Maternal Vitamin A Status as a Risk Factor of Hirschsprung Disease in the Child.

INTRODUCTION: The gene-environment interaction of the REarranged during Transfection ( RET ) gene with vitamin A in the etiopathogenesis of Hirschsprung disease (HSCR) has been suggested in rodents. The aim of this study was to evaluate vitamin A status in mothers of children with HSCR and to assess its association with pathogenic variants of the RET gene in affected children. METHODS: This was a case-control study of stable isotope-based vitamin A measurement stores of mothers of children diagnosed with HSCR (within 8 months from birth, n = 7) and age-matched mothers of normal children (n = 6). Next-generation sequencing of RET exons, along with their upstream promoter region, was performed in the 7 HSCR proband-parent triads to evaluate pathogenic variants. RESULTS: Maternal vitamin A stores in the HSCR group was almost 50% that of those in controls, tending toward significance (0.50 ± 0.17 vs 0.89 ± 0.51 µmol/g respectively, P = 0.079). Two novel pathogenic de novo mutations were identified in 2 cases, and a rare single-nucleotide deletion was detected in the 3.5-kb RET upstream region, in a heterozygous state, in all 7 proband-parent triads. Low-penetrance RET haplotypes associated with HSCR were detected in 5 cases. DISCUSSION: Mothers with children with HSCR had lower vitamin A liver stores than mothers with normal children, and the children who were affected had HSCR despite having no established pathogenic RET variants. Lower maternal vitamin A status may increase the penetrance of genetic mutations in RET , and vitamin-A mediated gene-environment interactions may underpin some of the etiology of HSCR.

Placental expression of miR-517-5p and miR-518f-5p: Fetal sex-specific relations with human fetoplacental growth.

OBJECTIVE: We aimed to assess association of chromosome 19 miRNA cluster microRNAs (miR-517-5p and miR-518f-5p) expression with maternal, placental and newborn parameters and with their potential angiogenesis-associated target genes ENG, VEGF and FLT in a set of 68 small- (SGA, n = 30) and appropriate- (AGA, n = 38) for gestational age full-term singleton pregnancies, in relation to fetal sex. STUDY DESIGN: In this retrospective case-control study, placental transcript abundances of miR-517-5p and miR-518f-5p were assessed by real-time quantitative PCR after normalization to reference miRNA, mir-16-5p. Placental transcript abundances of VEGF, FLT and ENG were assessed after normalizing to a set of reference genes. RESULTS: Placental miR-517-5p transcript abundance was negatively associated with birth weight [ß = -88.778, P = 0.006, 95% confidence interval (CI): -151.645, -25.911] and placental weight (ß = -14.683, P = 0.007, 95% CI: -25.254, -4.112) and this association with birth weight was specific to the AGA births (ß = -59.207, P = 0.037, 95% CI: -114.522, -3.891). miR-518f-5p transcript abundance was negatively associated with placental weight (ß = -6.250, P = 0.034, 95% CI: -11.940, -0.559) specifically in the AGA male births (n = 16). Placental VEGF transcript abundance was negatively associated with that of miR-517-5p specifically in SGA female births (n = 14; Spearman's ρ = -0.705, P = 0.005) and with miR-518f-5p transcript abundance specifically in SGA births (Spearman's ρ = -0.437, P = 0.016) and in SGA male births (n = 16; Spearman's ρ = -0.516, P = 0.041). CONCLUSION: We conclude that placental miR-517-5p could be playing a key role in the pathophysiology of fetal growth restriction, which can be potentially targeted through maternal lifestyle modifications for improving fetoplacental growth.

Intestinal Perforation Secondary to Mucormycosis Associated With Puerperal Sepsis.

