fundus and bulging isthmic part with placenta accreta/ percreta.

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 2, April-June 2017


clinical study placenta in place adhering either partially or totally to the myometrium, and to close the hysterotomy. Conservative treatment avoids a hysterectomy in about 75-80% of cases, but is associated with a risk of transfusion requirements, infection and severe

a

b

Figure 3 a and b. Placenta accreta/percreta invading lower uterine segment and bladder.

Figure 6. Image obtained 20 minutes after delivery. Note that if the placenta is not dislodged, bleeding does not occur.

Figure 4. After delivery of baby through vertical fundal uterine incision.

Placenta accreta

Figure 7. B-Lynch suture with intrauterine packing. Figure 5. Hysterectomy specimen opened. Note placenta previa percreta left in situ.

Figure 5 shows opened hysterectomy specimen with placenta previa percreta left in situ. Conservative Treatment This option consists of delivering the child, tie and then cut the umbilical cord at its base to leave the

maternal morbidity. Figure 6 shows image obtained 20 minutes after delivery. It is seen that if the placenta is not dislodged, bleeding does not occur. B-Lynch suture with intrauterine packing may be given to prevent PPH (Fig. 7). The one step-conservative surgery (Fig. 8 a-c) It consists of resecting the invaded area together with the placenta and performing the reconstruction as a one-step procedure. The main stages of this alternative

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23


clinical study technique achieved through a median or transverse suprapubic incision are: zz Vascular disconnection of newly-formed vessels and the separation of invaded uterine from invaded vesical tissues zz Performing an upper-segmental hysterectomy zz Resection of all invaded tissue and the entire placenta in one piece with previous local vascular control zz Use of surgical procedures for hemostasis zz Myometrial reconstruction in two planes zz Bladder repair if necessary.

Uterus body

To cover the uterine defect, a reabsorbable mesh is used. When fixed, it will allow an accurate uterine repair and prevent postoperatory injuries (Fig. 9). Sutures are placed on second layer. Fibrin glue and collagen are placed (Fig. 10). After the second layer has been closed uterine repair is performed (Fig. 11). Under temporary aortic clamping, the placenta is safely removed (Fig. 12). Localized Packing of Thinned Placental Site with Absorbable Gel (Abgel) After delivery of baby and placenta if there is local thinning of uterus with bleeding seen, you have to put some pieces of Abgel to pack the involved area tightly and obliterate the cavity by putting compression sutures. Uterus body

Bladder a

Absorbable mesh

Fundal hysterotomy

Figure 9. To cover the uterine defect, a reabsorbable mesh is used. When fixed, it will allow an accurate uterine repair and prevent postoperatory injuries.

b

c

Figure 8 a-c. The one step-conservative surgery.

24

Figure 10. Sutures are placed on second layer. Fibrin glue and collagen are placed.

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 2, April-June 2017


clinical study zz

Implications and recommendations for future pregnancies may be discussed during the postoperative stay and reinforced at the postdischarge visit.

Main Outcome Measure(s)

Comparison of the effectiveness of conservative surgical techniques, separately or together, with respect to success rate (ability to stop bleeding and preserve the uterus). zz Fertility rate (subsequent pregnancies or the return of regular menstrual cycles). zz Complication rate of the procedure. zz The outcomes of subsequent pregnancies in terms of type of delivery and eventual delivery complications. zz

Figure 11. After the second layer has been closed uterine repair is performed. Fundus

Round ligament

Results Follow-up data were available for 96 (73.3%) of the 131 women included in the study (Fig. 13).

Figure 12. Under temporary aortic clamping, the placenta is safely removed. Through the uterine defect, the surgeon's fingers are clearly seen.

Triple-P procedure Reconstruction of the uterine wall-as a safe and effective alternative to conservative management or peripartum hysterectomy. It involves: zz Perioperative placental localization and delivery of the fetus via transverse uterine incision above the upper border of the placenta zz Pelvic devascularization zz Placental nonseparation with myometrial excision.

Compressive sutures, intrauterine packing and vessel embolization, etc. may be considered life-saving procedures by achieving the best hemostatic efficacy. Data on restoration of menses and pregnancy rates after these procedures are limited by short-term follow-up and by the paucity of studies, especially for vascular ligation. Demographic and obstetrical characteristics at the first conservative treatment for the women included in the study and those lost to follow-up is given in Table 1 and 2.

96 patients

88-normal menses

6 (placenta accreta) 4 asso. With placenta previa

Follow-up

Full documentation of the case is imperative. zz Careful explanation of events and interventions must be given to the patient and family. zz Caregivers must be available and approachable for questions.

8amenorrheic

zz

27-wanted children

21-3rd trim preg del healthy baby

3-attempting 24-preg

1ectopic

2miscarriages

4 developed PPH

Figure 13. Follow-up data of 96 of the 131 women included in the study.

