Annie Regi

New birth weight reference standards customised to birth order and sex of babies from South India

BackgroundThe foetal growth standards for Indian children which are available today suffer due to methodological problems. These are, for example, not adhering to the WHO recommendation to base gestational age on the number of completed weeks and secondly, not excluding mothers with risk factors. This study has addressed both the above issues and in addition provides birthweight reference ranges with regard to sex of the baby and maternal parity.MethodsData from the labour room register from 1996 to 2010 was obtained. A rotational sampling scheme was used i.e. the 12 months of the year were divided into 4 quadrants. All deliveries in January were considered to represent the first quadrant. Similarly all deliveries in April, July and October were considered to represent 2nd, 3rd and 4th quadrants. In each successive year different months were included in each quadrant. Only those mothers aged 20–39 years and delivered between 24 to 42 weeks gestational age were considered. Those mothers with obstetric risk factors were excluded. The reference standards were fitted using the Generalized Additive Models for Location Scale and Shape (GAMLSS) method for Box – Cox t distribution with cubic spline smoothing.ResultsThere were 41,055 deliveries considered. When women with risk factors were excluded 19,501 deliveries could be included in the final analysis. The male babies of term firstborn were found to be 45 g heavier than female babies. The mean birthweights were 2934 g and 2889.5 g respectively. Similarly, among the preterm babies, the first born male babies weighed 152 g more than the female babies. The mean birthweights were 1996 g and 1844 g respectively.In the case of later born babies, the term male babies weighed 116grams more than the females. The mean birth weights were 3085 grams and 2969 grams respectively. When considering later born preterm babies, the males outweighed the female babies by 111 grams. The mean birthweights were 2089 grams and 1978 grams respectively. There was a substantial agreement range from k=.883, (p<.01) to k=.943, (p<.01) between adjusted and unadjusted percentile classification for the subgroups of male and female babies and first born and later born ones.Birth weight charts were adjusted for maternal height using regression methods. The birth weight charts for the first born and later born babies were regrouped into 4 categories, including male and female sexes of the babies. Reference ranges were acquired both for term and preterm babies.With economic reforms, one expects improvement in birthweights. The mean (sd) birthweights of the year 1996 was 2846 (562) as compared to year 2010 (15 years later) which was 2907 (571). There was only a difference of 61 grams in the mean birthweights over one and a half decade.ConclusionNew standards are presented from a large number of deliveries over 15 years, customised to the maternal height, from a south Indian tertiary hospital. Reference ranges are made available separately for first born or later born babies, for male and female sexes and for term and preterm babies.

Magnesium sulphate for prevention of eclampsia: are intramuscular and intravenous regimens equivalent? A population pharmacokinetic study

To compare magnesium sulphate concentrations achieved by intramuscular and intravenous regimens used for the prevention of eclampsia.

Low prevalence of Chlamydia trachomatis infection in non-urban pregnant women in Vellore, S. India

Objective To determine the prevalence and risk factors for Chlamydia trachomatis (CT) infection in pregnant women and the rate of transmission of CT to infants. Methods Pregnant women (≥28 weeks gestation) in Vellore, South India were approached for enrollment from April 2009 to January 2010. After informed consent was obtained, women completed a socio-demographic, prenatal, and sexual history questionnaire. Endocervical samples collected at delivery were examined for CT by a rapid enzyme test and nucleic acid amplification test (NAAT). Neonatal nasopharyngeal and conjunctival swabs were collected for NAAT testing. Results Overall, 1198 women were enrolled and 799 (67%) endocervical samples were collected at birth. Analyses were completed on 784 participants with available rapid and NAAT results. The mean age of women was 25.8 years (range 18–39 yrs) and 22% (95% CI: 19.7–24.4%) were primigravida. All women enrolled were married; one reported >one sexual partner; and six reported prior STI. We found 71 positive rapid CT tests and 1/784 (0.1%; 95% CI: 0–0.38%) true positive CT infection using NAAT. Conclusions To our knowledge, this is the largest study on CT prevalence amongst healthy pregnant mothers in southern India, and it documents a very low prevalence with NAAT. Many false positive results were noted using the rapid test. These data suggest that universal CT screening is not indicated in this population.