Mucormycosis is a rare opportunistic infection, usually seen in diabetics, immunocompromised, or those with coronavirus disease 2019 (COVID-19). Gastrointestinal involvement is uncommon but often deadly. We report a case of gastrointestinal mucormycosis causing intestinal perforation in a non-diabetic, COVID-19 negative, immunocompetent woman, associated with puerperal sepsis. A 22-year-old woman presented to our center on post-natal day five, following delivery with insertion of an intrauterine contraceptive device (IUCD). She had complaints of breathlessness, fatigue, and giddiness. Examination revealed tachycardia, tachypnea, hypotension, and bilateral pedal edema. Following appropriate investigations, she was diagnosed with puerperal sepsis with pre-renal acute kidney injury. Imaging was suggestive of retained products of conception, and she subsequently underwent dilation and evacuation (D&E) on day eight of admission. Following brief symptomatic improvement, on day 10 of admission, she developed vomiting, abdominal distension, and pain, with obstipation. Erect X-ray showed air under the diaphragm, suggestive of perforation. She emergently underwent laparotomy with limited right hemicolectomy, ileostomy with mucous fistula. Intraoperative findings revealed a closed-loop obstruction involving terminal ileum, with two perforations. The biopsy report later revealed colonization of Mucor and hemorrhagic necrosis along the entire length of the resected specimen. She was started on amphotericin B, and after a slow recovery, was discharged. Gastrointestinal mucormycosis is rare and has a mortality rate of 94%. It is usually seen in those with predisposing factors for mucormycosis. This is the first report of mucormycosis associated with puerperal sepsis. It is typically acquired via ingestion and may cause perforation, where mortality is further increased. Diagnosis can only be confirmed by histopathology demonstrating the characteristic morphology of Mucor. Treatment requires resection of necrotic tissues, intensive treatment with amphotericin B, and correction of predisposing factors. Our case highlights the need for a high degree of suspicion for mucormycosis in patients with intestinal perforation, even if immunocompetent, and its potential association with puerperal sepsis.

Prevalence and predictors of sleep deprivation and poor sleep quality and their associated perinatal outcomes during the third trimester of pregnancy.

OBJECTIVES: Maternal sleep deprivation not only affects the pregnant mother but also has profound effects on the well-being of the foetus. This study aims to assess the prevalence and predictors of excessive daytime sleepiness (EDS) and poor sleep quality (PSQ). METHODS: This was a cross-sectional study conducted among in-patient post-natal women of a tertiary care teaching hospital. A pretested semi-structured standardised questionnaire was administered. EDS was assessed using the Epworth sleepiness scale and PSQ was measured using the Pittsburgh Sleep Quality Index. RESULTS: A total of 225 participants were enrolled. The prevalence of EDS was 29.3% (95% confidence interval [CI] = 23.5, 35.8) and the prevalence of PSQ was 72.9% (95% CI = 66.6, 78.6). The factors (adjusted odds ratio; 95% CI; p-value) that were significantly associated with EDS were age (1.082; 1.019, 3.102; 0.042), being overweight (1.248; 1.012, 3.834; 0.041), low haemoglobin (1.246; 1.007, 4.572; 0.043), and gestational diabetes mellitus (GDM) (1.267; 1.001, 7.239; 0.049). On the other hand, the factors associated with PSQ were young age (1.092; 1.035, 3.763; 0.028), being overweight (1.602; 1.029, 2.995; 0.035), low haemoglobin (1.328; 1.004, 4.963; 0.047), and GDM (1.659; 1.284, 4.112; 0.016). No significant associations were found between perinatal outcomes and EDS or PSQ. Additionally, poor sleep practices were observed in our study participants. CONCLUSION: In this study, EDS and PSQ were significantly prevalent among participants, and their major predictors were age, haemoglobin, being overweight, and GDM.

Placental expression of angiogenesis-related genes and their receptors in IUGR pregnancies: correlation with fetoplacental and maternal parameters.

Objectives: Aberrations in placental vascular development compromising fetal supply of oxygen and essential nutrients can be a significant contributor to intrauterine growth restriction (IUGR). The development of placental vascular tree is under the influence of two families of growth factors, namely the vascular endothelial growth factor (VEGF) family and angiopoietin/TEK family. In this study, we have examined the expression of angiogenesis-related growth factors, mainly VEGF family and angiopoietin-TEK (endothelial-specific receptor tyrosine kinase) family genes in placentae from IUGR pregnancies uncomplicated by preeclampsia (PE) compared to normal pregnancies.Methods: Placentae from normotensive IUGR (n = 42) and appropriate for gestational age (AGA) pregnancies (n = 47) were collected and examined histologically. Clinical parameters were obtained from the medical records. Real-time quantitative PCR was performed to assess placental transcript abundance of VEGF, PGF, FLT1, ANGPT1, ANGPT2, and TEK normalized to a panel of reference genes. Associations of placental transcript abundance of the genes with maternal, placental, and neonatal parameters were tested.Results: Placental transcript abundance for VEGF (relative expression 10.81 versus 12.98, p < .001), PGF (12.14 versus 13.8, p < .001) and ANGPT2 (3.67 versus 9.55, p = .002) were significantly lower in IUGR placentae compared to AGA. The transcript level of VEGF showed significant negative correlation with birth weight (r = -0.419, p = .006), placental weight (r = -0.318, p = .040), placental length (r = -0.389, p = .011) and breadth (r = -0.308, p = .047) only in the IUGR group. Presence of histopathological features of hypoxia correlated with significantly higher transcript levels of PGF in IUGR placentae (12.6 versus 10.9, p = .046).Conclusion: The low levels of VEGF transcripts may be responsible for the impaired angiogenesis in IUGR placentae. The significance of higher relative expression of PGF in the presence of chronic hypoxia needs to be explored.

