Rubella immunity among pregnant women and the burden of congenital rubella syndrome (CRS) in India, 2022.

BACKGROUND: India aims to eliminate rubella and congenital rubella syndrome (CRS) by 2023. We conducted serosurveys among pregnant women to monitor the trend of rubella immunity and estimate the CRS burden in India following a nationwide measles and rubella vaccination campaign. METHODS: We surveyed pregnant women at 13 sentinel sites across India from Aug to Oct 2022 to estimate seroprevalence of rubella IgG antibodies. Using age-specific seroprevalence data from serosurveys conducted during 2017/2019 (prior to and during the vaccination campaign) and 2022 surveys (after the vaccination campaign), we developed force of infection (FOI) models and estimated incidence and burden of CRS. RESULTS: In 2022, rubella seroprevalence was 85.2% (95% CI: 84.0, 86.2). Among 10 sites which participated in both rounds of serosurveys, the seroprevalence was not different between the two periods (pooled prevalence during 2017/2019: 83.5%, 95% CI: 82.1, 84.8; prevalence during 2022: 85.1%, 95% CI: 83.8, 86.3). The estimated annual incidence of CRS during 2017/2019 in India was 218.3 (95% CI: 209.7, 226.5) per 100, 000 livebirths, resulting in 47,120 (95% CI: 45,260, 48,875) cases of CRS every year. After measles-rubella (MR) vaccination campaign, the estimated incidence of CRS declined to 5.3 (95% CI: 0, 21.2) per 100,000 livebirths, resulting in 1141 (95% CI: 0, 4,569) cases of CRS during the post MR-vaccination campaign period. CONCLUSION: The incidence of CRS in India has substantially decreased following the nationwide MR vaccination campaign. About 15% of women in childbearing age in India lack immunity to rubella and hence susceptible to rubella infection. Since there are no routine rubella vaccination opportunities for this age group under the national immunization program, it is imperative to maintain high rates of rubella vaccination among children to prevent rubella virus exposure among women of childbearing age susceptible for rubella.

Can Medical Nutrition Therapy Affect Feto-Maternal Outcomes in Gestational Glucose Intolerance: An Open-Label Pilot Randomized Control Trial in World's Diabetes Capital.

Introduction: Gestational diabetes is defined as the carbohydrate intolerance of variable severity with onset or first recognition during pregnancy. Gestational glucose intolerance (GGI) is used to indicate pregnant women whose 2-h postprandial glucose is > 120 mg/dl and below 140 mg/dl (Diabetes in Pregnancy Study Group of India, DIPSI criteria). Aim: This study was planned to see whether intervention in GGI group helps to improve feto-maternal outcomes. Methodology: This open-label randomized control trial was conducted in Department of Obstetrics and Gynaecology of King George's Medical University, Lucknow. Inclusion criteria were all the antenatal women attending the antenatal clinic and diagnosed as GGI, and exclusion criteria were overt diabetes. Results: Total of 1866 antenatal women were screened, and among them, 220 (11.8%) women were diagnosed as gestational diabetes; 412 (22.1%) women were diagnosed as GGI. The mean fasting blood sugars in the women with GGI who had medical nutrition therapy were much lower than the women with GGI who did not have any intervention. The present study showed the women with GGI had higher complications like polyhydramnios, PPROM, foetal growth restriction, macrosomia, preeclampsia, preterm labour and vaginal candidiasis more in the women with GGI as compared to euglycaemic women. Conclusion: The present study of nutritional intervention in GGI group has shown trend towards lesser complication if we start medical nutrition therapy reflected by delayed development of GDM and less neonatal hypoglycaemia and hyperbilirubinemia.

Gestational glucose intolerance (GGI) and gestational diabetes mellitus (GDM) among antenatal women attending urban community health centers of Lucknow: A cross-sectional study.