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clinical study Table 1. Demographic Characteristics at the First Conservative Treatment for the Women Included in the Study and those Lost to Follow-up Demographic characteristics

Women included in the study (n = 96)

Women lost to follow-up (n = 35)

P value

Age (years)

33.3 ± 4.6

32.5 ± 5.2

0.38

Parity

1 (0-8)

0 (0-5)

0.80

Number of pregnancies

3 (1-12)

3 (1-11)

0.82

Table 2. Obstetrical Characteristics at the First Conservative Treatment for the Women Included in the Study and those Lost to Follow-up Obstetrical characteristics

Women included in the study (n = 96)

Women lost to follow-up (n = 35)

P value

5 (5.2)

5 (14.3)

0.13

Gestational age at delivery (week)

33.9 ± 5.2

35.0 ± 4.4

0.27

Cesarean section

74 (77.1)

29 (82.9)

0.63

Placenta percreta

Placenta left entirely in situ

35 (36.4)

13 (37.1)

>0.99

Primary PPH*

41 (42.7)

15 (42.9)

>0.99

Additional uterine devascularization procedure†

66 (68.8)

21 (60.0)

0.40

Transfusion patients

30 (31.2)

9 (25.7)

0.67

Transfer to ICU

15 (15.6)

8 (22.3)

0.44

Infection‡

23 (24.0)

8 (22.3)

>0.99

1 (1.0)

0

>0.99

Severe maternal morbidity$ Data are mean ± SD, n (%) or median (range).

*Primary PPH was defined as bleeding requiring medical or interventional treatment in the 24 hours after delivery. Uterine devascularization procedures included pelvic arterial embolization, surgical vessel ligation (uterine or hypogastric artery ligation, stepwise uterine devascularization) and/or uterine compression sutures (B-Lynch and Cho sutures). †

‡ Infection included endometritis, wound infection, peritonitis, pyelonephritis, vesicouterine fistula, uterine necrosis and isolated postpartum fever higher than 38.5°C for 24 hours.

Severe maternal morbidity was defined as any of the following: sepsis, septic shock, peritonitis, uterine necrosis, post-partum uterine rupture, fistula, injury to adjacent organs, acute pulmonary edema, acute renal failure, deep vein thrombophlebitis or pulmonary embolism, or maternal death.

§

Complications

Immediate zz Hemorrhage (3,000-5,000 mL). zz Disseminating intravascular coagulation (DIC). zz Transfusion reactions. zz Other complications accompanying blood transfusion (human immunodeficiency virus [HIV] and hepatitis). zz Surgical complications (emergency hysterectomy, bowel injury, urological injuries, etc.). zz Pulmonary embolism. zz Adult respiratory distress syndrome (ARDS). Delayed zz Hypopituitarism following severe PPH (Sheehan syndrome) is due to critical ischemia of the hypertrophied pituitary. 26

zz

Complications like sterility, uterine perforation, uterine synechiae (Asherman syndrome).

zz

Venous thrombosis and embolic events.

Discussion Our results suggest that successful conservative treatment for placenta accreta does not appear to compromise women’s subsequent fertility or obstetric outcome, but that the risk of recurrence of placenta accreta during future deliveries is high. An additional strength is the systematic follow-up of a relatively large cohort (n = 96), including evaluation of desire and attempts to conceive, in order to obtain information about women with presumed preserved fertility who either had no desire for pregnancy, or did desire pregnancy but have not become pregnant. Their demographic and obstetric characteristics for the first

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 2, April-June 2017


clinical study conservative treatment did not differ from those of women who were included in the study. It is possible that some women did not actually have placenta accreta; pathological confirmation is of course impossible after successful conservative treatment (i.e., in cases without a hysterectomy specimen). Nevertheless, our results reflect the long-term consequences in real-life of conservative treatment for placenta accreta. Placenta accreta is thought to be due to an absence or deficiency of Nitabuch’s layer or the decidua spongiosa, following the failure of the endometrium/decidua basalis to reform after trauma to the endometrium from surgical procedures. The pathophysiology of placenta accreta is therefore similar to that of intrauterine synechiae, based as it is on endometrial alteration that might promote abnormal implantation, resulting in infertility, miscarriage or recurrent placenta accreta. Our results are therefore reassuring in suggesting that successful conservative treatment for placenta accreta does not appear to compromise the patients’ subsequent fertility or obstetrical outcome. The absence of pregnancy complications observed in our study, except for abnormal placentation and PPH, is consistent with the few previous reports on pregnancy after conservative treatment for placenta accreta. Four earlier studies report similar results: women with a history of severe PPH requiring pelvic arterial embolization and/or uterine-sparing surgical procedures are likely to decide against another pregnancy because of their fear of another hemorrhage. Conclusions Successful conservative treatment for placenta accreta does not appear to compromise the patients’ subsequent fertility or obstetrical outcome. Nevertheless, patients should be advised of the high risk that placenta accreta may recur during future pregnancies. Intrauterine packing, pelvic vessel embolization and compressive sutures are associated with high rates of restoration of regular menses and successive pregnancies. Randomized trials would be desirable to define the best management of PPH. A review of the literature demonstrates a 76.9% success rate and an 11% complication rate. Suggested Reading 1. AbdRabbo SA. Stepwise uterine devascularization: a novel technique for management of uncontrolled postpartum hemorrhage with preservation of the uterus. Am J Obstet Gynecol. 1994;171(3):694-700.