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.

Estimation of protein requirements in Indian pregnant women using a whole-body potassium counter.

BACKGROUND: The 2007 World Health Organization/Food and Agriculture Organization/United Nations University (WHO/FAO/UNU) recommendation for the Estimated Average Requirement (EAR) of additional protein during pregnancy for a gestational weight gain (GWG) of 12 kg (recalculated from a GWG of 13.8 kg) is 6.7 and 21.7 g/d in the second and the third trimester, respectively. This EAR is based on measurements of potassium accretion in high-income country (HIC) pregnant women. It is not known if low- to middle-income country, but well-nourished, pregnant women have comparable requirements. OBJECTIVE: We aimed to estimate total body potassium (TBK) accretion during pregnancy in Indian pregnant women, using a whole-body potassium counter (WBKC), to measure their additional protein EAR. METHODS: Well-nourished pregnant women (20-40 y, n = 38, middle socioeconomic stratum) were recruited in the first trimester of pregnancy. Anthropometric, dietary, and physical activity measurements, and measurements of TBK using a WBKC, were performed at each trimester and at birth. RESULTS: The mid-trimester weight gain was 2.7 kg and 8.0 kg in the second and the third trimester, respectively, for an average 37-wk GWG of 10.7 kg and a mean birth weight of 3.0 kg. Protein accretion was 2.7 and 5.7 g/d, for an EAR of 8.2 and 18.9 g/d in the second and the third trimester, respectively. The additional protein EAR, calculated for a GWG of 12 kg, was 9.1 and 21.2 g/d in the second and the third trimester, respectively. CONCLUSION: The additional protein requirements of well-nourished Indian pregnant women for a GWG of 12 kg in the second and third trimesters were similar to the recalculated 2007 WHO/FAO/UNU requirements for 12 kg.

CD15 as a marker of fetoplacental endothelial immaturity in IUGR placentas.

BACKGROUND: Structural or functional defects in the placenta, are the primary cause of growth restriction of the fetus. Morphological examination of such placentas from intrauterine growth restricted (IUGR) fetuses often appears deceptively normal. Evaluation of angiogenesis and fetoplacental vasculature is critical to understand the underlying pathogenesis of fetal growth restriction in both idiopathic as well as cases where it is thought to be secondary to complications like preeclampsia (PE). We analyzed the immaturity of fetoplacental vasculature using CD15, which is a stage specific embryonic antigen known to be expressed in immature endothelium. MATERIAL AND METHODS: One hundred and twelve placentas (81 from IUGR and 31 from gestationally appropriate samples (appropriate for gestational age (AGA)) were collected based on stringent inclusion criteria, and subjected to detailed examination of morphology and microscopy along with immunostaining for CD15. IUGR placentas known to have villous immaturity such as those associated with gestational diabetes, Rh negative pregnancies and anemia were excluded. The time of clinical onset of IUGR, associated complications like PE and oligohydramnios along with clinical variables were recorded. CD15 expression was scored in both distal and proximal vasculature and the values in IUGR and AGA pregnancies were compared and correlated with clinical variables. RESULTS: The mean CD 15 scores in both proximal vasculature (PV) as well as distal (DV) vasculature were significantly higher in the IUGR group compared to AGA (17.7 versus 5.16 in PV and 50.8 versus 23.7 in distal vasculature (DV)). Gestational age had no influence on CD15 staining in PV or DV in IUGR group, whereas preterm AGAs expressed higher CD15 only in the distal vessels. PE, oligohydramnios and the time of onset of IUGR did not influence the fetal vascular immaturity, as measured by CD15 scores. Although none of the clinical or obstetric factors influenced CD15 staining in AGA, fetal vessel immaturity in the IUGR group remained high even after adjusting for confounding variables like maternal age, gestational age and birth weight. Histological features suggestive of chronic hypoxia were significantly higher in IUGR placentas, compared to AGA and correlated positively with CD15 expression. CONCLUSION: Fetoplacental endothelium in both PV and DV is immature in IUGR irrespective of the gestational age or any other associated factors and CD15 immunodetection is a valuable marker for assessment of immaturity.

