Ajog jan mar 2015

Volume 1, Number 4, 2015

With Best Compliments from

Asian Journal of

Online Submission

Volume 1, Number 4, 2015

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 Padma Shri, Dr BC Roy & National Science Communication Awardee Dr KK Aggarwal Group Editor-in-Chief 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)

Contents from the issue editor

Women above 65 to take extra care of Their Health Dr Alka Kriplani

FROM THE DESK OF the GROUP EDITOR-IN-CHIEF

Women Should Quit Smoking to Lower Their Risk of Heart Disease 6 Dr KK Aggarwal

REVIEW ARTICLE

Health Maintenance in Women Margaret Riley, Margaret Dobson, Elizabeth Jones, Nell Kirst

Subclinical Hypothyroidism During Pregnancy: A Clinical Review

16

Rajat Mohanty, Sudipta Patnaik, Babita Ramani

Editorial Board ENT Dr Jasveer Singh

Cardiology Dr Praveen Chandra Dr SK Parashar

Gastroenterology Dr Ajay Kumar

Diabetology Dr CR Anand Moses Dr Sidhartha Das Dr A Ramachandran Dr Samith A Shetty

7

Dr Garima Kachhawa

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

Paediatrics Dr Swati Y Bhave

5

Dentistry Dr KMK Masthan Dr Rajesh Chandna

Dermatology Dr Hasmukh J Shroff Neurology Dr V Nagarajan Journal of Applied Medicine and Surgery Dr SM Rajendran Dr Jayakar Thomas

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

CLINICAL STUDY

Detection of Fetal Malnutrition by Clinical Assessment of Nutritional Status Score at Birth and Its Comparison with Other Methods of Determining Intrauterine Growth

22

Vikram Singhal, Prashant Agal, Nutan Kamath

Iron folic acid intake among pregnant women in PHC Anumanthai of Villupuram, Tamil Nadu 27 Kumar S, Sitanshu Sekhar Kar, Sonali Sarkar, Ganesh Kumar S

Progesterone and Prevention of Preterm Labor Ruchika Garg, Urvashi Verma, Rajni Rawat, Somya shrivastava, Renu Rajvanshi

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Asian Journal of Volume 1, Number 4, 2015

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

Secondary Abdominal Pregnancy Following Rupture of Rudimentary Horn 32

Printed at Crystal Offset, Chennai

Vishwakarma Kshama, Shukla P, Yadav K

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JOURNAL SCAN

Research Review

36

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from the issue editor

Women above 65 Should take extra care of Their Health

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

• Women aged 65 and above should take low dose aspirin routinely to prevent heart attack and paralysis.

• All women are urged to exercise a minimum of 30 minutes/day, but women who need to lose weight or maintain weight loss are now advised to engage in 60-90 minutes of moderate-intensity activity on most, or preferably all, days of the week.

• A heart-healthy diet should be rich in fruits, whole grains and fiber foods with a limited intake of alcohol and sodium.

• Women aged 65 and over should consider taking low-dose aspirin on a routine basis, regardless of their risk. Aspirin has been shown to prevent both heart attacks and stroke in this age group. The upper dose of aspirin for high-risk women is 325 mg/day.

• Hormone replacement therapy, selective estrogen receptor modulators or antioxidant supplements such as vitamins C and E should be used to prevent heart disease.

• Folic acid should also not be used to prevent cardiovascular disease.

• Saturated fat should be reduced to less than 7% of calories.

• Women should eat oily fish or some other source of omega-3 fatty acids at least twice a week.

• Women at very high-risk for heart disease should try to lower their low-density lipoprotein ("bad") cholesterol to <70 mg/dL.

• Women should not only quit smoking but should use counseling, nicotine replacement or other forms of smoking cessation therapy.

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

5

FROM THE DESK OF the GROUP EDITOR-IN-CHIEF

Women should quit smoking to lower their risk of heart disease

Prof. Dr KK Aggarwal

Padma Shri, Dr BC Roy & National Science Communication Awardee Sr. Physician and Cardiologist, Moolchand Medcity President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group and eMedinewS

S

moking is still the leading preventable cause of death. Not only does tobacco smoke cause lung cancer, it is also implicated in heart disease, other cancers and respiratory diseases. As per World Health Organization (WHO), an estimated 3 million people in industrialized countries will have died as a result of tobacco use by 2030, and an additional 7 million people in developing countries face the same fate.

The harms of smoking are reversible and can decline to the level of nonsmokers, as per a report in Journal of the American Medical Association.

Women who quit smoking have a 21% lower risk of dying from coronary heart disease within 5 years of quitting their last cigarette. The risk of dying from other conditions also declines after quitting, although the time frame varies depending on the disease. For chronic obstructive pulmonary disease, it may take up to 20 years. Its never too early to stop, and its never too late to stop.

6

Women who are current smokers have almost triple their risk of overall death compared with nonsmoker women. Current smokers also have a 63% increased risk for colon cancer compared with never-smokers, while former smokers have a 23% increased risk. There was no significant association between smoking and ovarian cancer.

Women who started smoking early in life are at a higher risk for overall mortality, i.e. of dying from respiratory disease and from any smoking-related disease. However, a smoker's overall risk of dying returns to the level of a never-smoker 20 years after quitting. The overall risk declines by 13% within the first 5 years of abstaining.

Most of the excess risk of dying from coronary heart disease vanishes within 5 years of quitting.

For chronic obstructive pulmonary disease, the return to normal takes 20 years, although there is an 18% reduction in the risk of death seen within 5-10 years after quitting. And the risk for lung cancer does not return to normal for 30 years after quitting, although there is a 21% reduction in risk within the first 5 years.

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

REVIEW ARTICLE

Health Maintenance in Women Margaret Riley, Margaret Dobson, Elizabeth Jones, Nell Kirst

Abstract The health maintenance examination is an opportunity to focus on disease prevention and health promotion. The patient history should include screening for tobacco use, alcohol misuse, intimate partner violence and depression. Premenopausal women should receive preconception counseling and contraception as needed, and all women planning or capable of pregnancy should take 400 to 800 mcg of folic acid per day. High-risk sexually active women should be counseled on reducing the risk of sexually transmitted infections, and screened for chlamydia, gonorrhea, and syphilis. All women should be screened for human immunodeficiency virus. Adults should be screened for obesity and elevated blood pressure. Women 20 years and older should be screened for dyslipidemia if they are at increased risk of coronary heart disease. Those with sustained blood pressure greater than 135/80 mm Hg should be screened for type 2 diabetes mellitus. Women 55 to 79 years of age should take 75 mg of aspirin per day when the benefits of stroke reduction outweigh the increased risk of gastrointestinal hemorrhage. Women should begin cervical cancer screening by Papanicolaou test at 21 years of age, and if results have been normal, screening may be discontinued at 65 years of age or after total hysterectomy. Breast cancer screening with mammography may be considered in women 40 to 49 years of age based on patients’ values and potential benefits and harms. Mammography is recommended biennially in women 50 to 74 years of age. Women should be screened for colorectal cancer from 50 to 75 years of age. Osteoporosis screening is recommended in women 65 years and older, and in younger women with a similar risk of fracture. Adults should be immunized at recommended intervals according to guidelines from the Centers for Disease Control and Prevention.

Key words: Health maintenance examination, disease prevention, health promotion, preconception counseling, sexually transmitted infections

T

he health maintenance examination is an opportunity to spend focused time with patients on disease prevention and health promotion.

There is no consensus on the optimal frequency, though most patients and physicians think that a yearly physical examination is important and necessary.1,2 One review found that an annual examination improves delivery of recommended preventive services, and may lessen patient worry.3 It is also a chance for physicians to strengthen their relationship with patients and to provide a medical home. Physicians may use this time to discuss issues such as family relationships or endof-life care.

MARGARET RILEY, MD, is an assistant professor in the Department of Fam­ily Medicine at the University of Michigan Medical School in Ann Arbor.

MARGARET DOBSON, MD, is a clinical lecturer in the Department of Fam­ily Medicine at the University of Michigan Medical School.

ELIZABETH JONES, MD, is a clinical lecturer in the Department of Family Medicine at the University of Michigan Medical School.

NELL KIRST, MD, is an academic fellow at the University of Michigan Fam­ily Medicine Residency Program in Ann Arbor.

Source: Adapted from Am Fam Physician. 2013;87(1):30-37.

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

This article reviews several evidence-based recommendations to help physicians select services that best promote health in asymptomatic women.

These recommendations come primarily from the U.S. Preventive Services Task Force (USPSTF) and are supported by the American Academy of Family Physicians (AAFP). Other professional societies may publish guidelines that agree or conflict with USPSTF recommendations; the most relevant are described here.

History During the health maintenance examination, the patient’s medical, social, and family histories should be discussed, in addition to a comprehensive review of systems to find pertinent risk factors that will guide screening and counseling recommendations.

Medications should be reconciled and allergies reviewed.

Physicians should ask all adults about tobacco use and provide cessation interventions for those who use tobacco products.4 Patients should be screened for alcohol misuse; the CAGE questionnaire and 7

Review Article AUDIT-C screening test are tools that have been validated in a primary care setting.5-7 Behavioral counseling interventions to reduce alcohol misuse should be provided to those who engage in risky or hazardous drinking.5 There is insufficient evidence to recommend routine screening for illicit drug use although physicians should be alert to suggestive signs or symptoms.8 The USPSTF has provisionally recommended that physicians screen women of childbearing age for intimate partner violence, based on evidence that effective interventions can reduce violence, abuse, and physical and mental harms.9 Women who screen positive should be provided with or referred to intervention services.9 Adults should be screened for depression when the office has support to ensure accurate diagnosis, effec­tive treatment, and follow-up through care coordina­tion, case management, or mental health treatment.10 Asking patients “Over the past two weeks, have you felt down, depressed, or hopeless?” and “Over the past 2 weeks, have you felt little interest or pleasure in doing things?” has been found to be an effective way to screen for depression. An affirmative response to either ques­tion should prompt further evaluation for depression.11 Family Planning Premenopausal women should be asked about their reproductive plans. If the patient does not currently want to get pregnant, options for contraception should be reviewed. For those who are attempting to conceive, medical history, family history, weight, nutrition, immu­ nization status, environmental exposures, sexually trans­ mitted infection (STI) risk, and substance use should be reviewed and appropriate counseling provided.12,13 To reduce the incidence of neural tube defects, all women planning or capable of pregnancy should take a folic acid supplement of 400 to 800 mcg per day.14 Physicians may choose to counsel women on expectations of perimeno­ pause and menopause, when relevant.

Sexually Transmitted Infections High-risk sexually active adults include those with multiple partners, those who have an STI or have had one within the past year, and those in a nonmonogamous rela­tionship living in an area with a high rate of STIs. These patients should receive intensive behavioral counseling (more than 30 minutes in one session 8

or delivered in multiple sessions in a health care or community setting) focused on abstinence, condom use, limiting the number of sex partners, modification of sexual practices, and vac­cination to reduce transmission of STIs.15,16 According to the USPSTF, high-risk women should be screened at least annually for chlamydia, gonorrhea, and syphilis, and all sexually active women 24 years and younger should be screened annually for chlamydia.17-19 The USPSTF and Centers for Disease Control and Prevention (CDC) rec­ommend screening all adolescents and adults through 65 years of age for human immunodeficiency virus.20,21 Coronary Heart Disease Heart disease is the leading cause of death in U.S. women.22 In addition to a review of medical and family history and tobacco use status, adults should receive targeted screen­ ing for other coronary heart disease (CHD) risk factors, including overweight or obesity, hypertension, dyslipid­ emia, and diabetes mellitus.

In adults without preexisting cardiovascular disease or risk factors, medium- to high-intensity behavioral counseling to promote a healthful diet and physical activity for cardiovascular disease pre­ vention has demonstrated only a small health benefit.23 Therefore, the USPSTF advises physicians to consider selective rather than routine counseling, depending on other health care and preventive service priorities.23 Overweight and obesity

The disease burden associated with obesity has grown in proportion to the increasing weight of the U.S. popula­ tion; in 2009 to 2010, approximately onethird of U.S. adults were obese.24 Elevated body mass index (BMI) is a marker of unhealthy weight, and all adults should be screened for elevated BMI. A BMI between 25 and 29.9 kg per m2 is defined as overweight, and a BMI of 30 kg per m2 or greater indicates obesity.25 A BMI calculator is available at http://www.nhlbisupport.com/bmi/.26 The USPSTF recommends that physicians refer patients who are obese to intensive, multicomponent behavioral interventions. Components of such interventions include setting weight-loss goals, improving diet or nutrition, participating in physical activity sessions, addressing barriers to change, actively self-monitoring, and strat­egizing how to maintain lifestyle changes.25 Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

Review Article Hypertension

The risks of uncontrolled hypertension include prema­ ture death, heart attack, renal insufficiency and stroke.

The USPSTF recommends screening for elevated blood pressure (greater than 140/90 mm Hg) in all adults 18 years and older.27 The Seventh Report of the Joint National Committee on Prevention, Detection, Evalua­ tion, and Treatment of High Blood Pressure recommends screening every other year in adults with normal blood pressure (less than 120/80 mm Hg) and yearly in those with prehypertension (systolic of 120 to 139 mm Hg; dia­stolic of 81 to 90 mm Hg).28 Dyslipidemia

Dyslipidemias, including high levels of low-density lipo­protein cholesterol and low levels of high-density lipopro­tein cholesterol, are known risk factors for CHD. There is evidence that lipid-lowering therapy reduces the risk of developing CHD, though there is ongoing debate on the benefit of primary prevention.29-31 The AAFP and USPSTF recommend screening women 20 years and older for dyslipidemia only if they are at increased risk of CHD.32,33 Screening guidelines from the USPSTF and AAFP, and from the National Cholesterol Education Pro­ gram, Adult Treatment Panel III are outlined in Table 1.31-33 Type 2 diabetes

An estimated 13.3 percent of women older than 20 years have type 2 diabetes, and the prevalence

is increasing.34,35 More than one-third of these women are undiagnosed.35 However, the benefit of screening and treating asymp­tomatic women remains controversial. The USPSTF rec­ommends screening for type 2 diabetes in asymptomatic adults with sustained blood pressure greater than 135/80 mm Hg (treated or untreated), but found insufficient evidence to support routine screening for asymptom­atic adults with a blood pressure below this level.36 The American Diabetes Association recommends screening in persons at risk of type 2 diabetes.37 Recommendations from both organizations are summarized in Table 2.36,37 Screening tests include A1C level, fasting plasma glucose level, and 2-hour 75-g oral glucose tolerance test.37 Stroke Prevention The USPSTF recommends that women 55 to 79 years of age take approximately 75 mg of aspirin per day when the net benefit of ischemic stroke reduction outweighs the increased risk of gastrointestinal hemorrhage.38 A tool to help to determine an individual’s risk of stroke is available at http://www.westernstroke.org/ PersonalStrokeRisk1.xls.

Cancer Screening Cancer is the second leading cause of death in the United States, accounting for nearly one in every four deaths.39 For select cancers, screening can lead to early diagno­sis and the greatest chance of survival. Screening for average-risk women is outlined here. Women who have a family history of cancer or other risk factors (i.e.,

Table 1. Summary of Dyslipidemia Screening Guidelines for Women Organization

When to screen

Frequency

Additional information

AAFP and USPSTF

Women 45 years and older if at increased risk of CHD (strongly recommended)

Optimal screening interval is unknown; a reasonable option is every five years, with longer or shorter interval based on risk factors and lipid levels

Increased risk of CHD is defined as one or more of the following risk factors:

Women 20 to 45 years of age if at increased risk of CHD No recommendation for or against routine screening in women 20 years and older if not at increased risk of CHD

Diabetes mellitus Personal history of CHD or noncoronary atherosclerosis Family history of cardiovascular disease before 50 years of age in men or 60 years of age in women Tobacco use Hypertension Obesity

NCEP–ATP III

All adults 20 years and older

Every five years

Recommend screening with a fasting lipoprotein profile

AAFP = American Academy of Family Physicians; CHD = Coronary heart disease; NCEP–ATP III = National Cholesterol Education Program, Adult Treat­ment Panel III; USPSTF = U.S. Preventive Services Task Force.

