Ajog js 17

Volume 1, Number 3, July-September 2017

ISSN 0971-8788

Asian Journal of

Obstetrics &

Gynaecology Practice In this Issue Prevalence of RTIs/STIs Among Women in a Tertiary Care Hospital: An Observational Study Analysis of Maternal Mortality in a Rural Referral Medical College Hospital in Hassan, Karnataka State, India Role of Aspirin in Prevention of PIH and IUGR in Primigravida Women with Abnormal First and Early Second Trimester Uterine Artery Doppler Wilson’s Disease in Pregnancy Heterologous Malignant Mixed Mullerian Tumor of Uterus: An Uncommon Tumor with Uncommon Presentation Subseptate Uterus Presenting as Unstable Lie at Term News and Views

Asian Journal of

Online Submission

Volume 1, Number 3, July-September 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 Dr KK Aggarwal Group Editor-in-Chief IJCP Group, eMedinewS and eMediNexus

CONTENTS FROM THE ISSUE EDITOR

Exposure to Air Pollution in Early Pregnancy Linked to Miscarriage

5

Alka Kriplani

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

FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

Newer Technology is not Necessarily Better Than its Predecessor

6

KK Aggarwal

CLINICAL STUDY

Prevalence of RTIs/STIs Among Women in a Tertiary Care Hospital: An Observational Study

7

Ruby Bhatia, Parmjit Kaur, Santosh Kumari, Aman Dev

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

Analysis of Maternal Mortality in a Rural Referral Medical College Hospital in Hassan, Karnataka State, India

12

Premalatha HL, Abhilasha

Nephrology Dr Georgi Abraham Neurology Dr V Nagarajan Dr Vineet Suri Dr AV Srinivasan 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

REVIEW ARTICLE

Role of Aspirin in Prevention of PIH and IUGR in Primigravida Women with Abnormal First and Early Second Trimester Uterine Artery Doppler 18 Payel Roy, Pallab Kumar Mistri, Bandana Biswas, Avishek Bhadra, Chatali Datta Roy, Sudip Mukhopadhayay

Asian Journal of Volume 1, Number 3, July-September 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

CASE REPORT

Wilson’s Disease in Pregnancy

26

Shreyasi Bid, Sambhunath Bandyopadhyay, Anik Das, Srijani Chowdhury

Printed at Bon Graphics, Chennai 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.

Heterologous Malignant Mixed Mullerian Tumor of Uterus: An Uncommon Tumor with Uncommon Presentation

28

Bhavana S

Editorial Policies The purpose of IJCP Academy of CME is to serve the medical profession and provide print continuing medical education as a part of their social commitment. The information and opinions presented in IJCP group publications reflect the views of the authors, not those of the journal, unless so stated. Advertising is accepted only if judged to be in harmony with the purpose of the journal; however, IJCP group reserves the right to reject any advertising at its sole discretion. Neither acceptance nor rejection constitutes an endorsement by IJCP group of a particular policy, product or procedure. We believe that readers need to be aware of any affiliation or financial relationship (employment, consultancies, stock ownership, honoraria, etc.) between an author and any organization or entity that has a direct financial interest in the subject matter or materials the author is writing about. We inform the reader of any pertinent relationships disclosed. A disclosure statement, where appropriate, is published at the end of the relevant article.

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.

Subseptate Uterus Presenting as Unstable Lie at Term

31

Shikha Singh, Saroj Singh, Ankita Kumari, Ruchita Sinha

JOURNAL SCAN

News and Views

33

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FROM THE ISSUE EDITOR

Exposure to Air Pollution in Early Pregnancy Linked to Miscarriage

Dr Alka Kriplani

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

T

he adverse effects of air pollution on the lungs and heart are well-known and often spoken about.

zz

Ninety-seven (28%) of the 343 couples who achieved pregnancy experienced an early pregnancy loss before 18 weeks.

Exposure to the toxic pollutants in the air can affect even the reproduction system.

zz

Couples with higher exposure to ozone had a 12% greater risk of suffering an early pregnancy loss.

zz

Couples exposed to particulate matter were 13% more likely to experience a loss.

A study conducted by the National Institutes of Health (NIH) has suggested that exposure to common air pollutants, such as ozone and fine particles, may increase the risk of early pregnancy loss.

The study published online November 16, 2017 in the journal Fertility and Sterility examined the effect of the exposure to ozone in 501 couples based on pollution levels in their residential communities. Ozone is a highly reactive form of oxygen that is a primary constituent of urban smog.

Although the cause of pregnancy loss is not well understood, impaired fetal development due to increased inflammation of the placenta and oxidative stress has been suggested as a possible factor. Based on the findings of the study, pregnant women are advised to curtail outdoors activity when pollution levels are high and the air quality is of hazardous level.

(Source: NIH, November 16, 2017)

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Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

5

FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

Newer Technology is not Necessarily Better Than its Predecessor

Dr KK Aggarwal

Padma Shri Awardee President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group

T

he impact of technology has percolated through almost every corner of our lives in the past few years. The advent of social media has revolutionized communication.

Newer stents may be easy to maneuver, but may be required in only 1-2% of cases. And, in the hands of an experienced interventional cardiologist, this may not even matter.

Medicine too has benefited tremendously from the advances in technology, which have made it easier to practice medicine. Doctors are now better equipped to diagnose and manage their patients. But on the flip side of it, there is a pressure to keep up with the rapidly changing and advancing technology. The older version then becomes outdated and may even be publicized as that.

Any technology lasts for 6-10 years. This means that spares and service will be available for this period of time.

We don’t buy a new computer every year or for that matter, an ultrasound, or an echocardiography machine or CT scan every year.

Whenever a new technology is introduced in the market, we face a dilemma whether to acquire the latest version or not.

Any new advancement in technology definitely comes with some improvements or some new features.

But just because something is new, does not mean that it is better. Newer technology is not necessarily better than its predecessor or its earlier version.

For instance, most advances in echocardiography machine may help the echocardiographer by making diagnosis easy, but may not offer any additional advantage to the patient.

Earlier, technological advances came to India 6-10 years late, but now they happen parallel to those in the West. But this does not mean that one should shift to the newer technology, each time it is introduced.

A stent which is available today cannot be outdated tomorrow.

Availability, accessibility and most importantly, affordability are key concerns in healthcare delivery, especially in a country like ours. Hence, focus should not be just on the acquisition of the newer technology.

For the large majority of the population, affordable healthcare means anything introduced in the last 6-10 years, but with the caution that it is not banned or prohibited in terms of safety. Effective use of technology, clinically as well as in terms of cost, will make healthcare more affordable and accessible and ensure best care possible for patients.

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Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

CLINICAL STUDY

Prevalence of RTIs/STIs Among Women in a Tertiary Care Hospital: An Observational Study Ruby Bhatia*, Parmjit Kaur†, Santosh Kumari‡, Aman Dev#

ABSTRACT Background: Reproductive tract infections/sexually transmitted infections (RTIs/STIs) are an important public health problem; 6% of adult population in India has one or more RTI/STI. Approximately 30-35 million new episodes of RTI/STI occur every year in our country. RTI/STI are an important cause of infertility. Roughly 21% pregnancies result in stillbirth and 9% in neonatal death due to untreated syphilis. Aims and objectives: To study the prevalence of RTI/STI in women, to find out commonest RTI/STI and its correlation with human immunodeficiency virus/Venereal Disease Research Laboratory (HIV/VDRL) and Pap smear abnormality, if any. Material and methods: This is a cross-sectional observational study undertaken for 1 year in 2,294 consecutive women with RTI/STI in the age group of 15-49 years, attending the Gynecology Outpatient Department of a tertiary care hospital in North India. Result: The prevalence of RTI/STI in our study was 13.19%.

Majority of patients were married (94.86%), Para 1 and above (93.4%) from low socioeconomic group (90.6%), illiterate (72.5%) between 26-35 years of age (67.47%). Vaginal discharge (62.51%) and lower abdominal pain/backache (43.42%) were most common presenting complaints. Vaginitis (62.51%), cervicitis (27.81%) and chronic pelvic inflammatory disease (PID) (15.63%) were most frequently encountered RTI/STI. Bacterial vaginosis (49.79%), candidiasis (35.84%) and trichomoniasis (21.33%) were important causes of vaginal discharge either alone or in combination. HIV and VDRL were reactive in only 15 (0.68%) and 11 (0.56%) RTI/STI females, respectively. Inflammatory Pap smear was observed in 36.4% cases while 9 cases (0.9%) had dysplasia of varying degree. Conclusion: Vaginal discharge and lower abdominal pain are the commonest presenting complaints. Mixed vaginitis, cervicitis and chronic PID are the frequently encountered RTI/STI in Gyne OPD practice. Bacterial vaginosis, candidiasis and trichomoniasis remain important causes of vaginal discharge. Counseling, testing for HIV/VDRL and Pap smear analysis along with syndromic management helps in prevention of RTI/STI. Keywords: Reproductive tract infections, sexually transmitted infections, vaginal discharge, condom

S

exually transmitted infections/reproductive tract infections (STIs/RTIs) are an important public health problem in developing world and rank in the top five disease categories for which adults seek healthcare. They are a silent epidemic for women of reproductive age group in developing countries.1 RTIs are defined as any infection of the reproductive system. They include STIs and also other infections of the reproductive system that are not caused by sexual

contact. STIs are infections transmitted from person to person by sexual contact.2 Globally, 499 million new episodes of STIs (trichomoniasis, chlamydia, gonorrhea, syphilis) occur yearly in the age group 15-49 years of which a significant proportion (80%) of these infections occur in developing countries and 79 million in India alone.3 Women are more susceptible to STIs for socioeconomic and biological reasons.

The vaginal surface is larger and more vulnerable to sexual secretions than primarily skin covered penis.

*Associate Professor † Professor ‡ Postgraduate Student # Civil Surgeon 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

Around 11% women and 5% men in 15-49 years age group have RTI/STI related symptoms.4 STI/RTI are known to cause infertility and reproductive morbidity affecting not only mother but also newborn adversely. STIs have been associated with number of adverse pregnancy outcomes: spontaneous abortion, stillbirths, prematurity, low birth weight, postpartum endometritis and sequelae in surviving neonates.

With the recognition of human immunodeficiency virus (HIV) infection in 1980s and subsequent

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

7

CLINICAL STUDY behavior, social and psychological changes, the pattern of genital ulcer disease has shifted from bacterial to viral STIs.5 There is significant decline of bacterial STIs (syphilis and gonorrhea). Chancroid is on verge of disappearance while viral STIs are showing an increasing trend. STIs are markers for high risk behavior for HIV infection. STIs are biological cofactors for acquisition and transmission of HIV infection.6 Material and Methods It was an observational study conducted in Outpatient Department of Obstetrics and Gynecology (STI Clinic), Govt. Medical College, Patiala for a period of 1 year (1-9-2009 to 31-8-2010) on a total of 2,294 RTI/STI female patients in the age group of 15-49 years, with an aim to study the prevalence of RTI/STI, to find out commonest RTI/STI and its correlation with HIV, Venereal Disease Research Laboratory (VDRL) and Pap smear abnormality, if any. A detailed history with special reference to any abnormal vaginal discharge amount, color, odor, rash or pruritus over genitalia, frequency/ burning micturition, pain lower abdomen/backache, dysmenorrhea, post coital bleeding, menorrhagia, infertility was taken. History of high risk sexual behavior (oral/anal sex), and number of sexual partners was sought. Gynecological examination including per speculum and per vaginum examination undertaken with complete audio visual privacy was undertaken.

Women with carcinoma cervix were excluded from the study. All patients with RTI/STI were referred to Integrated Counseling and Testing Centers (ICTC) for voluntary counseling and testing for HIV antibody test and VDRL/RPR (rapid plasma reagin) for syphilis.

Wet mount, 10% potassium hydroxide (KOH), Whiff test and Gram stain of the vaginal discharge and Pap smear with Ayre’s spatula was made in all the cases.

All RTI/STI patients were treated as per user friendly syndromic approach to management with color-coded kits, partner management and provision of condoms, counseling for safe sex with correct and consistent use of condoms done in all cases.

8

in 11 (0.56%) RTI/STI cases (Table 1). Majority of RTI/STI females were married (94.86%), > Para 1 and above (93.36%), belonged to 26-35 years of age (67.47%), from low and low middle socioeconomic group (90.68%) and 72.5% were illiterate (Table 2).