Background: Gestational diabetes mellitus (GDM) is an emerging public health concern in India, which has detrimental effects on both the mother and the baby. The data on prevalence of GDM was unavailable at secondary urban health facilities, from where a majority of pregnant women seek antenatal services, and the following study identifies this burden. Methods: A cross-sectional study was conducted from May 2019 to June 2020 among pregnant women attending the antenatal outpatient department (OPD) at secondary level health facilities in urban Lucknow. A semi-structured interview schedule was administered to the study subjects for collecting the relevant information and 75 g of oral glucose tolerance test was performed irrespective of the meal. The cut-off points taken for the diagnosis of GDM and gestational glucose intolerance (GGI) was as per the guidelines of the Ministry of Health and Family Welfare for diagnosis of GGI/GDM. Results: The overall prevalence of GDM and GGI in the study was 11.6% and 16.8%, respectively. Three-fourth of the women (22/29) were diagnosed with GDM in the second trimester of pregnancy. The prevalence of GDM (16.7%) was significantly higher in pregnant women aged more than 25 years and in those who were overweight. Mean birth weight (3.2 ± 8.1 kg) of the babies was significantly higher in the women with GDM. Among the fetal complications was respiratory distress observed among 28 pregnant women and 31% of them had GDM and this was statistically significant. Conclusion: The prevalence of GGI and GDM was found 16.8% and 11.6%, respectively. Gestational age, pre-pregnancy weight, pre-pregnancy BMI, weight gain during the pregnancy, family history of diabetes. PCOS, macrosomia and GDM in prior pregnancies was found to significant with GDM in the study.

Correlation of sFlt/PlGF ratio with severity of preeclampsia in an Indian population.

Background: Preeclampsia affects 2% to 8% of pregnant women and significantly increases the risk for maternal and perinatal morbidity, especially in low- and middle-income countries. There is increasing evidence to support the use of biochemical markers such as placental growth factor and soluble fms-like tyrosine kinase-1 in predicting the severity of preeclampsia and to rule out severe disease in clinical conditions masquerading as severe preeclampsia. OBJECTIVE: This study aimed to assess the role of the sFlt-1/PlGF ratio in predicting adverse perinatal and maternal outcomes in women with preeclampsia in a South Asian population with a higher rate of the disease and its associated complications. STUDY DESIGN: This was a prospective cohort study of women diagnosed with preeclampsia or suspected to have preeclampsia who underwent biophysical and biochemical investigations to measure the severity, including determining maternal hemodynamic indices, mean arterial pressure, fetal biometric and Doppler parameters, and soluble fms-like tyrosine kinase-1 and placental growth factor levels. The performance of these markers, individually or in combination, in predicting adverse perinatal and maternal outcomes was then assessed using receiver operating characteristic curve analysis. An adverse maternal outcome was defined as 1 or more of severe hypertension; admission to the intensive care unit; eclampsia; placental abruption; hemolysis, elevated liver enzymes, low-platelet count syndrome; disseminated intravascular coagulation; platelets <100×109/L; creatinine >1.1 mg/dL; and alanine aminotransferase >100 U/L. An adverse perinatal outcome was defined as 1 or more of preterm birth ≤34+0 weeks' gestation, neonatal intensive care unit admission for >48 hours, respiratory distress syndrome, intraventricular hemorrhage, hypoxic ischemic encephalopathy, necrotizing enterocolitis, retinopathy of prematurity, and confirmed fetal infection. RESULTS: We recruited 91 women with preeclampsia with a mean gestational age of 30.63±2.86 weeks. Women who had adverse maternal events had higher median maternal concentrations of soluble fms-like tyrosine kinase (11,500.0 pg/mL vs 3051.0 pg/mL; P<.001), lower concentrations of placental growth factor (44.88 pg/mL vs 148.50 pg/mL; P<.001), and a higher sFlt-1/PlGF ratio (306.22 vs 30.63; P<.001) than women who did not. Pregnancies with an adverse perinatal outcome also had a higher soluble fms-like tyrosine kinase concentration (12,100.0 pg/mL vs 3051.0 pg/mL; P<.001), lower placental growth factor concentration (27.2 pg/mL vs 148.50 pg/mL; P<.001), and higher sFlt-1/PlGF ratio (378.45.4 vs 30.63; P<.001). The area under the receiver operating characteristic curve showed that soluble fms-like tyrosine kinase and placental growth factor were the best biomarkers when compared with other biochemical markers to predict adverse maternal (area under the curve, 0.81; 95% confidence interval, 0.72-0.90) and fetal (area under the curve, 0.88; 95% confidence interval, 0.80-0.96) outcomes in preeclampsia. CONCLUSION: The sFlt-1/PlGF ratio correlates better with adverse maternal and perinatal outcomes than any other biochemical marker in an Indian population. The incorporation of the sFlt-1/PlGF ratio in women with preeclampsia can help in predicting the severity of the condition and the timings of the delivery.