Comprehensive Maturity Onset Diabetes of the Young (MODY) Gene Screening in Pregnant Women with Diabetes in India.

Pregnant women with diabetes may have underlying beta cell dysfunction due to mutations/rare variants in genes associated with Maturity Onset Diabetes of the Young (MODY). MODY gene screening would reveal those women genetically predisposed and previously unrecognized with a monogenic form of diabetes for further clinical management, family screening and genetic counselling. However, there are minimal data available on MODY gene variants in pregnant women with diabetes from India. In this study, utilizing the Next generation sequencing (NGS) based protocol fifty subjects were screened for variants in a panel of thirteen MODY genes. Of these subjects 18% (9/50) were positive for definite or likely pathogenic or uncertain MODY variants. The majority of these variants was identified in subjects with autosomal dominant family history, of whom five were in women with pre-GDM and four with overt-GDM. The identified variants included one patient with HNF1A Ser3Cys, two PDX1 Glu224Lys, His94Gln, two NEUROD1 Glu59Gln, Phe318Ser, one INS Gly44Arg, one GCK, one ABCC8 Arg620Cys and one BLK Val418Met variants. In addition, three of the seven offspring screened were positive for the identified variant. These identified variants were further confirmed by Sanger sequencing. In conclusion, these findings in pregnant women with diabetes, imply that a proportion of GDM patients with autosomal dominant family history may have MODY. Further NGS based comprehensive studies with larger samples are required to confirm these finding

How safe is metformin when initiated in early pregnancy? A retrospective 5-year study of pregnant women with gestational diabetes mellitus from India

BACKGROUND The initiation of metformin in early pregnancy in Gestational Diabetes mellitus (GDM) remains controversial. The aim of our study was to assess the influence of Metformin on maternal and fetal outcomes when initiated within the first trimester of pregnancy in GDM. METHODS AND MATERIALS A retrospective analysis of 540 women with diabetes complicating pregnancy (IADPSG criteria) over five years (January 2011 to May 2016) was done. The study population comprised of patients initiated on (a) metformin within the first trimester (Group A:n = 186), (b) metformin after the first trimester (Group B:n = 203) and (c) insulin at any time during their pregnancy (Group C:n = 151). The primary outcomes compared were prematurity, respiratory distress, birth trauma, 5-min APGAR score, neonatal hypoglycaemia and need for phototherapy, while secondary outcomes compared were neonatal anthropometric measurements, maternal glycemic control, maternal hypertensive complications, postpartum glucose tolerance. RESULTS Individual and composite primary or secondary outcomes in group A were similar to Groups B and C, though numerically higher premature births were seen in Group A. There was a 1.3% overall incidence of stillbirths/IUD, while 1.11% congenital anomalies were noted of which 2.15% were in group A and 1.32% were in Group C (p = .16). CONCLUSIONS The initiation of metformin within the first trimester of pregnancy has no significant adverse maternal or fetal outcomes. However, vigilance for premature births is recommended in women exposed to metformin in early pregnancy.

Absence of G1528C mutation in long-chain 3-hydroxyacyl-CoA dehydrogenase in four Indian patients with pregnancy-related liver disease