Information from references 31 through 33.

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

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Review Article Table 2. Summary of Type 2 Diabetes Mellitus Screening Guidelines for Women Organization When to screen

Frequency

ADA

If results are normal, repeat screening in three years

All adults beginning at 45 years of age All adults with body mass index ≥ 25 kg per m2 and one of the following additional risk factors: Physical inactivity First-degree relative with diabetes High-risk race or ethnicity (black, Hispanic, Native American, Asian American, Pacific Islander) Delivering a baby weighing > 9 lb (4.05 kg) or a history of gestational diabetes Hypertension (blood pressure > 140/90 mm Hg or being treated for hypertension)

Repeat screening yearly for those with prediabetes Consider more frequent screening depending on risk status

High-density lipoprotein cholesterol level < 35 mg per dL (0.91 mmol per L) or triglyceride level > 150 mg per dL (1.69 mmol per L) Polycystic ovary syndrome A1C level > 5.7 percent, impaired glucose tolerance, or impaired fasting glucose on previous testing Other clinical conditions associated with insulin resistance (severe obesity, acanthosis nigricans) History of cardiovascular disease USPSTF

Asymptomatic adults with sustained blood pressure (treated or untreated) > 135/80 mmHg Insufficient evidence to recommend for or against screening adults with blood pressure ≤ 135/80 mm Hg

Optimal screening interval is unknown

ADA = American Diabetes Association; USPSTF = U.S. Preventive Services Task Force.

Information from references 36 and 37.

a history of high-dose chest radiation, diethylstilbestrol exposure in utero, or immunosuppression) may require different screening paradigms.

Cervical cancer

Incidence and mortality rates of cervical cancer have decreased because of prevention and screening with Papanicolaou (Pap) tests.39 Women should be screened for cervical cancer with Pap tests beginning at 21 years of age. Low-risk women should receive Pap testing every three years. Co-testing for human papillomavirus is an option beginning at 30 years of age, and can extend the screening interval to five years. Cervical cancer screening should be discontinued at 65 years of age or after total hysterectomy if the woman has a benign gynecologic his­tory.40,41 Table 3 summarizes clinical recommendations for cervical cancer screening.40-43 Breast cancer

Breast cancer is the second most commonly diagnosed cancer in women.39 Small tumors confined to the breast are more likely to be successfully treated.

10

In women 40 to 49 years of age, the USPSTF recommends shared deci­sion making about whether to start mammography, tak­ing into account patients’ values and potential benefits and harms. Compared with older women, screening women 40 to 49 years of age results in a lower absolute reduction in breast cancer mortality and higher rates of false-positive results.44 The USPSTF and AAFP recom­mend routine biennial screening beginning at 50 years of age with discontinuation at 75 years of age.44,45 The American College of Obstetricians and Gynecologists (ACOG) and the American Cancer Society recommend annual screening beginning at 40 years of age without a specific discontinuation age.46,47 In contrast to ACOG’s recommendations, the USPSTF has found insufficient evidence to assess the benefits and harms of clinical breast examination, and recommends against teaching breast self-examination.44,46 eTable A summarizes clini­cal recommendations for breast cancer screening.

Colorectal cancer

Colorectal cancer mortality rates have decreased in the past 20 years, likely secondary to improved screen­ing and Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

Review Article Table 3. Summary of Cervical Cancer Screening Guidelines for Average-risk Women Organization

When to begin Frequency

AAFP, ACOG, ACS/ 21 years of age Every three years with cytology alone ASCCP/ ASCP and for women 21 to 29 years of age USPSTF Every three years with cytology alone or every five years if combined with HPV testing in women 30 to 65 years of age

When to discontinue

Co-testing for HPV

After total hysterectomy for benign indication and no history of CIN 2 or 3 or cervical cancer

Appropriate for women 30 to 65 years of age; if Pap and HPV test results are negative, wait at least five years to rescreen

After 65 years of age with adequate prior screening*

AAFP = American Academy of Family Physicians; ACOG = American College of Obstetricians and Gynecologists; ACS/ASCCP/ASCP = American Cancer Society/American Society for Colposcopy and Cervical Pathology/American Society for Clinical Pathology; CIN 2 or 3 = cervical intraepithelial neoplasia grade 2 or 3; HPV = human papillomavirus; Pap = Papanicolaou; USPSTF = U.S. Preventive Services Task Force. *The USPSTF, ACOG, and the ACS/ASCCP/ASCP agree on the definition of adequate prior screening as three consecutive negative cytology results or two consecutive negative HPV results within 10 years before cessation of screening, with the most recent test occurring within the past five years. They also state that routine screening should continue for at least 20 years after spontaneous regression or appropriate management of a high-grade precancerous lesion (CIN 2 or 3), even if this extends screening past 65 years of age.

Information from references 40 through 43.

eTable A. Summary of Breast Cancer Screening Guidelines for Average-Risk Women Organization

Mammography When to begin

Frequency

When to discontinue

Clinical breast examination

Breast selfexamination

USPSTF

50 years of age; consider Biennially at 40 to 49 years of age based on discussion of values, benefits, and harms

Insufficient evidence to recommend for or against screening in women 75 years and older

Insufficient evidence Recommend to recommend for or against against

ACOG

40 years of age

No recommendation; consider medical comorbidity and life expectancy when screening women 75 years and older

Every one to three years for women 20 to 39 years of age

AAFP and

ACS

40 years of age

Yearly

Yearly

Yearly for women 40 years and older

Continue as long as the patient Every three years is in good health for women 20 to 39 years of age

Encourage breast self-awareness, which can include self- examination Optional, starting at 20 years of age

Yearly for women 40 years and older AAFP = American Academy of Family Physicians; ACOG = American College of Obstetricians and Gynecologists; ACS = American Cancer Society; USPSTF = U.S. Preventive Services Task Force.

Information from: American Academy of Family Physicians. Clinical preventive services. Breast cancer. 2009. http://www.aafp.org/online/en/home/clinical/ exam/breast cancer.html. Accessed February 7, 2012.

U.S. Preventive Services Task Force. Screening for breast cancer. November 2009. http://www.uspreventiveservicestaskforce.org/uspstf/uspsbrca. htm.

Accessed January 12, 2012.

American College of Obstetricians-Gynecologists. Practice bulletin no. 122: Breast cancer screening. Obstet Gynecol. 2011;118(2 pt (1):372-382.

American Cancer Society. Breast cancer: early detection. 2011. http://www.cancer.org/Cancer/BreastCancer/MoreInformation/BreastCancer EarlyDetection/ breast-cancer-early-detection-toc. Accessed January 11, 2012.

treatment options. Adults 50 to 75 years of age should undergo screening. Per USPSTF recommenda­tions, fecal occult blood test (annually), sigmoidoscopy (every five years) plus fecal occult blood test (every three years), and colonoscopy (every 10 years) are acceptable methods of screening.48,49 Because each method entails different risks, benefits, costs, and availability, the choice should be based on patient preference. When any other initial screening result is positive, colonoscopy is the next recommended Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

step in evaluation. Of note, digital rectal examination is not recommended for colorectal cancer screening. Table 4 summarizes clinical recommendations for colorectal cancer screening.48-51 Ovarian cancer

Routine screening for ovarian cancer with bimanual examination, transvaginal ultrasonography, or cancer antigen 125 testing is not recommended.

11

Review Article It does not reduce ovarian cancer mortality and leads to complications from diagnostic evaluation of false-positive results.52,53 Osteoporosis Screening and Prevention In 2010, osteoporosis and osteopenia affected an esti­ mated 35 million women older than 50 years. This number is expected to increase to 41 million by 2020.54 Screening with dual energy x-ray absorptiometry (DEXA) is recommended for women 65 years and older. Additionally, the USPSTF recommends using the World Health Organization’s Fracture Risk Assessment Tool to risk-stratify women younger than 65 years. Screening younger women is recommended if the risk of fracture is greater than or equal to that of a 65-year-old white woman without additional risk factors (9.3 percent over 10 years).55,56 ACOG

also recommends that the decision to screen women younger than 65 years be based on spe­cific risk factor assessment.57 Table 5 summarizes recom­mendations for osteoporosis screening.55-57 A 2011 meta-analysis conducted for the USPSTF found that calcium and vitamin D supplements may reduce fracture risk in older adults.58 However, a 2012 USPSTF draft recommendation statement concluded that the current evidence is insufficient to assess the risks and benefits of calcium and vitamin D supplementation for prevention of fracture in premenopausal and noninsti­tutionalized postmenopausal women.59 Formal recom­ mendation is forthcoming. The National Institutes of Health recommends a total daily intake of 1,000 mg of calcium for women 19 to 50 years of age and 1,200 mg for women older than 50 years, in addition to 600 to 800 IU of vitamin D.60,61 ACOG

Table 4. Summary of Colorectal Cancer Screening Guidelines for Average-risk Women Organization

When to begin

Frequency for screening options

When to discontinue

AAFP and USPSTF

50 years of age

FOBT* annually

Routinely at 75 years of age (certain persons 76 to 85 years of age may warrant screening)

Sigmoidoscopy every five years, with FOBT* every three years Colonoscopy every 10 years

No screening after 85 years of age

Insufficient evidence to recommend for or against CT colonography or fecal DNA testing† ACG

50 years of age (45 years of age in blacks)

Preferred:

No recommendation

Colonoscopy every 10 years Alternatives: Hemoccult SENSA (high-sensitivity FOBT) annually Fecal DNA every three years† CT colonography every five years Flexible sigmoidoscopy every five to 10 years

ACS

50 years of age

Fecal immunochemical test annually

No recommendation

FOBT* annually CT colonography every five years Double-contrast barium enema every five years Sigmoidoscopy every five years Colonoscopy every 10 years Fecal DNA testing,† interval uncertain AAFP = American Academy of Family Physicians; ACG = American College of Gastroenterology; ACS = American Cancer Society; CT = computed tomography; FOBT = fecal occult blood test; USPSTF = U.S. Preventive Services Task Force. *FOBT requires multiple samples. † Per updated ACS recommendations, fecal DNA testing is no longer available in the United States.

Information from references 48 through 51.

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Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

Review Article Table 5. Summary of Osteoporosis Screening Guidelines for Women Organization

When to begin

Frequency

Additional information

AAFP and USPSTF

65 years of age

No recommendation on screening interval

Fracture risk calculated using World Health Organization’s Fracture Risk Assessment Tool at http://www.shef.ac.uk/FRAX/

ACOG

Postmenopausal women 65 years of age

In the absence of new risk factors, screening interval should be no less than every two years

Risk factors: previous fracture, family history of osteoporosis, white race, dementia, poor nutrition, smoking, low weight and body mass index, estrogen deficiency, early menopause (younger than 45 years), prolonged premenopausal amenorrhea (more than one year), long-term low calcium intake, alcoholism, impaired eyesight despite adequate correction, history of falls, inadequate physical activity

Women younger than 65 years with fracture risk ≥ that of a 65-year-old white woman with no additional risk factors (9.3 percent over 10 years)

Women younger than 65 years with one or more risk factors for osteoporosis Postmenopausal women with fracture (to confirm diagnosis of osteoporosis and assess severity)

AAFP = American Academy of Family Physicians; ACOG = American College of Obstetricians and Gynecologists; USPSTF = U.S. Preventive Services Task Force.

Information from references 55 through 57.

recommends counseling women on other modifiable osteoporosis risk factors, including regular weightbearing and muscle-strengthening exer­cises, smoking cessation, moderation of alcohol intake, and fallprevention strategies.57 Immunizations The AAFP recommends immunizing all adults at recom­ mended intervals, unless the vaccine is contraindicated in an individual patient.62 The CDC’s Advisory Com­ mittee on Immunization Practices releases yearly recom­mendations for adult immunizations, which are available at http://www.cdc.gov/vaccines/schedules/ easy-to-read/ adult.html.63 The CDC’s annual updates to the immuniza­ tion schedule will be published February 1, 2013. Immuni­ zation status should be reviewed at the health maintenance examination and at visits for routine medical care.

disease in adults and pregnant women. April 2009. http:// www.uspreventiveservicestaskforce.org/ uspstf/uspstbac2.htm.

Accessed January 3, 2012.

5. U.S. Preventive Services Task Force. Screening and behavioral coun­seling interventions in primary care to reduce alcohol misuse. http:// www.uspreventiveservicestaskforce.org/uspstf/ uspsdrin.htm. Accessed December 5, 2012.

6. Ewing JA. Detecting alcoholism. The CAGE questionnaire.

JAMA. 1984;252(14):1905-1907.

7. Bradley KA, Boyd-Wickizer J, Powell SH, Burman ML. Alcohol screening questionnaires in women: a critical review.

JAMA. 1998;280(2):166-171.

8. U.S. Preventive Services Task Force. Screening for illicit drug use. January 2008. http://www.uspreventiveservicestaskforce. org/uspstf/uspsdrug. htm. Accessed January 3, 2012.

9. Nelson HD, Bougatsos C, Blazina I. Screening women for intimate part­ner violence: a systematic review to update the U.S. Preventive Services Task Force recommendation. Ann Intern Med. 2012;156(1):796-808.

References

10. U.S. Preventive Services Task Force. Screening for depression in adults. December 2009. http://www. uspreventiveservicestaskforce.org/uspstf/uspsaddepr.htm.

Accessed January 3, 2012.

1. Oboler SK, et al. Public expectations and attitudes for annual physical examinations and testing. Ann Intern Med. 2002;136(9):652-659.

11. Whooley MA, et al. Case-finding instruments for depression.

Two ques­ tions are as good as many. J Gen Intern Med. 1997;12(7):439-445.

2. Prochazka AV, Lundahl K, Pearson W, Oboler SK, Anderson RJ. Support of evidence-based guidelines for the annual physical examination: a survey of primary care providers. Arch Intern Med. 2005;165(12):1347-1352.

12. Centers for Disease Control and Prevention. Clinical care for women: health promotion. Family planning and reproductive life plan. May 2012. http://www.cdc.gov/preconception/ careforwomen/promotion. html. Accessed June 4, 2012.

3. Boulware LE, et al. Systematic review: the value of the periodic health evaluation. Ann Intern Med. 2007; 146(4):289-300.

13. Atrash H, Jack BW, Johnson K. Preconception care: a 2008 update. Curr Opin Obstet Gynecol. 2008;20(6):581-589.

4. U.S. Preventive Services Task Force. Counseling and interventions to pre­ vent tobacco use and tobacco-caused

14. U.S. Preventive Services Task Force. Folic acid for the prevention of neu­ ral tube defects. May 2009. http://

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Review Article www.uspreventiveservicestaskforce.org/uspstf09/folicacid/ folicacidrs.htm. Accessed February 7, 2012.

15. U.S. Preventive Services Task Force. Behavioral counseling to prevent sexually transmitted infections. October 2008. http:// www.uspreven tiveservicestaskforce.org/uspstf08/sti/stirs.htm.

Accessed February 7, 2012.

16. Centers for Disease Control and Prevention. Sexually transmitted dis­ eases treatment guidelines, 2010. Clinical prevention guidance. January 2011. http://www.cdc.gov/std/ treatment/2010/clinical.htm. Accessed June 6, 2012.

17. U.S. Preventive Services Task Force. Screening for chlamydial infec­tion. June 2007. http://www.uspreventiveservicestaskforce. org/uspstf/ uspschlm.htm. Accessed February 7, 2012.

18. U.S. Preventive Services Task Force. Screening for gonorrhea.

May 2005. http://www.uspreventiveservicestaskforce.org/ uspstf/uspsgono.htm. Accessed February 7, 2012.

19. U.S. Preventive Services Task Force. Screening for syphilis. July 2004. http://www.uspreventiveservicestaskforce.org/uspstf/ uspssyph.htm. Accessed February 7, 2012.