2. Alanis M, Hurst BS, Marshburn PB, Matthews ML. Conservative management of placenta increta with selective arterial embolization preserves future fertility and results in a favorable outcome in subsequent pregnancies. Fertil Steril. 2006;86(5):1514.e3-7. 3. Committee on Obstetric Practice. ACOG committee opinion. Placenta accreta. Number 266, January 2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 2002;77(1):77-8. 4. Bretelle F, Courbière B, Mazouni C, Agostini A, Cravello L, Boubli L, et al. Management of placenta accreta: morbidity and outcome. Eur J Obstet Gynecol Reprod Biol. 2007;133(1):34-9. 5. Daskalakis G, Anastasakis E, Papantoniou N, Mesogitis S, Theodora M, Antsaklis A. Emergency obstetric hysterectomy. Acta Obstet Gynecol Scand. 2007;86(2):223-7. 6. Eller AG, Porter TF, Soisson P, Silver RM. Optimal management strategies for placenta accreta. BJOG. 2009;116(5):648-54. 7. Kayem G, Pannier E, Goffinet F, Grangé G, Cabrol D. Fertility after conservative treatment of placenta accreta. Fertil Steril. 2002;78(3):637-8. 8. Kayem G, Davy C, Goffinet F, Thomas C, Clément D, Cabrol D. Conservative versus extirpative management in cases of placenta accreta. Obstet Gynecol. 2004;104(3):531-6. 9. Miller DA, Chollet JA, Goodwin TM. Clinical risk factors for placenta previa-placenta accreta. Am J Obstet Gynecol. 1997;177(1):210-4. 10. Nizard J, Barrinque L, Frydman R, Fernandez H. Fertility and pregnancy outcomes following hypogastric artery ligation for severe post-partum haemorrhage. Hum Reprod. 2003;18(4):844-8. 11. Oyelese Y, Smulian JC. Placenta previa, placenta accreta, and vasa previa. Obstet Gynecol. 2006;107(4):927-41. 12. Salomon LJ, deTayrac R, Castaigne-Meary V, Audibert F, Musset D, Ciorascu R, et al. Fertility and pregnancy outcome following pelvic arterial embolization for severe post-partum haemorrhage. A cohort study. Hum Reprod. 2003;18(4):849-52. 13. Sentilhes L, Trichot C, Resch B, Sergent F, Roman H, Marpeau L, et al. Fertility and pregnancy outcomes following uterine devascularization for severe postpartum haemorrhage. Hum Reprod. 2008;23(5):1087-92. 14. Sentilhes L, Gromez A, Razzouk K, Resch B, Verspyck E, Marpeau L. B-Lynch suture for massive persistent postpartum hemorrhage following stepwise uterine devascularization. Acta Obstet Gynecol Scand. 2008;87(10):1020-6. 15. Sentilhes L, Gromez A, Descamps P, Marpeau L. Why stepwise uterine devascularization should be the first-line conservative surgical treatment to control severe postpartum hemorrhage? Acta Obstet Gynecol Scand. 2009a;88:490-2. 16. Sentilhes L, Gromez A, Clavier E, Resch B, Verspyck E, Marpeau L. Predictors of failed pelvic arterial embolization

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clinical study for severe postpartum hemorrhage. Obstet Gynecol. 2009;113(5):992-9.

19. Sentilhes L, Descamps P, Marpeau L. Has B-Lynch suture hidden long-term effects? Fertil Steril. 2010;94(4):e62.

17. Sentilhes L, Ambroselli C, Kayem G, Provansal M, Fernandez H, Perrotin F, et al. Maternal outcome after conservative treatment of placenta accreta. Obstet Gynecol. 2010;115(3):526-34.

20. Tseng JJ, Hsu SL, Wen MC, Ho ES, Chou MM. Expression of epidermal growth factor receptor and c-erbB-2 oncoprotein in trophoblast populations of placenta accreta. Am J Obstet Gynecol. 2004;191(6):2106-13.

18. Sentilhes L, Gromez A, Clavier E, Resch B, Verspyck E, Marpeau L. Fertility and pregnancy following pelvic arterial embolisation for postpartum haemorrhage. BJOG. 2010;117(1):84-93.

21. Wu S, Kocherginsky M, Hibbard JU. Abnormal placentation: twenty-year analysis. Am J Obstet Gynecol. 2005;192(5):1458-61.

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...Cont'd from page 16 14. Gupta S, Gupta R, Singh S. Seroprevalence of HIV in pregnant women in North India: a tertiary care hospital based study. BMC Infect Dis. 2007;7:133. 15. Bansal V, Bansal A, Bansal AK, Kumar A. Seroprevalence of HBV in pregnant women and its co-infection with HCV and HIV. Int J Rec Sci Res. 2015;6(4):3590-3. 16. Maiques V, Garcia-Tejedor A, Diago V, Molina JM, Borras D, Perales-Puchalt A, et al. Perioperative cesarean delivery morbidity among HIV-infected women under highly active antiretroviral treatment: a case-control study. Eur J Obstet Gynecol Reprod Biol. 2010;153(1):27-31.