The Effect of Insulin Resistance on Ovulation Induction With Clomiphene Citrate in Non-polycystic Ovary Syndrome (PCOS) Women.

Objective To study the status of insulin resistance (IR) in non-polycystic ovary syndrome (PCOS) infertile women and to assess its effects on response to ovulation induction (OI) with clomiphene citrate (CC). Methods and materials A prospective cohort study was conducted at the Department of Obstetrics and Gynecology, King George Medical University, Lucknow, India, over a one-year period. One hundred two women who underwent treatment for infertility were enrolled and evaluated for insulin resistance. Insulin resistance was assessed using fasting serum insulin levels and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. All participants were given ovulation induction with clomiphene citrate and were then followed up for the occurrence of ovulation and conception. Results Insulin resistance was found in 20.5% of infertile subjects and 95.4% of anovulatory subjects. Of the subjects with insulin resistance, 80.5% showed monofollicular development. The pregnancy rate was 5.8%, but there was no conception among subjects with insulin resistance. Conclusions Insulin resistance was found to be present in 20.5% of infertile women. Women with insulin resistance are more likely to have monofollicular development on ovulation induction and are less likely to conceive as compared with women without insulin resistance (OR = 0.2079).

Association of long and short interpregnancy intervals with maternal outcomes.

Background: Interpregnancy interval (IPI) is spacing between live birth and beginning a new pregnancy. Both long and short IPIs have been associated with adverse maternal outcomes. There is paucity in the Indian literature regarding the impact of IPI on maternal outcomes. Materials and Methodology: The cross-sectional study was conducted in the Department of Obstetrics and Gynecology, King George's Medical University, Lucknow, from July 2019 to June 2020. Women with previous abortions, previous stillbirth, nulliparity, or multiple pregnancies were excluded. A pre-structured pro forma was used for demographic details. IPI was categorized as <6 months, 6 to <24 months, 24 to <60 months, and 60 months. Maternal outcomes were studied, and odds ratios were calculated. Results: There were 6984 deliveries in the period. A total of 4812 women were enrolled after following the inclusion and exclusion criteria. Of 4812 women, 142 (2.9%) had IPI <6 months, 3336/4812 women (69.3%) had IPI 6 to <24 months, 1144/4812 women (23.7%) had IPI 24 to <60 months, and 3.9% women (190/4812) had IPI ≥60 months. High risk of fetal malposition (OR 3.84), fetal growth restriction (OR 2.06), and hypertension (OR 1.86) were seen in women with short IPI <6 months. Women with longer IPI (≥ 60 months) had higher chances of preterm labor (OR 3.82), oligoamnios (OR 2.54), gestational diabetes (OR 2.19), and anemia (OR 1.45). Conclusion: Three-fourths of women had IPI less than 24 months recommended as minimum interval by WHO. Efforts are needed to increase awareness and availability of contraceptive choices for postpartum women to ensure adequate spacing.

Prevalence of Dengue, Chikungunya, and Zika Viruses in Febrile Pregnant Women: An Observational Study at a Tertiary Care Hospital in North India.

Dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV) are arboviruses that can affect maternal and fetal outcome if acquired during pregnancy. This study was done to estimate the positivity of DENV, CHIKV, and ZIKV in febrile pregnant women attending a tertiary care hospital in north India. Symptomatic pregnant women were tested for these viruses by IgM ELISA and/or by Trioplex real-time polymerase chain reaction. Their symptoms and laboratory parameters were recorded and were followed up till delivery to know their immediate delivery outcome. Of 104 women tested, 50 (48.1%) were positive for viral markers. Of these, evidence of infection by DENV, CHIKV, and both was found in 34 (32.7%), 10 (9.6%), and 6 (5.8%), respectively. ZIKV was not detected in any woman. Maximum DENV positivity occurred in the third trimester of pregnancy and in women residing in urban than rural areas. Chills and rigors, arthralgia, retro-orbital pain, anemia, and vaginal bleeding were more commonly associated with DENV positivity. Backache, arthralgia, jaundice, and vaginal bleeding were more common in CHIKV positives but the difference between positives and nonpositives regarding these symptoms was not statistically significant. Dengue infections were associated with more frequent hospitalizations (OR = 8.38, 95% confidence intervals [CI] = 3.29-21.30) and mortality (OR = 19.0, 95% CI = 1.01-357.10). Hence, to conclude, in India wherever possible, all symptomatic pregnant women should be screened for DENV, CHIKV, and ZIKV as part of sentinel surveillance for ZIKV.