20. U.S. Preventive Services Task Force. Screening for HIV. http:// www. uspreventiveservicestaskforce.org/uspstf/uspshivi.htm.

Accessed Feb­ruary 7, 2012.

21. Branson BM, Handsfield HH, Lampe MA, et al.; Centers for Disease Control and Prevention (CDC). Revised recommendations for HIV test­ing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006;55(RR-14):1-17.

22. Roger VL, Go AS, Lloyd-Jones DM, et al.; American Heart Associa­ tion Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2012 update: a report from the Ameri­can Heart Association [published correction appears in Circulation. 2012;125(22):e1002].

Circulation. 2012;125(1):e2-e220.

23. U.S. Preventive Services Task Force. Behavioral counseling to promote a healthful diet and physical activity for cardiovascular disease prevention in adults. June 2012. http:// www.uspreventiveservicestaskforce.org/uspstf/uspsphys.htm.

Accessed October 22, 2012.

24. Centers for Disease Control and Prevention. Overweight and obesity. Adult obesity facts. August 2012. http://www.cdc.gov/ obesity/data/ adult.html. Accessed October 22, 2012.

25. U.S. Preventive Services Task Force. Screening for and management of obesity in adults. June 2012. http://www. uspreventiveservicestaskforce.org/uspstf/uspsobes.htm.

Accessed October 22, 2012.

26. National Heart Lung and Blood Institute. Calculate your body mass index. http://www.nhlbisupport.com/bmi/. Accessed February 3, 2012.

27. U.S. Preventive Services Task Force. Screening for high blood pressure in adults. December 2007. http://www. uspreventiveservicestaskforce.org/uspstf/uspshype.htm.

Accessed February 3, 2012.

28. Chobanian AV, Bakris GL, Black HR, et al.; National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coor­ dinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pres­sure.

Hypertension. 2003;42(6):1206-1252.

14

29. Pignone M, Phillips C, Mulrow C. Use of lipid lowering drugs for primary prevention of coronary heart disease: meta-analysis of randomised tri­als. BMJ. 2000;321(7267):983-986.

30. Taylor F, et al. Statins for the primary prevention of cardiovascular dis­ease. Cochrane Database Syst Rev. 2011;(1): CD004816.

31. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143-3421.

32. U.S. Preventive Services Task Force. Screening for lipid disorders in adults. June 2008. http://www.uspreventiveservicestaskforce. org/ uspstf/uspschol.htm. Accessed February 7, 2012.

33. American Academy of Family Physicians. Guide to clinical preventive services. Lipid disorders. 2008. http://www.aafp. org/online/en/home/clinical/exam/lipiddisorders.html.

Accessed February 7, 2012.

34. Cowie CC, et al. Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population: National Health And Nutrition Examina­ tion Survey 1999-2002. Diabetes Care.

2006;29(6):1263-1268.

35. Cowie CC, Rust KF, Ford ES, et al. Full accounting of diabetes and pre-diabetes in the U.S. population in 1988-1994 and 2005-2006 [published correction appears in Diabetes Care.

2011;34(10):2338.]. Diabetes Care. 2009;32(2):287-294.

36. U.S. Preventive Services Task Force. Screening for type 2 diabetes mel­ litus in adults. June 2008. http://www. uspreventiveservicestaskforce.org/uspstf/uspsdiab.htm.

Accessed February 7, 2012.

37. American Diabetes Association. Standards of medical care in diabe­tes—2012. Diabetes Care. 2012;35(suppl (1):S11-S63.

38. U.S. Preventive Services Task Force. Aspirin for the prevention of car­ diovascular disease. March 2009. http:// www.uspreventiveservicestaskforce.org/uspstf/uspsasmi.htm.

Accessed February 7, 2012.

39. American Cancer Society. Cancer Facts & Figures 2011.

Atlanta, Ga.: American Cancer Society; 2011. http://www. cancer.org/acs/groups/content/@epidemiologysurveilance/ documents/document/acspc-029771.pdf. Accessed February 3, 2012.

40. U.S. Preventive Services Task Force. Screening for cervical cancer. March 2012. http://www.uspreventiveservicestaskforce. org/uspstf/uspscerv. htm. Accessed May 22, 2012.

41. American Academy of Family Physicians. Clinical preventive services. Cervical cancer. 2012. http://www.aafp.org/online/ en/home/clinical/exam/cervicalcancer.html. Accessed May 22, 2012.

42. Screening for cervical cancer. Obstet Gynecol. 2012;120(5): 1222-1238.

43. Saslow D, et al. American Cancer Society, American Society for Col­poscopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin.

2012;62(3):147-172.

44. U.S. Preventive Services Task Force. Screening for breast cancer.

Novem­ ber 2009. http://www.uspreventiveservicestaskforce. org/uspstf/uspsbrca.htm. Accessed January 12, 2012.

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

Review Article 45. American Academy of Family Physicians. Clinical preventive services. Breast cancer. 2009. http://www.aafp.org/online/ en/home/clinical/exam/breastcancer.html. Accessed February 7, 2012.

46. American College of Obstetricians-Gynecologists. Practice bulletin no. 122: Breast cancer screening. Obstet Gynecol.

2011;118(2 pt 1):372-382.

47. American Cancer Society. Breast cancer: early detection. 2011. h t t p : / / w w w. c a n c e r . o r g / C a n c e r / B r e a s t C a n c e r MoreInformation/BreastCancerEarlyDetection/breast-cancerearly-detection-toc. Accessed January 11, 2012.

48. U.S. Preventive Services Task Force. Screening for colorectal cancer. October 2008. http://www.uspreventiveservicestaskforce. org/uspstf/uspscolo.htm. Accessed January 19, 2012.

49. American Academy of Family Physicians. Clinical preventive services. Colorectal cancer. http://www.aafp.org/online/en/home/ clinical/exam/colorectalcancer.html. Accessed January 19, 2012.

50. American Cancer Society. Colorectal cancer early detection.

2012. http://www.cancer.org/Cancer/ColonandRectumCancer/ MoreInformation/ColonandRectumCancerEarlyDetection/ colorectal-cancer-early-detection-acs-recommendations.

Accessed October 22, 2012.

51. Rex DK, et al. American College of Gastroenterology guidelines for colorectal cancer screening 2009 [corrected] [published correction appears in Am J Gastroenterol. 2009; 104(6):1613]. Am J Gastroenterol. 2009;104(3):739-750.

52. U.S. Preventive Services Task Force. Screening for ovarian cancer.

Sep­ tember 2012. http://www.uspreventiveservicestaskforce. org/uspstf/uspsovar.htm. Accessed October 22, 2012.

53. Buys SS, Partridge E, Black A, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011;305(22): 2295-2303.

54. U.S. Department of Health and Human Services. Bone Health and Osteoporosis. A Report of the Surgeon General. Rockville, Md.: U.S. Department of Health and Human Services, Office of the Surgeon Gen­eral; 2004.

55. U.S. Preventive Services Task Force. Screening for osteoporosis.

January 2011. http://www.uspreventiveservicestaskforce.org/ uspstf/uspsoste. htm. Accessed February 7, 2012.

56. American Academy of Family Physicians. Clinical preventive services. Osteoporosis. 2011. http://www.aafp.org/online/en/ home/clinical/exam/osteoporosis.html. Accessed February 7, 2012.

57. American College of Obstetricians and Gynecologists, Women’s Health Care Physicians. ACOG practice bulletin.

Clinical management guide­lines for obstetrician-gynecologists.

Number 50, January 2003. Obstet Gynecol. 2004;103(1): 203-216.

58. Chung M, et al. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med. 2011;155(12):827-838.

59. U.S. Preventive Services Task Force. Vitamin D and calcium supplemen­tation to prevent cancer and osteoporotic fractures. http://www.uspreventiveservicestaskforce.org/uspstf/uspsvitd. htm. Accessed December 5, 2012.

60. National Institutes of Health. Office of Dietary Supplements.

Dietary supplement fact sheet: calcium. 2010. http://ods. od.nih.gov/factsheets/Calcium-HealthProfessional/. Accessed October 22, 2012.

61. National Institutes of Health. Office of Dietary Supplements.

Dietary sup­plement fact sheet: vitamin D. 2011. http://ods. od.nih.gov/factsheets/VitaminD-HealthProfessional/. Accessed February 15, 2012.

62. American Academy of Family Physicians. Clinical preventive services. Immunizations. 2010. http://www.aafp.org/online/ en/home/clinical/exam/immunizations.html. Accessed January 16, 2012.

63. Centers for Disease Control and Prevention. Immunization schedules. http://www.cdc.gov/vaccines/schedules/index.html.

Accessed February 13, 2012.

Complementary Therapy in Polycystic Ovary Syndrome Polycystic ovary syndrome (PCOS) is an endocrine disease. PCOS afflicts 5 to 10% of women of reproductive age. The symptoms are: amenorrhea, oligomenorrhea, hirsutism, obesity, infertility, chronic hyperandrogenic anovulation and acne. Other risk factors aggravate this condition: insulin resistance, obesity, hypertension, dyslipidemia, inflammation and subclinical cardiovascular disease. Anxiety, depression and reduced quality-of- life are also common. This review highlights the mechanisms and the beneficial effects of acupuncture, exercise and resveratrol on animal models and on humans affected by PCOS. PCOS is an endocrine disease. PCOS afflicts 5 to 10% of women of reproductive age. The symptoms are: amenorrhea, oligomenorrhea, hirsutism, obesity, infertility, chronic hyperandrogenic anovulation and acne. Other risk factors aggravate this condition: insulin resistance, obesity, hypertension, dyslipidemia, inflammation and subclinical cardiovascular disease. Anxiety, depression and reduced quality-of-life are also common. This review highlights the mechanisms and the beneficial effects of acupuncture, exercise and resveratrol on animal models and on humans affected by PCOS. Source: Transl Med UniSa. 2014;9:56-65.

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REVIEW ARTICLE

Subclinical hypothyroidism during pregnancy: A Clinical review Rajat Mohanty*, Sudipta Patnaikt, Babita Ramaniลง

Abstract Traditionally, overt hypothyroidism cases during pregnancy have been treated due to its adverse effect on fetus as well as on mother. Evidences are now available for the need of treatment of subclinical hypothyroidism (SCH) during pregnancy. SCH is the commonest form of hypothyroidism in pregnancy and is usually due to progressive thyroid destruction due to autoimmune thyroid disease. The prevalence and incidence of SCH is found to be more in South Asia than other parts of the world. This review revealed that screening should be mandatory followed by identification of antithyroid antibody positive cases because they require treatment with oral levothyroxine.

Key words: Subclinical hypothyroidism, autoimmune thyroid disease, antithyroid antibody, levothyroxine

T

hyroid gland has an important role in brain development of fetus during pregnancy.

Subclinical hypothyroidism (SCH) is the commonest form of hypothyroidism in pregnancy.

SCH is present, when the thyroid-stimulating hormone (TSH) is high or normal but the thyroxine (T4) level is in the normal or low normal range. It is more predominant in South Asia. So, every pregnant women should be ruled out for SCH in first trimester.

Review of Literatures Interest in thyroid disease in pregnancy, especially SCH, has escalated in part because of reports suggesting that variously defined thyroid deficiency (including both overt and subclinical disease) during pregnancy results in impaired neurodevelopment in offspring.1,2 Further, other reports have associated SCH with preterm delivery, pre-eclampsia and postpartum thyroiditis.3,4 The prevalence of SCH could be anticipated to be between 2% and 5% of women screened, depending on the TSH and free T4 (FT4) level thresholds applied and this represents most women who would *Senior specialist and consultant Dept. of Obstetrics and Gynecology t Assistant Professor Dept. of Physiology SCB Medical College, Cuttack, Odisha ลง Senior Resident, Dept. of Obstetrics and Gynecology VSS Medical College Burla, Sambalpur, Odisha Address for correspondence Dr Rajat Mohanty Plot no-55, Satyanagar, Bhubaneswar, Odisha - 751 007 E-mail: sudirajat@yahoo.com

16

be identified with thyroid deficiency through routine screening.3 These complications have led some national societies as well as public interest groups to recommend routine thyroid screening during pregnancy.5 Treatment of subclinical thyroid disorders is still controversial.

This review is going to evaluate the necessity for screening of SCH during pregnancy and the diagnostic technique for confirmation. We also discuss about the requirements of treatment with levothyroxine as well as the recommendations for SCH in pregnancy provided by United State Preventive Service Task Force (USPSTF) and analyzed the gravity of the condition.

Hypothyroidism is common in pregnancy with an estimated prevalence of 2-3% and 0.3-0.5% for subclinical and overt hypothyroidism, respectively in West6 and it is dependent on the TSH and FT4 level thresholds applied, and this represents most women who would be identified with thyroid deficiency through routine screening. There are a few reports of prevalence of hypothyroidism during pregnancy from India with prevalence rates ranging from 4.8% to 11%.7,8 It is also supported by some other studies.9,10 It seems that prevalence of hypothyroidism is more in Asian countries compared with the West.

In a large Chinese study, which included 2,899 pregnant women, the prevalence of hypothyroidism was significantly higher in the high-risk group than in the non-high-risk group (10.9% vs 7.0%, p = 0.008).11 In North India, there is a high prevalence of hypothyroidism (14.3%), majority being subclinical Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

Review Article in pregnant women during first trimester as shown by Dhanwal et al (2013), necessitating routine screening.12 During pregnancy, there is a transient fall in TSH in the first trimester due to the structural homology between the TSH and human chorionic gonadotropin (hCG) molecules and their receptors, allowing hCG stimulation of the thyroid with an increase in thyroid hormone production. Thyroid hormone concentrations in blood are increased in pregnancy, partly due to the high levels of hyperestrogenic state of pregnancy and due to the weak thyroid stimulating effects of hCG that acts like TSH. Action of hCG is by cross reactivity of this hormone with TSH receptors.13 T4 levels rise from about 6-12 weeks, and peak by mid-gestation but at the same time the TSH level start decreasing.14 During pregnancy, the thyroid gland may enlarge by 10% in countries where iodine sources are sufficient, and to a greater extent in iodine-poor countries.15 Production of thyroid hormones and iodine requirement each increases by approximately 50% during pregnancy.16 Gestation specific reference ranges for thyroid function tests are not widely in use although many centers are now preparing them.17,18 Fetal T4 is wholly obtained from maternal sources in early pregnancy since the fetal thyroid gland only becomes functional in the second trimester of gestation. As T4 is essential for fetal neurodevelopment it is critical that maternal delivery of T4 to the fetus is ensured early in gestation.

In pregnancy, iodide losses through the urine and the fetoplacental unit contribute to a state of relative iodine deficiency.19 Thus, pregnant women require additional iodine intake.

Probable causes of SCH are many and chronic autoimmune thyroiditis (e.g., Hashimoto’s disease, thyroiditis) with a prevalence of 3-8% in the general population is said to be the most common cause.20 The prevalence is said to be higher in women and increases with age.20 Drugs like lithium, amiodarone, interferon-a, interleukin-2, rifampicin, sunitinib and thalidomide,21 presence of goitrogens in diet is also reported from India as probable causes;22 micronutrient deficiency such as selenium and iron deficiency may cause hypothyroidism and goiter.23 Environmental toxins such as pesticides, fluoride, heavy metals may lead to hypothyroid state. High estrogen states (in pregnancy, it causes decrease in FT4 level),24 and chronic stress - both physical as well as mental25 along Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

with other diseases like diabetes (specially type-1) are conditions affecting the pituitary or hypothalamus are some other causes.26 Women with family history of hypothyroidism or an autoimmune disease are also at increase risk of developing SCH. Radiation therapy used to treat cancers of the head and neck can cause problems with the thyroid gland.27 Thyroid surgery is more likely to develop a thyroid problem. de-Quervain’s thyroiditis is thought to be due to viral infection where there is transient hyperthyroidism followed by persistent hypothyroidism.28 Recommendations for screening: Baloch et al in 2003 found that more than 95% of rigorously screened normal euthyroid volunteers have serum TSH values between 0.4 and 2.5 mIU/L.29 Still universal screening of SCH by serum TSH, is not recommended in women with pregnancy without any evidence of fetal and maternal improvement with treatment of SCH. Serum TSH is the more accurate indication of thyroid status in pregnancy than any of the alternative (FT4, thyroid antibodies) methods, as declared by USPSTF 201130 and the gestation age for screening is 12-16 weeks of gestation. Routine screening of pregnant women after consultation by a physician has however been recommends by the American Association of Clinical Endocrinology (AACE). But, AACE recommends thyroid antibody test as the best screening test.31 It is noteworthy that controversy still remains over what is the best screening test in this situation (TSH or antibody).