Remote biomonitoring of temperatures in mothers and newborns: design, development and testing of a wearable sensor device in a tertiary-care hospital in southern India.

OBJECTIVE: Newer technologies such as wearables, sensors, mobile telephony and computing offer opportunities to monitor vital physiological parameters and tackle healthcare problems, thereby improving access and quality of care. We describe the design, development and testing of a wearable sensor device for remote biomonitoring of body temperatures in mothers and newborns in southern India. METHODS: Based on client needs and technological requirements, a wearable sensor device was designed and developed using principles of 'social innovation' design. The device underwent multiple iterations in product design and engineering based on user feedback, and then following preclinical testing, a techno-feasibility study and clinical trial were undertaken in a tertiary-care teaching hospital in Bangalore, India. Clinical trial phases I and IIa for evaluation of safety and efficacy were undertaken in the following sequence: 7 healthy adult volunteers; 18 healthy mothers; 3 healthy babies; 10 stable babies in the neonatal care intensive unit and 1 baby with morbidities. Time-stamped skin temperature readings obtained at 5 min intervals over a 1-hour period from the device secured on upper arms of mothers and abdomen of neonates were compared against readings from thermometers used routinely in clinical practice. RESULTS: Devices were comfortably secured on to adults and neonates, and data were efficiently transmitted via the gateway device for secure storage and retrieval for analysis. The mean skin temperatures in mothers were lower than the axillary temperatures by 2°C; and in newborns, there was a precision of -0.5°C relative to axillary measurements. While occasional minimal adverse events were noted in healthy volunteers, no adverse events were noted in mothers or neonates. CONCLUSIONS: This proof-of-concept study shows that this device is promising in terms of feasibility, safety and accuracy (with appropriate calibration) with potential for further refinements in device accuracy and pursuit of further phases of clinical research for improved maternal and neonatal health.

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.

Effectiveness of Onsite Nurse Mentoring in Improving Quality of Institutional Births in the Primary Health Centres of High Priority Districts of Karnataka, South India: A Cluster Randomized Trial.

BACKGROUND: In India, although the proportion of institutional births is increasing, there are concerns regarding quality of care. We assessed the effectiveness of a nurse-led onsite mentoring program in improving quality of care of institutional births in 24/7 primary health centres (PHCs that are open 24 hours a day, 7 days a week) of two high priority districts in Karnataka state, South India. Primary outcomes were improved facility readiness and provider preparedness in managing institutional births and associated complications during child birth. METHODS: All functional 24/7 PHCs in the two districts were included in the study. We used a parallel, cluster randomized trial design in which 54 of 108 facilities received six onsite mentoring visits, along with an initial training update and specially designed case sheets for providers; the control arm received just the initial training update and the case sheets. Pre- and post-intervention surveys were administered in April-2012 and August-2013 using facility audits, provider interviews and case sheet audits. The provider interviews were administered to all staff nurses available at the PHCs and audits were done of all the filled case sheets during the month prior to data collection. In addition, a cost analysis of the intervention was undertaken. RESULTS: Between the surveys, we achieved coverage of 100% of facilities and 91.2% of staff nurse interviews. Since the case sheets were newly designed, case-sheet audit data were available only from the end line survey for about 80.2% of all women in the intervention facilities and 57.3% in the control facilities. A higher number of facilities in the intervention arm had all appropriate drugs, equipment and supplies to deal with gestational hypertension (19 vs.3, OR (odds ratio) 9.2, 95% C.I 2.5 to33.6), postpartum haemorrhage (29 vs. 12, OR 3.7, 95% C.I 1.6 to8.3); and obstructed labour (25 vs.9, OR 3.4, 95% CI 1.6 to8.3). The providers in the intervention arm had better knowledge of active management of the third stage of labour (82.4% vs.35.8%, AOR (adjusted odds ratio) 10, 95% C.I 5.5 to 18.2); management of maternal sepsis (73.5% vs. 10.9%, AOR 36.1, 95% C.I 13.6 to 95.9); neonatal resuscitation (48.5% vs.11.7%, AOR 10.7, 95% C.I 4.6 to 25.0) and low birth weight newborn care (58.1% vs. 40.9%, AOR 2.4, 95% C.I 1.2 to 4.7). The case sheet audits revealed that providers in the intervention arm showed greater compliance with the protocols during labour monitoring (77.3% vs. 32.1%, AOR 25.8, 95% C.I 9.6 to 69.4); delivery and immediate post-partum care for mothers (78.6% vs. 31.8%, AOR 22.1, 95% C.I 8.0 to 61.4) and for newborns (73.9% vs. 32.8%, AOR 24.1, 95% C.I 8.1 to 72.0). The cost analysis showed that the intervention cost an additional $5.60 overall per delivery. CONCLUSIONS: The mentoring program successfully improved provider preparedness and facility readiness to deal with institutional births and associated complications. It is feasible to improve the quality of institutional births at a large operational scale, without substantial incremental costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02004912.

