Association of maternal prenatal selenium concentration and preterm birth: a multicountry meta-analysis

BackgroundSelenium (Se), an essential trace mineral, has been implicated in preterm birth (PTB). We aimed to determine the association of maternal Se concentrations during pregnancy with PTB risk and gestational duration in a large number of samples collected from diverse populations.MethodsGestational duration data and maternal plasma or serum samples of 9946 singleton live births were obtained from 17 geographically diverse study cohorts. Maternal Se concentrations were determined by inductively coupled plasma mass spectrometry analysis. The associations between maternal Se with PTB and gestational duration were analysed using logistic and linear regressions. The results were then combined using fixed-effect and random-effect meta-analysis.FindingsIn all study samples, the Se concentrations followed a normal distribution with a mean of 93.8 ng/mL (SD: 28.5 ng/mL) but varied substantially across different sites. The fixed-effect meta-analysis across the 17 cohorts showed that Se was significantly associated with PTB and gestational duration with effect size estimates of an OR=0.95 (95% CI: 0.9 to 1.00) for PTB and 0.66 days (95% CI: 0.38 to 0.94) longer gestation per 15 ng/mL increase in Se concentration. However, there was a substantial heterogeneity among study cohorts and the random-effect meta-analysis did not achieve statistical significance. The largest effect sizes were observed in UK (Liverpool) cohort, and most significant associations were observed in samples from Malawi.InterpretationWhile our study observed statistically significant associations between maternal Se concentration and PTB at some sites, this did not generalise across the entire cohort. Whether population-specific factors explain the heterogeneity of our findings warrants further investigation. Further evidence is needed to understand the biologic pathways, clinical efficacy and safety, before changes to antenatal nutritional recommendations for Se supplementation are considered.

Effect of Thrombocytopenia on Age and Method of Delivery among Pregnant Women in Late Trimester

Aim: To evaluate the effect of thrombocytopenia in pregnant women. Study design: Descriptive cross-sectional hospital based study Place and duration of study: Department of Obstetrics & Gynaecology, Liaquat University of Medical and Health Science Jamshoro from 1st June 2018 to 31st June 2019. Methodology: One hundred and seventy-six patients were observed. Women with pre-eclampsia, platelets less than 50X1010, singleton pregnancy and pregnancy greater than 32 weeks were included. Results: Most of the participants 91(51.9%) were 26 to 30 years with mean age was 30.71±4.45 years. Gestational duration in last trimester was 50(28.4%), 98(55.7%) and 28 (15.9%) of 28 to 32 Weeks, 32 to 36 Weeks and greater than 36 weeks respectively. Mean gestational duration was 35.11±2.3 Weeks. Seventy-one were falling in range of platelets of 30x1010 to 40x1010 (40.3%). Others were 46 (26.1%) of >40x1010, 43(24.4%) of 20x10-30x1010 and 16(9.1%) of 10x10-20x1010. One hundred and 41(80.1%) had vaginal deliveries and 35(19.9%) had lower segment caesarean section deliveries. Conclusion: The young participants of thrombocytopenia were more prevalent than old age participants. Keywords: Gestational thrombocytopenia, Platelet count, Pregnancy

The Association between Preterm Birth and Ambient Air Pollution Exposure in Shiyan, China, 2015–2017

Shortening of the gestational duration has been found associated with ambient air pollution exposure. However, the critical exposure windows of ambient air pollution for gestational duration remain inconsistent, and the association between ambient air pollution and early term births (ETB, 37 to 38 weeks) has rarely been studied relative to preterm births (PTB, 28–37 weeks). A time-series study was conducted in Shiyan, a medium-sized city in China. Birth information was collected from the Shiyan Maternity and Child Health Hospital, and 13,111 pregnant women who gave birth between 2015 and 2017 were included. Data of the concentrations of air pollutants, including PM10, PM2.5, NO2, and SO2 and meteorological data, were collected in the corresponding gestational period. The Cox regression analysis was performed to estimate the relationship between ambient air pollution exposure and the risk of preterm birth after controlling the confounders, including maternal age, education, Gravidity, parity, fetal gender, and delivery mode. Very preterm birth (VPTB, 28–32 weeks) as a subtype of PTB was also incorporated in this study. The risk of VPTB and ETB was positively associated with maternal ambient air pollution exposure, and the correlation of gaseous pollutants was stronger than particulate matter. With respect to exposure windows, the critical trimester of air pollutants for different adverse pregnancy outcomes was different. The exposure windows of PM10, PM2.5, and SO2 for ETB were found in the third trimester, with HRs (hazard ratios) of 1.06 (95%CI: 1.04, 1.09), 1.07 (95%CI: 1.04, 1.11), and 1.28 (95%CI: 1.20, 1.35), respectively. However, for NO2, the second and third trimesters exhibited similar results, the HRs reaching 1.10 (95%CI: 1.03, 6.17) and 1.09 (95%CI: 1.03,1.15), respectively. This study extends and strengthen the evidence for a significant correlation between the ambient air pollution exposure during pregnancy and the risk of not only PTB but, also, ETB. Moreover, our findings suggest that the exposure windows during pregnancy vary with different air pollutants and pregnancy outcomes.

