Child Neurodevelopment After Multidomain Interventions From Preconception Through Early Childhood: The WINGS Randomized Clinical Trial.

Importance: Multidomain interventions in pregnancy and early childhood have improved child neurodevelopment, but little is known about the effects of additional preconception interventions. Objective: To evaluate the effect of a multifaceted approach including health; nutrition; water, sanitation, and hygiene (WASH); and psychosocial support interventions delivered during the preconception period and/or during pregnancy and early childhood on child neurodevelopment. Design, Setting, and Participants: In this randomized trial involving low- and middle-income neighborhoods in Delhi, India, 13 500 participants were assigned to preconception interventions or routine care for the primary outcome of preterm births and childhood growth. Participants who became pregnant were randomized to pregnancy and early childhood interventions or routine care. Neurodevelopmental assessments, the trial's secondary outcome reported herein, were conducted in a subsample of children at age 24 months, including 509 with preconception, pregnancy, and early childhood interventions; 473 with preconception interventions alone; 380 with pregnancy and early childhood interventions alone; and 350 with routine care. This study was conducted from November 1, 2000, through February 25, 2022. Interventions: Health, nutrition, psychosocial care and support, and WASH interventions delivered during preconception, pregnancy, and early childhood periods. Main Outcomes and Measures: Cognitive, motor, language, and socioemotional performance at age 24 months, assessed using the Bayley Scales of Infant and Toddler Development 3 tool. Results: The mean age of participants at enrollment was 23.8 years (SD, 3.0 years). Compared with the controls at age 24 months, children in the preconception intervention groups had higher cognitive scores (mean difference [MD], 1.16; 98.3% CI, 0.18-2.13) but had similar language, motor, and socioemotional scores as controls. Those receiving pregnancy and early childhood interventions had higher cognitive (MD, 1.48; 98.3% CI, 0.49-2.46), language (MD, 2.29; 98.3% CI, 1.07-3.50), motor (MD, 1.53; 98.3% CI, 0.65-2.42), and socioemotional scores (MD, 4.15; 98.3% CI, 2.18-6.13) than did controls. The pregnancy and early childhood group also had lower incidence rate ratios (RRs) of moderate to severe delay in cognitive (incidence RR, 0.62; 98.3% CI, 0.40-0.96), language (incidence RR, 0.73; 98.3% CI, 0.57-0.93), and socioemotional (incidence RR, 0.49; 98.3% CI, 0.24-0.97) development than did those in the control group. Children in the preconception, pregnancy, and early childhood intervention group had higher cognitive (MD, 2.60; 98.3% CI, 1.08-4.12), language (MD, 3.46; 98.3% CI, 1.65-5.27), motor (MD, 2.31; 98.3% CI, 0.93-3.69), and socioemotional (MD, 5.55; 98.3% CI, 2.66-8.43) scores than did those in the control group. Conclusions and Relevance: Multidomain interventions during preconception, pregnancy and early childhood led to modest improvements in child neurodevelopment at 24 months. Such interventions for enhancing children's development warrant further evaluation. Trial Registration: Clinical Trials Registry-India CTRI/2017/06/008908.

Burden, risk factors and outcomes associated with adequately treated hypothyroidism in a population-based cohort of pregnant women from North India.

Hypothyroidism is the commonest endocrine disorder of pregnancy, with known adverse feto-maternal outcomes. There is limited data on population-based prevalence, risk factors and outcomes associated with treatment of hypothyroidism in early pregnancy. We conducted analysis on data from an urban and peri-urban low to mid socioeconomic population-based cohort of pregnant women in North Delhi, India to ascertain the burden, risk factors and impact of treatment, on adverse pregnancy outcomes- low birth weight, prematurity, small for gestational age and stillbirth. This is an observational study embedded within the intervention group of the Women and Infants Integrated Interventions for Growth Study, an individually randomized factorial design trial. Thyroid stimulating hormone was tested in 2317 women in early (9-13 weeks) pregnancy, and thyroxin replacement started hypothyroid (TSH ≥2.5mIU/mL). Univariable and multivariable generalized linear model with binomial family and log link were performed to ascertain risk factors associated with hypothyroidism and association between hypothyroidism and adverse pregnancy outcomes. Of 2317 women, 29.2% (95% CI: 27.4 to 31.1) had hypothyroidism and were started on thyroxin replacement with close monitoring. Overweight or obesity was associated with increased risk (adjusted RR 1.29, 95% CI 1.10 to 1.51), while higher hemoglobin concentration was associated with decreased risk (adjusted RR 0.93, 95% CI 0.88 to 0.98 for each g/dL) for hypothyroidism. Hypothyroid women received appropriate treatment with no increase in adverse pregnancy outcomes. Almost a third of women from low to mid socio-economic population had hypothyroidism in early pregnancy, more so if anemic and overweight or obese. With early screening and adequate replacement, adverse pregnancy outcomes may be avoided. These findings highlight the need in early pregnancy for universal TSH screening and adequate treatment of hypothyroidism; as well as for attempts to reduce pre and peri-conception overweight, obesity and anemia. Clinical trial registration: Clinical trial registration of Women and Infants Integrated Interventions for Growth Study Clinical Trial Registry-India, #CTRI/2017/06/008908; Registered on: 23/06/2017, (http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies).

