Combined Vitamin B-12 and Balanced Protein-Energy Supplementation Affect Homocysteine Remethylation in the Methionine Cycle in Pregnant South Indian Women of Low Vitamin B-12 Status.

Background: Low-quality dietary protein intake and vitamin B-12 deficiency could interact to decrease methionine transmethylation and remethylation rates during pregnancy and may affect epigenetic modifications of the fetal genome.Objective: The objective of this randomized, partially open-labeled intervention trial was to examine the effect of supplemental high-quality protein and vitamin B-12 on third-trimester methionine kinetics in pregnant Indian women with a low vitamin B-12 status.Methods: Pregnant women with low serum vitamin B-12 concentrations (<200 pmol/L) were randomly assigned to 1 of 3 groups: the first group received balanced protein-energy supplementation of 500 mL milk/d plus a 10-µg vitamin B-12 tablet/d (M+B-12 group; n = 30), the second group received milk (500 mL/d) plus a placebo tablet (M+P group; n = 30), and the third group received a placebo tablet alone (P group; n = 33). Third-trimester fasting plasma amino acid kinetics were measured by infusing 1-13C,methyl-2H3-methionine, ring-2H5-phenylalanine, ring-2H4-tyrosine,1-13C-glycine, and 2,3,3-2H3,15N-serine in a subset of participants. Placental mRNA expression of genes involved in methionine pathways, placental long interspersed nuclear elements 1 (LINE-1) methylation, and promoter methylation levels of vascular endothelial growth factor (VEGF) were analyzed.Results: Remethylation rates in the M+B-12, M+P, and P groups were 5.1 ± 1.7, 4.1 ± 1.0, and, 5.0 ± 1.4 µmol ⋅ kg-1 ⋅ h-1, respectively (P = 0.057), such that the percentage of transmethylation remethylated to methionine tended to be higher in the M+B-12 group (49.5% ± 10.5%) than in the M+P group (42.3% ± 8.4%; P = 0.053) but neither differed from the P group (44.2% ± 8.1%; P > 0.1). Placental mRNA expression, LINE-1, and VEGF promoter methylation did not differ between groups.Conclusions: Combined vitamin B-12 and balanced protein-energy supplementation increased the homocysteine remethylation rate in late pregnancy. Thus, vitamin B-12 along with balanced protein-energy supplementation is critical for optimal functioning of the methionine cycle in the third trimester of pregnancy in Indian women with low serum vitamin B-12 in early pregnancy. This trial was registered at clinicaltrials.gov as CTRI/2016/01/006578.

Energy and Protein Supplementation Does Not Affect Protein and Amino Acid Kinetics or Pregnancy Outcomes in Underweight Indian Women.

BACKGROUND: In India, the prevalence of low birth weight is high in women with a low body mass index (BMI), suggesting that underweight women are not capable of providing adequate energy and protein for fetal growth. Furthermore, as pregnancy progresses, there is increased need to provide methyl groups for methylation reactions associated with the synthesis of new proteins and, unlike normal-BMI American women, low-BMI Indian women are unable to increase methionine transmethylation and remethylation rates as pregnancy progresses from trimester 1 to 3. This also negatively influences birth weight. OBJECTIVE: The aim was to determine the effect of dietary supplementation with energy and protein from 12 ± 1 wk of gestation to time of delivery compared with no supplement on pregnancy outcomes, protein kinetics, and the fluxes of the methyl group donors serine and glycine. METHODS: Protein kinetics and serine and glycine fluxes were measured by using standard stable isotope tracer methods in the fasting and postprandial states in 24 pregnant women aged 22.9 ± 0.7 y with low BMIs [BMI (in kg/m(2)) ≤18.5] at 12 ± 1 wk (trimester 1) and 30 ± 1 wk (trimester 3) of gestation. After the first measurement, subjects were randomly assigned to either receive the supplement (300 kcal/d, 15 g protein/d) or no supplement. RESULTS: Supplementation had no significant effect on any variable of pregnancy outcome, and except for fasting state decreases in leucine flux (125 ± 7.14 compared with 113 ± 5.06 µmol ⋅ kg(-1) ⋅ h(-1); P = 0.04) and nonoxidative disposal (110 ± 6.97 compared with 101 ± 3.69 µmol ⋅ kg(-1) ⋅ h(-1); P = 0.02) from trimesters 1 to 3, it had no effect on any other leucine kinetic variable or urea, glycine, and serine fluxes. CONCLUSION: We conclude that in Indian women with a low BMI, supplementation with energy and protein from week 12 of pregnancy to time of delivery does not improve pregnancy outcome, whole-body protein kinetics, or serine and glycine fluxes.