Indications for screening of high-risk group includes history of thyroid dysfunction or prior thyroid surgery, age >30 years, symptoms of thyroid dysfunction or the presence of goiter, thyroid peroxidase antibody (TPOAb) positivity, type 1 diabetes or other autoimmune disorders, history of miscarriage or preterm delivery (RPL), history of head or neck radiation, family history of thyroid dysfunction, morbid obesity (body mass index [BMI] ≥40 kg/m2), use of amiodarone or lithium, or recent administration of iodinated radiologic contrast, history of infertility and residing in an area of known moderate-to-severe iodine sufficiency.

In view of the wide variation in the results of FT4 assays, method-specific and trimester-specific reference ranges of serum FT4 are required.30 17

Review Article It is very difficult to distinguish the symptoms of SCH from that of normal pregnancy as these are not always classical. There may be no signs and symptoms or mild general signs and symptoms of hypothyroidism, like depression, weight gain,32 dry or flaky skin, body weakness or feeling cold easily, slow pulse, low body temperature and increased need for sleep. Some women may experience difficulty in concentrating, irritability and anxiety with slow movement, thinking, and learning33 as well as slow circulation and heart rate.

Diagnosis can be best done by serum TSH and FT4.34 tri-iodothyronine (FT3), total T3 and T4 are to be done when there is disturbed TSH level to know the secondary reason for hypothyroidism. Next step is antithyroid antibodies31 (maternal thyroid peroxidase) should be done in all cases where serum TSH is out of range. Other least important tests includes red cell selenium, urinary T3 (recent studies show that symptoms of hypothyroidism correlate best with 24-hour urinary FT3)35 urinary iodine concentration, thyroid ultrasound, serum cholesterol, which may be elevated in hypothyroidism, prolactin as a widely available test of pituitary function, testing for anemia and basal body temperature.

These tests are important because the risk complications arising from hypothyroidism either overt or subclinical is very high. These includes a three-fold increase in risk of placental abruption and a two-fold risk of preterm delivery; reported in mothers with SCH.3 StagnaroGreen et al (2005)4 reported the higher prevalence of SCH in women with preterm delivery (before 32 weeks) compared to matched controls delivering at term. Neuromuscular symptoms and dysfunction are common in patients with SCH and can be reversed by levothyroxine treatment.36 Wilson et al37 found that the overall incidences of hypertension in pregnancy were 6.2%, 8.5% and 10.9% in the subclinical hyperthyroid, euthyroid and subclinical hypothyroid groups, respectively and were found to be significant when unadjusted (p = 0.016). After adjusting for confounding factors, there was a significant association between SCH and severe pre-eclampsia (adjusted odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1-2.4; p = 0.03). Therefore, they recommend screening in every case of severe pre-eclampsia. The risk of developing gestational diabetes increases with thyrotropin level as reported by Tudela et al.38 This 18

supports a relationship between SCH and diabetes diagnosed during pregnancy. It may progress to overt hypothyroidism in approximately 2-5% of cases annually.20 Pre-eclampsia, eclampsia and pregnancyinduced hypertension have a significantly higher incidence in SCH (15%; n = 7 of 45) compared with the incidence in the general population (7.6%).39 Neuromuscular symptoms and dysfunction.37 Postpartum thyroid dysfunction- significantly developed in presence of antithyroid antibody with a prevalence ranging from 1.1% to 16.7% with a mean of 7.5%.40 Post-partum depression can also occur but no significant difference was found.41 van der Zanden et al showed that SCH was found in 19.6% of women having history of vascular complicated pregnancy. It occurred more often when pregnancy ended before 32 weeks of gestation (p = 0.008).42 Coming to the risk to fetus; 7-point reduction in intelligence quotient in children aged 7-9 years, whose mothers had SCH at pregnancy compared with the children of euthyroid mothers shown in a study by Haddow et al.1 However, in one study,1 even when hypothyroid pregnant women were insufficiently treated with levothyroxine (LT4), the intelligence quotient (IQ) scores of their offspring were not different from those of controls. Pregnant women with SCH have higher incidence of neonatal morbidity and mortality,43 although contradictory results have also been reported.10 Two-fold risk increase in neonate intensive care nursery admission (RR 1.8; 95% CI 1.12.9%) and incidence of respiratory distress syndrome defined as ventilator assistance >24 hours.3 Thyroid hormones are regulators of the mitochondrial activity so hypothesis can be made that all the complications in SCH may be due to mitochondrial dysfunction.

It can be prevented providing a minimum of 250 Âľg iodine daily to all pregnant and lactating women (Level A-USPSTF). Preconception ingestion of 150 mg iodine daily along with preconception screening for hypothyroidism can prevent the major complications.30 The goal of treatment is to normalize maternal serum TSH values within the trimester-specific pregnancy reference range. If trimester-specific reference ranges for TSH are not available in the laboratory, the following reference ranges are recommended by USPSTF;31 first trimester (0.1-2.5 mIU/L) second trimester (0.2-3.0 mIU/L) third trimester (0.3-3.0 mIU/L).

Recent guidelines proposed by the Antithyroid Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

Review Article Association (ATA) and National Association of Clinical Biochemistry have stated that it is likely that in the future the upper limit of the serum TSH euthyroid reference range will be reduced to 2.5 mIU/L for all adults, because more than 95% of rigorously screened normal euthyroid volunteers have serum TSH values between 0.4 and 2.5 mIU/L.29 However, the American Association of Clinical Endocrinologists (AACE) and the Endocrine Society44 consensus panel have continued to recommend that 4.5 mIU/L be maintained as the upper limit of normal, reasoning that although some individuals within the range of 2.6-4.5 mIU/L may have subclinical thyroid disease, there is a lack of evidence of adverse outcome in this group.

SCH has been associated with adverse maternal and fetal outcomes. However, due to the lack of randomized controlled trials, there is insufficient evidence to recommend for or against universal LT4 treatment in thyroglobulin antibody-negative (TAb-) pregnant women with SCH (Level I-USPSTF). Women who are positive for (TPO-Ab) and have SCH should be treated with LT4. (Level B-USPSTF) 2010 Cochrane review of such potential interventions45 concluded that it may be useful to treat women with SCH that are also antithyroid antibody positive with exogenous thyroid hormone in an attempt to improve pregnancy outcomes. Surks et al44 found that the consequences of subclinical thyroid disease are minimal so they recommend against routine treatment of patients with TSH levels in these ranges. In light of the safety in pregnancy of levothyroxine (pregnancy category A drug), the AACE recommends treatment of all pregnant women, even those with SCH or positive TPO-Ab.46 Abalovich et al43 studied a group of 114 women (16-39 years old) with primary hypothyroidism; of which 51 pregnancies (34%) were conceived under hypothyroidism (16 overt and 35 SCH) and 99 pregnancies were conceived under euthyroidism, while undergoing thyroid therapy. When treatment with levothyroxine was inadequate, the outcome of pregnancy was abortion (60% vs 71.4%), premature delivery (20% vs 7.2%) and term delivery (20% vs 21.4%) in overtly hypothyroid patients and subclinically hypothyroid patients, respectively. When treatment was adequate, term delivery (100% vs 90.5%) in overtly hypothyroid and subclinically hypothyroid patients respectively; there were no abortions in any of Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

the groups. Abortions, premature and term deliveries in patients who were euthyroid on levothyroxine at the time of conception were 4%, 11.1% and 84.9%, respectively. So, they concluded that the evolution of pregnancies did not depend on whether the hypothyroidism was overt or subclinical but mainly on the treatment received. The adequate treatment of hypothyroidism during gestation minimizes risks and generally, makes it possible for pregnancies to be carried to term without complications.

Oral levothyroxine is the drug of choice as it is category A drug and has a long half-life (7 days) and is partially converted to T3 in the body, resulting in a constant physiological level of both T3 and T4 with a single daily dose. It should be started at a low-dose of 12.5-25 mg and the maintenance dose should be 2-2.4 mg/kg/day.

Treatment significantly results in higher delivery rate as shown by Velkeniers et al.47 Conclusion The prevalence of SCH in South Asia especially in India is more than in other parts of the world and mostly due to autoimmune thyroiditis and nutrition deficiency. The gravity of the complications like abortion, preterm birth, weight gain, postpartum thyroiditis and converting to overt hypothyroidism in future, outweighs the cost of screening. The child may suffer from low IQ, decreased memory and concentrating power. In this view, we propose screening of all pregnant women in the first trimester by doing serum TSH and FT4 followed by antithyroid antibody for diagnosis. It should be made mandatory, so that not a single mother will be deprived of it.

Finally, we conclude that treatment should be given to the antibody positive cases because complications are usually associated with it.

References 1. Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med 1999;341(8): 549-55.

2. Pop VJ, Kuijpens JL, van Baar AL, Verkerk G, van Son MM, de Vijlder JJ, et al. Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy. Clin Endocrinol (Oxf ) 1999;50(2):149-55.

19

Review Article 3. Casey BM, Dashe JS, Wells CE, McIntire DD, Byrd W, Leveno KJ, et al. Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol 2005;105(2):239-45.

4. Stagnaro-Green A, Chen X, Bogden JD, Davies TF, Scholl TO. The thyroid and pregnancy: a novel risk factor for very preterm delivery. Thyroid 2005;15(4):351-7.

5. Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA, McDermott MT; American Association of Clinical Endocrinologists; American Thyroid Association; Endocrine Society. Consensus Statement #1: Subclinical thyroid dysfunction: a joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and The Endocrine Society.

Thyroid 2005;15(1):24-8; response 32-3.

6. Klein RZ, Haddow JE, Faix JD, Brown RS, Hermos RJ, Pulkkinen A, et al. Prevalence of thyroid deficiency in pregnant women. Clin Endocrinol (Oxf) 1991;35(1):41-6.

7. Nambiar V, Jagtap VS, Sarathi V, Lila AR, Kamalanathan S, Bandgar TR, et al. Prevalence and impact of thyroid disorders on maternal outcome in Asian-Indian pregnant women. J Thyroid Res 2011;2011:429097.

8. Sahu MT, Das V, Mittal S, Agarwal A, Sahu M. Overt and subclinical thyroid dysfunction among Indian pregnant women and its effect on maternal and fetal outcome. Arch Gynecol Obstet 2010;281(2):215-20.

9. Stagnaro-Green A. Thyroid antibodies and miscarriage: Where are we at a generation later? J Thyroid Res 2011;2011:841949.

10. Männistö T, Vääräsmäki M, Pouta A, Hartikainen AL, Ruokonen A, Surcel HM, ET et al. Perinatal outcome of children born to mothers with thyroid dysfunction or antibodies: a prospective population-based cohort study. J Clin Endocrinol Metab 2009;94(3):772-9.

11. Wang W, Teng W, Shan Z, Wang S, Li J, Zhu L, et al. The prevalence of thyroid disorders during early pregnancy in China: the benefits of universal screening in the first trimester of pregnancy. Eur J Endocrinol 2011;164(2):263-8.

12. Dhanwal DK, Prasad S, Agarwal AK, Dixit V, Banerjee AK. High prevalence of subclinical hypothyroidism during first trimester of pregnancy in North India. Indian J Endocrinol Metab 2013;17(2):281-4.

13. Ballabio M, Poshychinda M, Ekins RP. Pregnancy-induced changes in thyroid function: role of human chorionic gonadotropin as putative regulator of maternal thyroid. J Clin Endocrinol Metab 1991;73(4):824-31.

14. Glinoer D, de Nayer P, Bourdoux P, Lemone M, Robyn C, van Steirteghem A, et al. Regulation of maternal thyroid during pregnancy. J Clin Endocrinol Metab 1990;71(2): 276-87.

15. van Raaij JM, Vermaat-Miedema SH, Schonk CM, Peek ME, Hautvast JG. Energy requirements of pregnancy in The Netherlands. Lancet 1987;2(8565):953-5.

16. Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev 1997;18(3):404-33.

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17. Dashe JS, Casey BM, Wells CE, McIntire DD, Byrd EW, Leveno KJ, et al. Thyroid-stimulating hormone in singleton and twin pregnancy: importance of gestational age-specific reference ranges. Obstet Gynecol 2005;106(4):753-7.

18. Casey BM, Dashe JS, Spong CY, McIntire DD, Leveno KJ, Cunningham GF. Perinatal significance of isolated maternal hypothyroxinemia identified in the first half of pregnancy.

Obstet Gynecol 2007;109(5):1129-35.

19. Smyth PP, Hetherton AM, Smith DF, Radcliff M, O’Herlihy C. Maternal iodine status and thyroid volume during pregnancy: correlation with neonatal iodine intake. J Clin Endocrinol Metab 1997;82(9):2840-3.

20. Fatourechi V. Subclinical hypothyroidism: an update for primary care physicians. Mayo Clin Proc 2009;84(1):65-71.

21. Chakera AJ, Pearce SH, Vaidya B. Treatment for primary hypothyroidism: current approaches and future possibilities.

Drug Design Devel Ther 2012;6:1-11.

22. Marwaha RK, Tandon N, Gupta N, Karak AK, Verma K, Kochupillai N. Residual goitre in the postiodization phase: iodine status, thiocyanate exposure and autoimmunity. Clin Endocrinol (Oxf ) 2003;59(6):672-81.

23. Das S, Bhansali A, Dutta P, Aggarwal A, Bansal MP, Garg D, et al. Persistence of goitre in the post-iodization phase: micronutrient deficiency or thyroid autoimmunity? Indian J Med Res 2011;133:103-9.

24. Steingold KA, Matt DW, DeZiegler D, Sealey JE, Fratkin M, Reznikov S. Comparison of transdermal to oral estradiol administration on hormonal and hepatic parameters in women with premature ovarian failure. J Clin Endocrinol Metab 1991;73(2):275-80.

25. Sapolsky RM, Krey LC, McEwen BS. The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis.

Endocr Rev 1986;7(3):284-301.

26. Ongphiphadhanakul B, Fang SL, Tang KT, Patwardhan NA, Braverman LE. Tumor necrosis factor-alpha decreases thyrotropin-induced 5’-deiodinase activity in FRTL-5 thyroid cells. Eur J Endocrinol 1994;130(5):502-7.

27. Rivkees SA. Pediatric Graves’ disease: controversies in management. Horm Res Paediatr 2010;74(5):305-11.

28. Sharma M, Aronow WS, Patel L, Gandhi K, Desai H. Hyperthyroidism. Med Sci Monit 2011;17(4):RA85-91.

29. Baloch Z, Carayon P, Conte-Devolx B, Demers LM, FeldtRasmussen U, Henry JF, et al; Guidelines Committee, National Academy of Clinical Biochemistry. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid 2003;13(1):3-126.

30. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al; American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and Postpartum. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011;21(10):1081-125.

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

Review Article 31. Gharib H, Cobin RH, Dickey RA. Subclinical hypothyroidism during pregnancy: position statement from the American Association of Clinical Endocrinologists.

Endocr Pract 1999;5(6):367-8.

32. Yeum CH, Kim SW, Kim NH, Choi KC, Lee J. Increased expression of aquaporin water channels in hypothyroid rat kidney. Pharmacol Res 2002;46(1):85-8.

33. Samuels MH. Cognitive function in untreated hypothyroidism and hyperthyroidism. Curr Opin Endocrinol Diabetes Obes 2008;15(5):429-33.