Burden of congenital rubella syndrome (CRS) in India based on data from cross-sectional serosurveys, 2017 and 2019-20.

BACKGROUND: India has set a goal to eliminate measles and rubella/Congenital Rubella Syndrome (CRS) by 2023. Towards this goal, India conducted nationwide supplementary immunization activity (SIA) with measles-rubella containing vaccine (MRCV) targeting children aged between 9 months to <15 years and established a hospital-based sentinel surveillance for CRS. Reliable data about incidence of CRS is necessary to monitor progress towards the elimination goal. METHODS: We conducted serosurveys in 2019-20 among pregnant women attending antenatal clinics of 6 hospitals, which were also sentinel sites for CRS surveillance, to estimate the prevalence of IgG antibodies against rubella. We systematically sampled 1800 women attending antenatal clinics and tested their sera for IgG antibodies against rubella. We used rubella seroprevalence data from the current survey and the survey conducted in 2017 among antenatal women from another 6 CRS surveillance sites to construct a catalytic models to estimate the incidence and burden of CRS. RESULT: The seroprevalence of rubella antibodies was 82.3% (95% CI: 80.4-84.0). Rubella seropositivity did not differ by age group and educational status. Based on the constant and age-dependent force of infection models, we estimated that the annual incidence of CRS in India was 225.58 per 100,000 live births (95% CI: 217.49-232.41) and 65.47 per 100,000 live births (95% CI: 41.60-104.16) respectively. This translated to an estimated 14,520 (95% CI: 9,225-23,100) and 50,028 (95% CI: 48,234-51,543) infants with CRS every year based on age-dependent and constant force of infection models respectively. CONCLUSIONS: Our findings indicated that about one fifth of women in the reproductive age group in India were susceptible for rubella. The estimates of CRS incidence will serve as a baseline to monitor the impact of MRCV SIAs, as well progress towards the elimination goal of rubella/CRS.

Pregnancy in women with previous two healthy children, associated factors, and acceptability of contraception among these women: A questionnaire-based, cross-sectional KAP study in world's second most populated country advocating two-child norm.

INTRODUCTION: Indian subcontinent carries 17 % of world's population, being the second largest populated country. The maternal mortality rate of the country is still high. The study was aimed to study factors leading to pregnancy in women with previous two living children and their knowledge about limiting family and their practice for use of contraceptives. METHODS: Questionnaire-based study was conducted in the Department of Obstetrics and Gynaecology. RESULTS: 961 pregnant women attending antenatal outpatient department were interrogated and amongst them 167 (17.3 %) multigravida with previous two healthy children were enrolled in study and were asked to document in Questionnaire. Reasons for current pregnancy were gender bias, no desire to limit family, incorrect contraceptive use, contraceptive failure, doctor's mistake and religious belief. Desire for male child emerged as most common reason (37%) followed by improper or no use of contraception. Most significant associated factor was poor education of female partner (p = 0.010). CONCLUSION: This cross-sectional study evaluated the possible reasons of multiparity. We conclude that preference for male gender child is still very much prevalent in India, along with unmet need of family planning. Improving education of women might help to change attitude towards birth spacing and family size.

Pilot Interventional Study Comparing Fetomaternal Outcomes of 150 mg Versus 75 mg Aspirin Starting Between 11 and 14 Weeks of Pregnancy in Patients with High Risk of Preeclampsia: A Randomized Control Trial.