Comparison of the efficacy and safety of sublingual misoprostol with that of vaginal misoprostol for labour induction at term.

OBJECTIVE: To compare the efficacy and safety of 50 mcg of sublingual misoprostol with 25 mcg of vaginal misoprostol for induction of labour at term. METHOD: Non blinded randomized prospective control study. 200 women with singleton term pregnancy, admitted for induction of labour, were randomized to receive either 25 mcg of vaginal misoprostol or 50 mcg of sublingual misoprostol. Outcome measures compared were the number of vaginal deliveries, induction-delivery interval, caesarean section for foetal distress, oxytocin for acceleration, number of doses required, side effects and neonatal outcome. RESULT: Mean dose was smaller and induction to delivery interval was significantly shorter in the sublingual group (13.1 ± 4.1 h) compared with the vaginal group (17.9 ± 5.4 h), p value 0.001. There were no statistically significant differences in the other secondary outcome measures. CONCLUSION: 50 mcg of sublingual misoprostol was more effective than and as safe as 25 mcg vaginal misoprostol for labour induction at term.

Autoimmune Hemolytic Anaemias in Pregnancy: Experience in a Tertiary Care Hospital in South India.

BACKGROUND: Autoimmune hemolytic anaemia is very rare and there is limited data regarding their pregnancy outcomes. Hence we aimed to study the maternal and perinatal outcomes in pregnancies with autoimmune hemolytic anaemias (AIHA). METHODS: A retrospective descriptive study of pregnant women with AIHA, who delivered at SJMCH between January 2011 and January 2016 was carried out. Their antenatal and labour records were reviewed and demographic details noted.The primary outcome measures studied were-the prevalence of AIHA, gestational age at delivery, antepartum, intrapartum and postpartum complications, mode of delivery and requirement of transfusion of blood and blood products. The secondary outcome measures studied included neonatal outcomes such as low birth weight, intrauterine growth restriction and need for intensive care. The data is presented as descriptive statistics, including means and percentage. RESULTS: The prevalence of AIHA was (18/12,420) 0.14%. The mean gestational age at delivery was 34 weeks; 100%, 77% and 50% had antenatal, intra partum or postpartum complications, respectively. 44% had preeclampsia, 38% intrauterine growth restriction and 16% preterm labour. 83% required additional drugs for treatment of AIHA.72% had vaginal delivery; 28% had caesarean delivery; 33% were transfused antenatally and 22% postnatally; 50% of the babies were preterm and required intensive care, 66% had low birth weight. There was no maternal mortality. CONCLUSION: Multidisciplinary approach, early diagnosis and detection of autoimmune hemolytic anaemia and complications, good antenatal care, judicious transfusions and delivery at tertiary care centre are the keys to successful outcomes.

Placental expression of ENG, VEGF, and FLT: Gender-specific associations with maternal vitamin B12 status.

OBJECTIVES: Adequate vitamin B12 is a requisite during pregnancy and its deficiency is linked with increased risk for adverse outcomes, likely mediated by impaired placental angiogenesis. Thus, we aimed to test associations of maternal vitamin B12 status with the placental expression of angiogenesis-associated genes ENG, VEGF, and FLT. SUBJECTS/METHODS: In this retrospective case-control study, placental and maternal trimester 1 blood samples (n = 104) were collected from small for gestational age (SGA) and appropriate for gestational age (AGA) full-term singleton pregnancies. Maternal trimester 1 vitamin B12 status was measured. Placentae and neonates were weighed at birth. Realtime quantitative PCR was performed to assess placental transcript abundance of ENG, VEGF, and FLT normalized to a panel of reference genes. Associations of placental transcript abundance of the genes with maternal trimester 1 vitamin B12 status were evaluated. RESULTS: Placental ENG transcript abundance associated negatively with maternal trimester 1 vitamin B12 status (ß = -0.461, P = 0.017, n = 104). This association was specific to the female births (ß = -0.590, P = 0.014, n = 60). Placental VEGF transcript levels were negatively associated with maternal trimester 1 vitamin B12 status only in the female births (ß = -1.995, P = 0.029). Placental FLT transcript levels were not associated with maternal trimester 1 vitamin B12 status. CONCLUSION: Maternal trimester 1 vitamin B12 status was associated negatively with placental ENG and VEGF expression predominantly in the female births. Therefore, we hypothesize that the placenta adapts to low maternal vitamin B12 status by up-regulating angiogenic pathways in a gender-specific manner.