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.

Maternal fat and fatty acid intake and birth outcomes in a South Indian population.

BACKGROUND: The quantity and quality of dietary fat during pregnancy play a key role in the growth and development of the fetus. The aim of this study was to examine the association between fat and fatty acid intakes in early pregnancy and birth outcomes in an apparent healthy normal South Indian population. METHODS: The study was a prospective observational cohort of 1838 pregnant women, conducted in South India. Intakes of total fat, saturated fatty acids (SFA) and polyunsaturated fats (PUFA) were assessed by a validated food-frequency questionnaire, and correlated with birthweight and incidence of small for gestational age (SGA) infants. RESULTS: This is a population that traditionally consumes diets that are low in SFA and n-3 PUFA, but high in linoleic acid (LA, 18:2 n-6). The data show that consumption of low SFA was associated with decreased birthweight and an increased risk of SGA [adjusted odds ratio (AOR) 1.45; 95% confidence interval (CI): 1.1, 2.1). Similar results were seen with n-3 PUFA: low intakes of alpha linolenic acid (ALNA, 18:3 n-3) as well as low intakes of long-chain (LC) n-3 PUFA were associated with increased risk of SGA (AOR 1.70; 95% CI: 1.1, 2.6, and AOR 1.27; 95% CI: 1.1, 2.1, respectively). Increased intakes of SFA and ALNA were predominantly associated with lower intakes of cereals and higher intakes of milk and milk products. CONCLUSIONS: These findings show that higher intakes of SFA and n-3 PUFA in early stages of pregnancy are associated with increased birthweight and reduced incidence of SGA in a South Indian population.

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.

Effects of yoga on utero-fetal-placental circulation in high-risk pregnancy: a randomized controlled trial.

Introduction. Impaired placentation and inadequate trophoblast invasion have been associated with the etiology of many pregnancy complications and have been correlated with the first trimester uterine artery resistance. Previous studies have shown the benefits of yoga in improving pregnancy outcomes and those of yogic visualization in revitalizing the human tissues. Methods. 59 high-risk pregnant women were randomized into yoga (n = 27) and control (n = 32) groups. The yoga group received standard care plus yoga sessions (1 hour/day, 3 times/week), from 12th to 28th week of gestation. The control group received standard care plus conventional antenatal exercises (walking). Measurements were assessed at 12th, 20th, and 28th weeks of gestation. Results. RM-ANOVA showed significantly higher values in the yoga group (28th week) for biparietal diameter (P = 0.001), head circumference (P = 0.002), femur length (P = 0.005), and estimated fetal weight (P = 0.019). The resistance index in the right uterine artery (P = 0.01), umbilical artery (P = 0.011), and fetal middle cerebral artery (P = 0.048) showed significantly lower impedance in the yoga group. Conclusion. The results of this first randomized study of yoga in high-risk pregnancy suggest that guided yogic practices and visualization can improve the intrauterine fetal growth and the utero-fetal-placental circulation.

Assessment of facility readiness and provider preparedness for dealing with postpartum haemorrhage and pre-eclampsia/eclampsia in public and private health facilities of northern Karnataka, India: a cross-sectional study.