It was seen that 62.51% RTI/STI women presented with vaginal discharge followed by 43.42% with Table 1. Distribution of Gynecology OPD Patients (1.9.2009 to 31.8.2010) Number

Percentage (%)

Total OPD patients

17,392

100

Total RTI/STI females

2,294

13.19

RTI/STI patients with positive HIV test

15

0.68

RTI/STI patients with reactive VDRL/RPR

11

0.56

Table 2. Socio-demographic Characteristics (Total = 2,294/100%) Age in years

Number

Percentage (%)

<20

123

5.36

21-25

238

10.37

26-30

912

39.75

36-40

636

27.72

>41-49

233

10.16

Married

2,176

94.86

Unmarried

9,118

5.14

151

6.64

2,143

93.36

1,663

72.5

Up to Class V

353

15.4

Class VI-X

163

7.1

Results

>Class X

115

5.0

With a total outpatient attendance of 17,392 for 1 year study period, 2294 females were diagnosed suffering from various RTIs/STIs. Overall prevalence of RTI/STI was 13.91%. Fifteen (0.68%) patients were positive for HIV antibody test, while VDRL/RPR was reactive

Socioeconomic group 1,600

69.75

Low middle

480

20.93

Upper middle

214

9.30

Marital status

Parity Nulliparous >Para 1 Literacy Illiterate

Low

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

CLINICAL STUDY Table 3. Distribution as per Presenting Complaints (Total = 2,294/100%)

Table 5. Causative Organism in Vaginal Discharge (Total = 1,434/100%)

Presenting complaints

Types of vaginal discharge

Number

Percentage (%)

1,434

62.51

Lower abdominal pain and backache

996

43.42

Pruritus (local)

402

17.52

Dyspareunia

358

15.63

Dysmenorrhea

358

15.63

Polymenorrhagia

321

13.99

Dysuria/Burning micturition

102

4.44

Post coital bleeding

26

1.13

Anorectal discharge

11

0.44

Vaginal discharge

Causative organism

Number

Percentage (%)

Bacterial vaginosis

Gardnerella vaginalis

713

49.79

Candidiasis

Candida albicans

514

35.84

Trichomoniasis

Trichomonas vaginalis

306

21.33

Bacterial

N. gonorrhoea

84

13.27

Table 6. Pap Smear Analysis (Total = 996/100%) Number

Percentage (%)

Table 4. Distribution According to Diagnosis (Total = 2,294/100%)

Normal

618

62.04

Diagnosis

Inflammatory

363

36.4

Number

Percentage (%)

Dysplasia

09

0.9

1,434

62.51

Mild

3

0.3

Chronic cervicitis

638

27.81

Moderate

4

0.4

Chronic pelvic inflammatory disease

358

15.63

Severe

2

0.2

Koilocytosis

6

0.6

Urethritis

96

4.18

Anorectal discharge

10

0.44

Syphilis

11

0.48

Herpes simplex

4

0.17

Condyloma accuminata

4

0.17

Vaginitis

lower abdominal pain and backache. Pruritus vulvi, dyspareunia, dysmenorrhea, polymenorrhagia, dysuria, post coital bleeding and anorectal discharge were other presenting complaints (Table 3). Majority of patients had more than one complaint. A diagnosis of vaginitis mostly mixed vaginitis was made in 62.51% RTI/STI women. Chronic cervicitis was seen in 27.8 and chronic pelvic inflammatory disease in 15.63% followed by urethritis in 4.18% and syphilis in 0.48% of cases (Table 4). Many patients had vaginitis with cervicitis along with pelvic inflammatory disease.

Bacterial vaginosis (49.79%) was the most important cause of vaginal discharge followed by candidiasis in 35.84%, trichomoniasis in 21.33% and bacterial

(Neisseria gonorrhoeae) in 13.27% only (Table 5).

Mixed vaginitis due to more than one microorganisms was observed in many cases.

Pap smear cytology report of 996 RTI/STI patients was analyzed; 36.4% patients had inflammatory Pap smear, 6 cases showed koilocytosis, while 9 women (0.9%) had cervical dysplasia of varying degree (Table 6).

Discussion The prevalence of RTI/STI in our study group was 13.19%, the National Family Health Survey III 2005 reports that 11% women and 5% men in 15-49 years age group have STI/RTI related symptoms4 almost similar to our results.

The prevalence of RTI was 36.3% among women in reproductive age group in Shimla town.7 Bohra et al in their study observed 30% of women had symptoms related to RTI and 19% had STIs.8 Prevalence of RTI was estimated to be 27% among women by Hedge et al.9 In our study group, 0.68% and 0.56% of females in an RTI/STI were

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

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CLINICAL STUDY seropositive for HIV and syphilis, respectively.

Ray et al10 reported low prevalence of HIV (0.1%) among women with RTI/STI. Khokhar et al reported 0.49% positive for syphilis and 0.39% for HIV.11 Majority of patients were married; (94.86%) were Para 1 and above (93.36%) were illiterate and 72.5% were from low socioeconomic status. Similar results were reported by Ray et al.10 Majority of our patients (67.47%) were in the age group of 26-35 years as observed by Jindal et al and Gupta.12,13 Vaginal discharge (62.51%) was the most common presenting complaint in the present study. We reported vaginal discharge in 80% HIV negative and 66% in HIV positive. RTI/STI females in our previous study.14 Vaginal discharge (62.51%) and lower abdominal pain/backache were the most common symptoms in our study in accordance with other authors.9,12,13 Majority of patients in our study had vaginitis (62.51%), followed by cervicitis in 27.81% and pelvic inflammatory disease in 15.63%. Thus, kit-1, kit-2 and kit-6 were utilized to the maximum. The most common cause of vaginitis was observed to be bacterial vaginosis (49.79%) followed by candidiasis in 35.84% and trichomonal in 21.33%, while bacterial (gonorrhea) only in 13.27% RTI/STI females. Many of the patients had mixed vaginitis. There is significant burden of lower RTI (trichomoniasis, bacterial vaginosis and candidiasis) among women with no evidence to suggest a decline in prevalence, thus affecting quality of their reproductive life.3 In our previous study also, we observed that in case of HIV negative women, the most common cause of vaginal discharge was bacterial vaginosis (28%) followed by candidiasis (22%), trichomoniasis 18% and gonorrhea in 2%.14 In our study, 36.4% RTI/STI females had inflammatory Pap smear, while 9 (0.9%) had cervical dysplasia of varying degree. Pap smear were inflammatory in 56% and 22% in HIV positive and HIV negative STI/RTI women, respectively as reported in our previous study.14 Seethalakshmi et al reported abnormal Pap smear in 58.8% and 43.75%. HIV positive and HIV negative women, respectively.15 In a study conducted

by Sharma et al, inflammatory smears were seen in 55% and 28%, while cervical dysplasia was reported in 5% and 3% HIV positive and HIV negative STI/RTI patients, respectively.16 10

Conclusion Prevalence of RTI/STI in our Gynecology OPD, a tertiary care hospital was reported to be 13.19% in women of reproductive group. Vaginitis, cervicitis and pelvic inflammatory disease are commonly encountered RTI/STI. There is significant burden of lower RTI (bacterial vaginosis, candidiasis and trichomoniasis) among women with no evidence to suggest a decline in prevalence. Counseling and testing for HIV/VDRL and Pap smear along with user friendly syndromic approach may go a long way in management of RTI/STI. References 1. Elahee SMA, Muhmud S, Tanvir S, Rahman MZ. Breaking the silence: reproductive tract infections (RTIs) among women in slums of Khulna City, Bangladesh. Bangladesh e-Journal of Sociology. 2013;10(2):119-34.

2. Sharma VK, Khandpur S. Epidemiology of sexually transmitted diseases. In: Sharma VK (Ed.). Sexually Transmitted Diseases and AIDS. New Delhi: Viva Books Private Limited; 2003. pp. 1-41.

3. National Guidelines on Prevention Management and Control of Reproduction Tract Infections and Sexually Transmitted Infections. July 2014.

4. National Family Health Survey III 2005-2006. Ministry of Health & Family Welfare, Government of India.

5. Sharma VK, Khandpur S. Changing patterns of sexually transmitted infections in India. Natl Med J India.

2004;17(6):310-9.

6. Fact Sheet: Sexually transmitted infections (Internet).

World Health Organization, 2011 Aug. Available at: http:// www.who.int/mediacentre/factsheets/FS/10/en/ 7. Prashar A, Gupta BP, Bhardwaj AK, Sarin R. Prevalence of RTIs among women of reproductive age group in Shimla town. Indian J Community Med. 2006;31:15-7.

8. Bohra MS, Joshi AB, Lekhak B, Gurung G. Reproductive tract infections among women attending gynaecology outpatient department. Int J Infect Microbiol. 2012;1(1): 29-33.

9. Hedge SKB, Aggarwal T, Ramesh N, Sugara M, Joseph PM, Singh S, et al. Reproductive tract infections among women in a peri-urban under privileged area in Bangalore, India: Knowledge, prevalence and treatment seeking behaviour.

Ann Trop Med Public Health. 2013;6(2):215-20.

10. Ray K, Muralidhar S, Bala M, Kumari M, Salhan S, Gupta SM, et al. Comparative study of syndromic and etiological diagnosis of reproductive tract infections/sexually transmitted infections in women in Delhi. Int J Infect Dis. 2009;13(6):e352-9.

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

CLINICAL STUDY 11. 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.

14. Chopra D, Sandhu I, Bahl RK, Bhatia R, Goyal A. Prevalence of sexually transmitted infections in HIV positive and HIV negative females, in a tertiary care hospital - An observational study. Indian J Sex Transm Dis. 2015;36(1):59-63.

12. Jindal N, Aggarwal A, Gill P, Sabharwal B, Sheevani BB. community-based study of reproductive tract infections, including sexually transmitted infections, among the rural population of Punjab, India. Indian J Community Med. 2009;34(4):359-61.

15. Seethalakshmi GV, Shoba D, Mohan KR, Sourabh C, Manoharan G, Chandrashekhar C. A comparative study of Pap smear findings among HIV positive and negative women at Government Hospital of Thoracic Medicine (GHTM) Tambaram. BMJ Infect Dis. 2012;12 (Suppl 1):p35.

13. Gupta A. Prevalence of STI/STDs among women of reproductive age group in Tribal district of North India. Sex Transm Infect. 2013;89:A172.

16. Sharma A, Marfatia YS, Modi M. Reproductive tract infections in HIV positive women: A case control study.

Indian J Sex Transm Dis. 2009;30(1):16-8.

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CLINICAL STUDY

Analysis of Maternal Mortality in a Rural Referral Medical College Hospital in Hassan, Karnataka State, India Premalatha HL*, Abhilasha

ABSTRACT Maternal mortality rate (MMR) is an indicator to measure the summary of information about mother and childbirth. It is estimated that about 350-450 maternal deaths occur per 1,00,000 live births each year in India.

Keywords: Retrospective study, maternal mortality, risk factors, causes of death

T

hough India has made an appreciable progress in improving the overall health status of its population, but it is far from satisfactory. Pregnancy is a normal health state that most women aspire to at some point in their lives.

This physiological process carries with it serious risks of maternal morbidity and mortality.

Maternal mortality rate (MMR) is the measure of number of maternal deaths due to pregnancy or within 42 days of termination of pregnancy, irrespective of the duration or site of the pregnancy from any cause related to or aggravated by the pregnancy and its management but not from accidental or incidental causes.

Although various safe motherhood initiatives have been taken, yet the decline in MMR is far from the desired level of 100 by 2012 set by the National Rural Health Mission (NRHM) and 109 by 2015 as per millennium development goals.

Maternal death is a greater social tragedy than a perinatal loss. In spite of advances in obstetrics, anesthesia and blood product transfusion and in antibiotics, decline in MMR in India has been slow. Those who suffer generally live in remote places and are poor and helpless. It is not

*Assistant Professor Dept. of Obstetrics and Gynecology Hassan Institute of Medical Sciences, Hassan, Karnataka Address for correspondence Dr Premalatha HL Assistant Professor Dept. of Obstetrics and Gynecology Hassan Institute of Medical Sciences, Hassan, Karnataka E-mail: premalatha.gowda@yahoo.in

12

only useful to evaluate the performance but also is a measure of the social status of community and availability of Maternal and Child Health Services. The major causes of maternal mortality are hemorrhage, hypertension disorder, sepsis, obstructed labor, unsafe abortions.