INTRODUCTION: Hypertensive disorders of pregnancies complicate around 5-10% of pregnancies worldwide, and together they are a member of the deadly triad along with haemorrhage and infection that contribute to a significant amount of maternal morbidity and mortality. AIMS AND OBJECTIVES: To compare differences in the fetomaternal outcomes with the use of 150 mg aspirin versus 75 mg aspirin in pregnant women found to be at high risk of PE. METHODOLOGY: This was a two-armed double-blind parallel randomized control trial conducted in the Department of Obstetrics and Gynaecology, King George's Medical University, carried over a period of 1 year. RESULTS: Preeclampsia occurred in 15 of 87 participants (17%) in the 75 mg aspirin group compared with 6 of 91 (6.5%) in the 150 mg aspirin group. There were a significantly higher incidence of PE, its severity and lesser period of gestation at delivery in the group given 75 mg dose compared to the group given 150 mg dose. There were significantly higher values of mean arterial pressure and uterine artery PI in women who developed preeclampsia compared to those who do not in both the groups. Foetal outcomes were observed in both the groups of women, and there was no statistically significant difference between them. CONCLUSION: This randomized trial showed that among women with singleton pregnancies who were identified by means of first-trimester screening as being at high risk of preterm preeclampsia, use of aspirin 150 mg per day started between 11 and 14 weeks till 36 weeks is a potent intervention to reduce the development of both early- and late-onset preeclampsia as compared to a dose of 75 mg per day.

Aberrant Akt Activation During Implantation Window in Infertile Women With Intramural Uterine Fibroids.

The objective of the study was to examine the expression and cellular distribution of key signaling components of the phosphatidylinositol-3-kinase (PI3K)/Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN)/Protein Kinase B (PKB/Akt) pathway during the window of implantation in infertile women with noncavity-distorting intramural uterine fibroids (n = 21) as compared to fertile controls (n = 15). Relative gene expression analysis of PIK3CA, PTEN, Akt1, and Akt2 genes in midluteal endometrial biopsies was performed by real-time polymerase chain reaction. Immunohistochemistry was used to evaluate the expression of PIK3CA, PTEN, phospho-PTEN, Akt1, Akt2, phospho-Akt1 (serine 473), phospho-Akt1 (threonine 308), and Ki67 proteins. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay was performed for apoptosis detection. In comparison to fertile controls, significant upregulation of Akt1 messenger RNA levels (2.16-fold; P < .05); cell-specific upregulation of the proteins phospho-PTEN ( P < .05), Akt1 ( P < .05), Akt2 ( P < .05), and p-Akt (S473; P < .001); and downregulation of PTEN ( P < .01) were observed in endometrium of infertile women with intramural fibroids. The ratio of p-PTEN/PTEN and p-Akt1 (S473)/Akt1 was also significantly higher in infertile women. Increased Ki67 labeling index in the glandular epithelium and significantly lower apoptotic index in glandular epithelium and stroma were seen in infertile women during the window of implantation. Aberrant Akt activation and the associated imbalance in endometrial proliferation and apoptosis observed in infertile women with intramural fibroids during the midsecretory phase might contribute to impaired endometrial receptivity leading to infertility in these patients.

Fetomaternal outcomes in pregnant women with hepatitis E infection; still an important fetomaternal killer with an unresolved mystery of increased virulence in pregnancy.

OBJECTIVE: Hepatitis is a prevalent infection in developing countries. While hepatitis B and C are deepening their roots in the developed world, hepatitis A and E are common in the developing world. The uniqueness of hepatitis is in its transformation from a relatively self-limiting disease in the non-pregnant state, to a highly virulent disease during pregnancy. MATERIALS AND METHODS: This retrospective observational study was conducted in the Department of Obstetrics and Gynecology, King George's Medical University, Lucknow, for a period of six months from June 2016 to November 2016 [probably during an endemic peak of hepatitis E virus (HEV)] to observe the clinical outcomes in HEV-infected pregnant women. RESULTS: A total of 32 anti-HEV immunoglobulin M-positive pregnant women were included, and fetomaternal outcomes were analyzed. Hepatitis E positivity was significantly associated with maternal mortality, intrauterine demise with prematurity, and premature rupture of membranes was the most common fetal complication noted. CONCLUSION: The difference in extent of virulence of infection and variations in maternal morbidity, mortality, and rates of intrauterine demise, signify the presence of some factors that play a role and need to be further studied and evaluated.

Maternal vitamin D supplementation in pregnancy and offspring outcomes: a double-blind randomized placebo-controlled trial.