Sir, Acute fatty liver of pregnancy (AFLP) is a rare pregnancyrelated liver disorder manifesting in late pregnancy with acute liver failure [1], while the hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is a microangiopathy affecting the liver and other organs in late pregnancy [2]. Long-chain 3-hydroxyacyl-coenzyme-A dehydrogenase (LCHAD) deficiency in the fetus has been associated with these hepatic disorders of the mother during pregnancy [3]. The commonest mutation is G1528C in exon 15 of the mitochondrial trifunctional protein (MTP) α subunit, which leads to a substitution of a glutamine for glutamate, which selectively decreases LCHAD activity [4]. Though the occurrence of the G1528C mutation has been studied in Western populations [4, 5], where it is common, the information on this from other populations is scarce. We studied the presence of the G1528C mutation in three patients with AFLP (all fulfilled “Swansea” criteria for diagnosis, none had liver biopsy, two had coexistent HELLP, and one had coexistent pre-eclampsia and partial HELLP) [6] and one patient with HELLP syndrome (coexistent preeclampsia). All patients (age: 23; 19–28 years, median; range) presented in third trimester (36; 32–38 weeks of gestation). Three were primigravida while one patient had a previous uneventful pregnancy. All patients were eventually discharged in stable condition, and the immediate fetal outcome was favorable in all. The placenta is known to carry out mitochondrial β oxidation, and its genetic make up is identical to the fetus [7], and hence, we used placental DNA for our genetic analysis by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) analysis. This study was approved by the Institutional Review Board, and consent was obtained from the patient for the study. As required by the criteria, all patients had an unyielding make up for the etiology of acute liver disease, including serology tests for acute viral hepatitis A, B, and E. Controls were placenta from normal deliveries of equal gestational age. The blood was drained, and the placental tissue was rinsed thrice with saline and stored at −80 °C. Baseline laboratory parameters in the four patients analyzed are summarized in Table 1. DNAwas isolated from 100 mg placenta and amplified using forward (5′-CCCTTGCCAGGTGATTGGC-3′) and reverse (5′-GTATAGAAGCCAGGTCCATCCTGCCAAG-3 ′) primers [8]. The PCR products were purified, digested with Pst1, and separated by agarose gel electrophoresis to identify the G1528C mutation. Purified PCR products were bidirectionally sequenced using the BigDye Terminator V3.1 kit in a 3130 genetic analyzer (Applied Biosystems, Carlsbad, USA) and analyzed using NovoSNP software (http://www.molgen. ua.ac.be/bioinfo/novosnp/). PCR was used to amplify the whole of exon 15 of the α subunit, which codes for LCHAD activity of the MTP (Fig. 1a, first lane on left). All healthy controls as well as AFLP and HELLP patients showed two characteristic fragments after Pst1 digestion (465 and 175 bp), indicating an absence of the G1528C mutation [8]. V. Raghupathy :K. R. Thangaraj :K. A. Balasubramanian : A. Ramachandran (*) The Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore 632 004, India e-mail: anup@cmcvellore.ac.in

OS034. Magnesium sulfate for prevention of eclampsia: Are intramuscularand intravenous regimens equivalent?

INTRODUCTION Magnesium sulfate is the agent of choice for the treatment and prevention of eclampsia. Optimal loading and maintenance dosing has not been determined. OBJECTIVES To compare the pharmacokinetic parameters if IM vs. IV magnesium sulfate. METHODS A pharmacokinetic study was performed as part of a randomized trial that enrolled 300 women comparing IM and IV regimens of magnesium dosing in two low resource sites in India. Data from 258 enrolled women were analyzed in the pharmacokinetic study. Due to infrastructure available at the sites, a single sample was drawn per subject with the expectation of utilizing samples in a pooled data analysis. RESULTS Magnesium clearance was estimated via pharmacokinetic modeling to be 48.1dL/h, volume of distribution 156dL and IM bioavailability 86.2%. The IM regimen produced higher initial serum concentrations, consistent with a substantially larger loading dose. At steady state, Mg concentrations in the IM and IV Groups were comparable. With either regimen, a substantial number of subjects would be expected to have serum concentrations lower than those generally expected to be therapeutic. CONCLUSION A larger loading dose for the IV regimen should be considered. Where feasible, individualized higher doses of magnesium sulfate would yield a greater number of treated women with clinically effective magnesium concentrations.