BACKGROUND: The maternal mortality ratio in India has been declining over the past decade, but remains unacceptably high at 212 per 100,000 live births. Postpartum haemorrhage (PPH) and pre- eclampsia/eclampsia contribute to 40% of all maternal deaths. We assessed facility readiness and provider preparedness to deal with these two maternal complications in public and private health facilities of northern Karnataka state, south India. METHODS: We undertook a cross-sectional study of 131 primary health centres (PHCs) and 148 higher referral facilities (74 public and 74 private) in eight districts of the region. Facility infrastructure and providers' knowledge related to screening and management of complications were assessed using facility checklists and test cases, respectively. We also attempted an audit of case sheets to assess provider practice in the management of complications. Chi square tests were used for comparing proportions. RESULTS: 84.5% and 62.9% of all facilities had atleast one doctor and three nurses, respectively; only 13% of higher facilities had specialists. Magnesium sulphate, the drug of choice to control convulsions in eclampsia was available in 18% of PHCs, 48% of higher public facilities and 70% of private facilities. In response to the test case on eclampsia, 54.1% and 65.1% of providers would administer anti-hypertensives and magnesium sulphate, respectively; 24% would administer oxygen and only 18% would monitor for magnesium sulphate toxicity. For the test case on PPH, only 37.7% of the providers would assess for uterine tone, and 40% correctly defined early PPH. Specialists were better informed than the other cadres, and the differences were statistically significant. We experienced generally poor response rates for audits due to non-availability and non-maintenance of case sheets. CONCLUSIONS: Addressing gaps in facility readiness and provider competencies for emergency obstetric care, alongside improving coverage of institutional deliveries, is critical to improve maternal outcomes. It is necessary to strengthen providers' clinical and problem solving skills through capacity building initiatives beyond pre-service training, such as through onsite mentoring and supportive supervision programs. This should be backed by a health systems response to streamline staffing and supply chains in order to improve the quality of emergency obstetric care.

Whole body methionine kinetics, transmethylation, transulfuration and remethylation during pregnancy.

BACKGROUND & AIMS: There is evidence from a study of pregnant American women that methionine transmethylation (TM) and remethylation (RM) rates increases and transulfuration (TS) decreases as pregnancy progresses from trimester 1 to 3. To determine whether pregnant Indian women can make this adaptation successfully, methionine kinetics, TS, TM, and RM were measured in Indian women in early and late pregnancy. METHODS: Measurements were made in the postabsorptive and fed states in the 1st and 3rd trimesters of pregnancy by infusing 1-(13)C,(2)H3-methionine in 24 women, 12 with low (≤150 pmol L(-1)) and 12 with normal (≥200 pmol L(-1)) vitamin B12 status at recruitment. RESULTS: From trimester 1 to 3, except RM which decreased significantly, there was no change in any weight-specific methionine kinetic parameter. When expressed per whole body, methionine flux from protein breakdown increased significantly from trimester 1 to 3 in the fed and postabsorptive states. Flux to protein synthesis also increased significantly in the fed state. Rates of TM, TS and RM did not change, regardless of vitamin B12 status at recruitment. Protein and methionine intakes correlated with TM and RM rates and the change in RM from trimester 1 to 3 correlated with the change in dietary protein intake. CONCLUSION: These results suggest that methionine flux and its utilization for protein synthesis increases in Indian women as pregnancy progresses from trimester 1 to 3. TM and RM rates do not increase however, possibly because of inadequate protein intake and not because of vitamin B12 deficiency at trimester 1.

High folate and low vitamin B-12 intakes during pregnancy are associated with small-for-gestational age infants in South Indian women: a prospective observational cohort study.

BACKGROUND: Folic acid supplementation in those with a low vitamin B-12 intake or status may have adverse effects. These effects are unknown with regard to birth outcome in pregnant Indian women who are routinely supplemented with high doses of folic acid. OBJECTIVE: The objective was to examine the association of unbalanced vitamin B-12 and total folate (folic acid supplement + dietary folate) intakes during pregnancy with outcomes in small-for-gestational-age (SGA) infants. DESIGN: This was a prospective observational cohort study of 1838 pregnant women in South India. Low intake of dietary vitamin B-12 in the presence of high total folate intake was examined as the ratio of vitamin B-12 intake to total folate intake. RESULTS: The inadequacy of vitamin B-12 intake (<1.2 µg/d) assessed by a food-frequency questionnaire in the first, second, and third trimesters of pregnancy was 25%, 11%, and 10%, respectively. Multivariate log binomial regression showed that low vitamin B-12 and folate intakes in the first trimester were independently associated with a higher risk of SGA. In a subgroup of women with high supplemental folic acid intakes in the second trimester, those with the lowest tertile of vitamin B-12:folate ratio had a higher risk of SGA outcome than did those in the highest tertile (adjusted RR: 2.73; 95% CI: 1.17, 6.37). A similar trend was observed in the analysis of blood micronutrient status in a random subset (n = 316) of the sample. CONCLUSIONS: These findings suggest that, in addition to vitamin B-12 and folate deficiencies alone, there may be adverse birth outcomes associated with unbalanced vitamin B-12 and folate intakes or status during pregnancy. These findings have important implications for the antenatal B vitamin supplementation policy in India. This trial was registered at the Clinical Trial Registry of India as 2013/07/005342.