17. Safir A, Levy A, Sikuler E, Sheiner E. Maternal hepatitis B virus or hepatitis C virus carrier status as an independent risk factor for adverse perinatal outcome. Liver Int. 2010;30(5):765-70. 18. Ryoo YG, Chang YH, Choi GS, Jeong WJ, Kim JW, Joung NK, et al. Hepatitis B viral markers in pregnant women and newborn infants in Korea. Korean J Intern Med. 1987;2(2):258-68. 19. Karegoudar D, Dhirubhai PR, Dhital M, Amgain K. A study of liver disorder and its consequences in pregnant women with jaundice in tertiary care centre in Belgaum, Karnataka, India. IOSR J Dent Med Sci. 2014;13(4):84-6.

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Case Report

Intrapartum HELLP Syndrome Associated with Mild Pre-eclampsia Jaya Kundan Gedam*, Minal Bhalerao†, Utkarsh‡

Abstract Pre-eclampsia can lead to a dreaded obstetric emergency, HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome, in a few cases leading to hemolysis, thrombocytopenia and liver enzymes dysfunction. It can occur mostly in third trimester of pregnancy and sometimes during postnatal period. We report a case of mild pre-eclampsia which was complicated with intrapartum HELLP syndrome. A 35-year-old pregnant woman with mild pre-eclampsia at 36 weeks of gestation was admitted to our hospital with labor pain. A cesarean section was performed, due to excessive bleeding per vagina during labor. A prompt diagnosis and appropriate management helped us to reduce morbidity and mortality related to HELLP syndrome. Keywords: Pregnancy-induced hypertension, pre-eclampsia, HELLP syndrome

H

ELLP syndrome is a life-threatening complication of pregnancy characterized by hemolysis, elevated liver enzymes and low platelets. It is usually considered to be a variant or complication of pre-eclampsia. However, in 20% of cases it may occur without pre-eclampsia during antenatal or intrapartum period. HELLP is a multisystemic disorder, leading to generalized vasospasm, microthrombi formation and coagulation defects. Clinical features include severe headache, malaise, nausea and vomiting, pain around upper abdomen and pedal edema. In about 20% of all women, disseminated intravascular coagulation (DIC) is also seen with HELLP syndrome.

Case Report A 35-year-old pregnant woman, primigravida, was admitted in emergency to our hospital in the 36th week of gestation, with mild pregnancyinduced hypertension (PIH). Her antenatal check-

*Associate Professor † Senior Resident Dept. of Obstetrics and Gynecology ‡ Senior Resident Dept. of Medicine ESI-PGIMSR, MGM Hospital, Parel, Mumbai, Maharashtra Address for correspondence Dr Jaya Kundan Gedam L-1, RH-2 Ground Floor, L-1, RH-2, Sector-6, Vashi, Navi Mumbai, Maharashtra E-mail: jayagedam@gmail.com

ups were infrequent but normal. On admission, her blood pressure was 140/90 mmHg (after 2 hours; 170/100 mmHg). Urine albumin was trace. Capsule nifedipine 5 mg was given orally. Prophylactic injection magnesium sulfate (MgSO4) was started. Her cervix was 2 cm dilated, 25% effaced. Augmentation of labor was done with oxytocin. All laboratory findings including hematological, biochemical and coagulation profile, were within their normal limits (Table 1). Three hours after her admission, cervical dilatation was 3-4 cm and 50-60% effaced, bleeding per vagina started with passage of clots. Artificial rupture of membrane was done to rule out abruptio placenta, liquor was clear. In view of excessive bleeding per vaginum, cesarean section was done under spinal anesthesia. Peroperative findings: A live born, 2800 g, female fetus with a 9 Apgar at 5th minute was delivered. As uterus was flabby, intravenous (IV) oxytocin infusion 30 units was started and injection carboprost 0.25 mg intramuscular (IM) given. Uterus became well-contracted, but excessive oozing from raw areas around uterine incision, muscle, skin continued. So, injection tranexamic acid IV was given. Patient became severely pale. Frank hematuria was observed. Though patient’s vitals were maintained but due to excessive bleeding and with probable diagnosis of DIC central line was inserted in operation theater. Patient was shifted to intensive care unit (ICU) postoperatively for further management. All necessary blood and urine investigations were sent. Injection vitamin K, IV antibiotics and injection tranexamic acids were given along with IV fluids.