Placental expression of leptin: fetal sex-independent relation with human placental growth.

OBJECTIVES: Leptin (LEP) is a vital placental hormone that is known to affect different aspects of placental function and fetal development. The present study aimed to determine the association of placental LEP transcript abundance with maternal, placental, and newborn parameters. SUBJECTS/METHODS: In this retrospective case-control study, placental samples (n = 105) were collected from small (SGA) and appropriate (AGA) for gestational age full-term singleton pregnancies (n = 44 SGA and n = 61 AGA). Placental transcript abundance of LEP was assessed by real-time quantitative PCR after normalization to a reference gene panel. LEP methylation was measured using a quantitative MethyLight assay in a subset of samples (n = 54). RESULTS: Placental LEP transcript abundance was negatively and significantly associated with placental weight (ß = -3.883, P = 0.015). This association continued to be significant in the SGA group (ß = -10.332, P = 0.001), both in female (ß = -15.423, P = 0.021) and male births (ß = -10.029, P = 0.007). LEP transcript abundance was not associated with LEP methylation levels (Spearman's ρ = 0.148, P = 0.287). CONCLUSION: We conclude that placental upregulation of LEP is an integral and fetal sex-independent component of placental growth restriction, which can be potentially targeted through maternal dietary modifications to improve fetoplacental growth.

Validation of the Risk Score for Maternal Cardiac Complications in Women with Cardiac Disease in Pregnancy: A Retrospective Study.

AIM OF THE STUDY: To validate the new cardiac risk scoring system, Sheela's Cardiac Disease in Pregnancy (SHE-CDIP), in predicting the cardiac complications in women with cardiac disease in pregnancy. MATERIALS AND METHODS: The study was conducted at a tertiary care hospital in South India, over a period of 5 years from January 2010 to January 2015. Pregnant women with heart disease included in this study were 102, and data was collected from medical records. Risk Score was calculated at booking according to both the new scoring system (SHE-CDIP) and the standard CARPREG scoring system. The validation was done by assessing the ability of the new scoring system to predict maternal cardiac complications by comparing with the CARPREG scoring system. STATISTICAL METHODS: The validation of the SHE-CDIP score was done against CARPREG score using cross tabulation between current cardiac risk score with CARPREG score. McNemar square test was done to compare the proportion between two scoring methods. Agreement between CARPREG and SHE-CDIP risk score was analyzed using Kappa statistics, and accuracy was reported. RESULTS: Comparing the two risk scores using Kappa statistics, accuracy and good agreement were noted (kappa = 0.70). Sensitivity of 83%, specificity of 88%, positive predictive value of 86% and negative predictive value of 84% for the SHE-CDIP scoring system were noted. CONCLUSION: The new risk score (SHE-CDIP) would be useful to stratify the risk in Indian cohort of women with cardiac disease in pregnancy as it is population specific.

Relationship of Early Vitamin D Concentrations and Gestational Diabetes Mellitus in Indian Pregnant Women.

Background: A high prevalence of vitamin D deficiency exists in pregnant Indian women (~90%). Increasing evidence suggests that vitamin D could play a pivotal role in maintaining normal glucose homeostasis. We aimed to determine the association between maternal vitamin D concentrations in early pregnancy and the risk of gestational diabetes mellitus (GDM). Methods: A prospective observational study was conducted on healthy pregnant women (n = 392) attending routine antenatal care at St. John's Medical College Hospital, Bangalore recruited at ~12 weeks of gestation. At baseline, details on socio-economic status, obstetric history, dietary intakes, and anthropometry were collected. Venous plasma total vitamin D concentration was assessed using tandem liquid chromatography mass spectrophotometry (LC-MS/MS). Oral glucose tolerance test (OGTT) at recruitment, followed by glucose tolerance test (GTT) at mid-pregnancy was conducted. GDM was diagnosed and confirmed using the International Association of Diabetes and Pregnancy Study Groups (IADPSG) classification. Univariate and adjusted logistic regression models were used to evaluate the associations between total vitamin D concentrations at enrollment with GDM. Results: Of the cohort, 10.2% were diagnosed as GDM. Women with GDM were older (26 vs. 24 years) and heavier (51.6 vs. 51.2 kg) compared to the rest. A higher prevalence of GDM was observed among women with 1st trimester plasma total vitamin D in the lowest quartile (≤23.6 nmol/L) compared to the subjects in the other three quartiles (16.1 vs. 8.6%, p = 0.033). Adjusted multivariable regression analysis showed that women in the lowest quartile of plasma total vitamin D had twice the odds of GDM compared to women belonging to the remaining quartiles [OR = 2.32 (95%CI: 1.10, 4.91), p = 0.028]. Conclusions: Low plasma total vitamin D concentrations in early pregnancy may be associated with a higher risk of GDM.