We studied bone mineral content (BMC), bone mineral density (BMD), and body composition in offspring of women supplemented with vitamin D during pregnancy. Pregnant women were randomized to receive oral cholecalciferol 60,000 units 4 weekly (group 1), 8 weekly (group 2), or placebo (group 3). All received 1 g calcium daily (groups 1 and 2 without, and group 3 with 400 units vitamin D). Offspring at 12-16 months underwent dual-energy X-ray absorptiometry. Maternal hypovitaminosis D at recruitment was common (serum 25OHD <50 nmol/L in 88 %) and severe (25OHD <25 nmol/L in 46 %). Groups 1 and 2 (n = 23 and 13, median age 14 months) had higher cord blood 25OHD (47.8 ± 13.8 and 31.0 ± 14.0 nmol/L) versus group 3 (n = 16, median age 16 months, 17.8 ± 13.5 nmol/L, p < 0.001). Babies in group 3 had higher whole-body BMC (250.8 ± 42.5 gm) and BMD (0.335 ± 0.033 gm/cm2) compared to group 1 (213.1 ± 46.2 gm and 0.295 ± 0.041 gm/cm2) and group 2 (202.9 ± 29.9 gm and 0.287 ± 0.023 gm/cm2) (p = 0.006 and 0.001, respectively). In multivariate analysis, age, weight z score, and lean body mass remained significant contributors to BMC. Parameters of body composition were comparable among the groups. Vitamin D supplementation to pregnant women with severe deficiency in doses that improved cord blood 25OHD did not result in improved bone health or body composition in offspring at 12-16 months, compared to a dose too small to improve 25OHD levels.

PI3K/Akt/mTOR signaling & its regulator tumour suppressor genes PTEN & LKB1 in human uterine leiomyomas.

BACKGROUND & OBJECTIVES: Despite their high occurrence and associated significant level of morbidity manifesting as spectrum of clinical symptoms, the pathogenesis of uterine leiomyomas (ULs) remains unclear. We investigated expression profile of tumour suppressor genes PTEN (phosphatase and tensin homolog deleted on chromosome ten) and LKB1 (liver kinase B1), and key signaling components of P13K (phosphatidylinositol 3-kinase)/Akt (protein kinase B)/mTOR (mammalian target of rapamycin) pathway in leiomyomas and adjacent normal myometrium in women of reproductive age, to explore the possibility of targeting this pathway for future therapeutic implications. METHODS: Real time PCR (qPCR) was used to quantify relative gene expression levels of PTEN, Akt1, Akt2, mTOR, LKB1 and VEGFA (vascular endothelial growth factor A) in leiomyoma as compared to adjacent normal myometrium. Immunohistochemistry was subsequently performed to analyze expression of PTEN, phospho-Akt, phospho-mTOR, phospho-S6, LKB1 and VEGFA in leiomyoma and adjacent normal myometrium. RESULTS: Significant upregulation of PTEN (2.52 fold; P=0.03) and LKB1 (3.93 fold; P0.01), and downregulation of VEGFA (2.95 fold; P=0.01) genes were observed in leiomyoma as compared to normal myometrium. Transcript levels of Akt1, Akt2 and mTOR did not vary significantly between leiomyoma and myometrium. An increased immunoexpression of PTEN (P=0.015) and LKB1 (P<0.001) and decreased expression of VEGFA (P=0.01) was observed in leiomyoma as compared to myometrium. Immunostaining for activated (phosphorylated) Akt, mTOR and S6 was absent or low in majority of leiomyoma and myometrium. INTERPRETATION & CONCLUSIONS: Upregulation of PTEN and LKB1 in concert with negative or low levels of activated Akt, mTOR and S6 indicates that PI3K/Akt/mTOR pathway may not play a significant role in pathogenesis of leiomyoma.

Effect of vitamin D supplementation, directly or via breast milk for term infants, on serum 25 hydroxyvitamin D and related biochemistry, and propensity to infection: a randomised placebo-controlled trial.