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Case Report Table 1. Laboratory Findings Investigations

Preoperative findings

Postoperative findings 2 hours

8 hours

16 hours

24 hours

48 hours

64 hours

84 hours

Hemoglobin (g/dL)

10

7.8

7.2

7

7.6

8

8.4

9.2

Platelet count (/uL)

180

71

50

46

46

58

68

200

AST (IU/L) SGOT

20

170

122

82

72

49

44

20

ALT (IU/L) SGPT

12

111

76

72

62

40

32

22

LDH (IU/L)

-

1,538

1,618

1,680

1,701

1,240

1,213

Serum haptoglobin (mg/dL)

-

≤7.56

≤5.56

≤5.56

Peripheral blood smear

-

Schistocytes +

-

-

-

-

-

-

Spherocytes+ Urine albumin

Nil

Serum urea (mmol/L) Serum creatinine (µmol/L)

+

++

++

Trace

Nil

Nil

-

16

11.44

12

10

10

10

-

0.6

0.2

0.9

0.9

0.6

0.6

Total bilirubin (mg/dL)

1

3.1

7

7

3.6

Serum proteins (g/dL)

6.8

4.6

4.2

5

5.2

5.4

-

-

2

0.9

5.8

6.4

Fibrinogen (mg/L)

-

243

-

-

-

-

-

-

D-Dimer (mg/L)

-

1.4

-

-

-

-

-

-

Plasma FDP (µg/L)

-

2.91

-

-

-

-

-

-

APTT(s)

-

30

32

32

30

26

38

PT(s)

-

14

12

12

12

12

12

INR

-

1.07

1.02

1

1

0.9

0.9

Hb = Hemoglobin; Plt = Platelet count; ALT = Alanine aminotransferase; AST = Aspartate aminotransferase; LDH = Lactate dehydrogenase; INR = International normalized ratio; PT = Prothrombin time.

Postoperative hematological parameters were: hemoglobin - 7.80 g/dL and platelet count - 71,000/uL after 2 hours of operation. Hematological and biochemical parameters, including serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and lactate dehydrogenase (LDH), were detected to be higher than their respective reference intervals; 170.4 IU/L, 111 IU/L and 1,538 IU/L, respectively. Peripheral blood smear-Schistocytes - occasional, spherocytes - present, urine albumin was trace, red blood cell (RBC) - 75-100/hpf, coagulation profile prothrombin time (PT) - 15 sec, mean PT/control value 13.3, fibrinogen - 243 mg/dL, D-dimer - 1.40 mg/L, plasma fibrin degradation products (FDP) level - 2.91 µg/L. Diagnosis of HELLP syndrome was made. Transfusion of 4 platelets, 2 units of fresh frozen plasma, 2 units of packed cells were done. After 8 hours, the laboratory findings were consistent with those of HELLP syndrome, which included hemolysis (hemoglobin - 7.2 g/dL, LDH - 1,618 IU/L), 30

elevated liver enzymes (SGOT - 122.4 IU/L, SGPT - 75.8 IU/L) and low platelet counts (platelet: 50,000/uL) (Table 1). Coagulation profile and other biochemical parameters such as electrolyte values were in normal limitation of references. An ultrasound examination showed a normal liver structure and an empty uterine cavity. MgSO4 infusion (2 g/hour; 24 hours) and steroids were administered (dexamethasone; total 30 mg for 48 hours), with supportive therapy such as: IV fluids, fresh frozen plasma and packed red blood cells. The laboratory findings improved dramatically after the treatment and at the 88th hour (4th day) of postpartum period, all of them completely regressed to normal value. Foley’s catheter was removed on post-op Day 5. Patient was shifted to ward on post-op Day 7. On Day 8, suture removal was done. Wound was healthy. Patient was discharged on iron and calcium supplements. Contraceptive counseling was done. She was discharged on the 10th day without any sequelae.

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Case Report Discussion Pregnancy-induced hypertensive disorders constitute 12-22% of all pregnancies and 17.6% maternal mortality.1 The HELLP syndrome is usually considered to be a variant or complication of pre-eclampsia. However, in 20% of cases it may occur without preeclampsia during antenatal or intrapartum period. It is difficult for clinicians to predict the development of pre-eclampsia due to absence of obvious signs.2,3 HELLP is a multisystemic disorder, leading to generalized vasospasm, microthrombi formation and coagulation defects. It is the final manifestation of insult that leads to microvascular endothelial damage and intravascular platelet aggregation.4 There is an important role of coagulopathy in causation of HELLP syndrome suggested by clinically evident DIC as a secondary pathophysiological phenomenon to the primary process is seen in 4-38% of the patients. If not treated timely may lead to renal failure.5 HELLP syndrome is a dreaded obstetric emergency usually associated with pre-eclampsia. Its incidence is 0.5-0.9% of all pregnancies. It is related with severe pre-eclampsia (10-20%). Both conditions occur after 20 weeks of gestation and may occur after 5-12 weeks of childbirth. Clinical features include severe headache (30%), malaise (90%), nausea and vomiting (30%), pain around upper abdomen (65%) and pedal edema. In about 20% of all women, DIC is also seen with HELLP syndrome.6 Our patient presented only with excessive bleeding per vaginum during first stage of labor. She had no other complaints. Pregnant women who present with HELLP syndrome can be misdiagnosed in the early stages, thereby increasing the risk of maternal morbidity. In a patient with PIH and suspected to have HELLP, following blood tests should be performed: full blood count, liver function tests including enzymes, renal function tests, coagulogram, serum electrolytes and D-dimer. We conducted all the above investigations in our patient and we diagnosed our patient was suffering from HELLP syndrome as D-dimer was positive. A positive D-dimer test in a patient of pre-eclampsia is predictive of HELLP syndrome.7 D-dimer is a more sensitive indicator of subclinical coagulopathy and may be positive before other coagulation studies become abnormal. According to Mississippi classification3,8 and Tennessee classification, the disease can be classified