Procalcitonin levels in maternal serum and cord blood as marker for diagnosis of early onset neonatal sepsis.

Objectives: To assess the diagnostic accuracy of Procalcitonin in maternal serum and umbilical cord blood samples to predict Early onset neonatal sepsis (EONS). Study Design: It was a Prospective analytical cohort study. Pregnant women ≥ 34 weeks gestation in active labour, with risk factors for EONS were included in the study. Maternal blood samples at recruitment and umbilical cord blood samples after delivery were taken for Total leucocyte count (TLC), high sensitivity C-Reactive Protein (hs-CRP) and Procalcitonin. Newborns were classified into non-infected, suspected and proven infection. Sensitivity, specificity and diagnostic accuracy of maternal and cord blood procalcitonin, TLC and hs-CRP were calculated. Results: A total of 200 women were recruited. Maternal procalcitonin had a superior diagnostic accuracy of 99% compared to maternal TLC and maternal hs-CRP. Also, cord blood procalcitonin had a diagnostic accuracy of 95%. Conclusion: Procalcitonin in both maternal as well as cord blood is a promising biomarker to detect EONS with high diagnostic accuracy.

Evaluation of acceptability, safety, and continuation rates of centchroman as postabortion nonsteroidal contraceptive pill.

OBJECTIVES: To evaluate acceptability, safety, and continuation rates of centchroman following abortion. STUDY DESIGN: Prospective, observational study. Following spontaneous/induced abortion, women were offered centchroman, 30-mg tablet twice weekly for first 3 months, then once weekly with 1 year of follow-up. RESULTS: Of 120 women who opted for centchroman, continuation rate was 91% at 12 months. There was one case of user failure and one method failure and 26% had infrequent cycles. CONCLUSIONS: Centchroman is safe, effective, has good acceptance, and continuation rate post abortion with infrequent menstrual cycles as the main limiting factor for its continuation. IMPLICATIONS: Centchroman, available in Government scheme for contraception, has good acceptance and continuation rate post abortion. Its inclusion in contraceptive choices offered for postabortion contraception can go a long way in spacing of pregnancies, decreasing repeated unintended pregnancies, unsafe abortions, maternal morbidity, and mortality.

Impact of a package of health, nutrition, psychosocial support, and WaSH interventions delivered during preconception, pregnancy, and early childhood periods on birth outcomes and on linear growth at 24 months of age: factorial, individually randomised controlled trial.

OBJECTIVE: To determine the effect of integrated and concurrent delivery of health, nutrition, water, sanitation and hygiene (WaSH), and psychosocial care interventions during the preconception period alone, during pregnancy and early childhood, and throughout preconception, pregnancy, and early childhood on birth outcomes and linear growth at 24 months of age compared with routine care. DESIGN: Individually randomised factorial trial. SETTING: Low and middle income neighbourhoods of Delhi, India. PARTICIPANTS: 13 500 women were randomised to receive preconception interventions (n=6722) or routine care (n=6778). 2652 and 2269 pregnant women were randomised again to receive pregnancy and early childhood interventions or routine care. The analysis of birth outcomes included 1290 live births for the preconception, pregnancy, and early childhood interventions (group A), 1276 for the preconception intervention (group B), 1093 for the pregnancy and early childhood interventions (group C), and 1093 for the control (group D). Children aged 24 months by 30 June 2021 were included in the 24 month outcome analysis (453 in group A, 439 in B, 293 in C, and 271 in D). INTERVENTIONS: Health, nutrition, psychosocial care and support, and WaSH interventions were delivered during preconception, pregnancy, and early childhood periods. MAIN OUTCOME MEASURES: The primary outcomes were low birth weight, small for gestational age, preterm, and mean birth weight. At 24 months, the outcomes were mean length-for-age z scores and proportion stunted. Three prespecified comparisons were made: preconception intervention groups (A+B) versus no preconception intervention groups (C+D); pregnancy and early childhood intervention groups (A+C) versus routine care during pregnancy and early childhood (B+D) and preconception, pregnancy, and early childhood interventions groups (A) versus control group (D). RESULTS: The proportion with low birth weight was lower in the preconception intervention groups (506/2235) than in the no preconception intervention groups (502/1889; incidence rate ratio 0.85, 98.3% confidence interval 0.75 to 0.97; absolute risk reduction -3.80%, 98.3% confidence interval -6.99% to -0.60%). The proportion with low birth weight was lower in the pregnancy intervention groups (502/2096) than in the no pregnancy intervention groups (506/2028) but the upper limit of the confidence interval crossed null effect (0.87, 0.76 to 1.01; -1.71%, -4.96% to 1.54%). There was a larger effect on proportion with low birth weight in the group that received interventions in the preconception and pregnancy periods (267/1141) compared with the control group (267/934; 0.76, 0.62 to 0.91; -5.59%, -10.32% to -0.85%). The proportion stunted at 24 months of age was substantially lower in the pregnancy and early childhood intervention groups (79/746) compared with the groups that did not receive these interventions (136/710; 0.51, 0.38 to 0.70; -8.32%, -12.31% to -4.32%), and in the group that received preconception, pregnancy, and early childhood interventions (47/453) compared with the control group (51/271; 0.49, 0.32 to 0.75; -7.98%, -14.24% to -1.71%). No effect on stunting at 24 months was observed in the preconception intervention groups (132/892) compared with the no preconception intervention groups (83/564). CONCLUSIONS: An intervention package delivered during preconception, pregnancy, and early childhood substantially reduced low birth weight and stunting at 24 months. Pregnancy and early childhood interventions alone had lower but important effects on birth outcomes and 24 month outcomes. Preconception interventions alone had an important effect on birth outcomes but not on 24 month outcomes. TRIAL REGISTRATION: Clinical Trial Registry-India CTRI/2017/06/008908.