UNICEF`s 2009 State of the World`s Children report, which was released in January said that India`s fight to lower MMR is failing due to growing social inequalities and shortages in primary healthcare facilities. In most developed nations MMR has been reduced to as low as 5-20/1,00,000 live births.

MMR in India stands at 230/1,00,000 live births against China`s 50/1,00,000 and Srilankaâ&#x20AC;&#x2122;s 35/1,00,000; by comparison and China is the most populated country in the world.

Maternal audit is essential to make critical appraisal of standards and to continue to improve the methods of management pattern of maternal complications. In 1960, four major causes of death were hemorrhage, abortion, hypertensive disorders and pulmonary embolism. Even today hemorrhage stands first as the cause for death as reported in some studies.

The health problems of mother and newborn arise as a result of synergistic effects of malnutrition, poverty, illiteracy, unhygienic living conditions, infections and unregulated fertility, ignorance, apathy. At the same time, poor infrastructure and ineffective public health services, failure of transport facilities, failure to provide adequate man power, failure to empower the woman resources, failure to provide adequate functioning blood banks, is also responsible for low inadequate obstetric care and rise in maternal mortality, rather than a lack

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

CLINICAL STUDY of technical knowledge (World Health Organization [WHO]).

The results of a large scale survey have however shown that there was no decline in the MMR in India over time indicating an urgent public health concern.

WHO estimates show that out of the 5,29,000 maternal deaths globally each year, 1,36,000 (25.7%) are likely to experience some obstetrical and medical complications and die in India. Recent estimates (WHO and UNICEF) place the figure around 300-500/1,00,000 live births. In Karnataka, MMR is 217/1,00,000 live births. But in reality, it may be higher because of under registration of deaths in the country and absence of cause of death information.

Table 1. Year-wise Distribution of Maternal Deaths Year

No. of maternal deaths

No. of live births

MMR/1,00,000 live births

2006

5

4,698

106.43

2007

8

4,982

160.58

2008

6

5,848

102.6

2009

11

7,529

146.1

180

Material and Methods Analysis of maternal deaths over 4 years were carried out from 2006 to 2009, which occurred at Hassan Institute of Medical Sciences, Hassan, Karnataka. Cases were scrutinized from various aspects likely to be related to maternal deaths like age, parity, locality, socioeconomic status, literacy, antenatal registration and check-ups, period of gestation, mode of delivery, admission to death interval, direct and indirect causes of death. All the data were collected from records and maternal mortality statistics of the year provided by the record section of the hospital. Maternal mortality was calculated by means of maternal deaths and total live births for that particular year.

Results and Analysis It was seen that the MMR/1,00,000 live births for the years 2006, 2007, 2008 and 2009 was 106.43, 160.58, 102.6, 146.1, respectively (Table 1 and Fig. 1).

Age- and parity-wise distribution of patients is shown in Table 2 and Figure 2 a and b.

146.1

140 120 MMR

Aims and Objectives To analyze the causes of maternal death in a rural referral hospital like Hassan Institute of Medical Sciences, Hassan, Karnataka. Analysis of maternal death is an essential exercise with a view to understand the common complications leading to maternal deaths and is helpful to find the remedies. This knowledge may help to decrease maternal deaths, for the majority of causes are preventable with the current day knowledge and technology.

160.58

160

106.43

102.6

100 80 60 40 20 0

2006

2007

2008

2009

Year

Figure 1. Year-wise distribution of maternal deaths.

Table 2. Age- and Parity-wise Distribution Age (years)

Priame gravida

Second Multi Grand Percentage gravida gravida multi (%)

<20

7

---

---

---

23.34

21-30

9

4

5

---

60

>30

---

1

4

---

16.66

It was observed that the maximum number of deaths occurred during postpartum period (80%).

Distribution of subjects based on time of maternal death is shown in Table 3 and Figure 3.

Maximum number of deaths occurred during the hospital vaginal delivery (43.33%) closely followed by cesarean delivery (33.33%), while equal number of deaths occurred during home delivery, laparotomy for rupture uterus and undelivered (6.67%). The least number of deaths (3.33%) occurred during forceps delivery (Table 4 and Fig. 4).

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CLINICAL STUDY CLINICAL STUDY Table 4. Distribution of Subjects Based on Type of Delivery

60

60

Percentage (%)

50

Type of delivery

No. of maternal deaths

Maternal deaths (%)

Home delivery

2

6.67

Hospital vaginal delivery

13

43.33

Forceps delivery

1

3.33

Cesarean delivery

10

33.33

Laparotomy for rupture uterus

2

6.67

Undelivered

2

6.67

40 30

23.34

20

16.66

10 0

<20

21-30

>30

Age group

(a)

<20

9

9

21-30

>30

8 7

7

4

Home delivery

%

4

6.67

4

6.67% % 67

5

5

6.

Number

6

Hospital vaginal delivery

3

Forceps delivery

2 1 0 Prime gravida

0 Second gravida

(b)

0 Multi gravida

43.33%

0 0 0 Grand Multi

Parity

Figure 2 a and b. Age- and parity-wise distributions of subjects.

Table 3. Distribution of Subjects Based on Time of Maternal Death Timing of maternal death

Cesarean delivery Laparotomy for rupture uterus Undelivered

3.33%

1 0

33.33%

Figure 4. Distribution of subjects based on type of delivery.

Table 5. Distribution of Subjects Based on Admission to Death Interval

No. of maternal deaths

Maternal deaths (%)

Antepartum

5

16.67

<24 hours

24

80

Intrapartum

----

0

1-3 days

1

3.33

Postpartum

24

80

>3 days

5

16.67

Post abortal

1

3.33

Admission (death interval)

No. of cases

Cases (%)

3%

16.67% 3.33

<24 hours

3.3

%

Antepartum

16.67% 0%

1-3 days

Intrapartum Postpartum

80%

>3 days

Post abortal 80%

Figure 3. Distribution of subjects based on time of maternal death.

14

Figure 5. Distribution of subjects based on admission to death interval.

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

CLINICAL STUDY The distribution of subjects based on admission to death interval is shown in Table 5 and Figure 5. It was seen that the maximum number of deaths occurred within 24 hours of delivery.

Analysis of causes of maternal mortality shows that maximum number of death occurred due to postpartum hemorrhage (PPH) in our study (Table 6 and Fig. 6).

Analysis of causes of maternal deaths in standard books is given in Figure 7.

Table 6. Analysis of Causes of Maternal Mortality

Discussion

Causes of death

Estimates for MMR of India was 150 to 350 as reported

by WHO in 2008. This study was conducted in a rural medical college to investigate the risk factors for maternal mortality. After going through the statistics, it was found that MMR was increased with increase in number of deliveries. Increased MMR was seen in woman aged between 21-30 years - 60%.

2006 2007 2008 2009 Percentage (%)

CHD with CCF APH abruption

1

Eclampsia

1

-

1

7.14

1

-

1

10.7

2

-

1

10.7

Postpartum sepsis and CVT

1

1

1

-

10.7

PPH

2

2

1

5

35.7

Anemia

1

1

1

1

14.2

Septic abortion

-

-

1

-

3.57

Jaundice

-

-

1

1

7.14

Rupture uterus

-

-

2

-

7.14

CHD with CCF APH Abruption %

7.14

4%

7.1 7.14

3.57%

10.70% 10.70%

%

10.70%

%

20 14.

Eclampsia Postpartum sepsis & CVT PPH Anemia Septic abortion

35.70%

Jaundice Rupture uterus

Figure 6. Analysis of causes of maternal mortality.

8%

Hemorrage

7% 25%

Indirect Causes Sepsis

12%

Unsafe abortion 20%

13% 15%

Eclampsia Obstructed labor Other direct causes

Figure 7. Causes of maternal deaths in standard books.

Eighty percent of deaths had occurred within 24 hours.

Forty-three percent were hospital vaginal deliveries and 33% were delivered by cesarean operation. Approximately 35.7% deaths were due to PPH and 14.2% were due to anemia. About 10.7% deaths were due to antepartum hemorrhage (APH), eclampsia and postpartum sepsis.

About 7.14% deaths were due to coronary heart disease (CHD) and congestive cardiac failure (CCF), ruptured uterus, jaundice; deaths due to abortion occurred in less than 3.57%; this may be due to safe abortion practices.

The causes of maternal deaths are multiple, complex but almost preventable. About 43% of deaths occurred following institutional delivery at Hassan Institute of Medical Sciences (HIMS), Karnataka. A study published in April 2010 in The Lancet shows that the number of annual maternal deaths worldwide declined from roughly 5,25,000 in 1980 to about 3,43,000 in 2008.

The troubling news in these two studies is that progress has been unequal: while many countries are showing a downward trend, in some maternal deaths actually increased. A study has shown that MMR also increased in America from 7.1% in 1999 to 13.3% in 2008.

The fact is that pregnancy always carries risk of unexpected complications, and 15% of pregnancies everywhere are life-threatening.

Mortality ratio measurements are difficult and complex.

As a matter of fact under registration is frequent in both developing and developed countries. MMR measurement should be simple affordable, effective and evidencebased, particularly in poorer countries. The information collected should be used to help improve maternal health outcome and empower health professionals to

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

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CLINICAL STUDY examine their current practices or those of the facility in which they work. For correct estimation of maternal mortality, it requires knowledge of death of pregnant women and cause of death, because the information obtained will be used as the basic for action. Health promoters and community health workers can be trained to report these events as part of their jobs, as can traditional birth attendants who provide antenatal care and attend deliveries. India’s long-standing strategy has been promotion of facility based intrapartum care.

One of the vowed goals of the National Population Policy (2000) is to attain an institutional delivery rate of 80% by 2010. Nationwide, the proportion of deliveries in institutions has increased from 34% in 1998-99 to 41% in 2002-2004.

Further acceleration in the direction is inevitable under NRHM launched in 2005. This scheme provides a conditional cash transfer to mothers for institutional deliveries and a cash incentive for health workers, who facilitate this process, with 24/7 delivery services and nearly 3,000 public facilities planned to be upgraded to provide comprehensive emergency obstetric care by 2012. In 1997-98, India’s MMR stood at 398, this declined to 301 in 2001-2003. The prediction for 2015 is 160, although this misses India’s 5th Millennium Development Goal (MDG 5), which is pegged at 109.

A faster decline in MMR is a distinct possibility because of the extraordinary attention given to maternal health under the NRHM, increased resources are also flowing to education, women’s empowerment and rural employment. One priority of the NRHM is to have a female health volunteer called ASHA (Accredited Social Health Activist). Other efforts are being made to provide quality reproductive health services including institutional delivery, safe abortions, treatment of reproductive tract infections (RTIs) and family planning services to meet unmet needs, while ensuring full reproductive choice to women.

Under NRHM, the main strategy to reduce MMR focuses on institutional deliveries and provision of mean emergency obstetric care (EmOC). The government has recently changed policy to allow staff nurse and auxiliary nurse midwives (ANMs) to initiate treatment of pregnancy related complications, including IV fluids, oxytocics, antibiotics and magnesium sulfate - all earlier restricted to administration by doctors. The government has also started the retraining of ANMs to improve 16

their skills as skilled birth attendants (SBAs). The central government has encouraged a 16-week training of MBBS doctors in anesthesia and comprehensive EmOC. Conclusion Maternal health services and maternal and child health (MCH) focused on antenatal care and high-risk approach. It is thought that good antenatal care and identifying high-risk woman, institutional deliveries, Janani Suraksha Yojana and help of ASHA’s will reduce the MMR. But after implementing several years of these Yojanas, the studies have shown that MMR is still high. After going through the statistics in our institution, it is not possible to predict which mother will develop complications and hence the high risk approach does not help much. Anemia should be eradicated in the society. The project development process should ensure that all the critical inputs such as staff, drugs, blood banks, equipments are provided which is woefully inadequate at present. Mass education about the importance of antenatal check-ups and registration, institutional deliveries and providing timely transportation facilities will reduce the MMR. Suggested Reading 1. WHO, UNICEF, UNFPA. Maternal mortality in 2000:

2.

3.

4.

5.

6.

7.

8.

9.

Estimates by WHO, UNICEF, UNFPA, GENEV A: available at: http://www.childinfo.org/areas/maternal mortality. Accessed on September 6, 2017.

India needs to make major strides on health front UNICEF. August 5, 2008 by IANS. Article – maternal mortality rate decrease not significant, experts. PTI (Press Trust of India), August 31st 2003.