as mild, moderate and severe. Our case was a severe variety of HELLP syndrome. Sibai has proposed strict criteria for true or complete HELLP syndrome platelet - <1,00,000, AST - >70 IU/L, LDH - >600 IU/L.9 The definitive treatment of HELLP syndrome is immediate delivery of baby either by cesarean section or normal vaginal route.9 As our patient was hemodynamically stable, she was operated under spinal anesthesia. Corticosteroids can reduce the severity of intravascular endothelial injury and improve blood flow. They also decrease hepatocyte and platelet consumption in HELLP syndrome.10 Conclusion In conclusion, when patients present with mild-PIH presents with excessive bleeding per vagina during labor, it must be kept in mind that it can be one of the signs of HELLP syndrome and if we are aware of this, we can significantly reduce the maternal morbidity and prevent the development of maternal mortality. References 1. Walker JJ. Pre-eclampsia. Lancet. 2000;356(9237):1260-5. 2. Ezri T, Abouleish E, Lee C, Evron S. Intracranial subdural hematoma following dural puncture in a parturient with HELLP syndrome. Can J Anaesth. 2002;49(8):820-3. 3. Lurie S, Sadan O, Oron G, Fux A, Boaz M, Ezri T, et al. Reduced pseudocholinesterase activity in patients with HELLP syndrome. Reprod Sci. 2007;14(2):192-6. 4. Haram K, Svendsen E, Abildgaard U. The HELLP syndrome: clinical issues and management. A review. BMC Pregnancy Childbirth. 2009;9:8. 5. Gul A, Aslan H, Cebeci A, Polat I, Ulusoy S, Ceylan Y. Maternal and fetal outcomes in HELLP syndrome complicated with acute renal failure. Ren Fail. 2004;26(5):557-62. 6. Crosby ET. Obstetrical anaesthesia for patients with the syndrome of haemolysis, elevated liver enzymes and low platelets. Can J Anaesth. 1991;38(2):227-33. 7. Ezri T, Abouleish E, Lee C, Evron S. Intracranial subdural hematoma following dural puncture in a parturient with HELLP syndrome. Can J Anaesth. 2002;49(8):820-3. 8. Hawkins JL, Koonin LM, Palmer SK, Gibbs CP. Anesthesiarelated deaths during obstetric delivery in the United States, 1979-1990. Anesthesiology. 1997;86(2):277-84. 9. Sibai BM, Taslimi MM, el-Nazer A, Amon E, Mabie BC, Ryan GM. Maternal-perinatal outcome associated with the syndrome of hemolysis, elevated liver enzymes, and low platelets in severe preeclampsia-eclampsia. Am J Obstet Gynecol. 1986;155(3):501-9. 10. Rolbin SH, Abbott D, Musclow E, Papsin F, Lie LM, Freedman J. Epidural anesthesia in pregnant patients with low platelet counts. Obstet Gynecol. 1988; 71(6 Pt 1):918-20.

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AROUND THE GLOBE

News and Views

Not to Go-to-sleep in Supine Position During Third Trimester Reduces Late Stillbirth by Nearly 9% Recently, a multicentre case-control study published in PloS One journal revealed that supine going-to-sleep position is accompanied by a 3.7 times higher risk of overall late stillbirth, regardless of other common risk factors. In this study, the researchers analyzed the primary hypothesis that maternal non-left, in particular supine going-to-sleep position, would be a risk factor for late stillbirth (≥28 weeks of gestation). The results showed that supine going-to-sleep position on the last night was associated with increased late stillbirth risk, with a population attributable risk of 9.4%. Other independent risk factors for late stillbirth were BMI per unit, maternal age ≥40, birthweight <10th customized centile, and < 6 hours of sleep on the last night. Moreover, this risk was relatively greater for term than preterm stillbirths. Thus, there is a need for a public health campaign to encourage women not to go-to-sleep supine in their third trimester to reduce late stillbirth by nearly 9%. Effect of Acupuncture and Clomiphene in Chinese Women with Polycystic Ovary Syndrome: A Randomized Clinical Trial A new study published in the JAMA Oncology assessed whether active acupuncture, either alone or in combination with clomiphene, could increase the probability of live births among women with polycystic ovary syndrome. In this study, equal number of Chinese women with polycystic ovary syndrome were randomized into 4 groups. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation, twice a week for 30 minutes per treatment; either with clomiphene or placebo (Group 1 & 2). The control acupuncture group received superficial needle insertion with mock electricity and without manual stimulation; either with clomiphene or placebo (Group 2 & 3). From the findings of this study, it was concluded that among 32

Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene did not increase live births. Hence it was stated that acupuncture was not an efficacious method of infertility treatment in such women. Outcomes in Women with Cytology Showing Atypical Squamous Cells of Undetermined Significance with vs Without Human Papillomavirus Testing A recent observational study published in the JAMA Oncology examined the 5-year outcomes after ASCUS cytology with and without human papillomavirus (HPV) testing. From the observations of this study, it was inferred that HPV testing led to faster and more complete diagnosis of cervical disease. However, in practice 55.8% more biopsies and 20.0% more loop electrosurgical excision procedures were performed than HPV testing. A majority of high-grade disease were found to manifest in 43.1% of the women found to be HPV positive. It was stated that this data can be used as screening guidelines for cervical cancer and in reinforcement of public health policies. Therapeutic Utility of Natural Estrogen Receptor beta Agonists on Ovarian Cancer A new study published in the Oncotarget tested the utility of two natural estrogen receptor beta (ERβ) agonists liquiritigenin (Liq) – isolated from Glycyrrhiza uralensis, and S-equol – isolated from soy isoflavone daidzein, for the treatment of ovarian cancer. ERβ and ERβ are said to mediate the biological effects of estrogens. The results of this study revealed that both natural ERβ ligands had significant growth inhibition in cell viability and survival assays, reduced migration and invasion, and promoted apoptosis. In addition, ERβ agonists showed tumor suppressive functions in therapyresistant ovarian cancer model cells and sensitized ovarian cancer cells to cisplatin and paclitaxel treatment. RNASeq analysis revealed that ERβ agonists control several tumor suppressive pathways, including downregulation of the NF-kB pathway. Immunoprecipitation assays

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 2, April-June 2017


AROUND THE GLOBE showed that ERβ interacts with p65 subunit of NF-kB and ERβ overexpression and ERβ overexpression diminished the expression of NF-kB target genes. In xenograft assays, ERβ agonists reduced tumor growth and promoted apoptosis. Therefore, the findings of this study demonstrated that natural ERβ agonists could significantly inhibit ovarian cancer cell growth by anti-inflammatory and proapoptotic actions. These natural estrogen receptors could be employed as novel therapeutic agents for the management of ovarian cancer. An Epigenetic Signature of Adhesion Molecules Predicts Poor Prognosis of Ovarian Cancer Patients A new study published in the Oncotarget examined epigenetic effects of cell adhesion molecules on survival and therapeutic outcomes in ovarian cancer. In this study, 106 highly methylated adhesion-related genes in ovarian cancer tissues integrated from methylomics and genomics datasets in The Cancer Genome Atlas were identified. From the results of this analysis, it was found that methylation status of eight genes related to progression-free survival. Additionally, four highly methylated genes (CD97, CTNNA1, DLC1, HAPLN2) and three genes (LAMA4, LPP, MFAP4) with low methylation could be correlated to poor progressionfree survival. Furthermore, patients with any two of CTNNA1, DLC1 or MFAP4 were associated with poor progression-free survival. Hence it was concluded that epigenetics of cell adhesion molecules is related to ovarian cancer prognosis. A more comprehensive methylomics of cell adhesion molecules is needed and may advance personalized treatment with adhesion molecule-related drugs. Inhibition Of COX2 Enhances the Chemosensitivity of Dichloroacetate in Cervical Cancer Cells A new article published in the Oncotarget reported that cervical cancer cells were insensitive to Dichloroacetate (DCA) – a traditional mitochondria-targeting agent and a potential sensitizer in fighting against malignancies including cervical cancer. The findings of this study revealed that DCA could upregulate COX2 which impeded the chemosensitivity of DCA in cervical cancer cells. In addition it was demonstrated that DCA reduced the level of RNA binding protein quaking (QKI), leading to adecline in the suppression of COX2 mRNA and

subsequent elevation of COX2 protein. Furthermore, inhibition of COX2 using celecoxib could sensitize DCA in repressing the growth of cervical cancer cells. Hence it was inferred that COX2 is a novel resistance factor of DCA, and a combination of celecoxib with DCA could prove to provide a potential treatment for cervical cancer. Age-based Differences in the Predictive Accuracy of a One-Size-Fits-All Risk-Cutoff Value in Prenatal Integrated Screening for Down’s Syndrome A recent study published in the Prenatal Diagnosis assessed the variation in detection and false positive rates and adverse pregnancy outcomes across different age groups when a generalized strategy is used in integrated screening for Down’s syndrome. The results of this study revealed that a one-size-fits-all risk-cutoff value, such as 1/270, can lead to high variations in detection and false positive rates across maternal ages. This may consequent in a number of adverse outcomes. From the findings, it was suggested that the one-size-fits-all risk-cutoff value of 1/270, commonly used in Down’s Syndrome screening, should be revisited and alternative (possibly age-based) cutoff values and strategies should be accurately reinstated. Clinical Utility of Noninvasive Prenatal Testing in Pregnancies with Ultrasound Anomalies A new study published in the Ultrasound in Obstetrics and Gynecology assessed the application of noninvasive prenatal testing (NIPT) as an alternative to invasive diagnostic prenatal testing in pregnancies with abnormal ultrasound findings. In this study, a retrospective analysis of 251 singleton and multiple pregnancies was conducted. The cases included were at high risk for fetal chromosomal abnormality, in which NIPT was performed as a first-tier genetic test, at a median gestational age of 20 weeks. Normal NIPT results were obtained from 89.2% of the pregnancies, whereas the outcomes were found to be abnormal in 10.4% of the cases and inconsistent in 0.4% of the cases. Where NIPT results were normal, sonographic follow-up of the neonate indicated the need for diagnostic genetic testing in 14.7% of the cases. The results showed clinically relevant genetic aberrations in 3.1% of the cases, two of which were whole-chromosome aneuploidies – trisomy