Burden, risk factors and outcomes associated with gestational diabetes in a population-based cohort of pregnant women from North India.

BACKGROUND: The burden of gestational diabetes mellitus (GDM) appears to be increasing in India and may be related to the double burden of malnutrition. The population-based incidence and risk factors of GDM, particularly in lower socio-economic populations, are not known. We conducted analyses on data from a population-based cohort of pregnant women in South Delhi, India, to determine the incidence of GDM, its risk factors and association with adverse pregnancy outcomes (stillbirth, preterm birth, large for gestational age babies) and need for caesarean section. METHODS: We analyzed data from the intervention group of the Women and Infants Integrated Interventions for Growth Study (WINGS), an individually randomized factorial design trial. An oral glucose tolerance test (OGTT) was performed at the time of confirmation of pregnancy, and for those who had a normal test (≤140 mg), it was repeated at 24-28 and at 34-36 weeks. Logistic regression was performed to ascertain risk factors associated with GDM. Risk ratios (RR) were calculated to find association between GDM and adverse pregnancy outcomes and need for caesarean section. RESULTS: 19.2% (95% CI: 17.6 to 20.9) pregnant women who had at least one OGTT were diagnosed to have GDM. Women who had prediabetes at the time of confirmation of pregnancy had a significantly higher risk of developing GDM (RR 2.08, 95%CI 1.45 to 2.97). Other risk factors independently associated with GDM were woman's age (adjusted OR (AOR) 1.10, 95% CI 1.06 to 1.15) and BMI (AOR 1.04, 95% CI 1.01 to 1.07). Higher maternal height was found to be protective factor for GDM (AOR 0.98, 95% CI 0.96 to 1.00). Women with GDM, received appropriate treatment did not have an increase in adverse outcomes and no increased need for caesarean section CONCLUSIONS: A substantial proportion of pregnant women from a low to mid socio-economic population in Delhi had GDM, with older age, higher BMI and pre-diabetes as important risk factors. These findings highlight the need for interventions for prevention and provision of appropriate management of GDM in antenatal programmes. CLINICAL TRIAL REGISTRATION: Clinical Trial Registry - India, #CTRI/2017/06/008908 ( http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies ).

A Cross-Sectional Study of Barriers in Prevention of Anemia in Pregnancy.