Obstetric Outcome in Women with Chronic Liver Disease.

AIM: This study determines the prevalence, causes and outcome of pregnancy in women with chronic liver diseases in a tertiary level teaching institute in Southern India. METHODS: Retrospective analysis of case records was carried out between December 2010 and May 2015 in the departments of Obstetrics and Gynecology and Gastroenterology including pregnant women diagnosed to have chronic liver diseases prenatally or during pregnancy. RESULTS: The frequency of chronic liver disease in pregnancy was 50 among 10,823 deliveries (0.4%). Twenty-six women with chronic liver disease had 50 pregnancies during the study period. Fifty percent of the women had cirrhosis. Maternal complications occurred in 22% of the study group. Variceal hemorrhage occurred in 4%, and hepatic decompensation occurred in 16%. There were two maternal deaths (4%). Obstetric complication such as preeclampsia, postpartum hemorrhage and puerperal infection occurred in 18, 14 and 18%, respectively. Abortion occurred in 34%, 55% in cirrhotic and 4.8% in non-cirrhotic. Live birth rate of 76% was significantly higher (p < 0.014) in the non-cirrhotic group compared to cirrhotic group. CONCLUSION: Pregnancies in chronic liver disease are associated with high rate of abortions. Live birth rates are better and complications such as variceal bleeding or decompensation of liver disease are less common than previously reported.

Screening for Postnatal Depression in a Tertiary Care Hospital.

AIM: To determine the need to screen postpartum women for postpartum depression. OBJECTIVE: This study was designed to determine the prevalence of an Edinburgh postnatal depression scale (EPDS) score of ≥13 in postpartum mothers and to evaluate the association of different sociodemographic and obstetric factors with postpartum depression. DESIGN: Prospective cohort study. METHOD: 1600 postpartum women who delivered a live born at St. John's Hospital were recruited into the study. Participants were screened for postnatal depression using the EPDS. A risk factor questionnaire that covered key sociodemographic and obstetric factors was also completed by all the subjects. MAIN OUTCOME MEASURE: Prevalence of a score of 13 or higher, on the EPDS. RESULTS: The prevalence of an EPDS score of ≥13 in our population was 7.5 % (120/1600). Participants with a family history of psychiatric illness, history of domestic abuse, delayed initiation of breastfeeding, and those who gave birth to a female infant were at a significantly higher risk for an EPDS score of 13 or higher, indicating probable postnatal depression. The mode of delivery, NICU admission of the newborn, and history of antenatal complications were not significant risk factors. CONCLUSION: Since the prevalence of an EPDS score ≥13 (which is suggestive of PPD) was found in a significant proportion of women, screening for PPD is indicated in all postpartum women to identify and promptly treat these women. Identification of a clear correlation between certain risk factors and PPD will lead to a more prompt diagnosis of PPD.

Implementation of WHO Near-Miss Approach for Maternal Health at a Tertiary Care Hospital: An Audit.

OBJECTIVE: The objective of this study was to evaluate severe maternal outcomes (including maternal deaths and maternal near-miss cases). MATERIALS & METHODS: A prospective study of severe maternal outcomes (including maternal deaths and maternal near-miss cases) from May 2012 to April 2013 was performed. For each woman, data were collected on the occurrence of selected severe pregnancy-related complications, the use of critical interventions, and admissions to intensive care unit. RESULTS: The total number of deliveries were 2340. The number of maternal deaths was three. The natures of the near-miss cases during the study period were recorded. Prevalence of SAMM (severe acute maternal morbidity) was 2.025 %. CONCLUSION: In areas where the maternal mortality is low, there is a need to shift focus to maternal near-miss cases or SAMM, which is a useful adjunct to maternal death enquiries.