Institute for Research in Medical Statistics-ICMR, Ansari Nagar, New Delhi, July 2009.

Singh R, Sinha N, Bhattacharyya K, Ram R. Pattern of maternal mortality in a tertiary care hospital of Patna, Bihar.

Indian J Community Med. 2009;34(1):73-4.

Aggarwal A, Pandey A, Bhattacharya BN. Risk factors for maternal mortality in Delhi slums: a community-based case-control study. Indian J Med Sci. 2007;61(9):517-26.

Mother-baby packages, implementing safe motherhood in countries. WHO, Geneva; 1994. World Health Day Safe Motherhood, 7 April, 1998.

Tinker AG. Improving women's health in Pakistan.

Human Development Network Health, Nutrition, and Population Series: Washington, DC, World Bank; 1998. vi, 34 p.

RCH II Document 2, The Principles and Evidence Base for State RCH II Programme Implementation

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

CLINICAL STUDY Plans (PIPs) Chapter 1: Improving Health Outcomes. pp. 23-5.

of care for severe obstetrical haemorrhage in three French regions. BJOG. 2001;108(9):898-903.

10. Gupta N, Kumar S, Saxena NC, Nandan D, Saxena BN. Maternal mortality in seven districts of Uttar Pradeshan ICMR task force study. Indian J Public Health.

2006;50(3):173-8.

20. Berg C, Danel I, Mora G. Guidelines for Maternal Mortality Epidemiological Surveillance. Washington, D.C., Pan American Health Organization [PAHO]; 1996. iv, 50 p.

11. Singh P, Pandey A, Aggarwal A. House-to-house survey vs. snowball technique for capturing maternal deaths in India: a search for a cost-effective method. Indian J Med Res. 2007;125(4):550-6.

12. Farooq N, Jadoon H, Masood TI, Wazir MS, Farooq U, Lodhi MS. An assessment study of maternal mortality ratio databank in five districts of North Western Frontier Province Pakistan. J Ayub Med Coll Abottabad. 2006;18(2):64-8.

13. Agarwal A, Pandey A. Eestimate of maternal mortality rate in India and its state–a pilot study–Institute for Research in Medical Statistics–ICMR. Ansari Nagar, New Delhi; July 2003. Available at: http://www.icmr.nic.in/final/Final%20 Pilot%20Report.pdf 14. India needs medical will to reduce maternal mortality.

World Health Organization, April 2, 2008.

15. Vora KS, Mavalankar DV, Ramani KV, Upadhyaya M, Sharma B, Iyengar S, et al. Maternal health situation in India: a case study. J Health Popul Nutr. 2009;27(2): 184-201.

16. National Family Health Survey 1992-1993. RGI 1999-registration System Bulletin Volume 33 No. 1 1999.

17. Mavalnkar D. IIM - Azad India Foundation, State of Maternal Health in India.

18. Jennifer Block reported for TIME in March, that study, based on data from the Centers for Disease Control and Prevention as well as other sources. Dr. Christopher Murray, University of Washington, Institute for Health Metrics and Evaluation.

19. Bouvier-Colle MH, Ould El Joud D, Varnoux N, Goffinet F, Alexander S, Bayoumeu F, et al. Evaluation of the quality

21. Paul VK. Meeting MDG 5: good news from India. The Lancet. 2007;369(9561): p. 558.

22. Registrar General of India. Maternal mortality in India: 1997-2003. Trends, Causes and Risk Factors. New Delhi: Registrar General of India, Report. 2006. p. 1-29.

23. Fauveau V. Strategies for reducing maternal mortality.

Lancet. 2006;368(9553):2121-2.

24. Vora KS, Mavalankar DV, Ramani KV, Upadhyaya M, Sharma B, Iyengar S, et al. Maternal health situation in India: a case study. J Health Popul Nutr. 2009;27(2): 184-201.

25. Trends in Maternal Mortality 1990-2008. Estimates developed by WHO, UNICEF, UNFPA, and the World Bank, September, 2010 http://www.unfpa.org/public/site/ global/lang/en/pid/ 6598. Accessed on September 17, 2017.

26. The United Nations Govt. New York. 55th Session of United Nations Millennium Declaration. Millennium Summit; 6-8 September 2000. Available at: www.un.org.

Accessed on September 17, 2017.

27. United Nations. A/RES/S-27/2. General Assembly District.

General 11 October, 2002. Available at: http://www.un.org.

Accessed on December 2017.

28. WHO. Maternal Mortality in 2005: estimates developed by WHO, UNICEF, and The World Bank. Available at: http:// www.who.int/whosis/mmr-2005pdf. Accessed on Sep 17, 2017.

29. Coeytaux F, Bingham D, Langer A. Reducing Maternal Mortality: A Global Imperative. Contraception Editorial February 2011. Available at: http://www.arhp.

org/Publications-and-Resources/Contraception-Journal/ February-2011.

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REVIEW ARTICLE

Role of Aspirin in Prevention of PIH and IUGR in Primigravida Women with Abnormal First and Early Second Trimester Uterine Artery Doppler Payel Roy*, Pallab Kumar Mistri†, Bandana Biswas‡, Avishek Bhadra#, Chatali Datta Roy†, Sudip Mukhopadhayay¥

ABSTRACT Aim of our study was to see whether low-dose aspirin started early in pregnancy was efficacious in preventing pre-eclampsia and IUGR in high risk primigravida patients. The present study was conducted in the Dept. of Obstetrics and Gynecology in association with the Dept. of Radiodiagnosis in the IPGME&R over a period of 1 year. A total of 124 primigravida patients were recruited in whom uterine artery Doppler at 11-14 weeks gestation showed diastolic notch and/or PI ≥1.7. Patients with abnormal bleeding per vagina, having any contraindications to aspirin, chronic liver disease/chronic hypertension/renal disease/overt diabetes mellitus and any other comorbid condition predisposing to vasculopathy, heart disease, documented fetal malformation and uterine malformation were excluded from the study. They were divided into two groups each comprising of 62 patients - test and control. Each woman of test group received tablet aspirin 75 mg o.d. from 16 to 34 weeks of gestation unless early termination became necessary. Women of control group did not receive aspirin. All these 124 women were followed till delivery at an interval of 1-4 weeks according to gestational age to see whether they were developing PIH and/or IUGR. After delivery, their babies were also examined to assess the perinatal outcome. SBP at 20 and 24 weeks gestation between different groups was comparable but it was decreased in aspirin-treated group at 28, 32, 34 and 36 weeks gestation and at term. Difference in the DBP at 20, 24, 28 and 36 weeks gestation and at term between different groups was not significant but it was significant at 32 and 34 weeks gestation. Hemoglobin and platelet values were comparable between the two groups. Urea and creatinine levels were also comparable between the two groups but uric acid levels decreased significantly in aspirin-treated group. LDH level was comparable between the two groups. Proteinuria decreased significantly in aspirintreated group at 28, 32 and 34 weeks gestation but not so at 36 weeks gestation and at term. It was seen that aspirin reduces the incidence of pre-eclampsia significantly in this high-risk population. Among the several parameters, NICU admission rate was significantly decreased in aspirin-treated group, respectively but other parameters like Apgar score at birth, birth weight, NICU stay could not be influenced significantly by aspirin. However, incidence of IUGR was significantly less in the patients treated with aspirin. Incidence of postpartum hemorrhage was comparable between the two groups.

Keywords: Pregnancy-induced hypertension, aspirin, uterine artery Doppler, proteinuria

H

ypertensive disorders complicate 5-10% of all pregnancies and together they form one member of the deadly triad, along with hemorrhage and infection, that contribute greatly to maternal and perinatal morbidity and mortality.1

Senior Resident Associate Professor ‡ Professor # Assistant Professor ¥ RMO cum Clinical Tutor Dept. of Obstetrics and Gynecology Medical College, Kolkata, West Bengal Address for correspondence Dr Bandana Biswas Professor Dept. of Obstetrics and Gynecology, Medical College, Kolkata, West Bengal E-mail: bandana.biswas2010@gmail.com *

†

18

The huge subset of this entity is pregnancy-induced hypertension (PIH) which is defined as hypertension (blood pressure [BP] >140/90 mmHg measured 2 times at least 6 hours apart when the patient is at rest) that develops as a direct effect of the gravid state.

It has many subsets-gestational hypertension, preeclampsia, eclampsia and pre-eclampsia or eclampsia superimposed on chronic hypertension. It may have various detrimental effects on the mother or fetus e.g., convulsions, intracranial hemorrhage, liver failure, renal failure, disseminated intravascular coagulation (DIC), placental abruption, intrauterine growth restriction (IUGR) and even intrauterine fetal death (IUFD).

IUGR is often associated with PIH, but it can also occur without any maternal hypertension or proteinuria.

Recent pathophysiological studies have focused on pre-eclampsia, which is increasingly recognized to be

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

REVIEW ARTICLE an early disease of the trophoblast characterized by maladaptation of spiral arteries, endothelial injury and secondary thrombosis. Although the exact etiology of pre-eclampsia is not certain, biochemical studies have suggested that it may be related to an imbalance between vasodilator and vasoconstrictor substances,2 the most relevant substances being prostacyclin I2 (PGI2) and thromboxane A2 (TXA2). Based on this assumption, a number of studies have demonstrated that low-dose aspirin can rectify the intravascular imbalance between PGI2 and TXA2, thus preventing or retarding the pathogenesis of the disease.3-5 IUGR is associated with high risk for perinatal morbidity and mortality. The risk rises with the severity of restriction. The definition of IUGR has been suggested by the American College of Obstetricians and Gynecologists (ACOG) describing it as “a fetus that fails to reach his potential growth”.6 It is suspected when fetal growth velocity is reduced, demonstrated by serial ultrasonographic scans, which determine an estimated fetal weight, which is below the 10th percentile or below two standard deviations of the mean for the gestational age. It has many short- and long-term problems e.g., respiratory distress, jaundice, necrotizing enterocolitis, growth failure, infection, intraventricular hemorrhage, periventricular leukomalacia, hydrocephalus, cerebral palsy, retinopathy, pulmonary hypertension. Currently a link has been established between IUGR and development of cardiovascular disease, type 2 diabetes mellitus and hyperlipidemia in adulthood.

IUGR and its concomitant fetal and neonatal morbidity and mortality continue to represent a formidable challenge in terms of both diagnosis and treatment. Intrauterine growth depends on the genetically determined growth potential, but various growth promoting and inhibiting factors also play a crucial role. Therefore, attempts at prenatal treatment have focused on improving uteroplacental perfusion and on improving substrate and energy supply.

Histologically, IUGR shows same defective placentation as pre-eclampsia.7 Consequently, if low-dose aspirin prophylaxis against pre-eclampsia is effective as shown in some trials, it might prevent not only that disorder but also some cases of IUGR by shifting the balance towards inhibition of TXA2 synthesis and thereby improving uteroplacental blood flow.

So, it is necessary to determine whether aspirin is really effective in prevention or amelioration of IUGR also, as has already been shown with PIH in many studies.

On the other hand, faulty trophoblastic invasion of spiral arteries results in diminished placental perfusion and upstream increased uterine artery resistance, which results in abnormal waveform represented by diastolic notch. So, increased uterine artery resistance or diastolic notch determined by Doppler ultrasound in first or early second trimester serves as a predictor of subsequent pre-eclampsia and IUGR. In this study, bilateral uterine artery notch and/or bilateral uterine artery PI >1.72 has been used to select the “high-risk” pregnancies.

The aim of our study was to determine the effectiveness of prophylactic low-dose aspirin in patients who are at high risk for developing pre-eclampsia and IUGR. The objectives of our study was to note correlation between early uterine artery abnormality and future development of PIH and/or IUGR. zz

To see how aspirin affects onset of PIH in patients who present with early uterine artery abnormality.

zz

To see how aspirin affects fetal growth in patients who present with early uterine artery abnormality.

zz

To see the perinatal outcome of giving aspirin to pregnant women who present with early uterine artery abnormality.

Material and Methods The present study was a prospective, randomized, open-ended, controlled, interventional, unicentric study conducted in the Dept. of Obstetrics and Gynecology and Dept. of Radiology, Institute of Postgraduate Medical Education and Research and Seth Sukhlal Karnani Memorial (IPGMER and SSKM) Hospital for 1 year (June 2013 to May 2014).