Introduction Anemia in pregnancy is a significant health challenge in India and other developing countries. Various health programs aiming anemia prevention are existing in India for many decades. Despite that, anemia affects more than half of pregnant women. Our objective for performing this study was to evaluate the barriers in the prevention of anemia and to evaluate the perceptions and practices of anemic women towards their condition. Methods A cross-sectional questionnaire-based study, including 210 anemic women, was conducted in a tertiary care center in Delhi, India. In-depth interviews were conducted with 50 participants. Results Our important observations were that anemia was more prevalent in multigravida, and 43.80% of anemic patients were not taking iron supplements at the time of diagnosis. Chronic diseases were associated with 28.2% (n=59) of anemic women. Only 19% (n=40) of women sought antenatal care in the first and second trimester; the rest all booked themselves in the third trimester only. Twenty-two percent (n=48) of women reached our hospital after 36 weeks. Ignorance to anemia symptoms and the importance of consistent intake of the oral iron supplements was seen in 35.2% (n=74). One hundred and sixty-five (74.8%) women accepted that healthcare provider had informed them about iron-rich and high protein diet, but only 47.1% (n=98) actually made dietary modifications. Only 9.5% (n=20) of women were consistent in iron intake. Side effects of iron were reported by 30% (n=64) of women, and 15% (n=32) were intolerant to oral iron. Non-availability, change of residence, and forgetfulness were the main reasons behind non-compliance to oral iron. Conclusion We emphasize motivation for early registration, regular antenatal care, adequate iron supplement supply, and persistent counseling to ensure compliance to iron supplements by the antenatal care provider. Behavior-changing communication is needed at a societal level for antenatal mothers and their families aiming to prevent anemia in pregnancy instead of focussing on treatment.

Management of cervical cancer during the corona virus disease-19 (COVID-19) era.

COVID-19 pandemic has had a catastrophic impact on the society, economy and heath-care system all over the globe with virus showing no signs of losing potency. As the situation appears to worsen, extra burden on other specialities like oncology seems to increase. Specific recommendations are necessary for management of cervical cancer in the current context. All concerned specialities must work together in the best interest of the patient. Attempts should be made at managing cervical cancer while limiting the viral spread among the patients and health-care workers without the loss of opportunity. Surgical intervention for early cervical cancer should be postponed or alternative modalities be considered. In a locally advanced disease, concurrent chemoradiation is the treatment of choice. In addition, the following under mentioned suggestions aim to discuss ways of minimizing infection spread, workload rationalization and providing guidance for management of cervical cancer in the presence of COVID-19 infection.

Burden of preconception morbidity in women of reproductive age from an urban setting in North India.

BACKGROUND: There is a growing interest in the life course approach for the prevention, early detection and subsequent management of morbidity in women of reproductive age to ensure optimal health and nutrition when they enter pregnancy. Reliable estimates of such morbidities are lacking. We report the prevalence of health or nutrition-related morbidities, specifically, anemia, undernutrition, overweight and obesity, sexually transmitted infections (STIs) or reproductive tract infections (RTIs), diabetes or prediabetes, hypothyroidism, hypertension, and depressive symptoms, during the preconception period among women aged 18 to 30 years. METHODS: A cross-sectional study was conducted among 2000 nonpregnant married women aged 18 to 30 years with no or one child who wished to have more children in two low- to middle-income urban neighborhoods in Delhi, India, in the context of a randomized controlled trial. STIs and RTIs were measured by symptoms and signs, blood pressure by a digital device, height by stadiometer and weight by a digital weighing scale. A blood specimen was taken to screen for anemia, diabetes, thyroid disorders and syphilis. Maternal depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Multivariable logistic regression analysis was performed to identify sociodemographic factors associated with individual morbidity. RESULTS: Overall, 58.7% of women were anemic; 16.5%, undernourished; 26%, overweight or obese; 13.2%, hypothyroid; and 10.5% with both symptoms and signs of STIs/RTIs. There was an increased risk of RTI/STI symptoms and signs in undernourished women and an increased risk of diabetes or prediabetes in overweight or obese women. An increased risk of undernutrition was also observed in women from lower categories of wealth quintiles. A decreased risk of moderate to severe anemia was seen in overweight women and those who completed at least secondary education. CONCLUSIONS: Our findings show a high burden of undernutrition, anemia, RTIs, hypothyroidism and prediabetes among women in the study. This information will aid policymakers in planning special programs for women of reproductive age.

Impact of an integrated nutrition, health, water sanitation and hygiene, psychosocial care and support intervention package delivered during the pre- and peri-conception period and/or during pregnancy and early childhood on linear growth of infants in the first two years of life, birth outcomes and nutritional status of mothers: study protocol of a factorial, individually randomized controlled trial in India.