We assessed the effect of vitamin D supplementation on related biochemistry, infection and dentition of the infant. In a double-blind, placebo-controlled trial conducted in Lucknow, India (latitude 26°N), 230 mother -newborn pairs were randomised to receive, for 9 months, 3000µg/month oral vitamin D3 by the mother (group A) or 10µg/d by the infant (group B) or double placebo (group C). All babies received 15 min of sun exposure (unclothed) during massage. Infants' median 25-hydroxyvitamin D (25(OH)D) was lower in group C (median 45·3; interquartile range (IQR) 22-59·5 nmol/l) than in groups A (median 60·8; IQR 41·3-80·5 nmol/l (P7.5µkat/l) was significantly more frequent in group C babies (16 %) than in group A (4 %) or group B (0 %) babies. The number of days with respiratory or diarrhoeal infection by 9 months of age was higher in group C (median 46·5; IQR 14·8-73·3 d) than in group A (median 18·5; IQR 8·8-31·0 d (P<0·01)) or group B (median 13·0; IQR 7·0-28·5 (P<0·05)). We conclude that monthly maternal or daily infant supplementation with vitamin D along with sun exposure is superior to sun exposure alone in maintaining normal infant 25(OH)D at 3·5 months, and provide protection from elevated alkaline phosphatase and infectious morbidity.

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.

Evaluation of obstetric near miss and maternal deaths in a tertiary care hospital in north India: shifting focus from mortality to morbidity.

OBJECTIVE: Near miss audit improves understanding of determinants of maternal morbidity and mortality and identifies areas of substandard care. It helps health professionals to revise obstetric policies and practices. METHODS: A retrospective review of obstetric case records was performed to assess frequency ad nature of maternal near miss (MNM) cases as per WHO criteria. For each case, primary obstetric complication leading to maternal morbidity was evaluated. Obstetric complications were analyzed to calculate prevalence ratio, case fatality ratio, and mortality index. RESULTS: There were 6,357 deliveries, 5,273 live births, 247 maternal deaths, and 633 MNM cases. As per WHO criteria for Near miss, shock, bilirubin >6 mg%, and use of vasoactive drugs were the commonest clinical, laboratory, and management parameters. Hemorrhage and hypertensive disorders of pregnancy were leading cause of MNM (45.7 and 24.2 %) and maternal deaths (28.7 and 21.5 %). Highest prevalence rate, case fatality ratio, and mortality index were found in hemorrhage (0.53), respiratory diseases (0.46), and liver disorders (51.9 %), respectively. CONCLUSION: Developing countries carry a high burden of maternal mortality and morbidity which may be attributed to improper management of obstetric emergencies at referring hospitals, poor referral practices, and poor access/utilization of health care services.

Alteration in endometrial proteins during early- and mid-secretory phases of the cycle in women with unexplained infertility.

BACKGROUND: Compromised receptivity of the endometrium is a major cause of unexplained infertility, implantation failure and subclinical pregnancy loss. In order to investigate the changes in endometrial protein profile as a cause of unexplained infertility, the current study was undertaken to analyze the differentially expressed proteins of endometrium from early-secretory (LH+2) to mid-secretory phase (LH+7), in women with unexplained infertility. METHODS: 2-D gel electrophoresis was performed to analyze the proteomic changes between early- (n = 8) and mid-secretory (n = 8) phase endometrium of women with unexplained infertility. The differentially expressed protein spots were identified by LC-MS analysis and validated by immunoblotting and immuno-histochemical analysis in early- (n = 4) and mid-secretory (n = 4) phase endometrium of infertile women. Validated proteins were also analyzed in early- (n = 4) and mid-secretory (n = 4) phase endometrium of fertile women. RESULTS: Nine proteins were found to be differentially expressed between early- and mid- secretory phases of endometrium of infertile women. The expression of Ras-related protein Rap-1b, Protein disulfide isomerase A3, Apolipoprotein-A1 (Apo-A1), Cofilin-1 and RAN GTP-binding nuclear protein (Ran) were found to be significantly increased, whereas, Tubulin polymerization promoting protein family member 3, Superoxide dismutase [Cu-Zn], Sorcin, and Proteasome subunit alpha type-5 were significantly decreased in mid- secretory phase endometrium of infertile women as compared to early-secretory phase endometrium of infertile women. Validation of 4 proteins viz. Sorcin, Cofilin-1, Apo-A1 and Ran were performed in separate endometrial biopsy samples from infertile women. The up-regulated expression of Sorcin and down-regulated expression of Cofilin-1 and Apolipoprotein-A1, were observed in mid-secretory phase as compared to early-secretory phase in case of fertile women. CONCLUSIONS: De-regulation of the expression of Sorcin, Cofilin-1, Apo-A1 and Ran, during early- to mid-secretory phase may have physiological significance and it may be one of the causes for altered differentiation and/or maturation of endometrium, in women with unexplained infertility.