34. Allahabadia A, Razvi S, Abraham P, Franklyn J. Diagnosis and treatment of primary hypothyroidism. BMJ 2009;338:b725.

35. Baisier WV, Hertoghe J, Eeckhaut W. Thyroid insufficiency.

Is TSH measurement the only diagnostic tool? J Nutr Environmen Med 2000;10(2):105-13.

36. Christ-Crain M, Meier C, Huber PR, Staub JJ, Muller B. Effect of l-thyroxine replacement therapy on surrogate markers of skeletal and cardiac function in subclinical hypothyroidism. Endocrinologist 2004;14(3):161-6.

37. Wilson KL, Casey BM, McIntire DD, Halvorson LM, Cunningham FG. Subclinical thyroid disease and the incidence of hypertension in pregnancy. Obstet Gynecol 2012;119(2 Pt 1):315-20.

38. Tudela CM, Casey BM, McIntire DD, Cunningham FG. Relationship of subclinical thyroid disease to the incidence of gestational diabetes. Obstet Gynecol 2012;119(5):983-8.

39. Wier FA, Farley CL. Clinical controversies in screening women for thyroid disorders during pregnancy.

J Midwifery Womens Health 2006;51(3):152-8.

40. Stagnaro-Green A. Postpartum thyroiditis. Best Pract Res Clin Endocrinol Metab 2004;18(2):303-16.

41. Pop VJ, de Vries E, van Baar AL, Waelkens JJ, de Rooy HA, Horsten M, et al. Maternal thyroid peroxidase antibodies during pregnancy: a marker of impaired child development?

J Clin Endocrinol Metab 1995;80(12):3561-6.

42. van der Zanden M, Hop-de Groot RJ, Sweep FC, Ross HA, den Heijer M, Spaanderman ME. Subclinical hypothyroidism after vascular complicated pregnancy. Hypertens Pregnancy 2013;32(1):1-10.

43. Abalovich M, Gutierrez S, Alcaraz G, Maccallini G, Garcia A, Levalle O. Overt and subclinical hypothyroidism complicating pregnancy. Thyroid 2002;12(1):63-8.

44. Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA 2004;291(2):228-38.

45. Reid SM, Middleton P, Cossich MC, Crowther CA. Interventions for clinical and subclinical hypothyroidism in pregnancy. Cochrane Database Syst Rev 2010;(7):CD007752.

46. Baskin HJ, Cobin RH, Duick DS, Gharib H, Guttler RB, Kaplan MM, Segal RL; American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract 2002;8(6):457-69.

47. Velkeniers B, Van Meerhaeghe A, Poppe K, Unuane D, Tournaye H, Haentjens P. Levothyroxine treatment and pregnancy outcome in women with subclinical hypothyroidism undergoing assisted reproduction technologies: systematic review and meta-analysis of RCTs. Hum Reprod Update 2013;19(3):251-8.

Effects of Resveratrol on Proliferation and Apoptosis in Rat Ovarian Theca-interstitial Cells Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction and associated with ovarian theca-interstitial (T-I) cell hyperplasia, hyperinsulinemia, systemic inflammation and oxidative stress. This in vitro study tested whether rat T-I cell growth with or without insulin can be altered by resveratrol, a natural polyphenol with anticarcinogenic, anti-inflammatory, antiproliferative and antioxidant properties. Rat T-I cells were cultured with and without resveratrol and/or insulin, and the effects on DNA synthesis, number of viable cells and markers of apoptosis were evaluated. Resveratrol alone induced a potent concentration-dependent inhibition of cell growth by inhibiting DNA synthesis, decreasing the number of viable cells and increasing the activity of executioner caspases 3 and 7; these effects of resveratrol counteracted the proproliferative and antiapoptotic effects of insulin. Immunofluorescence analysis of cells incubated with resveratrol showed concentration- and time-dependent morphological changes consistent with apoptosis. The present findings indicate that resveratrol promotes apoptosis to reduce rat T-I cell growth in vitro as well as inhibiting insulininduced rat T-I cell growth. This suggests a possibility that resveratrol and/or mechanisms mediating its effect may be relevant to the development of novel treatments for PCOS, which is characterized by both excessive ovarian mesenchyma growth and hyperinsulinemia.

Source: J Clin Endocrinol Metab. 2013;98(3):E455-62..

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

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CLINICAL STUDY

Detection of Fetal Malnutrition by Clinical Assessment of Nutritional Status Score at Birth and Its Comparison with Other Methods of Determining Intrauterine Growth Vikram Singhal, Prashant Agal, Nutan Kamath*

Abstract Background: Fetal malnutrition (FM) and the terms "small for gestational age (SGA)" and "intrauterine growth retardation (IUGR)" are not synonymous, one may occur without the other. FM can be clinically assessed by using the clinical assessment of nutritional (CAN) status score. CAN score can assess the prevalence of FM among term newborns and is comparable to other anthropometric criteria used to assess fetal growth. Material and methods: A prospective cohort study was carried out at a tertiary referral hospital affiliated to a medical college, consisting of 200 singleton full-term neonates over a period of 2 months. In all neonates, complete anthropometric assessment as per standard procedures and determination of weight for gestation was done. On the basis of Alexander and associates intrauterine growth curves, newborns were classified into SGA and appropriate for gestational age (AGA). FM was assessed using CAN score as a standard and compared with weight for gestation age and ponderal index (PI). Results: CAN score identified 17.5% (n = 35) malnourished neonates and 82.5% (n = 165) of babies as well-nourished by keeping the cut-off value of <25. Eight percent of AGA babies and 76.8% of SGA babies were found to be well-nourished on comparing weight for gestation age with CAN score. Sixteen (8%) babies were found to have FM using PI but by applying CAN score only 10 babies were found to have FM. The sensitivity and specificity of weight for gestational age were found to 82.85% and 41.81%, respectively and that of PI 28.57% and 96.36%, respectively, when CAN score was taken as standard. Conclusion: This implies that CAN score can identify fetal malnourishment in those neonates, which are missed by other methods.

Key words: CAN, anthropometry, fetal malnutrition

F

etal growth is a function of growth potential of the fetus, the availability of intrauterine nutrition and placental function. The net result of these factors is a wide distribution of birth size at any given gestational age (GA) and a wide variation in the state of nutrition at birth. The concept of fetal malnutrition (FM) was initially developed by Clifford1 and was defined by Scott and Usher2 as a clinical state of infants characterized by obvious intrauterine loss of failure to acquire normal amount of subcutaneous fat and muscle. FM and the terms "small for gestational age (SGA)" and "intrauterine growth retardation (IUGR)" are not synonymous, one may occur without the other.3,4 *Professor and Unit Head Dept. of Pediatrics, Kasturba Medical College (KMC), Mangalore, Karnataka Manipal University, Mangalore, Karnataka Address for correspondence Dr Nutan Kamath Professor and Unit Head Dept. of Pediatrics KMC Hospital, Attavar, Mangalore - 575 001 E-mail: nutankamath@yahoo.com

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FM can be clinically assessed by using the clinical assessment of nutritional (CAN) status score.3 There are various other methods, which are used to determine nutritional status of newborns at birth like weight for GA, ponderal index (PI) and mid arm/head circumference ratio. But, each has its own drawbacks.5,6 Detection of FM at birth is thus useful for identifying those newborns who are at higher risk for metabolic complications associated with abnormal fetal growth.3 The aim of this study was detection of FM by CAN score of term neonates at birth and its comparison with other methods of determining intrauterine growth.

Material and Methods A prospective cross-sectional study was carried out at a tertiary referral hospital affiliated to a medical college after taking the prior approval of the Institutional Ethics Committee. Two hundred singleton fullterm neonates (38-42 weeks of gestation) whose hospital stay exceeded 24 hours of age were enrolled in the study after taking informed consent from the parents. Neonates (both sexes), born as a result of multiple pregnancies and/or having major congenital Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

clinical study

Data were statistically analyzed with test of significance, calculated by chi-square test. Anthropometric measurements were expressed as percentiles. Sensitivity, specificity, positive and negative predictive values were also calculated, wherever required. A ‘p’ value of <0.05 was considered significant.

Results In this study, 200 singleton term neonates were analyzed to detect FM. Mean birth weight of study population was 2.73 ± 0.35 kg and the mean length was 45.43 ± 2.02 cm. In our study, when nutritional status of newborns was detected by CAN score, 82.5% newborns were well-nourished but 17.5% newborns had malnutrition. When nutritional status of newborns was detected on the basis of weight for GA, we found that 62.5% babies were SGA while 37.5% were AGA. When PI was used for detection of nutritional status in newborns, it was found that 92% newborns were wellnourished but 8% were malnourished (Fig. 1).

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

Table 1. The nine signs for CAN Status in the Newborn4 Hair

Large amount, smooth, silky, easily groomed (4); thinner, some straight, "staring" hair (3), still thinner, more straight, "staring" hair; which does not respond to brushing (2); straight "staring" hair with depigmented strip (flag sign) (1).

Cheeks

Progression from full buccal pads and round face (4), to significantly reduced buccal fat with narrow, flat face (1).

Neck and chin

Double or triple chin fat fold, neck not evident (4); to thin chin. No fat fold, neck with loose, wrinkled skin, very evident (1).

Arms

Full, round, cannot elicit "accordion" folds or lift folds of skin from elbow or tricep area (4); to a striking "accordion" folding of lower arm, elicited when examiner's thumb and fingers of the left hand grasps the arm just below the elbow of the baby and thumb and fingers of the examiners right hand circling the wrist of the baby are moved towards each other; skin is loose and easily grasped and pulled away from the elbow.

Legs

Like arms.

Back

Difficult to grasp and lift skin in the interscapular are (4); to skin loose, easily lifted in a thin fold from the interscapular area (1).

Buttocks

Full round gluteal fat pads (4); to virtually no evident gluteal fat and skin of the buttocks and upper posterior high loose and deeply wrinkled (1).

Chest

Full, round, ribs not seen (4); to progressively prominence of the ribs with obvious loss of intercostal tissues (1).

Abdomen

Full, round, no loose skin;4 to distended or scaphoid, but with very loose skin, easily lifted, wrinkled and "accordion" folds demonstrable.

100 90 80

Percentage (%)

malformations were excluded. The study was carried out over a period of 2 months. Before starting the study, the inter and intraobserver variations of the CAN score were tested and found to be within acceptable limits (p > 0.05). Neonatal anthropometry measurements (weight, length, head circumference) were carried out between 24 and 48 hours of newborn age using standard guidelines and instruments. PI was calculated as weight (grams)/length3 (cm) × 100; and values below 2.2 were taken as indicative of growth retardation.7 Infant’s age was assessed by using New Ballard score8 and it was further correlated with last menstrual period (LMP) and ultrasonic measurements taken antenatally. If in disagreement for over 2 weeks, the clinical score was taken as the final GA. All these data were recorded on the predesigned form, for each baby. On the basis of normograms of the Alexander and associates intrauterine growth curves,9 newborns were classified as SGA and AGA. Infants, whose weights were below the 10th percentile for their GA, were classified as SGA, whereas those with birth weight between 10th and 90th percentiles for their GA were designated as AGA babies.9 CAN score4 has nine superficial readily detectable signs, which are rated from 1 (worst-severe FM) to 4 (best well-nourished). The highest possible score is 36 and lowest possible score is.9 A CAN score of ≤24 was taken as fetally malnourished.4 CAN score is presented in Table 1.

92

82.5

Well-nourished

70

62.5

60

Malnourished AGA

50 40

SGA

37.5

30 20

17.5

10 0

8

CAN score weight for GA

PI

Figure 1. Comparison of CAN score, weight for GA and PI

In our study, 35 of 200 term neonates, were malnourished in utero (FM). Thus, 96 out of 125 SGA babies were small but not malnourished and six out of 75 AGA were fully grown but were malnourished.

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clinical study Table 2. Distribution of SGA and FM diagnoses in 200 neonates and comparison of CAN score with PI Weight for GA

CAN score

p value

FM (%)

Nourished (%)

Total (%)

AGA

6 (8)

69 (94)

75 (37.5)

SGA

29 (23.2)

96 (76.8)

125 (62.5)

Total

35 (17.5)

165 (82.5)

200 (100)

<2.2

10 (62.5)

6 (37.5)

16 (8)

>2.2

25 (13.58)

159 (86.41)

184 (92)

Total

35 (17.5)

165 (82.5)

200 (100)

<0.01#

PI

#

Highly significance.

Table 3. Comparison of CAN score with other methods for detection of FM Value

Birth weight for GA (%)

PI (%)

Sensitivity (%)

82.85

28.57

Specificity (%)

41.81

96.36

Positive predictive value (%)

23.2

62.5

Negative predictive value (%)

92

86.41

Sixteen babies were found to have FM using PI but by applying CAN score only 10 babies were found to have FM. Out of the 184 babies found to be well-nourished by using PI, 25 babies were found to be malnourished in utero by applying CAN score (Table 2). PI has low sensitivity in comparison to CAN score for diagnosis FM (Table 3). Also, using PI alone for diagnosing FM, some SGA babies may be misdiagnosed as FM and some AGA babies may be misdiagnosed as normal.

Discussion It is important to recognize babies with FM because of high incidence of neonatal morbidity and long-term sequelae-like metabolic syndrome.2,10,11 Depending on the period of gestation, when the malnutrition started, the clinical manifestations of FM vary. FM adversely affects body composition, including reduced muscle mass and protein content, organ structure and composition, bone, chemical composition and metabolic, and enzyme functions.4 The perinatal problems and/or central nervous system sequelae, occurred primarily in fetally malnourished 24

<0.01#

babies, whether AGA or SGA, but not those who were simply SGA but not malnourished was found in a study done by Hill et al.12 In utero growth restriction is not a uniform condition with respect to its severity and duration, the underlying pathogenesis and the developmental stage of the fetus at the time of its occurrence. If malnutrition happens early in the second trimester, length, head circumference and weight are significantly all reduced, whereas if length and head circumference are less affected but baby is small and underweight mostly the malnutrition happened in the beginning of the third trimester. If length and head circumference are within the normal range, and weight significantly less than the GA, an insufficient or unbalanced nutrient supply most likely occurred in the late third trimester.4,13,14 For the last two categories, weight, may be above the 10th percentile for GA. FM adversely affects body composition, including reduced muscle mass and protein content, organ structure and composition, bone, chemical composition and, metabolic and enzyme functions.4 FM is clinically characterized by obvious intrauterine loss of subcutaneous fat and muscle. Weight, length and head circumference may or may not be affected.15 Irrespective of cause, fetuses with inadequate nutrition will not deposit fat as long as their basic metabolic needs are not met, whereas a baby with abundant subcutaneous fat cannot have suffered from in utero malnutrition. On the basis of this principle, the evaluation of fat deposits is an appropriate means for the distinction between IUGR and non-IUGR neonates. Neither SGA nor IUGR are synonymous with FM. The current anthropometric criteria used to assess fetal nutritional status of newborn, have their Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

clinical study shortcomings.4,16 A simple, clinically applicable scoring system was developed by Metcoff4 to differentiate the malnourished from appropriate nourished babies irrespective of birth weight or clinical classification as IUGR, SGA or AGA. This scoring system rated clinical evidences of malnutrition in term babies determined by inspection and hands on estimates of loss of subcutaneous tissue and muscle and is independent of common confounding factors which affect weight of the baby.4 The CAN score is much simpler to learn and easy to do, particularly with the aid of cartoon illustrations of the signs and scores as described by Metcoff.4 Its major drawback is its subjective nature, like all other scoring methods used in the evaluation of neonates. The method could be used as a screening or confirmatory test.