Data were collected from outdoor and indoor primigravida pregnant mothers of IPGMER and SSKM Hospital. We included primigravid mothers with singleton pregnancy, gestational age <16 weeks and bilateral uterine artery notch and/or bilateral uterine artery PI >1.7 revealed in Doppler ultrasound scan at 11-14 weeks gestation. Mothers having

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19

REVIEW ARTICLE abnormal bleeding per vagina, any contraindications to aspirin e.g., allergy to aspirin, bleeding disorder, peptic ulcer, concomitant use of other nonsteroidal anti-inflammatory drugs (NSAIDs) or anticoagulants or antiplatelet drugs, chronic liver disease/chronic hypertension/renal disease/overt diabetes mellitus and any other comorbid condition predisposing to vasculopathy, heart disease, documented fetal malformation or uterine malformation were excluded from our study. One hundred twenty-four mothers were selected according to inclusion criterias by random sampling technique, subjects- 62 subjects in each group.

The following parameters were noted for data collections:

20

from them after explaining that the details obtained from them would be used only for study purposes.

Each subject was enquired of present pregnancy, duration of amenorrhea, detailed obstetric history, family and personal history. Detailed general physical examination was done along with routine hematological investigations, blood sugar level, ABORh grouping, renal function test (RFT), liver functon test (LFT), urine for albumin. All patients included in the study were subjected to congenital anomaly scan to rule out anomalies and routine sonological tests.

They were advised regular antenatal check-up and follow-up which enabled us to properly evaluate the fetomaternal outcomes.

zz

Identification of abnormal uterine artery Doppler - PI >1.7 and/or presence of diastolic notch.

zz

For PIH - Regular BP monitoring.

zz

For IUGR - Clinical palpation of fundal height (a lag of 4 weeks is suggestive of IUGR), estimated fetal weight - if <10th percentile for the average for gestational age is considered as IUGR in USG, head circumference (HC) and abdominal circumference (AC) ratios - if >1.0 even after 34 weeks suggests IUGR.

These 124 women were randomly divided into two groups according to computer-generated randomization table - test and control containing 62 women in each group. Each woman of test group received tablet aspirin 75 mg o.d. from 16 weeks up to 34 weeks of gestation unless early termination became necessary.

Women of control group did not receive aspirin.

All of these 124 women were followed up till delivery at an interval of 1-4 weeks according to gestational age to see whether they were developing PIH and/or IUGR. After delivery, their babies were also examined to see the perinatal outcome.

zz

Regular BP monitoring of the selected patients.

Analysis of Data

zz

Baby: Physical features at birth (Apgar score at birth, weight- <2,500 g at term is suggestive of IUGR, HC and AC), number of days of stay in NICU, resultant morbidity/mortality of newborn.

Data were summarized by routine descriptive parameters like mean, median, standard deviation (SD) and quartiles for numerical variables and counts and percentages for categorical variables.

Study tools used in our study were sphygmomanometer, USG for uterine artery Doppler velocimetry, fetal profile and amniotic fluid index, measuring tape, neonatal weighing machine. Antenatal mothers meeting inclusion and exclusion criteria were subjected to uterine artery Doppler at 11-14 weeks gestation.

Data were analyzed using statistical version 6 (Tulsa, Oklahoma: StatSoft Inc., 2001) to see whether aspirin had significant role in prevention of PIH and/or IUGR in high risk mothers.

The study protocol was submitted to Institutional Ethics Committee and clearance was obtained before the commencement of the study. One hundred twentyfour primigravida women were selected according to inclusion and exclusion criteria. The women included in the study were told in detail about the potential significance of the test and its benefit in detail in their own language and an informed consent was obtained

Numerical variables are normally distributed by Kolmogorov-Smirnoff goodness-of-fit test other than age, thyroid-stimulating hormone (TSH), creatinine, uric acid, lactate dehydrogenase (LDH), Apgar at birth, birth weight, HC_AC and NICU stay. Age distribution is comparable (p value by Mann-Whitney U-test = 0.844 insignificant) between control (mean ± SD: 23.82 ± 3.628) and study groups (mean ± SD: 23.81 ± 3.492).

Results and Analysis

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

REVIEW ARTICLE Table 1, it is seen that difference in the SBP at 20 and 24 weeks gestation between groups is not significant (p value 0.950 and 0.263, respectively) but at 28, 32, 34, 36 weeks gestation and at term is significant (p value 0.001, 0.000, 0.001, 0.0`01 and 0.031, respectively).

Table 1 shows systolic BP (SBP) and diastolic BP (DBP) range with mean ± SD at 20, 24, 28, 32, 34 and 36 weeks and at term gestation in control and test groups. P value in the last column is for intergroup comparison by Student’s unpaired t-test. From the

Table 1. Systolic Blood Pressure and Diastolic Blood Pressure Changes at Different Gestational Weeks 20 weeks

24 weeks

28 weeks

32 weeks

34 weeks

36 weeks

Term

SBP in mmHg (Range) control

100-136

110-136

112-166

116-190

112-170

114-178

112-196

SBP in mmHg (Range) test

110-134

112-132

112-136

112-150

114-160

112-180

114-176

SBP in mmHg (mean ± SD) control

120.71 ± 6.232

122.87 ± 6.654

128.55 ± 10.578

134.29 ± 13.051

141.08 ± 13.965

147.11 ± 14.366

147.30 ± 16.919

SBP in mmHg (mean ± SD) test

120.77 ± 5.202

121.77 ± 3.834

123.58 ± 5.458

127.29 ± 7.674

132.87 ± 11.410

138.16 ± 15.020

140.39 ± 15.078

P value

0.950

0.263

0.001

0.000

0.001

0.001

0.031

DBP in mmHg (Range) control

70-84

66-90

68-100

72-120

70-110

70-120

76-120

DBP in mmHg (Range) test

70-82

70-84

60-86

70-96

70-100

70-120

70-112

DBP in mmHg (mean ± SD) control

78.52 ± 3.176

80.42 ± 4.115

80.26 ± 8.977

84.55 ± 7.107

88.95 ± 8.411

91.50 ± 8.716

91.22 ± 10.553

DBP in mmHg (mean ± SD) test

77.39 ± 3.541

79.48 ± 2.171

79.45 ± 3.660

81.23 ± 4.366

84.56 ± 6.786

88.52 ± 10.249

88.60 ± 9.281

0.064

0.116

0.514

0.002

0.002

0.093

0.183

P value

Table 2. Hemoglobin Level (g/dL), Platelet Count, Urea, Creatinine, Uric Acid and LDH Levels in Different Groups Parameters Hemoglobin level (g/dL)

Platelet count

Urea

Creatinine

Uric acid

LDH (IU/L)

Control group

Test group

P value (Student’s unpaired t-test)

Range

9-13.6

8.6-14

0.060

Mean ± SD

11.63 ± 1.172

12.03 ± 1.148

Range

1,11,000-5,12,000

1,26,000-5,22,000

Mean ± SD

3,26,419.35 ± 1,00,495.91

3,06,661.29 ± 97,520.73

Range

10-62

16-56

Mean ± SD

29.5 ± 9.735

31.66 ± 7.384

Range

0.1-2.1

0.2-1.9

Mean ± SD

0.6 ± 0.261

0.62 ± 0.219

Range

1.2-8.2

1.30-5.20

Mean ± SD

4.15 ± 1.749

3.28 ± 1.002

Range

124-610

110-600

Mean ± SD

255.87 ± 110.709

240.32 ± 93.458

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

0.269

0.166

0.732

0.011

0.596

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REVIEW ARTICLE Table 3. Proteinuria at 28, 32 and 36 Weeks in Different Groups Proteinuria at weeks of gestational age (GA/Grade)

Control (62)

Test (62)

(28/nil)

54

62

(28/+)

8

0

(32/nil)

45

57

(32/+)

3

2

(32/++)

13

3

(32/++++)

1

0

(34/nil)

37

52

(34/++)

19

10

(34/+++)

4

0

(34/++++)

1

0

(36/nil)

19

30

(36/++)

30

28

(36/+++)

3

0

(36/++++)

5

4

(Term/nil)

23

19

(Term/++)

17

23

(Term/+++)

8

8

(Term/++++)

7

8

P value

Parameters

0.006 (Fisher’s exact test 2-tailed)

Control (n = 62)

Test (n = 62)

Preeclampsia

7

19

0.014 (Fisher’s exact test 2-tailed p value)

IUGR

17

6

0.019 (Fisher’s exact test 2-tailed p value)

PPH

2

1

1.00 (Fisher’s exact test 2-tailed p value)

Birth weight in kg (mean ± SD)

2432.26 ± 458.624

2599.68 ± 262.285

0.339 (MannWhitney U-test)

Apgar score (mean ± SD)

8.19 ± 1.084

8.63 ± 0.550

0.128 (MannWhitney U-test)

15

4

3.37 ± 7.382

0.66 ± 2.997

Chi-square test (Yate’s corrected) p value 0.031

0.016 (Chi-square test (Yate’s corrected)

NICU admission 0.142 (Chi-square test (Yate’s corrected)

0.737 (Chi-square test (Yate’s corrected)

Difference in the DBP at 20, 24, 28 and 36 weeks gestation and at term between groups is not significant (p value 0.064, 0.116, 0,514, 0.093 and 0.183) but it is significant at 32 and 34 weeks gestation (p value 0.002 and 0.002, respectively).

Table 2 shows hemoglobin level (g/dL), platelet count, urea, creatinine, uric acid and LDH (IU/L) in different groups. From the table, it is seen that difference in the hemoglobin level between groups is not significant (p value 0.060) and the difference in the platelet level between groups is not significant (p value 0.269). It is also seen that difference in the urea and creatinine level between groups is not significant (p value 0.166 and 22

Table 4. Occurrence of Pre-eclampsia, IUGR, PPH, Birth Weight, Apgar Score at Birth, NICU Admission and Stay in Different Groups

NICU stay (mean ± SD)

P value

0.011 (Fisher’s exact test 2-tailed p value) 0.082 (MannWhitney U-test)

0.732, respectively), but uric acid level is significantly decreased in aspirin-treated group (p value 0.011).

From the Table 3, it is seen that proteinuria at 28, 32 and 34 weeks aspirin-treated group is reduced significantly (p value 0.006, 0.031, 0.016, respectively) and proteinuria at 36 weeks and term pregnancy between groups is not significant (p value 0.142 and 0.737, respectively).

From the Table 4, it is obvious that reduction in the occurrence of pre-eclampsia, IUGR and NICU admission in aspirin-treated group are significant (p value 0.014, 0.019 and 0.011, respectively) but the difference in birth weight, the Apgar score at birth, NICU stay and occurrence of postpartum hemorrhage (PPH) between groups is not significant (p value 0.339, 0.128, 0.082 and 1.000, respectively).

There was no incidence of hypertension without proteinuria in any of the patients. Eclampsia also did not develop in any of the study groups.

There was no occurrence of altered sugar, thyroid profile, disturbed LFT, coagulation profile and

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

REVIEW ARTICLE antepartum hemorrhage (APH) in any of the study groups.

In this study, number needed-to-treat (NNT) for preeclampsia avoidance is 5.17 i.e., 5.17 subjects need to be on aspirin rather than on control treatment to avoid 1 additional case of pre-eclampsia.

NNT for IUGR avoidance is 5.64 i.e., 5.64 subjects need to be on aspirin rather than on control treatment to avoid 1 additional case of IUGR. Discussion Gestational hypertension and pre-eclampsia syndrome remains one of the most intriguing topics even in modern day obstetrics. Even though complications associated with PIH have been observed from ancient times and various treatment modalities have been suggested, till now appropriate preventive measures have not been devised.

In this context, we studied the effectiveness of lowdose aspirin started at 16 weeks gestation in prevention of pre-eclampsia and IUGR in high risk primigravida.

High risk group was defined by diastolic notch and/or PI ≥1.7 in uterine artery Doppler at 11-14 weeks gestation. One hundred twenty-four antenatal women carrying singleton pregnancy, fulfilling all inclusion and exclusion criteria were included in our prospective interventional study. All relevant patient data and investigations were analyzed statistically using Statistical version 6 (Tulsa, Oklahoma: StatSoft Inc., 2001).

We can see that the age distribution between the different groups is not statistically significant. Mean age in control and test group is 23.82 and 23.81 years, respectively.