Availability and distribution of emergency obstetric care services in Karnataka State, South India: access and equity considerations.

BACKGROUND: As part of efforts to reduce maternal deaths in Karnataka state, India, there has been a concerted effort to increase institutional deliveries. However, little is known about the quality of care in these healthcare facilities. We investigated the availability and distribution of emergency obstetric care (EmOC) services in eight northern districts of Karnataka state in south India. METHODS & FINDINGS: We undertook a cross-sectional study of 444 government and 422 private health facilities, functional 24-hours-a-day 7-days-a-week. EmOC availability and distribution were evaluated for 8 districts and 42 taluks (sub-districts) during the year 2010, based on a combination of self-reporting, record review and direct observation. Overall, the availability of EmOC services at the sub-state level [EmOC = 5.9/500,000; comprehensive EmOC (CEmOC) = 4.5/500,000 and basic EmOC (BEmOC) = 1.4/500,000] was seen to meet the benchmark. These services however were largely located in the private sector (90% of CEmOC and 70% of BemOC facilities). Thirty six percent of private facilities and six percent of government facilities were EmOC centres. Although half of eight districts had a sufficient number of EmOC facilities and all eight districts had a sufficient number of CEmOC facilities, only two-fifths of the 42 taluks had a sufficient number of EmOC facilities. With the private facilities being largely located in select towns only, the 'non-headquarter' taluks and 'backward' taluks suffered from a marked lack of coverage of these services. Spatial mapping further helped identify the clustering of a large number of contiguous taluks without adequate government EmOC facilities in northeastern Karnataka. CONCLUSIONS: In conclusion, disaggregating information on emergency obstetric care service availability at district and subdistrict levels is critical for health policy and planning in the Indian setting. Reducing maternal deaths will require greater attention by the government in addressing inequities in the distribution of emergency obstetric care services.

Sharing best practices through online communities of practice: a case study.

INTRODUCTION: The USAID-funded Capacity Project established the Global Alliance for Pre-Service Education (GAPS) to provide an online forum to discuss issues related to teaching and acquiring competence in family planning, with a focus on developing countries' health related training institutions. The success of the Global Alliance for Nursing and Midwifery's ongoing web-based community of practice (CoP) provided a strong example of the successful use of this medium to reach many participants in a range of settings. CASE DESCRIPTION: GAPS functioned as a moderated set of forums that were analyzed by a small group of experts in family planning and pre-service education from three organizations. The cost of the program included the effort provided by the moderators and the time to administer responses and conduct the analysis. DISCUSSION AND EVALUATION: Family planning is still considered a minor topic in health related training institutions. Rather than focusing solely on family planning competencies, GAPS members suggested a focus on several professional competencies (e.g. communication, leadership, cultural sensitivity, teamwork and problem solving) that would enhance the resulting health care graduate's ability to operate in a complex health environment. Resources to support competency-based education in the academic setting must be sufficient and appropriately distributed. Where clinical competencies are incorporated into pre-service education, responsible faculty and preceptors must be clinically proficient. The interdisciplinary GAPS memberships allowed for a comparison and contrast of competencies, opportunities, promising practices, documents, lessons learned and key teaching strategies. CONCLUSIONS: Online CoPs are a useful interface for connecting developing country experiences. From CoPs, we may uncover challenges and opportunities that are faced in the absorption of key public health competencies required for decreasing maternal mortality and morbidity. Use of the World Health Organization (WHO) Implementing Best Practices Knowledge Gateway, which requires only a low bandwidth connection, gave educators an opportunity to engage in the discussion even in the most Internet access-restricted places (e.g. Ethiopia). In order to sustain an online CoP, funds must come from an international organization (e.g. WHO regional office) or university that can program the costs long-term. Eventually, the long-term effectiveness and sustainability of GAPS rests on its transfer to the members themselves.