In a study by Deodhar et al,16 FM was present in 19.6% babies (84.2% of the SGA, 12.9% of AGA babies) while Metcoff4 reported FM in 5.5% of AGA and 54% of SGA babies. This variability in the results may be because of type of growth charts used to differentiate AGA/SGA babies. Several fetal growth curves have been developed from various populations and geographic locations.9,17,18 In the study by Hill et al,12 32.6% of FM infants would have been misclassified as AGA, if only birth weights, lengths and head circumferences were considered for detection of growth retardation. In our study, using CAN score, 76.8% of SGA infants were not malnourished and 8% of AGA infants were fetally malnourished. Hill et al12 have showed that 39% of later neurologic and intellectual handicaps occur predominantly in FM babies. This would have been missed if only a birth weight of less than the 10th percentile was used. Thus, apart from 23% of the SGA, 8% of the AGA malnourished babies are also at risk. Metcoff4 established. CAN score as a good indicator of FM. In a large sample of 1,382 term neonates, a simple brief CAN status revealed that 151 (10.9%) were FM, including 5.5% of 1,229 AGA and 83 (54%) of 153 SGA babies; nearly half 45.8% of the SGA infants were not malnourished in utero. Our data and previous reports4,15,16 suggest that using weight for gestation classification to identify malnourished neonates may not be entirely accurate, because it may identify many well-nourished neonates as SGA, or miss a proportion of malnourished AGA neonates.

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

To classify IUGR infants, PI has been used by various authors.19,20 PI relies on the principle that length spared at the expense of weight during period of acute inflammation; weight and length velocities may be proportionately impaired so infants with chronic insult in utero may be misclassified by PI. The other drawback of PI is that any error in calculating length is cubed in the calculation of the PI.2 In our study, 16 infants (8%) were found growth retarded according to PI (<2.2); out of these only 10 infants were fetally malnourished on using CAN score. When CAN score was compared with PI, it gave a sensitivity of 28.57% and a specificity of 96.36% in the present study.

Haggarty et al21 indicate that PI is a poor predictor of in utero growth retardation.5,21 Gardosi et al22 state that CAN score is a simple and rapid clinical scoring system for diagnosing FM. All AGA infants are not well-nourished and not all SGA babies are malnourished and those without FM have a better outcome and faster catch-up growth. In a developing country like India, CAN score can be used as a simple and effective tool to identify FM. The limitation of our study was small sample size and inability for long-term follow-up to assess development of these babies. Undoubtedly, further research is needed, using a greater range of confirmatory information. Search and evaluation of alternative indices or other simple indicators of growth restriction might also contribute to a more accurate identification of IUGR babies.

Conclusion Our study concluded that SGA and IUGR are not synonymous with FM. CAN score, which is a simple clinical index for identifying FM, is a good indicator for the same in comparison to other methods of determining IUGR-like weight for GA and PI. This implies that CAN score can identify fetal malnourishment in those neonates, which are missed by other methods.

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J Pediatr. 1954;44(1):1-13.

2. Scott KE, Usher R. Fetal malnutrition: its incidence, causes and effects. Am J Obstet Gynecol. 1966;94(7):951-63.

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clinical study 3. Georgieff MK, Sasanow SR. Nutritional assessment of the neonates. Clin Perinatol. 1986;13(1):73-89.

4. Metcoff J. Clinical assessment of nutritional status at birth: Fetal malnutrition and SGA are not synonymous. Pediatr Clin North Am. 1994;41(5):875-91.

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11. Gluckman PD, Hanson MA, Morton SMB, Pinal CS. Lifelong echoes: a critical analysis of the development origin of the adult disease model. Biol Neonate. 2005,87(2):127-39.

12. Hill RM, Verniaud WM, Deter RL, Tennyson LM, Rettig GM, Zion TE, et al. The effect of intrauterine malnutrition: a 14 year prospective study. Acta Pediatr Scand. 1984; 73(4):482-7.

13. Lubchenco LO, Hansman C, Dressler M, Boyd E. Intrauterine growth as estimated from liveborn birth-weight data at 24 to 42 weeks of gestation. Pediatrics. 1963;32:793-800.

14. Urrusti J, Yoshida P, Velasco L, Frenk S, Rosado A, Sosa A, et al. Human fetal growth retardation. 1: Clinical features of the sample with intrauterine growth retardation. Pediatrics.

1972;50(4):547-58.

15. Mehta S, Tandan A, Dua T. Clinical assessment of nutritional status at birth. Indian Pediatr. 1991;28(3):281-3.

16. Deodhar J, Jarad R. Study of the prevalence of and high risk factors for fetal malnutrition in term newborns. Ann Trop Paediatr. 1999;19(3):273-7.

17. Brenner WE, Edelman DA, Hendricks CH. A standard of fetal growth for the United States of America. Am J Obstet Gynecol. 1976;126(5):555-64.

18. Overpeck MD, Hediger ML, Zhang J, Trumble AC, Klebanoff MA. Birth weight for gestational age of Mexican American infants porn in the United States. Obstet Gynecol.

1999;93(6):943-7.

19. Mohan M, Prasad SR, Chellani HK, Kapani V. Intrauterine growth curves in North Indian babies: weight, length, head circumference, ponderal index. Indian Pediatr.

1990;27(1):43-51.

20. Miller HC, Hassanein K. Diagnosis of impaired fetal growth in newborn infants. Pediatrics. 1971;48(4):511-22.

21. Haggarty P, Campbell DM, Bendomir A, Gray ES, Abramovich DR. Ponderal index is a poor predictor of in utero growth retardation. BJOG. 2004;111(2):113-9.

22. Gardosi J, Chang A, Kalyan B, Sahota D, Symonds EM. Customized antenatal growth charts. Lancet. 1992;339 (8788):283-7.

Folic Acid Supplementation: Hope for Postmenopausal Females with Hot Flushes

Hot flushes, seen in 75% of menopausal females, are related to deprivation of estrogen. Estrogen was shown to ameliorate hot flushes by interacting with monoamine neurotransmitters in the brain; decreasing noradrenaline and raising serotonin. Hormone replacement therapy (HRT), the primary therapeutic approach, raises issue of possible high risks especially breast cancer. Folic acid is involved in the biosynthesis of serotonin and nordrenaline, which is responsible for its effects on mood and cognition, and degrees of folate inadequacy, not severe enough to produce megaloblastic anemia, were found to be associated with depression and cognitive malfunctioning. Also, raised age was observed to relate to decreased serum and cerebrospinal fluid folic acid levels. There is growing data that folic acid supplementation ameliorates hot flushes by the same mechanism as estrogen of hot flushes in postmenopausal females, and on the blood level of serotonin and noradrenaline.

Source: World J Obstet Gynecol. November 2013;2(4):87-93.

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Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

CLINICAL STUDY

Iron folic acid intake among pregnant women in PHC Anumanthai of Villupuram, Tamil Nadu Kumar S*, Sitanshu Sekhar Kar†, Sonali Sarkar†, Ganesh Kumar S†

Abstract Background: Prevalence of anemia in India is among the highest in the world. Apart from other causes of anemia, iron or folate deficiency is the most common cause, especially during pregnancy. Although, supplementation of diet with iron and folic acid (IFA) tablets has been a part of the Ministry of Health and Family Welfare Program for over three decades, levels of IFA intake during pregnancy remain low. Material and methods: A descriptive study was conducted among 132 postnatal women registered in Anumanthai primary health center (PHC), Villupuram, Tamil Nadu, catering to a population of 56,142 through eight subcenters to explore factors affecting compliance to IFA. One hundred thirty-two postnatal women were interviewed after taking informed consent in local language using a pretested structured proforma. Statistical analysis was done using SPSS Version 16. Results: Majority of the study subjects (134; 98%) were in the age group of 20-29 years. First-trimester registration was 99.4% and 99.3% received at least three antenatal visits at the PHC. Fifty-four (40%) of the study subjects did not consume any IFA tablet at all. Only 31.1% of the study subjects were aware that IFA tablets should be consumed for 100 days. About 25.9% consumed at least above 90 IFA tablets and only 5.9% consumed more than 100 IFA tablets.

Nausea and vomiting 85 (63%) and counseling by village health nurse 115 (89%) were reported to be the most common hindering and facilitating factors, respectively. Conclusion: Despite high rates of antenatal visits, the intake of IFA tablets was low.

Key words: Anemia in pregnancy, compliance, iron and folic acid tablets

I

ron-deficiency anemia is a serious public health problem that affects health and well-being. It is one of the most prevalent and preventable nutritional deficiencies in the world with prevalence being as high as 60% among pregnant women.1 Anemia burden among pregnant women in India is also high with 59% of the pregnant women being affected with the condition.2 It is estimated that about 20-40% of maternal deaths in India are due to anemia; India contributes to about 50% of global maternal deaths due to anemia.1,2 Apart from other causes of anemia, iron or folate deficiency is the most common cause, especially during pregnancy. Although, supplementation of diet with iron and folic acid (IFA) tablets has been

*PGDPHM Trainee † Assistant Professors Dept. of Preventive and Social Medicine, JIPMER, Puducherry, Tamil Nadu Address for correspondence Dr Sitanshu Sekhar Kar Assistant Professor Dept. of Preventive and Social Medicine, JIPMER, Puducherry - 605 006 Tamil Nadu E-mail: drsitanshukar@gmail.com

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

a part of the Ministry of Health and Family Welfare Program for over three decades, levels of IFA intake during pregnancy remain low.3 As per the National Family Health Survey (NFHS)-3, only 23% of women consumed IFA for at least 90 days in India.2 There has been a wide variation regarding IFA intake for 90 days among pregnant women in states with the highest Kerala (75.1%) and lowest in Nagaland (3.5%).3 In Tamil Nadu, more than 90% of pregnant women were anemic despite very high antenatal check-up (ANC) (96.5% of pregnant women had three or more ANC visits) and 91.1% were given or bought IFA tablets; however, only 43.2% took IFA for at least 90 days.4 District Level Household and Facility Survey (DLHS)-3 (2007-2008) showed that the percentage of mothers who consumed 100 IFA tablets was 54.7% (rural 51.0% and urban 60.6%) and mothers who had received ANCs was 98.8% (rural 98.6% and urban 99.3%) in Tamil Nadu.5 This study was planned to find out the compliance of IFA intake and to identify facilitating and hindering factors associated with intake of iron in a rural primary health center (PHC) of Villupuram district, Tamil Nadu.

27

clinical study Materials and Methods A descriptive study was conducted in Anumanthai PHC of Villupuram that provides comprehensive care to a population of 56,142 through eight subcenters.

The study subjects were the postnatal women registered during November 2009 to December 2010. Out of eight, four subcenters were selected by convenient sampling as the subcenters were similar in sociodemographic parameters. Considering the prevalence of intake of iron to be 43.2%2 and with 20% allowable error, the sample size was calculated to be 132. Thirty-five postnatal women registered during the reference period from each of these four subcenters were selected randomly using a random number table from the postnatal case register with the help of a village health nurse (VHN). All interviews were conducted in the local language after taking informed consent.

A structured questionnaire after pretesting was used to collect information on demographic variables, socioeconomic variables, awareness, regularity of intake of IFA, facilitating factors (motivation by VHN/husbands/community; availability of IFA) and hindering factors (side effects and packaging). Analysis was done by SPSS Version 16. All statistical analyses were carried out at 5% level of significance and the p value <0.05 was considered significant. This study was approved by the Institute of Research Council and the Institute of Ethics Committee. The compliance to IFA intake was defined as daily intake of IFA for at least 90 days from the second trimester of pregnancy.

Results Majority of the study subjects (134; 98%) were in the age group of 20-29 years and were Hindus (129; 95%). Eighty-three (61.5%) of them belonged to most backward caste and 98 (72%) were educated up to primary level (1-4 years of schooling). First-trimester registration was 99.4% and 99.3% who received at least three antenatal visits at the PHC. All of them who visited PHC were checked for blood pressure, height, weight, abdominal examination and blood and urine examination.

The IFA tablet consumption pattern is given in Table 1. Fifty-four (40%) of the study subjects did not consume any IFA tablet at all. Only 31.1% of the study subjects were aware that IFA tablets should be consumed for 100 days. The facilitating and hindering factors are reported in Tables 2 and 3. It was found 28

Table 1. IFA tablets consumed by the study population If a tablets consumed

No. of responses

Percentage (%)

Did not consume at all

54

40

1-30

25

18.5

61-90

14

10.3

91-100

35

25.9

101-120

7

5.9

Table 2. Facilitating factors as reported by study subjects for intake of IFA tablets Motivation

No. of responses

Percentage (%)

Counseling by village health nurse

115

85.2

Doctors

11

8

Private nursing homes

7

5

Husband

2

1.8

Table 3. Hindering factors reported by study subjects for not consuming IFA Tablets Reasons

No. of responses

Percentage (%)

Nausea and vomiting

85

63

Abdominal cramps

34

25

Constipation

2

1.5

that 95.6% felt good about the package of IFA tablets and 82.2% of the pregnant women felt that the smell was good. It was found that 88.9% of the pregnant women felt good about the taste of the IFA tablets.

Some of the quotes during the interviews are as follows: Mrs R said, “I felt nausea, giddiness and vomiting as soon as I took the tablets. So, I didn’t take any iron tablets.”

Mrs P said, “My mother-in-law told, don’t take iron tablets.

If you take iron tablets, your baby will be black in color.”

Discussion The study showed that 99.3% of postnatal women were registered with auxiliary nurse midwife (ANM) and received at least three ANC visits to the PHC. In Tamil Nadu, 96.5% had three or more antenatal visits.4 DLHS-3 (2007-2008) showed that mothers who had received ANC were 98.8% (rural 98.6% and urban 99.3%) that is close to the result of the study.5 A community-based cross-sectional study on utilization of antenatal care facilities in a rural population in Tamil Nadu showed that 95% of the women received at least Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

clinical study one antenatal visit. The median number of visits was four. High utilization of antenatal care was due to low parity and adverse obstetric history, short distance to healthcare facilities and literacy.6,7 Despite high rates of antenatal visit; the intake of IFA intake low. Our study showed that 18.5% of them consumed at least 30 IFA tablets and 25.9% consumed at least above 90 IFA tablets. Only 5.9% consumed more than 100 IFA tablets. This result is quite less than the NFHS-3 data showing that 91.1% were given IFA tablets and only 43.2% took IFA tablets for at least 90 days.4 DLHS-3 (2007-08) showed that mothers who consumed 100 IFA tablets was 54.7% (rural 51% and urban 60.6%).5 Evaluation of National Nutritional Anemia Control Program in Dharwad (Karnataka) showed that iron and folic acid tablets were not distributed regularly by the ANMs and 10% subjects did not receive any tablets even once. The tablets supplied were not consumed due to side effects and blind beliefs.6 Our study also depicts the similar findings.

The awareness about the IFA tablets was only 31.1% among the pregnant women; whereas, 68.9% were not aware about the IFA tablets. In a study conducted by Abel et al8 from June 1996 to August 1998, a significant decrease in the prevalence of anemia (19.9%) was observed in the postintervention period between the study and control area; therefore, awareness is one of the important factors in iron supplementation that is very close to our study.8,9 In our study, only 34.1% of the subjects were told by the VHNs about the importance and need for IFA tablets. In other studies, nonadherence was due to lack of motivation resulting from the lack of information about beneficial effects and some misconception about IFA therapy.10,11 In our study, only 12.6% of postnatal women received house visits by the VHNs. House visits done by the VHNs were not up to the expected level.

It is a matter of concern that with almost near 100% antenatal registration, the IFA intake rate is quite low.

Still misconceptions regarding iron tablets exist in the community. It will be apt to initiate the community

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

based educational campaign to increase awareness regarding beneficial effects and dispel myths.

References 1. de Benoist B, McLean E, Egli I, Cogswell M (Eds.).

Worldwide Prevalence of Anaemia 1993-2005: WHO Global Database on Anaemia. Available at: http://whqlibdoc. who. int/publications/2008/9789241596657_eng.pdf 2. Agarwal KN, Agarwal DK, Sharma A. Anemia in pregnancy interstate differences. Nutrition Foundation of India; Scientific Report 16, 2005. Available at: http:// nutritionfoundationofindia.res.in/pdfs/Scientific-report-16.pdf 3. International Institute for Population Sciences (IIPS) and Macro International 2007. National Family Health Survey (NFHS-3), 2005-06: India: Volume I. Mumbai: IIPS. 4. International Institute for Population Sciences (IIPS) and Macro International 2007. National Family Health Survey (NFHS-3), 2005-06: India. Fact sheet Tamil Nadu. Available at: http://www.nfhsindia.org/pdf/Tamil%20Nadu.pdf 5. International Institute for Population Sciences (IIPS), 2010.