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AROUND THE GLOBE 13 and monosomy X. Other incongruous findings were subchromosomal aberrations and monogenic aberrations. Hence it was recommended that NIPT should not be recommended for genetic evaluation of the etiology of ultrasound anomalies, as its resolution, sensitivity, and negative predictive value are inferior to those of conventional karyotyping and microarray analysis. Review of Lung and Pleural Biopsies Received in a Gynecologic Pathology Department Over a 14-Yr Period A recent study published in the International Journal of Gynecological Pathology elaborated on a review of pulmonary biopsies over a 14-yr period. This study analyzed 25 lung and 9 pleural biopsies obtained from 33 patients of which 21 patients had known gynecologic tumors. The results of this study revealed that in 4 of the biopsies, the review lead to an altered diagnosis. In 18 cases, the intervals between the primary diagnosis and pulmonary metastasis were known, which ranged from 1 to 17 years. Metastatic endometrial carcinomas were found in 43% of the cases. According to the International Federation of Gynecology and Obstetrics (FIGO) stage, the known data stated that 5 cases was categorized as Stage I, one case as Stage II, and another as Stage IIIA. Among the 12 patients without a history of gynecologic malignancy, 4 were found to have pleural metastasis from ovarian carcinomas; 3 were detected with primary lung carcinomas; 3 with primary carcinomas of unknown origin; 1 with endometrial stromal sarcoma; and another with a suspected Müllerian tumor. From the findings of this study, it was inferred that pulmonary metastas is can present many years even after a diagnosis of a low-stage gynecologic neoplasia. A specialist review of lung and pleural biopsies was recommended for a confirmatory diagnosis, in such cases. Spigelian Hernia in Gynecology A new study published in the Gynecological Surgery aimed at to increasing awareness towards spigelian

hernia in gynecology. It was stated that secondary trocar insertion may be a causative factor for spigelian hernia. The review illustrated through a case report that spigelian hernias may not be diagnosed and treated. It was suggested that gynecologist should consider a spigelian hernia in women who present with localized pain in the abdominal wall lateral of the rectus muscle, which is approximately 5 cm below the umbilicus. The proposed treatment for smaller hernias was closure by laparoscopy without a mesh, whereas for larger hernias, a mesh repair was recommended. Carcinoid of the Appendix During Pregnancy A recent literature review published in the Ceska Gynekologie emphasized on an early diagnosis of appendiceal carcinoid during first trimester of pregnancy. From the findings of this review it was inferred that in the case of an unclear clinical or intraoperative finding, appendectomy may reveal a serious disease, hence a thorough examination of the appendix should be a part of every gynecological surgery. Uterine Inversion A recent study published in the Ceska Gynekologie summarized the literature on uterine inversion. The findings of this review suggested that the prevalence of uterine inversion was varies greatly with geographical location. The incidence of this anomaly was mostly recorded in women above 45 years of age. Additionally, it was observed that 85% of the cases of an inversion of the uterus were caused by a benign pathology, while 15% were associated with cancer. From the findings of this review it was concluded that uterine inversion is a critical and rare complication in the third stage of labor and in nonpuerperal women, which leads to high rates of maternal morbidity and mortality. The associated complications include hemorrhage, disseminated intravascular coagulation and the development of hemorrhagic and neurogenic shock.

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Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes. Q. J. Expt. Physiol. 1955;40:89-111.

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Legends - These should be typed double spaces on a separate sheet and figure numbers (in Arabic numerals) corresponding with the order in which the figures are presented in the text. -

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Figures - Two complete sets of glossy prints of high quality should be submitted. The labelling must be clear and neat. - All photomicrographs should indicate the magnification of the print. - Special features should be indicated by arrows or letters which contrast with the background. - The back of each illustration should bear the first author’s last name, figure number and an arrow indicating the top. This should be written lightly in pencil only. Please do not use a hard pencil, ball point or felt pen. - Color illustrations will be accepted if they make a contribution to the understanding of the article.

The legend must include enough information to permit interpretation of the figure without reference to the text.

4. Number of figures ___________________________ 5. Special requests _____________________________ 6. Suggestions for reviewers (name and postal address)

Online Submission Also e-issue @ www.ijcpgroup.com For Editorial Correspondence

Dr KK Aggarwal

Group Editor-in-Chief Asian Journal of Obstetrics and Gynaecology Practice E - 219, Greater Kailash, Part - 1, New Delhi - 110 048. Phone: 011-40587513 E-mail: editorial@ijcp.com, Website: www.ijcpgroup.com

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 2, April-June 2017



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Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 2, April-June 2017


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Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 2, April-June 2017


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