BACKGROUND: The period from conception to two years of life denotes a critical window of opportunity for promoting optimal growth and development of children. Poor nutrition and health in women of reproductive age and during pregnancy can negatively impact birth outcomes and subsequent infant survival, health and growth. Studies to improve birth outcomes and to achieve optimal growth and development in young children have usually tested the effect of standalone interventions in pregnancy and/or the postnatal period. It is not clearly known whether evidence-based interventions in the different domains such as health, nutrition, water sanitation and hygiene (WASH) and psychosocial care, when delivered together have a synergistic effect. Further, the effect of delivery of an intervention package in the pre and peri-conception period is not fully understood. This study was conceived with an aim to understand the impact of an integrated intervention package, delivered across the pre and peri-conception period, through pregnancy and till 24 months of child age on birth outcomes, growth and development in children. METHODS: An individually randomized controlled trial with factorial design is being conducted in urban and peri-urban low- to mid-socioeconomic neighbourhoods in South Delhi, India. 13,500 married women aged 18 to 30 years will be enrolled and randomized to receive either the pre and peri-conception intervention package or routine care (first randomization). Interventions will be delivered until women are confirmed to be pregnant or complete 18 months of follow up. Once pregnancy is confirmed, women are randomized again (second randomization) to receive either the intervention package for pregnancy and postnatal period or to routine care. Newborns will be followed up till 24 months of age. The interventions are delivered through different study teams. Outcome data are collected by an independent outcome ascertainment team. DISCUSSION: This study will demonstrate the improvement that can be achieved when key factors known to limit child growth and development are addressed together, throughout the continuum from pre and peri-conception until early childhood. The findings will increase our scientific understanding and provide guidance to nutrition programs in low- and middle-income settings. TRIAL REGISTRATION: Clinical Trial Registry - India #CTRI/2017/06/008908; Registered 23 June 2017, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies.

Changing Scenario in Indian Contraceptive Methods: A Glimpse Through a Tertiary Hospital Statistics.

BACKGROUND: The patient scenario of a tertiary hospital changes with the implementation of various national programmes in any country. These programmes are conceived after understanding the felt need of the society. Though IUCD was available as an interval method of contraception in the past also and was meant to be effective for 10 years, the prerequisite to come again to the medical facility after 6 weeks of childbirth for insertion resulted in almost all patients to dropout and only the highly motivated would come on their own. Post-partum insertion of IUCD at the time of childbirth or within 48 h has addressed the need of contraception in the post-partum period as well as omitted the need for second visit to a health set-up. Earlier, after achieving the desired family goal of children, tubectomy was the preferred choice, irrespective of age of children but PPIUCD seems to have come up as a long-term reversible method of contraception. OBJECTIVE: The present study was conceived to study the shift of method of long-term contraception from tubal sterilization and vasectomy to PPIUCD over a period of 8 years from 2010 to 2017. METHOD: This study was a retrospective analytical study conducted at the Department of Obstetrics and Gynaecology in Safdarjung Hospital between the years 2010 and 2017. The number of IUCDs inserted post-placental (i.e. within 10 min of delivery of placenta) and within 48 h (of vaginal childbirth) and intra-caesarean (intrauterine insertion while performing caesarean) were recorded and analysed. Also, sterilizations (tubectomy) and interval IUCD insertions done during this time period were compared. RESULTS: With the introduction of PPIUCD in national family programme, more women are inclining towards long-term spacing method and not resorting to sterilizations. PPIUCD is preferred over interval IUCD. CONCLUSIONS: PPIUCD is there to stay as a method of long-term contraception.

Diagnostic Performance of Serum Human Epididymis Protein 4 (HE4) for Prediction of Malignancy in Ovarian Masses

Background: Early diagnosis of ovarian cancer is essential for long term disease control and mortality reduction. This has been achieved using tumor markers like cancer antigen 125 (CA-125) which is elevated in malignant as well as non-malignant conditions. This dilemma led to efforts towards development of newer markers like serum human epididymis secretory protein E4 (HE4). Present study aimed to evaluate role of HE4 in diagnosing ovarian cancers and comparing it with CA-125. Methods: Serum samples from 67 patients with ovarian cancer, 42 with benign ovarian masses and 26 healthy controls were collected preoperatively and tested for serum HE4 levels and CA-125 levels. Diagnostic performance of both tumor markers (HE4/CA-125) to diagnose malignancy in ovarian masses was calculated and compared to each other. Results: Mean CA-125 and HE4 levels were significantly higher in patients with ovarian cancer than in those with benign disease (p<0.001) or healthy controls (p< 0.001). Serum HE4 levels significantly increased in epithelial ovarian cancers when compared to non-epithelial ovarian cancers (p<0.01). Using benign control as comparison, receiver operating characteristic curve (ROC) was generated to predict a cut-off value for diagnosing malignancy for serum HE4 and CA-125. Compared to CA-125, HE4 had a similar sensitivity (83.6% vs. 85.10%) and higher specificity (100% vs. 90.48%); combination of serum HE4 and CA-125 improved the sensitivity to detect ovarian cancer to 92.54%. Sensitivity of HE4 to detect early stage ovarian cancer was superior to CA-125 (92.61% vs. 63.41%). Conclusion: Serum HE4, a novel tumor marker, discriminated epithelial ovarian cancer from benign ovarian masses. HE4 levels were related to the stage and histological types with the lowest levels in mucinous epithelial ovarian cancer and non-epithelial malignancy. Measuring serum HE4 levels alongwith CA-125 may provide higher accuracy for detecting epithelial ovarian cancer particularly in the early stages.