District Level Household and Facility Survey (DLHS-3), 2007-08: India. Mumbai: IIPS. 6. Iyenger L. Effects of dietary supplements late in pregnancy on the expectant mother and her newborn. Indian J Med Res 1967;55(1):85-9.

7. Assessment of Nursing Management Capacity in Tamil Nadu, National Institute of Health and Family Welfare in Collaboration with Indian Institute of Management Ahmedabad. Available at: http://nihfw.org/pdf/Nsg%20 Study-Web/Tamil%20Nadu%20Report.pdf.

8. Abel R, Rajaratnam J, Sampathkumar V. Anemia in Pregnancy: Impact of Iron Supplementation, Deworming and IEC. Reproductive Health Focus. Report on Projects for Reduction of Maternal Anemia. MotherCare/John Snow Inc. 1999: IDPAS# 532.

9. Prevalence of Micronutrient Deficiencies. National Nutrition Monitoring Bureau (NNMB) Technical Report No. 22, 2003. National Institute of Nutrition, Indian Council of Medical Research. Available at: http://nnmbindia.org/ NNMB%20MND%20REPORT%202004-Web.pdf 10. Kalaivani K. Prevalence & consequences of anaemia in pregnancy. Indian J Med Res 2009;130(5):627-33.

11. Agarwal KN, Agarwal DK, Sharma A, Sharma K, Prasad K, Kalita MC, et al. Prevalence of anaemia in pregnant & lactating women in India. Indian J Med Res 2006; 124(2):173-84.

29

CLINICAL STUDY

Progesterone and prevention of preterm labor Ruchika Garg*, Urvashi Verma*, Rajni Rawat†, Somya Shrivastava‡, Renu Rajvanshi#

Abstract Objectives: To evaluate the effect of vaginal progesterone in the prolongation of duration of pregnancy in women at highrisk of developing preterm labor. Material and methods: This is a prospective case-control study carried out in the Dept. of Obstetrics and Gynecology, SN Medical College, Agra on 100 patients chosen from inpatient and outpatient department (50 cases and 50 controls). Women with singleton pregnancy having history of preterm labor, uterine malformation, prophylactic cerclage and currently suffering from premature pains were given daily vaginal progesterone 200 mg from 24 weeks and discontinued at 34 weeks of gestation. In both groups, rate of preterm labor and neonatal outcome was determined. Results: The incidence of preterm labor in progesterone group was 17.8% and in control group it was 36%, p value is <0.05. Conclusion: Administration of progesterone in women at high-risk of developing preterm labor reduces the incidence of preterm labor, neonatal mortality and morbidity and increases of babies who weight <2.5 kg.

Key words: Preterm labor, progesterone

P

reterm labor is defined by World Health Organization (WHO) as contraction of sufficient strength and frequency to effect progressive effacement of cervix between 20-37 weeks. Worldwide incidence of preterm labor is 6-10%.1 Vidaeff et al promoted the progesterone see-saw theory, according to it high progesterone levels prevent uterine contractions and low levels facilitate such contractions.2 Aims of Study To compare the effect of vaginal progesterone versus placebo on the prevention of preterm labor, among women at increased risk of preterm labor.

Material and methods The study was conducted at the Dept. of Obstetrics and Gynecology, SN Medical College, Agra (UP). High-risk

*Assistant Professor Dept. of Obstetrics and Gynecology, SN Medical College, Agra, Uttar Pradesh † Assistant Professor Dept. of Obstetrics and Gynecology UP Rural Institute of Medical Sciences and Research, Saifai Etawah, Uttar Pradesh ‡ Senior Resident # Resident Dept. of Obstetrics and Gynecology, SN Medical College, Agra, Uttar Pradesh Address for correspondence Dr Ruchika Garg SN Medical College, Agra, Uttar Pradesh D1, Sulahkul Nagar, Bodla Road, Agra, Uttar Pradesh E-mail: ruchikagargagra@gmail.com

30

patients seen in outpatient department and admitted in emergency were recruited. Women with singleton pregnancy in the age group 20-35 years having history of preterm labor, prophylactic cerclage, uterine malformation or currently suffering from premature pains on the basis of clinical information and evaluation of ultrasonography (USG) were included in the study.

Fifty antenatal women were given 200 mg micronized sustained-release progesterone, while another 50 antenatal women were provided placebo. Daily micronized sustained-release vaginal progesterone 200 mg 12-hourly was started beyond 12-14 weeks and discontinued after 36 weeks gestation or early if they get into labor. Patients with multiple pregnancies, major fetal anomaly, allergy to progesterone, premature rupture of membrane, cervical dilation >4 cm, coexisting maternal medical disease, fetal distress and chorioamnionitis were excluded from the study.

Results and discussion The incidence of preterm labor was 36% in placebo and 17.8% in progesterone group in our study (p < 0.05) (Table 1). The incidence of preterm labor was 54.9% in placebo group and 36.3% in progesterone-treated group in the study by Sibai et al.3 In the study by Fonseca et al,4 it was 28.5% and 13.8%, respectively, while it was 35.9% and 26.2% in the study by Luis Sanchez et al (Table 2). In the study by Meis et al,5 babies with birth weight <2.5 kg were 27% in progesterone-treated group and 41% in control group with relative risk (0.66), Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

clinical study Table 1. Distribution of Women According to Profile Patient profile

Group A (progesterone)

Group B (placebo)

Mean age (years)

28.6 years

27.6 years

Gravida 2

24 (48%)

22 (44%)

Gravida >3

26 (52%)

28 (56%)

Class III - 20 (40%)

Class III - 28 (44%)

Class IV - 30 (60%)

Class IV - 22 (56%)

<2

16 (32%)

24 (48%)

=2

24 (48%)

18 (36%)

>2

10 (20%)

8 (16%)

Socioeconomic status Preterm deliveries

Table 2. Incidence of Preterm Labor in Progesteronetreated Group versus Placebo Study done by

Cases (progesterone

Controls (placebo-

treated group) (%)

group) (%)

Sibai et al

36.3

54.9

Fonseca et al

13.8

28.5

Luis Sanchez Ramos et al

26.2

35.9

Johnson et al

12.8

40.9

Present study (p â&#x2030;¤ 0.05)

17.8

36

Table 3. Birth Weight (<2.5 kg) in Progesterone Group versus Placebo Group Study done by

Cases (%)

Controls (%)

27

41

38.02

55

Meis et al (RR = 0.66) Present study (RR = 0.65)

Conclusion Preterm birth complicates one in eight deliveries and remains a major cause of perinatal morbidity and mortality. Appropriate candidates should be counseled about the potential benefits of progesterone supplementation from 16 to 20 weeks up to 36 weeks of gestation to prevent preterm birth in any subsequent pregnancy. The results of current study has shown promising result in reducing the incidence of preterm birth and low-birth weight babies.

References 1. Goldenberg RL. The management of preterm labor. Obstet Gynecol. 2002;100(5 Pt 1):1020-37.

2. Vidaeff AC, Ramin SM. From concept to practice: the recent history of preterm delivery prevention. Part I: cervical competence.

Am J Perinatol. 2006;23(1):3-13.

3. Sibai B, Meis PJ, Klebanoff M, Dombrowski MP, Weiner SJ, Moawad AH, et al; Maternal Fetal Medicine Units Network of the National Institute of Child Health and Human Development.

Plasma CRH measurement at 16 to 20 weeksâ&#x20AC;&#x2122; gestation does not predict preterm delivery in women at high-risk for preterm delivery. Am J Obstet Gynecol. 2005;193(3 Pt 2):1181-6.

4. Fonseca EB, et al. J Obstet Gynecol. 1990;97;149-54.

Table 4. Mean Gestational Age in Progesterone Group versus Placebo Group Study done by

In our study, delivery of cases was postponed up to 38 weeks and of controls up to 34.5 weeks (Table 4).

In the study of Meis et al,8 infants treated with progesterone had significantly lower rate of necrotizing enterocolitis, intraventricular hemorrhage and need for supplemental oxygen. Dodd et al,9 found that infants with intraventricular hemorrhage were very less in progesterone-treated group. In our study, it was found that number of days of neonatal intensive care unit (NICU) stay was significantly reduced in infants delivered in the progesterone-treated group.

Cases (weeks)

Controls (weeks)

Johnson et al

38.6

35.2

Fonseca et al

37

36

Our study

38

34.5

confidence interval (CI) 0.51-0.87. In our study, babies with birth weight <2.5 kg were 28% in progesteronetreated group and 54% in control group (Table 3).

It was found that labor was postponed by 2-4 weeks in 88% of cases. In the study done by Johnson et al6 and Da Fonseca et al7 delivery of cases occurred at 38.6 weeks and 35.2 weeks, respectively while that of controls, occurred at 37 weeks and 36 weeks, respectively.

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

5. Meis PJ; Society for Maternal-Fetal Medicine. 17 hydroxyprogesterone for the prevention of preterm delivery.

Obstet Gynecol. 2005;105(5 Pt 1):1128-35.

6. Johnson JW, Lee PA, Zachary AS, Calhoun S, Migeon CJ. Highrisk prematurity-progestin treatment and steroid studies. Obstet Gynecol. 1979;54(4):412-8.

7. American College of Obstetricians and Gynecologists. ACOG Committee Opinion. Use of progesterone to reduce preterm birth.

Obstet Gynecol. 2003;102(5 Pt 1):1115-6.

8. Spong CY, Meis PJ, Thom EA, Sibai B, Dombrowski MP, Moawad AH, et al. National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network.

Progesterone for prevention of recurrent preterm birth: impact of gestational age at previous delivery. Am J Obstet Gynecol.

2005;193(3 Pt 2):1127-31.

9. Dodd JM, Jones L, Flenady V, Cincotta R, Crowther CA. Prenatal administrationofprogesteroneforpreventingpretermbirthinwomen considered to be at risk of preterm birth. Cochrane Database Syst Rev. 2013;(7):CD004947.

31

CASE REPORT

Secondary Abdominal Pregnancy Following Rupture of Rudimentary Horn Vishwakarma Kshama*, Shukla P*, Yadav Kt

Abstract Pregnancy in the rudimentary horn of the uterus is a rare form of ectopic pregnancy; most of the cases were being diagnosed at laparotomy for hemorrhagic shock due to rupture of horn when the patient presents in the second trimester. Abdominal pregnancy is an extremely rare and serious form of extrauterine gestation, accounting for first 1% of ectopic pregnancies.

Pre-rupture diagnosis is possible in the early pregnancy in suspicious cases. Pregnancy in the rudimentary horn has a poor maternal and fetal outcome and 90% of them present with intraperitoneal hemorrhage in the second trimester due to rupture of the horn. A case of secondary abdominal pregnancy following rupture of rudimentary horn at 14-16 weeks with severe anemia is reported. Excision of the rudimentary horn with placenta in situ was done.

Key words: Unicornuate uterus, rudimentary horn pregnancy, pre-rupture

T

he incidence of mĂźllerian duct anomalies in general population is found to be 3.2%.

Unicornuate uterus occurs in 1 in 4,020 women in the general population and a rudimentary horn is present in about 84% of the cases.1 Most of these rudimentary horns are noncommunicating.

Ectopic pregnancy occurring in a noncommunicating rudimentary horn has an estimated incidence of 1 per 1,00,000-1,40,000 pregnancies.2 Pregnancy in the rudimentary horn usually culminates in rupture during second trimester in about 90% of the cases. Pre-rupture diagnosis is unusual and challenging but possible with high index of suspicion in the early pregnancy.

Abdominal pregnancy is an extremely rare and serious form of extrauterine gestation with an incidence of 1 per 10,000 births.3 Abdominal pregnancies account for almost 1% of ectopic pregnancies.4 It has reported incidence of 1 in 2,200 to 1 in 10,200 of all pregnancies.5 The gestational sac is implanted outside the uterus, ovaries and fallopian tubes. The maternal mortality rate can be as high as 20%.5 This is primarily because of the risk of massive hemorrhage *Assistant Professor t Associate Professor Dept. of Obstetrics and Gynecology, GMH and associated SSMCC, Rewa, Madhya Pradesh Address for correspondence Dr Vishwakarma Kshama Dept. of Obstetrics and Gynecology, GMH and associated SSMCC, Rewa, Madhya Pradesh - 486 001 E-mail: kshamavishwakarma86@gmail.com

32

from partial or total placental separation. The placenta can be attached to the uterine wall, bowel, mesentery, liver, spleen, bladder and ligaments. It can detach at any time during pregnancy leading to torrential blood loss.6 It is thought that abdominal pregnancy is more common in developing countries, probably because of the high frequency of pelvic inflammatory disease in these areas.7 Abdominal pregnancy is classified as primary or secondary according to Studdifordâ&#x20AC;&#x2122;s criteria.8 In these criteria, the diagnosis of primary abdominal pregnancy is based on the following anatomic conditions: (1) normal tubes and ovaries, (2) absence of an uteroplacental fistula and (3) attachment exclusively to a peritoneal surface early enough in gestation to eliminate the likelihood of secondary implantation.

We report a case of secondary abdominal pregnancy following rupture of rudimentary horn who presented in the second trimester.

Case Report A 28-year-old, multipara was admitted to Shyam Shah Medical College (SSMC), Rewa (Madhya Pradesh) on 12/01/14 in emergency hours. She was referred from a private practitioner. She presented with complaints of 3 months amenorrhea, pain abdomen since 15 days, bleeding per vaginum and weakness since 3 days and one fainting episode 1 day back. She had history of medical termination of pregnancy (MTP) followed by LTT at a camp on 28/11/2013 (about 45 days back) at Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

Case Report a primary healthcare center. On examination, she had average general condition with pallor and pulse rate 120 beats/min, which was of good volume and regular; blood pressure 110/70 mmHg, generalized tenderness was present on lower abdomen. On per vaginal examination, uterus was 8-10 weeks, anteverted, there was fullness and tenderness in both fornices and no cervical motion tenderness. There was slight vaginal bleeding.

Her hemoglobin on admission was 7.2 gm% and other laboratory parameters were within normal limits. She came with an ultrasonography (USG) report of 13 weeks fetus lying within uterine cavity. A provisional diagnosis of septic abortion with peritonitis was made. Antibiotics were given and patient was managed conservatively. USG whole abdomen and pelvis was done which revealed: (1) dilated bowel loops with fluid and gas, (2) free fluid with internal septation was seen in peritoneal cavity and (3) uterus normal ET 12 mm. Even after antibiotic coverage, there was no symptomatic improvement, so the decision was taken for laparotomy. Under spinal anesthesia laparotomy was performed and 1.5 liters of hemoperitoneum was found. Old ruptured rudimentary horn of uterus was found on left side. It had placenta with the cord attached. The ruptured rudimentary horn was excised. Uterus was bulky deviated to right with normal right ovary and right fallopian tube. Left ovary was normal, left fallopian tube was healthy and attached to rudimentary horn.

Omentum was plastered with clots; on removal of clots umbilical cord was seen going toward right hypochondrium, up to the mesentery of transverse colon (Fig. 1). The adjacent areas were cleaned, which

Figure 1. Laparatomy was performed which revealed omentum was plastered with blood clots.

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

lead us to visualize the fetus embedded in the mesentery.

Fetus was removed, hemostasis achieved. Peritoneal cavity was washed with normal saline. Patient received 1 unit blood intraoperatively. Her postoperative period was uneventful and she was discharged on 7th postoperative day.

Discussion Unicornuate uterus results from the failure in the development of one of the paramesonephric ducts, either partially or completely. Partial development of one of the duct gives rise to a rudimentary uterine horn. As per revised classification for mĂźllerian anomalies given by American Society of Reproductive Medicine, unicornuate uterus is a type 2 classification with unilateral hypoplasia or agenesis. It can be further subclassified into communicating, noncommunicating, no cavity and no horn.