Table 1 shows that SBP at 20 and 24 weeks gestation between different groups is comparable but it is significantly decreased in aspirin-treated group at 28, 32, 34 and 36 weeks gestation and at term (p value 0.001, 0.000, 0.001, 0.001 and 0.031, respectively).

Table 1 also shows that difference in the DBP at 20, 24, 28 and 36 weeks gestation and at term between different groups is not significant but it is significant at 32 and 34 weeks gestation (p value 0.002 and 0.002, respectively).

As we all know that severe pre-eclampsia is characterized by vasoconstriction and a ‘leaky’ microcirculation,

resulting in fluid moving into the extracellular interstitial space and relative hypovolemia. The red cell volume in pre-eclampsia is no different than in normal pregnancy.

Thus, the hemoglobin concentration or hematocrit is a reasonable surrogate measure of plasma volume in preeclampsia. Abnormally high hemoglobin levels correlate with adverse perinatal outcome.1-6 On the other hand, thrombocytopenia is the most frequent hemostatic abnormality in established pre-eclampsia7,8 and one of the components of the dreaded complication of pre-eclampsiaHELLP syndrome. From Table 4 and 5; however, we can see that in our study hemoglobin and platelet values are comparable between the two groups i.e., aspirin does not appear to have any effect on hemoglobin and platelet levels.

It is noteworthy that in our study population hemoglobin level seems to be quite improved in comparison to the general population (mean value 11.63 and 12.03, respectively for control and test groups), which may be due to good antenatal care and/or hemoconcentration as a result of the leaky microcirculation of the pre-eclampsia syndrome.

Table 2 shows that urea, creatinine levels are comparable between the two groups but uric acid level has decreased significantly in aspirin-treated group (p value is 0.011). Uric acid levels are usually found to be significantly elevated in patients with pre-eclampsia6 - our study corroborates well with this finding - as incidence of pre-eclampsia is significantly higher in the control group - uric acid level is also significantly elevated in that group.

Serum LDH is most often measured to evaluate tissue damage in pre-eclampsia. Elevated LDH level indicates microangiopathic hemolytic anemia, which is the result of vascular endothelial damage.9 LDH level >800 IU/L is most often associated with adverse maternal and fetal outcome. Increased LDH, thus indicates the severity of the pre-eclampsia syndrome.10 However in this study, it is seen that LDH level is comparable between the two groups.

In Table 3, we can see that proteinuria has decreased significantly in aspirin-treated group at 28, 32 and 34 weeks gestation (p value 0.006, 0.031 and 0.016, respectively) but not so at 36 weeks gestation and at term.

From Table 4, it is evident that aspirin reduces the incidence of pre-eclampsia significantly in this highrisk population (p value 0.014).

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

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REVIEW ARTICLE The Perinatal Antiplatelet Review of International Studies (PARIS) Collaborative Group10 performed a meta-analysis of the effectiveness and safety of lowdose aspirin for the prevention of pre-eclampsia and concluded that low-dose aspirin has small-to-moderate benefits when used for prevention of pre-eclampsia and is also safe. Results from a meta-analysis11 suggested that low-dose aspirin improves pregnancy outcome in women with persistent increases in uterine Doppler resistance index at both 18 and 24 weeks’ gestation.

Findings of our study corroborates well with the findings of these studies. However, in other studies with abnormal Doppler measurements of uterine arteries at 22-24 weeks gestation, low-dose aspirin after 23 weeks gestation did not prevent pre-eclampsia.

Table 4 represent the perinatal outcome. Among the several parameters of perinatal outcome, NICU admission rate are significantly decreased in aspirintreated group (p value 0.011), but other parameters like Apgar score at birth, birth weight and NICU stay were not influenced significantly by aspirin. However, incidence of IUGR was significantly less in the patients treated with aspirin (p value 0.019).

Table 4 also shows that incidence of PPH is comparable between the two groups. It is noteworthy that APH did not occur in any of the study groups.

There was no incidence of hypertension without proteinuria in any of the patients. Eclampsia also did not develop in any of the study groups. There was no alteration of glycemic, thyroid, liver or coagulation status in either group.

Pre-eclampsia, one of the most discussed enigmatic diseases in obstetrics, affects 2-8% of all pregnancies.

Abruptio placentae, renal failure, cerebral hemorrhage, DIC, pulmonary edema, circulatory collapse, IUGR and IUD are the problems associated with pre-eclampsia.

There has been an explosion of research activities worldwide for early prediction and prevention of preeclampsia but till date it remains an uphill task for all obstetricians and researchers. Various methods have been tried but none is full proof. Some studies have shown that low-dose aspirin started early in pregnancy in high risk group may be quite efficacious in preventing pre-eclampsia and IUGR. In our study, we came to the conclusion that treatment with low-dose aspirin starting early in pregnancy in high risk group (defined by diastolic notch and/or PI ≥1.7 in uterine artery Doppler done at 11-14 weeks gestation) is efficacious in preventing pre-eclampsia and IUGR. Perinatal outcome is also improved in aspirin-treated group.

However, further studies with large number of patients are needed to establish the definite role of low-dose aspirin in this context.

References 1. Cunningham F, Leveno K, Bloom S, Hauth J, Rouse D, Spong C. Pregnancy hypertension (Chapter 34). In: Williams Obstetrics. 23rd Edition; 706.

In this study, NNT for pre-eclampsia avoidance is 5.17 i.e., 5.17 subjects need to be on aspirin rather than on control treatment to avoid 1 additional case of pre-eclampsia.

2. Gómez O, Figueras F, Fernández S, Bennasar M, Martínez JM, Puerto B, et al. Reference ranges for uterine artery mean pulsatility index at 11-41 weeks of gestation. Ultrasound Obstet Gynecol. 2008;32(2):128-32.

NNT for IUGR avoidance is 5.64 i.e., 5.64 subjects need to be on aspirin rather than on control treatment to avoid additional case of IUGR.

3. Martin AM, Bindra R, Curcio P, Cicero S, Nicolaides KH. Screening for pre-eclampsia and fetal growth restriction by uterine artery Doppler at 11-14 weeks of gestation.

Ultrasound Obstet Gynecol. 2001;18(6):583-6.

Limitations zz zz zz zz zz

24

Conclusions

Small sample size (less time).

Absence of blinding.

Measurement of proteinuria by dipstick method.

Absence of follow-up of patients up to 12 weeks postpartum.

Absence of follow-up of babies after discharge.

4. Papageorghiou AT, Yu CK, Nicolaides KH. The role of uterine artery Doppler in predicting adverse pregnancy outcome. Best Pract Res Clin Obstet Gynaecol.

2004;18(3):383-96.

5. Cnossen JS, Morris RK, ter Riet G, Mol BW, van der Post JA, Coomarasamy A, et al. Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable metaanalysis. CMAJ. 2008;178(6):701-11.

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REVIEW ARTICLE 6. Mandruzzato G, Antsaklis A, Botet F, Chervenak FA, Figueras F, Grunebaum A, et al; WAPM. Intrauterine restriction (IUGR). J Perinat Med. 2008;36(4):277-81.

7. CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. Lancet.

1994;343(8898):619-29.

8. Villar J, Say L, Gulmezoglu AM, Meraldi M, Lindheimer MD, et al. Eclampsia and pre-eclampsia: a health problem for 2000 years. In: Critchly H, MacLean A, Poston L,

Walker J (Eds.). Pre-eclampsia. RCOG Press: London; 2003, pp. 189-207.

9. Ronsmans C, Graham WJ; Lancet Maternal Survival Series steering group. Maternal mortality: who, when, where, and why. Lancet. 2006;368(9542):1189-200.

10. Farag K, Hassan I, Ledger WL. Prediction of preeclampsia: can it be achieved? Obstet Gynecol Surv. 2004;59(6):46482; quiz 485.

11. Nanda S, Sharma JB, Gulati N. Perinatal mortality in eclampsia. J Obstet Gynecol India. 1989;39:792-5.

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CASE REPORT

Wilson’s Disease in Pregnancy Shreyasi Bid*, Sambhunath Bandyopadhyay†, Anik Das‡, Srijani Chowdhury‡

ABSTRACT Wilson’s disease has a deleterious effect on fertility as it causes hepatic, pancreatic and cerebral dysfunction and menstrual irregularities. Here, we present a known case of Wilson’s disease who conceived spontaneously after 3 miscarriages. With regular antenatal check-up and neurological consultation she had a good pregnancy outcome.

Keywords: Wilson’s disease, pregnancy and zinc

S

uccessful pregnancy in a case of Wilson’s disease has rarely been reported. Both Wilson’s disease and pregnancy are associated with alteration in copper metabolism, in particular, that of ceruloplasmin. While this protein is markedly reduced in most of the cases of Wilson’s disease, it is usually increased in pregnancy due to increased estrogen levels. So, it appears that there had been significant clinical improvement in the severity of the disease during and months following pregnancy. Here, we present a case report of successful pregnancy following three abortions in a patient with long-standing Wilson’s disease and who has been under continuous therapy with zinc for 4 years.

Case Report A 28-year-old woman G4P0+3 nondiabetic, nonhypertensive, euthyroid admitted on 09.11.13 with dribbling and pain abdomen at 38 weeks of gestation. She is a known case of Wilson’s disease. She is suffering from gradually progressive tremor all over the body for last 4 years. It is associated with thinning of proximal aspect of all limbs followed by distal parts. She was

*RMO cum Clinical Tutor † Associate Professor ‡ Postgraduate Trainee Dept. of Obstetrics and Gynecology Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal Address for correspondence Dr Shreyasi Bid Dakshi Apartment, 75 James Long Sarani, Joka, Kolkata, West Bengal E-mail: drshreyasibid@gmail.com

26

diagnosed as a case of Wilson’s disease in 2009.

She conceived spontaneously after 3 consecutive abortions. The laboratory work-up revealed an elevated urinary copper level and low serum ceruloplasmin.

Her brother was also suffering from Wilson’s disease.

She has been using zinc sulfate 60 mg thrice-daily, trihexyphenidyl 2 mg thrice-daily, since the time of diagnosis and continued it throughout her pregnancy.

All the antenatal laboratory tests were within normal limits. Her urinary copper level was obtained in first trimester which was normal. Anomaly scan performed at 19 weeks revealed no gross congenital anomalies.

Oral glucose tolerance test done at 24 weeks of gestation, which ruled out gestational diabetes. Ultrasonography (USG) of whole abdomen at 32 weeks revealed coarse liver disease suggestive of chronic liver disease (CLD), chronic calculous cholecystitis and normal growth pattern of the fetus. Maternal echocardiogram was performed which was within normal limits. Magnetic resonance imaging (MRI) of brain showed bilateral basal ganglia, thalamic and midbrain hyperintensity with sparing of red nuclei and tegmentum. There was minimal cerebral and cerebellar atrophy. Complete blood count, thyroid profile test, liver function test, coagulation profile were performed 7 days prior to admission, all are within normal limits.

The patient underwent emergency LUCS on 09.11.13 due to oligohydramnios. Intraoperative course of events was unremarkable and a healthy boy baby weighing 2.5 kg with a good Apgar score was born.

The postoperative period was unremarkable with proper wound healing.

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

CASE REPORT Discussion Wilson’s disease is a rare autosomal recessive disorder with prevalence of 1:50,000-1:1,00,000 live birth.

Although copper is a trace mineral and accounts for only 0.01% of total body weight, it plays an important role in electron transport, neurotransmitter synthesis, collagen cross - linkage, melatonin production and important factor in coagulation cascade. Copper is absorbed by the proximal small intestine and transported to the liver. In the liver copper is incorporated into apoceruloplasmin. Ceruloplasmin represent 90% of circulating copper and excess are excreted into bile.

The protein responsible for copper transport from liver to bile is ATP7B on chromosome 13q14. Absence or diminished function of ATP7B results in decreased copper excretion, the excess copper accumulates in the liver, brain, heart and pancreas. This results in liver cirrhosis, neurological abnormalities, cardiac dysfunction, pancreatic dysfunction.1 Moreover, it can lead to menstrual irregularities due to hepatotoxicity and recurrent miscarriages due to copper deposition in the uterus in women in reproductive age group.2,3 Women with Wilson’s disease may require infertility treatment but many patients conceive spontaneously. In our case, the patient conceived spontaneously after 3 miscarriages.

The serum copper and ceruloplasmin levels have been observed to change as the pregnancy progresses.