Asymptomatic bacteriuria & obstetric outcome following treatment in early versus late pregnancy in north Indian women.

BACKGROUND & OBJECTIVES: Asymptomatic bacteriuria during pregnancy if left untreated, may lead to acute pyelonephritis, preterm labour, low birth weight foetus, etc. Adequate and early treatment reduces the incidence of these obstetric complications. The present study was done to determine presence of asymptomatic bacteriuria (ASB) and obstetric outcome following treatment in early versus late pregnancy. METHODS: A prospective cohort study was conducted at a tertiary care teaching hospital of north India. Pregnant women till 20 wk (n=371) and between 32 to 34 wk gestation (n=274) having no urinary complaints were included. Their mid stream urine sample was sent for culture and sensitivity. Women having > 10 [5] colony forming units/ml of single organism were diagnosed positive for ASB and treated. They were followed till delivery for obstetric outcome. Relative risk with 95% confidence interval was used to describe association between ASB and outcome of interest. RESULTS: ASB was found in 17 per cent pregnant women till 20 wk and in 16 per cent between 32 to 34 wk gestation. Increased incidence of preeclamptic toxaemia (PET) [RR 3.79, 95% CI 1.80-7.97], preterm premature rupture of membrane (PPROM)[RR 3.63, 45% CI 1.63-8.07], preterm labour (PTL) [RR 3.27, 95% CI 1.38-7.72], intrauterine growth restriction (IUGR)[RR 3.79, 95% CI 1.80-79], low birth weight (LBW) [RR1.37, 95% CI 0.71-2.61] was seen in late detected women (32-34 wk) as compared to ASB negative women, whereas no significant difference was seen in early detected women (till 20 wk) as compared to ASB negative women. INTERPRETATION & CONCLUSIONS: Early detection and treatment of ASB during pregnancy prevents complications like PET, IUGR, PTL, PPROM and LBW. Therefore, screening and treatment of ASB may be incorporated as routine antenatal care for safe motherhood and healthy newborn.

Effect of vitamin D supplementation during pregnancy on neonatal mineral homeostasis and anthropometry of the newborn and infant.

Hypovitaminosis D is common in India. In the present prospective partially randomised study of vitamin D (D3) supplementation during pregnancy, subjects were randomised in the second trimester to receive either one oral dose of 1500 µg vitamin D3 (group 1, n 48) or two doses of 3000 µg vitamin D3 each in the second and third trimesters (group 2, n 49). Maternal 25-hydroxyvitamin D (25(OH)D) at term, cord blood (CB) alkaline phosphatase (ALP), neonatal serum Ca and anthropometry were measured in these subjects and in forty-three non-supplemented mother-infant pairs (usual care). Median maternal 25(OH)D at term was higher in group 2 (58·7, interquartile range (IQR) 38·4-89·4 nmol/l) v. group 1 (26·2, IQR 17·7-57·7 nmol/l) and usual-care group (39·2, IQR 21·2-73·4 nmol/l) (P = 0·000). CB ALP was increased (>8.02 µkat/l or >480 IU/l) in 66·7 % of the usual-care group v. 41·9 % of group 1 and 38·9 % of group 2 (P = 0·03). Neonatal Ca and CB 25(OH)D did not differ significantly in the three groups. Birth weight, length and head circumference were greater and the anterior fontanelle was smaller in groups 1 and 2 (3·08 and 3·03 kg, 50·3 and 50·1 cm, 34·5 and 34·4 cm, 2·6 and 2·5 cm, respectively) v. usual care (2·77 kg, 49·4, 33·6, 3·3 cm; P = 0·000 for length, head circumference and fontanelle and P = 0·003 for weight). These differences were still evident at 9 months. We conclude that both 1500 µg and two doses of 3000 µg vitamin D3 had a beneficial effect on infant anthropometry, the larger dose also improving CB ALP and maternal 25(OH)D.