Pregnancy in a noncommunicating rudimentary horn occurs through the transperitoneal migration of the spermatozoa or the fertilized ovum, as evidenced by the 8% prevalence of a corpus luteum on the side contralateral to the rudimentary horn containing the pregnancy.2 In most of the cases, the pregnancy in the rudimentary horn leads to spontaneous abortion, preterm labor, intrauterine growth restriction or fetal demise. The most dreaded complication is the massive intraperitoneal hemorrhage due to rupture of the horn, which can be life-threatening to the mother. Rarely, embryo is expelled into abdomen and remains attached to the horn and embryo continues to live and grow, which is referred as secondary abdominal pregnancy.

The usual outcome of the rudimentary horn pregnancy is rupture in the second trimester in about 90% of the cases with fetal demise, which can be catastrophic.2 Unlike tubal ectopic pregnancy, bleeding is more severe in rupture of the rudimentary horn, the uterine wall is much thicker and more vascular. The uterine rupture associated with rudimentary horn was first reported in 1669 by Mauriceau.9 The timing of rupture varies from 5 to 35 weeks depending on the horn musculature and its ability to hypertrophy and dilate. Maternal mortality due to rupture was 47.6% before 1,900 but no case of maternal death has been reported since 1,960.10 Few cases of pregnancies with late or false diagnosis which progressed to third trimester resulting in live births have been reported.11 Among these 33

Case Report neonatal survivability was only 6%.11 A patient with abdominal pregnancy typically presents with constant abdominal pain, progressive anemia and sudden loss of fetal movements.12 As the consequences of rupture can cause significant mortality and morbidity, early diagnosis is essential for management. However, the prerupture diagnosis of rudimentary horn pregnancy is challenging. A careful ultrasound in the first trimester and with a high index suspicion, one should be able to make a diagnosis of pregnancy in the rudimentary horn. Ultrasound examination is the usual diagnostic procedure of choice, but the findings are sometimes questionable. They are dependent on the examinerâ&#x20AC;&#x2122;s experience and the quality of the ultrasound. Transvaginal ultrasound is superior to transabdominal ultrasound in the evaluation of ectopic pregnancy, since it allows a better view of the adnexa and uterine cavity. Tsafrir et al have proposed a set of criteria for diagnosing pregnancy in the rudimentary horn: (1) a pseudo pattern of asymmetrical bicornuate uterus; (2) absent visual continuity tissue surrounding the gestational sac and the uterine cervix and (3) presence of myometrial tissue surrounding the gestational sac.13 The sensitivity of ultrasound is only 26% and sensitivity decreases as the pregnancy advances.14 In such cases, magnetic resonance imaging (MRI) is very useful not only in confirming the diagnosis, but it also helps in planning of the surgery.15 Tubal pregnancy, cornual pregnancy and abdominal pregnancy are common sonographic and clinical misdiagnosis. It is very difficult to establish diagnosis in second trimester due to lack of definitive clinical criteria.

The traditional and established treatment for rudimentary horn pregnancy is surgical removal of the pregnant horn even in unruptured case to prevent rupture and recurrent rudimentary horn pregnancy. In this, case laparatomy was performed and excision of the rudimentary horn was done successfully. Laparoscopic excision of the rudimentary horn pregnancy prior to rupture has been done successfully since last two decades.16 Renal anomalies are found in 36% of cases; hence, it is mandatory to assess renal anomalies by scan.

Conclusion Rudimentary horn pregnancy is a rare complication, which carries grave risk to the mother. More than 90% of the cases present in second trimester with 34

intraperitoneal hemorrhage due to rupture of the horn.

Diagnosis prior to rupture should be the concern in early pregnancy with either ultrasound or MRI to prevent life-threatening complications. The recent trend is to do laparoscopic excision of the rudimentary horn; laparotomy is still an option when the patient has developed abundant hemoperitoneum or is in shock.

References 1. Reichman D, Laufer MR, Robinson BK. Pregnancy outcomes in unicornuate uteri: a review. Fertil Steril.

2009;91:1886-94.

2. O'Leary JL, O'Leary JA. Rudimentary horn pregnancy.

Obstet Gynecol. 1963;22:371-5.

3. Yildizhan R, Kurdoglu M, Kolusari A, Erten R. Primary omental pregnancy. Saudi Med J. 2008;29:606-9.

4. Ludwig M, Kaisi M, Bauer O, Diedrich K. The forgotten child: a case of heterotopic, intra-abdominal and intrauterine pregnancy carried to term. Hum Reprod. 1999;14:1372-4.

5. Alto WA. Abdominal pregnancy. Am Fam Physician.

1990;41:209-14.

6. Ang LP, Tan AC, Yeo SH. Abdominal pregnancy: a case report and literature review. Singapore Med J. 2000;41:454-7.

7. Maas DA, Slabber CF: Diagnosis and treatment of advanced extra-uterine pregnancy. S Afr Med J. 1975;49:2007-10.

8. Studdiford WE. Primary peritoneal pregnancy. Am J Obstet Gynecol. 1942;44:487-91.

9. Mauriceau F. Traite des maladies des femmes Grosses vol. 1.

Paris, France: Compaigne des libraries; 1721. p. 4.

10. Nahum GG. Rudimentary uterine horn pregnancy. The 20th-century worldwide experience of 588 cases. J Reprod Med. 2002;47:151-63.

11. Shin JW, Kim HJ. Case of live birth in a non-communicating rudimentary horn pregnancy. J Obstet Gynaecol Res. 2005;31:329-31.

12. Shanbhag A, Singh A. Secondary intra-abdominal pregnancy: a case report. NJOG. 2011;6(2):44-6 13. Tsafrir A, Rojansky N, Sela HY, Gomori JM, Nadjari M. Rudimentary horn pregnancy: first-trimester prerupture sonographic diagnosis and confirmation by magnetic resonance imaging. J Ultrasound Med. 2005;24:219-23.

14. Jayasinghe Y, Rane A, Stalewski H, Grover S. The presentation and early diagnosis of the rudimentary uterine horn. Obstet Gynecol. 2005;105:1456-67.

15. Lawhon BP, Wax JR, Dufort RT. Rudimentary uterine horn pregnancy diagnosed with magnetic resonance imaging.

Obstet Gynecol. 1998;91(5 Pt 2):869.

16. Sharma D, Usha MG, Gaikwad R, Sudha S. Laparoscopic resection of unruptured rudimentary horn pregnancy. Int J Reprod Contracept Obstet Gynecol. 2013;2:95-8.

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

clinical study

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

35

JOURNAL SCAN

A Zinc-based Mechanism Regulates Meiotic Progression in Mammalian Oocytes Adequate regulation of meiotic progression is an important determinant of an egg's ability to be fertilized successfully, and zinc has evolved as an important regulatory factor for this function. An initial development of a regulatory role for this transition metal is the substantial rise in total intracellular zinc. This accumulation is essential for meiotic progression beyond telophase I and the establishment of meiotic arrest at metaphase II. The subsequent developmental event, fertilization, results in a rapid expulsion of labile zinc that is a significant event in meiotic resumption. Study showed that the zinc fluxes work, in part, by altering the activity of the cytostatic factor (CSF), the cellular activity required for the establishment and maintenance of metaphase II arrest in the mature, unfertilized egg. A model in which zinc exerts concentration-based control of meiosis through the CSF component EMI2, a zinc-binding protein was proposed. Together, the data suggest the conclusion that zinc itself, through its interaction with EMI2, is a central component of the CSF. Source: Biol Reprod. 2012;86(4):114.

Resveratrol stops the release of soluble fms-like tyrosine kinase (sFlt-1) from human placenta Objective: Soluble vascular endothelial growth factor receptor-1 (also know as soluble fms-like tyrosine kinase [sFlt]-1) is an important etiological factor of pre-eclampsia.

Resveratrol, a plant phytoalexin, has anti-inflammatory and cardioprotective effects. A study was performed to analyze resveratrolâ&#x20AC;&#x2122;s efficacy on release of sFlt-1. Study design: Human umbilical vein endothelial cells, transformed human trophoblast-8 (HTR/SVneo)-8/SVneo trophoblast cells, or placental explants were incubated with cytokines and/or resveratrol. Conditioned media were assayed for sFlt-1 by enzyme-linked immunosorbent assay and cell proteins used for Western blotting. Results: Resveratrol stopped cytokineinduced release of sFlt-1 from normal placental explants and from pre-eclamptic placental explants. Preincubation of human umbilical vein endothelial cells or HTR-8/SVneo cells with resveratrol abrogated sFlt-1 release. Resveratrol prevented the upregulation of early growth response protein-1 (Egr-1), a transcription factor essential for induction of the vascular endothelial growth factor receptor-1 gene and caused up-regulation of heme oxygenase-1, a cytoprotective enzyme found to be dysfunctional in pre-eclampsia.

Conclusion: Hence, resveratrol can stop sFlt-1 release and

36

upregulate heme oxygenase-1; and therefore, may provide treatment benefit in pre-eclampsia.

Source: Am J Obstet Gynecol. 2012;206(3):253.

Advantages of the Association of Resveratrol with Oral Contraceptives for Management of Endometriosis-related Pain A study was conducted to assess the effects of resveratrol on the management of endometriosis-related pain in 12 patients who failed to obtain pain relief with an oral contraceptive containing drospirenone + ethinylestradiol. Researchers noted that the addition of 30 mg of resveratrol to the contraceptive regimen led to a significant reduction in pain scores, with 82% of patients reporting complete resolution of dysmenorrhea and pelvic pain after 2 months of use.

In a separate experiment, aromatase and cyclooxygenase-2 expression were monitored in the endometrial tissue of 42 patients submitted to laparoscopy and hysteroscopy for the management of endometriosis. Sixteen of these patients were using oral contraceptives alone prior to hospital admission, while the remaining 26 were using them in combination with resveratrol. It appeared that the inhibition of both aromatase and cyclooxygenase-2 expression was significantly more in the eutopic endometrium of patients using combined drospirenone + resveratrol therapy compared with the endometrium of patients using oral contraceptives alone. The results thus highlight that resveratrol potentiates the effect of oral contraceptives in the management of endometriosis-associated dysmenorrhea by further reducing aromatase and cyclo-oxygenase-2 expression in the endometrium.

Source: Maia Jr H, Haddad C, Pinheiro N, Casoy J. International Journal of Women's Health. 2012;4:543-9.

Resveratrol Suppresses Inflammatory Responses in Endometrial Stromal Cells Derived from Endometriosis: A Possible Role of the Sirtuin 1 Pathway Endometriosis signifies a chronic inflammatory disease.

Sirtuin 1 (SIRT1) is known to play a pivotal role in the regulation of inflammation. The role of SIRT1 in endometriosis is not clearly known. A novel research assessed the anti-inflammatory effects of SIRT1 on endometriosis.

The expression of SIRT1 in human ovarian endometriomas and eutopic endometria were evaluated using immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Endometriotic stromal cells Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

JOURNAL SCAN (ESCs) attained from endometriomas were exposed to either resveratrol or sirtinol, an activator or inhibitor of sirtuins, respectively. Researchers intended to assess the release of tumor necrosis factor (TNF)-α-induced interleukin (IL)-8 from the ESC at mRNA and protein levels.

Both immunochemistry and RT-PCR demonstrated that SIRT1 was expressed in ESC and normal endometrial stromal cells. Resveratrol tends to suppress TNF-α-induced IL-8 release from the ESC in a dose-dependent manner while sirtinol increased IL-8 release. The results thus suggest that IL-8 release from the ESC is modulated through the SIRT1 pathway and that resveratrol may have the potential to ameliorate local inflammation in endometriomas.

Source: Taguchi A, Wada-Hiraike O, Kawana K, et al. Journal of Obstetrics and Gynaecology Research. 2014;40(3):770-8..

A Pilot Clinical Study of Resveratrol in Postmenopausal Women with High Body Mass Index: Effects on Systemic Sex Steroid Hormones Breast cancer risk is partly determined by several hormonerelated factors. Preclinical and clinical evidence point that resveratrol may alter these hormonal factors. Chow et al recently conducted a pilot study in postmenopausal women with high body mass index (BMI ≥ 25 kg/m2) to ascertain the clinical effect of resveratrol on systemic sex steroid hormones. Forty subjects were randomized to receive resveratrol intervention (1 gm daily for 12 weeks); however six withdrew early due to adverse events (AEs). Thirty-four subjects completed the intervention. Resveratrol intervention did not result in significant changes in serum concentrations of estradiol, estrone, and testosterone but led to an average of 10% increase in the concentrations of sex steroid hormone binding globulin (SHBG). Resveratrol brought about a 73% increase in urinary 2-hydroxyestrone (2-OHE1) levels leading to a favorable change in urinary 2-OHE1/16α-OHE1 ratio.

One participant had asymptomatic Grade 4 elevation of liver enzymes at the end of study intervention. Two subjects had Grade 3 skin rashes. The remaining adverse events were Grade 1 or 2 events. The most common adverse events were diarrhea and increased total cholesterol, reported in 30% and 27.5% of the subjects, respectively. Researchers thus concluded that among overweight and obese postmenopausal women, daily 1 gm dose of resveratrol has favorable effects on estrogen metabolism and SHBG. Source: Chow HHS, Garland LL, Heckman-Stoddard BM, et al. Journal of Translational Medicine. 2014;12:223.

Resveratrol Effect on Ovarian Response to Controlled Ovarian Hyperstimulation in ob/ob Mice Objective: To analyze antidiabetic and anti-inflammatory role of resveratrol on the ovarian response to controlled ovarian hyperstimulation (COH) in obesity-linked Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

infertility. Design: Experimental. Setting: University laboratory. Animal(s): Sixteen female ob/ob mice and 16 female C57BL/6J mice undergoing COH. Intervention(s): Wild-type placebo group; wild-type resveratrol group; ob/ ob mice placebo group; ob/ob mice resveratrol group.

Resveratrol 3.75 mg/kg daily for 20 days and undergoing COH protocol. Main outcome measure(s): Body and reproductive system weight, food consumption, fasting blood glucose, plasma insulin and T levels, and homeostatic index of insulin resistance; interleukin-6 and tumor necrosis factor-α levels in adipose tissue by Western blot; assessment of quality and quantity of oocytes retrieved; and quantitative analysis of ovarian follicles. Result(s): Plasma insulin and T levels decreased and homeostatic index of insulin resistance improved in ob/ob mice treated with resveratrol.

Interleukin-6 and tumor necrosis factor-α levels were substantially returned back to near normalcy post resveratrol therapy in obese mice. Administration of resveratrol resulted in a significantly higher number of oocytes collected in wildtype mice. The number of primary, growing, preovulatory, and atretic follicles was found to be decreased in the group of obese mice treated with resveratrol when compared with the obese control group. Conclusion(s): Resveratrol administration could have benefits against loss of ovarian follicles, and these actions may be partly due to antiinflammatory, insulin-sensitizing, and antihyperandrogenism effects. These observations further validate the therapeutic potential of resveratrol to protect ovarian reserve in conditions associated with obesity. The results suggest the possible clinical use of resveratrol to enhance the ovarian response to COH in normal-weight females.

Source: Fertil Steril. 2015;103(2):570-9.

Folic Acid: Prevention of Neural Tube Defects The American Academy of Pediatrics supports the US Public Health Service (USPHS) recommendation that all females capable of becoming pregnant consume 400 μg of folic acid daily to prevent neural tube defects (NTDs). Studies have shown that periconceptional folic acid supplementation can prevent 50% or more of NTDs such as spina bifida and anencephaly. For females who have previously had an NTDaffected pregnancy, the Centers for Disease Control and Prevention (CDC) recommends raising the consumption of folic acid to 4,000 μg per day starting at least 1 month before conception and continuing through the first trimester.

Implementation of these recommendations is important for the primary prevention from such serious and disabling birth problems. Since less than 1 in 3 females take the quantity of folic acid advised by the USPHS, the Academy notes that the prevention of NTDs depends on an immediate and efficacious campaign to close this prevention gap.

Source: Pediatrics. 1999;104(2):325-7.

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