Early IUD insertion after medically induced abortion.

OBJECTIVE: There is insufficient evidence on the continuation, safety and acceptability of immediate insertion of the intrauterine device (IUD) after medical abortion. The objective of the present study was to evaluate clinical outcomes of early IUD insertion, compared with those of delayed IUD insertion, following medical abortion. METHODS: Women undergoing medical abortion with mifepristone and misoprostol up to 49 days' gestation and opting for Copper T 380A IUD contraception underwent early (5-14 days after mifepristone) or delayed insertion (3-4 weeks after mifepristone). The primary outcome measure was 6 month IUD continuation rate after medical abortion. Secondary outcome measures included user acceptability and safety. RESULTS: Between October 2015 and October 2016, post-medical abortion IUD insertion was performed in 120 eligible women fulfilling the inclusion and exclusion criteria. There was no statistically significant difference in the continuation rates of the early and delayed IUD insertion groups at 6 months (76.7 versus 83.3%, p = .75). The 6 month IUD expulsion rates were 6.7 and 3.3% in the early and delayed insertion groups, respectively (p = .56). There were 10 (16.7%) removals in the early and eight (13.3%) in the delayed insertion groups (p = .77). Level of satisfaction with postabortal IUD use was comparable in both groups. Adverse events were rare and did not differ significantly between the two groups. CONCLUSION: We demonstrated high continuation rates, safety and acceptability of early IUD insertion after medical abortion.

Primary Cutaneous Amyloidosis: A Clinical, Histopathological and Immunofluorescence Study.

INTRODUCTION: Primary Localized Cutaneous Amyloidosis (PLCA) is a relatively rare chronic condition characterized by amyloid deposition in dermis without associated deposits in internal organs. Histopathology of cutaneous amyloidosis using Haematoxylin and Eosin (H&E) stain shows eosinophilic hyaline material in papillary dermis, which can be further confirmed by Congo Red (CR) staining or Direct Immunofluorescence (DIF) Test or immunohistochemistry. AIM: To assess the concordance between the clinical, histo pathological and DIF findings in various subtypes of (PLCA). MATERIALS AND METHODS: Data was collected from patients attending the Outpatient Department (OPD) at a tertiary care centre in Karnataka, India, over a period of one and half years. A total of 50 patients with clinical features suggestive of cutaneous amyloidosis were subjected to histopathological examination with H&E, CR stain and immunofluorescence. RESULTS: Among 50 clinically suspected patients, the most common subtype was macular amyloidosis (70%) and lichen amyloidosis seen only in 16%. A biphasic pattern comprising of both macular and lichen amyloidosis was seen in 14% cases. Extensor aspect of the arm was the most frequently (76%) involved area. All the cases had multiple site involvement. Immunofluorescence positivity was 88% as compared to 86% on histopathology using CR stain. Amyloid deposits were detected in 80% of clinically diagnosed macular amyloidosis cases by histopathology using CR stain and in 85.7% by DIF, whereas in 5.7% cases, it was not detectable by both CR stain and DIF. Both immunofluorescence and CR staining were able to detect amyloid in all the cases of lichen amyloidosis. In biphasic amyloidosis, amyloid was detected in 100% cases on histopathology versus 85.7% cases on immunofluorescence. CONCLUSION: CR stain and DIF are complimentary to each other for detection of macular amyloidosis. In case of lichen and biphasic amyloidosis, both CR and DIF are comparable modalities.

Visibility of Strings After Postplacental Intracesarean Insertion of CuT380A and Cu375 Intrauterine Contraceptive Device: A Randomized Comparative Study.

OBJECTIVES: To compare the incidence of visible strings after postplacental intracesarean insertion of Cu375 and CuT380A intrauterine contraceptive devices (IUD). METHODS: This was a prospective, randomized comparative study. A total of 100 women fulfilling the inclusion and exclusion criteria underwent postplacental intracesarean insertion of either Cu375 IUD or CuT380A IUD. Women were followed up at 1, 6 weeks and 3 months after IUD insertion and were questioned about IUD expulsion or removal at each visit. The cervix was inspected to visualize the IUD strings. Data were analyzed by Chi-square test. RESULTS: At 6-week follow-up, 97.9% women in group A versus 41.7% women in group B had strings visible at the cervical os and at 3 months 100% women in group A versus only 47.9% women in group B (p < 0.001) had visible strings of IUD. CONCLUSION: Both Cu375 and CuT380A IUD are safe postpartum method of contraception but Cu375 if used for intracesarean IUD insertion increases the incidence of visible IUD strings. Hence, it avoids radiological investigations and invasive procedures at follow-up visits required to locate the IUD when strings are not visible. CTRI No. CTRI/2015/09/006221.