The levels may increase till 24 weeks followed by a modest decline probably due to fetal intake of copper. There is approximately 12 mg copper in a neonate and the fetus is thought to remove an average of 0.044 mg of copper per day from the maternal serum, due to which improvement in symptoms of Wilson’s disease have also been reported.4,5 Recent studies have shown that during pregnancy, ATP7B plays a role in transporting copper from placenta to maternal circulation, thus preventing fetal overload. If dysfunctional, excess copper remain in the fetus, placenta and endometrium resulting in fetal loss or damage. Wilson’s disease can be associated with pre-eclampsia, the fetus can be growth restricted and have neurological sequel due to oxidative damage caused by copper accumulation in the placenta and fetal tissue.6,7

However, such complications were not encountered in our patient. Wilson’s disease, if not treated promptly, can lead to significant morbidity and can be potentially fatal.

Penicillamine is the category D drug in pregnancy.

Fetal connective tissue anomaly can occur as a result of inhibition of collagen synthesis - neonatal inguinal hernia, reversible cutis laxa, hyperflexible joints, vascular fragility and poor wound healing have all been reported.

Although the evidence is incomplete, maintaining the daily dose at 500 mg or less may reduce the incidence of penicillamine-induced toxicity to newborn. If cesarean section is planned reduce the dose to 250 mg/day for 6 weeks before delivery and postoperatively in order to prevent delayed wound healing.8-10 Trientine is an oral chelating drug used as an alternate when patients develop a reaction to penicillamine.

Its effectiveness has been proven and case reports regarding its use in pregnancy do not show any adverse fetomaternal outcomes.11,12 More recently, zinc is increasingly being used as a therapeutic option in managing Wilson’s disease.

Zinc interferes with absorption of copper from the gastrointestinal tract. Zinc performs its function by induction of intestinal cells metallothionein, which has a high affinity for copper and prevents serosal transfer of copper into blood.13 In our case, the patient was treated with zinc sulfate without occurrence of any congenital anomaly in neonate. It is evident that the outcome of pregnancy in women with Wilson’s disease is determined by compliance with the prescribed regimen or deviation from it, rather than the choice of medication.

The available data do not support the claim that zinc is “optimal” or that the patient should be advised to change a well-tolerated, effective regimen. Additionally, counseling and timely delivery, can greatly improve neonatal and maternal outcome.

References 1. Roberts EA, Schilsky ML; American Association for Study of Liver Diseases (AASLD). Diagnosis and treatment of Wilson disease: an update. Hepatology. 2008;47(6):2089-111.

2. Mustafa MS, Shamina AH. Five successful deliveries following 9 consecutive spontaneous abortions in a patient with Wilson disease. Aust N Z J Obstet Gynaecol.

1998;38(3):312-4.

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Continued on page 30...

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CASE REPORT

Heterologous Malignant Mixed Mullerian Tumor of Uterus: An Uncommon Tumor with Uncommon Presentation Bhavana S

ABSTRACT A malignant mixed mullerian tumor (MMMT) is an extremely rare and aggressive neoplasm with biphasic pattern, consisting of both mesenchymal and epithelial components. The tumor presents in MMMT with heterologous elements women, in 5-7th decade of life accounting for 2-5% of all malignant neoplasm of the uterine corpus. We report the case of a 65-yearold, elderly woman who presented to Gynecology OPD, with complaints of difficulty in passing urine for the past 1 month and acute retention of urine for the past 2 days. The ultrasound revealed markedly enlarged uterus due to large mass filling the uterus 10.9 × 11.4 × 9.6 cm3 with multiple cystic areas within the lesion. The patient was posted for laparotomy and subjected to total abdominal hysterectomy with bilateral salpingo-oophorectomy was done. The histopathology of the tumor confirmed the diagnosis of MMMT with heterologous elements.

Keywords: Malignant mixed mullerian tumor, uterine corpus, menopausal, total abdominal hysterectomy with bilateral salpingo-oophorectomy

T

he uterine malignant mixed mullerian tumor (MMMT) is an uncommon neoplasm with biphasic pattern, consisting of both mesenchymal and epithelial components. They are very aggressive tumors with extremely poor prognosis, presenting in elderly menopausal women.

Case Report A 65-year-old, elderly woman presented to Gynecology OPD, with complaints of difficulty in passing urine for the past 1 month and acute retention of urine for the past 2 days. She had 8 children. She attained menopause 15 years back.

On examination, patient was moderately built and poorly nourished. Weight 35 kg, height 136 cm. Body mass index (BMI) - 18.9 kg/m2. After catheterization;

Assistant Professor Dept. of Obstetrics and Gynecology Sree Mookambika Institute of Medical Sciences, Kulasekharam, Kanyakumari, Tamil Nadu Address for correspondence Dr Bhavana S W/o: Dr Rakesh Kumar Gupta No. 27, Karthik Nilaya, C-Layout, 2nd Cross, Hanumanthanagar, Bannimantap, Mysore - 570 015, Karnataka E-mail: bhavana_yajat@yahoo.com

28

on per abdomen examination, a suprapubic mass was felt, corresponding to uterus of 16-18 weeks, with irregular borders, firm in consistency, dullness on percussion, with grossly reduced mobility, with no free fluid in the abdomen. On per speculum examination, cervix appeared healthy. On per vaginum examination, uterine mass of 16-18 weeks felt, firm in consistency, impacted in pelvis, with gross reduction in mobility.

The ultrasound revealed markedly enlarged uterus due to large mass filling the uterus 10.9 × 11.4 × 9.6 cm3 with multiple cystic areas within the lesion. No breech of surface, no ascites, no definite adjacent organ infiltration, with mechanical bladder outlet obstruction with left-sided hydronephrosis.

The patient was diabetic on routine investigation and insulin therapy was started. The patient was posted for laparotomy. Intraoperatively, uterus was 18 weeks size, ovaries, parametrium, peritoneum, omentum were normal, with no ascites/adhesions. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was done. The cut section of the uterus showed a large 12 × 12 × 8 cm3 broad based pedunculated polyp arising from the fundus, distending the entire cavity of the uterus (Fig. 1). Cross-section of the tumor showed pinkish, white, solid tumor with areas of extensive necrosis. The histopathology of the tumor showed carcinomatous component composed of

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

CASE REPORT

Figure 1. Cut section of uterus with the large pedunculated tumor arising from the fundus.

Figure 4. Heterologous component showing cartilaginous areas of MMMT (H&E stain high power).

with extensive areas of tumor necrosis - MMMT with heterologous elements (Figs. 2-4).

The clinical and pathological staging was Stage 1B MMMT of uterus. The patient and the family were counseled and prognosis was explained and the option of adjuvant radiotherapy/chemotherapy was advised.

But patient refused further treatment, was discharged on the 10th day and follow-up was advised.

Figure 2. Carcinomatous component with necrotic areas of MMMT (H&E stain high power).

Figure 3. Sarcomatous component of MMMT (H&E stain high power).

adenocarcinomatous, clear cell and undifferentiated areas. Sarcomatous areas with elongated spindle cells.

Focal areas with malignant cartilaginous differentiation

Discussion The MMMT’s account for 2-5% of all malignant neoplasm of the uterine corpus. The tumor presents in postmenopausal women, in 5-7th decade of life.

The reported median interval from menopause to presentation is 15-17 years.1,2 Nulliparity, obesity, diabetes and hypertension are recognized predisposing factors for MMMT’s. The neoplasm has been associated with previous pelvic radiation therapy.1,2 Some patients have developed MMMT while taking tamoxifen and raloxifene.1 In our case, there was no predisposing factors except that she was diagnosed to be diabetic after routine investigation.

The MMMT’s contain admixture of carcinomatous and sarcomatous elements. The epithelial component may be any type of mullerian carcinoma: mucinous, squamous, endometroid, high grade papillary, clear cell or undifferentiated. On the basis of the appearance of sarcomatous component, the neoplasm is classified into homologous (leiomyosarcoma, stromal sarcoma,

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CASE REPORT fibrosarcoma) or heterologous (chondrosarcoma, rhabdomyosarcoma, osteosarcoma, liposarcoma).1 The commonest symptoms are postmenopausal bleeding, lower abdominal pain, loss of weight and abdominal mass.1,3,4 The MMMT’s are highly aggressive neoplasms. Staging is the most important predictive factor in prognosis.1-3 The International Federation of Gynecology and Obstetrics (FIGO) staging of MMMT’s of the uterus is the same as for endometrial carcinoma. Five-year survival rate are about 30-40% in Stage I disease (confined to uterine corpus) and considerably less in Stage II and III (when disease extended to cervix, vagina or parametrium) and there were no survivors in those with disease outside the pelvis (Stage IV).1 Due to aggressive nature of MMMT’s and its poor prognosis, various modalities of treatment have

been employed. Surgery in the form of abdominal hysterectomy and bilateral salpingo-oophorectomy remains the principle treatment.1,4 Adjuvant radiotherapy and chemotherapy (cisplatin and ifosfamide) has been shown to be beneficial.4 References 1. Ho SP, Ho TH. Malignant mixed mullerian tumours of the uterus - a ten-year experience. Singapore Med J. 2002;43(9):452-6.

2. Moghaddam NA, Pooralborzi F, Aram S, Moghaddas D. Heterologous malignant mixed mullerian tumor in a diabetic patient. JRMS. 2008;13(6):349-53.

3. Rosai J. Uterus - Corpus. In: Rosai J (Ed.). Rosai and Ackerman’s Surgical Pathology. Philadelphia: Mosby; 2004. pp. 1599-602.

4. Wong L, See HT, Khoo-Tan HS, Low JS, Ng WT, Low JJ. Combined adjuvant cisplatin and ifosfamide chemotherapy and radiotherapy for malignant mixed müllerian tumors of the uterus. Int J Gynecol Cancer. 2006;16(3):1364-9.

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... Continued from page 27 3. Morimoto I, Ninomiya H, Komatsu K, Satho M. Pregnancy and penicillamine treatment in a patient with Wilson’s disease. Jpn J Med. 1986;25(1):59-62.

8. Geever EF, Youssef S, Seifter E, Levenson SM. Penicillamine and wound healing in young guinea pigs. J Surg Res. 1967;7(4):160-6.

4. Sherwin AL, Beck IT, McKenna RD. The course of Wilson’s disease (hepatolenticular degeneration) during pregnancy and after delivery. Can Med Assoc J. 1960;83:160-3.

9. Walshe JM. Pregnancy in Wilson’s disease. Q J Med. 1977;46(181):73-83.

5. Brewer GJ, Johnson VD, Dick RD, Hedera P, Fink JK, Kluin KJ. Treatment of Wilson’s disease with zinc. XVII: treatment during pregnancy. Hepatology. 2000;31(2): 364-70.

6. Young T, Downey G, Maheshwari MB, Nicholl DJ. A cupric pregnancy - thirteenth time lucky. JRSM Short Rep. 2010;1(6):51.

7. Kaplan JH, Lutsenko S. Copper transport in mammalian cells: special care for a metal with special needs. J Biol Chem. 2009;284(38):25461-5.

10. Nimni ME, Bavetta LA. Collagen defect induced by penicillamine. Science. 1965;150(3698):905-7.

11. Walshe JM. The management of pregnancy in Wilson’s disease treated with trientine. Q J Med. 1986;58(225):81-7.

12. Dupont P, Irion O, Béguin F. Pregnancy in a patient with treated Wilson’s disease: a case report. Am J Obstet Gynecol.

1990;163(5 Pt 1):1527-8.

13. Yuzbasiyan-Gurkan V, Grider A, Nostrant T, Cousins RJ, Brewer GJ. Treatment of Wilson’s disease with zinc: X. Intestinal metallothionein induction. J Lab Clin Med. 1992;120(3):380-6.

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Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

CASE REPORT

Subseptate Uterus Presenting as Unstable Lie at Term Shikha Singh*, Saroj Singh†, Ankita Kumari‡, Ruchita Sinha#

ABSTRACT Subseptate uterus presenting as unstable lie at term is uncommon. In this article, we report two rare cases, first where presentation of baby changed four times and in the other lie of the fetus changed twice in a short period of time. On exploration of uterus at the time of cesarean section, it was found to be subseptate.

Keywords: Subseptate uterus, unstable lie, mullerian abnormalities

I

n the past, anomalies of genital tract have aroused interest as anatomical curiosity because of the relative infrequency with which they are thought to occur. In recent years, several investigators have focused attention upon these abnormalities because of their important bearing upon the frequency of abortion, premature labor, abnormal presentation of the fetus and complications of labor and of the immediate postpartum period. Among the mullerian anomalies subseptate uterus is the most common congenital uterine anomaly with an incidence of 33.6%.1 Case History Case 1

A 22-year-old multiparous woman (G3P1L0A1) presented on 3/3/2010 with amenorrhea of 8 months at 36 weeks of gestational age (according to her ultrasonography [USG] report done 4 days back, exact last menstrual period [LMP] was not known) for routine antenatal

*Assistant Professor † Professor and Head ‡ Senior Resident # PG Student Dept. of Obstetrics and Gynecology SN Medical College, Agra, Uttar Pradesh Address for correspondence Dr Shikha Singh Assistant Professor Dept. of Obstetrics and Gynecology SN Medical College, Agra, Uttar Pradesh E-mail: drshikhasingh.shikha@gmail.com

check-up. Her obstetric history had unsuccessful outcome with history of emergency lower-segment cesarean section (LSCS) done for cord prolapse done 2.5 years back, which resulted in intrauterine death of the and one spontaneous abortion at 3 months of gestational age, 1.5 years back. Her medical history was unremarkable. She had an USG done 4 days back, which showed a single live intrauterine fetus with mean gestational age of 35 weeks 4 days with breech presentation.

Abdominal examination, at the time of presentation revealed a fundal height of 34 weeks with cephalic presentation. She was advised a repeat USG which revealed a single live intrauterine fetus of gestational age 35 weeks 4 days with cephalic presentation and scar thickness of 2.2 mm and placenta of Grade III maturity.

In view of thin scar and persistent mild but infrequent uterine contractions and Grade III placenta, she was admitted and kept under observation. During observation her lie kept on changing from breech to transverse or cephalic. Because of thin uterine scar an elective cesarean section was decided at 37 weeks.

On the day of elective cesarean, the presentation of baby was found to be transverse with head on right side and back posterior. This was confirmed on USG. She was taken up for cesarean section and on exploration of uterus, a septa measuring 3 inch was found arising from fundus i.e., subseptate uterus was discovered.

Her postoperative period was uneventful. Patient was discharged after 9 days in a satisfactory condition.

She has not reached for follow-up yet.

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CASE REPORT Case 2

In the second case, a 23-year-old, primigravida presented on 3/10/2010 with amenorrhea for 9 months at 39 weeks of gestational age (according to her LMP and 37 weeks 6 days according to USG done at the time of admission), pain in abdomen for 6 hours and leaking per vaginum for 1 hour.

On examination, lie of the baby was found to be transverse, cervix was 2 cm dilated and 80% effaced and membranes were absent, which was confirmed on USG. Patient was taken for cesarean section in view of transverse lie and at the time of operation lie was found to be longitudinal with breech presentation.

On exploration, a septa of about 2 inches was found arising from the fundus and incompletely dividing the uterine cavity. Her postoperative period was uneventful.

She was discharged after 8 days in a satisfactory condition. She was advised for follow-up at 6 weeks.

Discussion Incidence of uterine malformation in population is 0.5%. Subseptate uterus belong to Class III B according to American Fertility Society (AFS) classification of mullerian anomalies. Apoptosis has been proposed as a mechanism by which the septum regresses. Bcl-2, a protein involved in regulating apoptosis was found absent in septa of subseptate uterus. Absence of this protein plays a pivot role in persistence of septum.2 Patients with this anomaly often have recurrent abortions which is due to abundant muscle tissue in the septum, abnormal endometrium overlying the septum leading to abnormal implantation. Only about 40% of pregnancies reach term with a constantly changing fetal presentation even beyond 36 weeks of pregnancy when it should have been stabilized. This was the presentation in our case in which the lady within 1 week of our observation had breech, cephalic and transverse lie on different occasions which were confirmed by USG also.

In the other case, lie of the fetus changed at term in a short period of time in labor within few hours.

After 22 weeks of gestation, enlargement of uterus obliterates some subtle findings suggestive of anatomic variablity, so the patient should be examined before this juncture with a conventional transabdominal or transvaginal approach. Using 3D studies with power Doppler in first trimester scar (4-9 weeks) may be best performed for diagnosis.3 Patient usually gives history of dysmenorrhea, menorrhagia in the interval period. They may be pregnant despite presence of an intrauterine contraceptive device (IUCD) because of incomplete occupancy of IUCD of whole of the uterus. Various diagnostic modalities like hysterosalpingogram, hysteroscopy and laparoscopy are helpful to detect the anomaly before the patient conceives.

The recommended therapy for subseptate uterus in the past was abdominal metroplasty. During the past several years, hysteroscopic resection of uterine septum with intrauterine resectoscope, hysteroscopic resection of uterine septum using flexible or rigid scissors or neodymium-doped yttrium aluminum garnet (Nd-YAG) laser or transcervical septum resection using Metzenbaum scissors under fluoroscopic guidance has replaced the transabdominal approach.4 Unstable lie at term or in labor should arouse suspicion for the obstetricians to be aware of any mullerian anomaly, most common culprit of which may be subseptate uterus.

References 1. Williams Obstetrics. 23rd Edition, pg. 968-9, 893.

2. Te Lende’s Operative Gynaecology. 10th Edition, pg. 567, 565.

3. Ian Donald’s Practical Obstetrics Problems. 6th Edition, pg. 73.

4. Berman MC, Cohen HL. Obstetrics and Gynecology. pg. 60.

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Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

JOURNAL SCAN

News and Views

Perioperative Complications of Cesarean Delivery Myomectomy A new study published in Obstetrics and Gynecology assessed the association of myomectomy during cesarean delivery with intraoperative and perioperative maternal morbidity. In this meta-analysis, a search was conducted MEDLINE (1966-2017), Scopus (2004-2017), ClinicalTrials.gov (2008-2017), EMBASE (19802017), and Cochrane Central Register of Controlled Trials CENTRAL (1999-2017) databases to include all observational studies that reported outcomes on patients undergoing myomectomy at the time of cesarean delivery. Overall, 19 studies were selected which comprised 3,900 women. Among these, 2,301 women had myomectomy during cesarean delivery and 1,599 had cesarean delivery only.

The review revealed that women undergoing concomitant myomectomy had a mild decline in hemoglobin, when compared to those who had cesarean delivery only. Myomectomy at the time of cesarean delivery was found to be associated with longer surgical time compared to cesarean delivery alone. Whereas, blood transfusion and postoperative fever rates did not differ between the two groups (myomectomy compared with no myomectomy).

Furthermore, a statistically, but not clinically, significant increase in postoperative hospitalization was obvious in the myomectomy group. The findings of this study demonstrated an association with increased operative time and hemoglobin drop in patients who underwent cesarean myomectomy compared to cesarean delivery alone. Whereas no increased rate of major hemorrhage or need for transfusion was identified. It was suggested that cesarean myomectomy may be considered in cases of isolated myomas.

Placental Complications Associated with Psychostimulant Use in Pregnancy A new study published in Obstetrics and Gynecology evaluated whether psychostimulants used to treat attention deficit hyperactivity disorder (ADHD) are

associated with risk of adverse placental-associated pregnancy outcomes including pre-eclampsia, placental abruption, growth restriction and preterm birth. This population-based cohort study, examined a cohort of pregnant women and their live-born neonates enrolled in Medicaid from 2000 to 2010. Pregnancies exposed to amphetamine-dextroamphetamine (n = 3,331), methylphenidate (n = 1,515), and atomoxetine (n = 453) monotherapy in early pregnancy were compared to 1,461,493 unexposed pregnancies. The results showed that among unexposed women, the risks of the outcomes were 3.7% for pre-eclampsia; 1.4% for placental abruption; 2.9% for small for gestational age and 11.2% for preterm birth. The adjusted risk ratio for stimulant use was 1.29 for pre-eclampsia; 1.13 for placental abruption; 0.91 for small for gestational age; and 1.06 for preterm birth.

In comparison with discontinuation, the adjusted risk ratio for continuation of stimulant use in the latter half of pregnancy was 1.26 for pre-eclampsia; 1.08 for placental abruption; 1.37 for small for gestational age and 1.30 for preterm birth. On the other hand, atomoxetine was not associated with the outcomes studied. Hence, it was inferred that psychostimulant use during pregnancy was associated with a small increased relative risk of pre-eclampsia and preterm birth. It was stated that the absolute increases in risks are small and, thus, women with significant ADHD should not be advised to suspend their ADHD treatment.

Serum Squamous Cell Carcinoma Antigen â&#x20AC;&#x201C; an Early Indicator of Response in Cervical Cancer Therapy.

A new study published in the British Journal of Cancer hypothesized that changes in serum squamous cell carcinoma antigen (SCCA) during definitive chemoradiation therapy (CRT) predicts treatment response; and that SCCA1 (SERPINB3) mediates radiation resistance. This study included patients treated with definitive CRT for cervical squamous carcinoma with measured serum SCCA. The results showed that persistently elevated serum SCCA during definitive CRT was an independent predictor of positive post-

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

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JOURNAL SCAN 18 therapy F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT), recurrence, and mortality. An SCCA1-expressing vector increased radioresistance while SCCA knock out increased radiosensitivity of cervical tumor cell lines in vitro. From the findings, it was inferred that an early response assessment with serum SCCA is a powerful prognostic tool. It was suggested that an escalation of therapy in patients with elevated or sustained serum SCCA and molecular targeting of SCCA1 should be considered.

Circulating B-type Natriuretic Peptide in Women with and without Recent Gestational Diabetes A new study published in Clinical Endocrinology aimed to determine whether gestational glucose tolerance relates to N-terminal fragment of its prohormone (NT-proBNP) in the years after delivery. Here, 340 women underwent a glucose challenge test (GCT) and an oral glucose tolerance test (OGTT) in pregnancy, yielding 4 gestational glucose tolerance groups: GDM (n = 105); gestational impaired glucose tolerance (n = 59); abnormal GCT with a normal OGTT (n = 98); and normal GCT with normal OGTT (n = 75).

At 3-years postpartum, they underwent cardiometabolic characterization (including measurement of estimated glomerular filtration rate (eGFR), adiponectin, and NT-proBNP); and the OGTT was repeated which revealed 69 women with glucose intolerance (prediabetes/diabetes). It was observed that at 3-years postpartum, serum NT-proBNP did not differ between the four original gestational glucose tolerance groups, but progressively decreased across current glucose tolerance strata, from normal to prediabetes to diabetes. NT-proBNP was found to be a negative predictor of pre-diabetes/diabetes. On the other hand, the significant association of NT-proBNP with

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current glucose intolerance was ultimately attenuated in a fully-adjusted model, exhibiting two independent determinants of NT-proBNP: eGFR. Hence, it was inferred that serum NT-proBNP relates to current glucose intolerance, rather than preceding gestational dysglycemia. Therefore, it was stated that the diabetic (rather than vascular) risk implications of NT-proBNP predominate in young women.

Hyperinsulinemia-induced PAX6 Expression Promotes Endometrial Epithelial Cell Proliferation A new article published in Biomedicine & Pharmacotherapy reported a key role for the transcription factor â&#x20AC;&#x201C; PAX6, in the modulation of polycystic ovarian syndrome (PCOS)-induced endometrial epithelial proliferation. This article elaborated that PAX6 was significantly induced in the endometrial tissues from PCOS patients and this induction, regulated upstream by high levels of insulin, was closely correlated to the pathogenesis of insulin resistance (IR) in endometrial epithelial cells. Overexpression of the exogenous PAX6 potentiated the insulin-elicited accumulation of S phase in endometrial epithelial cells and thereby promoted endometrial epithelial proliferation. It was demonstrated that on using luciferase reporter and ChIP assay, PAX6 directly bound to the promoter of CDKN1B gene (the gene encoding p27 protein, a negative regulator of cell cycle) and inhibited CDKN1B transcription in the insulin-stimulated endometrial epithelial cells. Thus, it was concluded that excessive PAX6 expression in insulin-challenged endometrial epithelial cells may contribute to the uncontrollable endometrial epithelial proliferation. The findings conferred a mechanistic explanation for the functional link between hyperinsulinemia and p27 loss in the pathogenesis of endometrial epithelial hyperplasia in PCOS patients.

Asian Journal of Obstetrics and Gynaecology Practice, Vol. 1, No. 3, July-September 2017

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Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato 5-hydroxytryptamine and their role in respiratory and cardiovascular reflexes.

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