Diagnostic Performance of Serum Human Epididymis Protein 4 in Endometrial Carcinoma: A Pilot Study.

INTRODUCTION: Endometrial Cancer (EC) is a common female malignant disorder. To date, there are no specific tumour markers for EC that may be routinely used in clinical practice for diagnosis. AIM: To evaluate the diagnostic performance of the serum Human Epididymis protein 4 (HE4) as biomarker for EC and to determine its association with clinicopathological variables. MATERIALS AND METHODS: The study population included 60 postmenopausal women with a diagnosis of EC and 60 healthy postmenopausal female subjects (control group). Concentrations of serum HE4 and CA-125 in EC patients and control group were determined using Enzyme-Linked Immunosorbent Assays (ELISA). The value of serum HE4 and CA-125 for the diagnosis and prediction of stage, histology, myometrial invasion and lymph nodal metastasis was analysed. RESULTS: The mean serum HE4 and CA-125 levels were significantly higher in patients with EC than those with control group (p<0.05). Comparison for HE4 and CA-125 between different stages showed a statistically significant difference. Stage I EC patients with <50% myometrial invasion had a significantly lower mean serum HE4 value than patients with >50% myometrial invasion (p=0.007). Corresponding values of CA-125 showed a similar trend (p=0.023). There were significantly higher levels of HE4 and CA-125 in cases with lymph node involvement. The levels of serum HE4 and CA-125 were higher in the non-endometroid histology, but the difference was not statistically significant. The Receiver Operating Characteristics (ROC) curve analysis for EC and control group showed that HE4 had greater Area Under Curve (AUC) when compared with CA-125. Using ROC curve, a serum HE4 concentration of 69.8 pmol/l (AUC 0.974) and/or serum CA-125 level of 34.50 U/mL (AUC 0.714) was used to predict malignancy. Sensitivity of combined biomarkers showed no additional improvement in comparison to HE4 or CA-125 alone. CONCLUSION: Our results show that HE4 is a sensitive diagnostic serum marker for detection of EC patients, exhibiting a better diagnostic performance compared to CA-125. Good performance of HE4 in diagnosis of early stages EC indicates its usefulness as a prognostic marker and also to monitor therapy and detect early recurrence.

Non-visualisation of strings after postplacental insertion of Copper-T 380A intrauterine device.

AIM: To assess the incidence of visible strings of intrauterine contraceptive devices (IUDs) after postplacental insertion following vaginal or caesarean delivery and to establish a management protocol of follow-up visits when strings are not visualised. METHODS: This was a prospective study of a cohort of 348 women who underwent postplacental insertion of Copper-T 380A IUDs following vaginal or caesarean delivery, conducted at a hospital in New Delhi, India. Women were followed up at 6 weeks, 3, 6 and 12 months after IUD insertion and were questioned about IUD expulsion or removal at each visit. The cervix was inspected to visualise the IUD strings. All women whose IUD strings could not be visualised at the cervical os at any given follow-up were identified. We analysed the cumulative incidence of visible strings and of procedures performed to locate the IUD when strings were not visible. RESULTS: At 1 year follow-up, the IUD was in situ in 313/348 (89.9%) women. There were eight (2.3%) expulsions and 15 (4.3%) IUD removals. Among women with IUDs in situ, the strings were not visible in 73 (21%) cases. Pelvic ultrasound confirmed intrauterine position of the IUDs in these cases. At 1 year, string visibility was significantly lower after intra-caesarean insertions as compared to vaginal insertions (72.4% vs 98.1%; p<0.05). CONCLUSIONS: Visualisation of strings after postplacental vaginal insertion is more common than after intra-caesarean insertion. Pelvic ultrasonography can be used to verify the presence of the device in cases of missing strings.

A Dedicated Postpartum Intrauterine Device Inserter: Pilot Experience and Proof of Concept.

OBJECTIVE: To assess the feasibility, acceptability, and safety of a dedicated postpartum intrauterine device (PPIUD) inserter specifically designed for the post-delivery setting. Primary objectives of fundal placement and expulsion rates were assessed. Secondary objectives were participant satisfaction and IUD retention. METHODS: In this pilot proof of concept, we enrolled 80 women who presented for PPIUD insertion at 2 government hospitals in Delhi and Lucknow, India, between March and July 2015. PPIUD insertion was completed with the dedicated inserter in all cases, by trained providers with no prior experience in PPIUD insertion, followed immediately by ultrasound to assess location and fundal placement of the IUD. Follow-up took place at 6 to 8 weeks post-insertion, and ultrasound was used to assess IUD location. Providers and participants also completed satisfaction surveys. RESULTS: High fundal placement (≤10 mm from uterine fundus) was achieved with the dedicated PPIUD inserter in 82% of cases (n = 65). There were no perforations or infections among the participants and no other complications associated with use of the dedicated inserter. The mean distance between the IUD and the endometrial verge immediately post-insertion was 5.8 mm (range, 0-31; N = 80); this distance at follow-up was also 5.8 mm (range, 0-25; n = 50). Complete expulsion was observed in 6 cases (7.5%), and asymptomatic partial expulsion in 8 cases (10%). Providers reported the majority (93%, n = 74) of insertions to be easy. The majority (74%, n = 59) of participants reported the same level of pain before and after insertion. CONCLUSIONS: This dedicated PPIUD inserter performed as intended and was found to be safe, with high acceptability among the participants and providers. Further study and use of the dedicated inserter may reveal reduced risk of infection among PPIUD users as well as increased convenience compared with standard PPIUD insertion techniques, and could improve acceptability of postpartum IUD provision among providers. The success of this study has led to the initiation of a formal randomized controlled trial in India to further investigate the acceptability of the dedicated inserter.

Feto-maternal Outcome Using New Screening Criteria of Serum TSH for Diagnosing Hypothyroidism in Pregnancy.

INTRODUCTION: Evidence suggests that by using the classical non pregnant reference range for serum TSH (STSH), one might miss hypothyroidism in pregnancy. Therefore, upper normal cut off value of S TSH should be taken as <2.5 mIU/L in the first trimester and <3mIU/L in the second and third trimester. However, two Indian studies have reported higher trimester specific reference ranges in the Indian pregnant women. OBJECTIVES: To assess the maternal and fetal outcomes using new screening criteria with upper S TSH cut off as >3mIU/L, for diagnosing hypothyroidism in pregnancy. MATERIALS AND METHODS: This study was a cross sectional study, carried out in the Department of Obstetrics and Gynaecology of a tertiary care hospital, in collaboration with the Department of Endocrinology. Pregnant women with ≤ 20 weeks gestation, attending antenatal OPD from December 2010 to January 2012 were included in the study. On the basis of S TSH level, women were divided into Study Group with S TSH level between 3.1 to 6.2 mIU/L, (new range to be studied) and an equal number of age and parity matched Control Group with S TSH levels between 0.4 to 3 mIU/L. The maternal and fetal outcomes were compared between study and control groups. RESULTS: During the study period, a total of 66 women had S TSH between 3.1-6.2 mIU/L. Maternal and fetal outcomes in both the groups were comparable. There was no difference in the mode of delivery between study and control groups. CONCLUSION: The lower S TSH cut off recommended for diagnosing hypothyroidism in pregnancy may not be applicable to pregnant Indian women.

Clinical Outcome of Postplacental Copper T 380A Insertion in Women Delivering by Caesarean Section.

INTRODUCTION: Short interconception period after caesarean section and its associated risk of increased morbidity, mortality and surgical interventions could be avoided by postplacental IUCD insertion during the procedure. Despite the safety reports on intracaesarean IUCD insertion, obstetricians are still hesitant to extend the benefit of this long acting reversible contraception to women undergoing operative delivery. OBJECTIVE: To study the clinical outcome (safety, efficacy, expulsion and continuation rates) of postplacental Copper T 380A insertion in primiparous women undergoing caesarean section. MATERIALS AND METHODS: This study was a prospective observational study, carried out in the Department of Obstetrics and Gynaecology, Safdarjung hospital, which is a tertiary care hospital of Northern India. Primiparous women who delivered by caesarean section over a period of six months (July 2012 to December 2012), willing for postplacental intracaesarean IUCD insertion, and willing to comply with the study protocol, were recruited for the study. All these subjects fulfilled the WHO Standard Medical Criteria for PPIUCD insertion; follow up visits were scheduled at 1, 3, 6 and 12 months. RESULTS: A total of 300 primiparous women underwent postpartum intracaesarean insertion of Copper T 380A. The mean age of women included in the study was 23.12 ± 2.42 years. Most common postinsertion complication observed in the immediate postoperative period was febrile morbidity (2%). Majority of women (94.33%) had hospital stay of less than 4 days. The common adverse events observed during follow-up of 12 months were menstrual complaints, excessive vaginal discharge and persistent pelvic pain. At the end of one year, there were 16 expulsions, 21 removals, and 2 pregnancies with gross cumulative expulsion, removal, failure and continuation rates of 5.33%, 7%, 0.67% and 91%, respectively. CONCLUSION: Postplacental intracaesarean Copper T 380A insertion in primiparous women is a safe and effective method of reversible contraception, with low expulsion and high continuation rates.