Transcriptome and regulatory maps of decidua-derived stromal cells inform gene discovery in preterm birth

While a genetic component of preterm birth (PTB) has long been recognized and recently mapped by genome-wide association studies (GWASs), the molecular determinants underlying PTB remain elusive. This stems in part from an incomplete availability of functional genomic annotations in human cell types relevant to pregnancy and PTB. We generated transcriptome (RNA-seq), epigenome (ChIP-seq of H3K27ac, H3K4me1, and H3K4me3 histone modifications), open chromatin (ATAC-seq), and chromatin interaction (promoter capture Hi-C) annotations of cultured primary decidua-derived mesenchymal stromal/stem cells and in vitro differentiated decidual stromal cells and developed a computational framework to integrate these functional annotations with results from a GWAS of gestational duration in 56,384 women. Using these resources, we uncovered additional loci associated with gestational duration and target genes of associated loci. Our strategy illustrates how functional annotations in pregnancy-relevant cell types aid in the experimental follow-up of GWAS for PTB and, likely, other pregnancy-related conditions.

Changes in data management contribute to temporal variation in gestational duration distribution in the Swedish Medical Birth Registry

Multiple factors contribute to gestational duration variability. Understanding the sources of variability allows to design better association studies and assess public health measures. Here, we aimed to assess geographical and temporal changes in the determination of gestational duration and its reporting in Sweden between 1973 and 2012. Singleton live births between 1973 and 2012 were retrieved from the Swedish Medical Birth Register. Gestational duration trends in percentiles and rates of pre- and post-term deliveries were analyzed by plotting the values over time. Temporal changes in gestational duration based on ultrasound and last menstrual period (LMP) estimation methods were compared. Intervals between LMP date and LMP-based due date were analyzed to assess changes in expected gestational duration. In total, 3 940 577 pregnancies were included. From 1973 until 1985, the median of gestational duration estimated based on LMP or ultrasound decreased from 283 to 278 days, and remained stable until 2012. The distribution was relatively stable when ultrasound-based estimates were used. Until the mid-1990s, there was a higher incidence than expected of births occurring on every seventh gestational day from day 157 onward. On an average, these gestational durations were reported 1.8 times more often than adjacent durations. Until 1989, the most common expected gestational duration was 280 days, and thereafter, it was 279 days. The expected gestational duration varied from 279 to 281 days across different Swedish counties. During leap years, the expected gestational duration was one day longer. Consequently, leap years were also associated with significantly higher preterm and lower post-term delivery rates than non-leap years. Changes in data handling and obstetrical practices over the years contribute to gestational duration variation. The resulting increase in variability might reduce precision in association studies and hamper the assessment of public health measures aimed to improve pregnancy outcomes.

Protein Concentrations of Thrombospondin-1, MIP-1β, and S100A8 Suggest the Reflection of a Pregnancy Clock in Mid-Trimester Amniotic Fluid

The development of immunoassays enables more sophisticated studies of the associations between protein concentrations and pregnancy outcomes, allowing early biomarker identification that can improve neonatal outcomes. The aim of this study was to explore associations between selected mid-trimester amniotic fluid proteins and (1) overall gestational duration and (2) spontaneous preterm delivery. A prospective cohort study, including women undergoing mid-trimester transabdominal genetic amniocentesis, was performed in Gothenburg, Sweden, 2008–2016 (n = 1072). A panel of 27 proteins related to inflammation was analyzed using Meso-Scale multiplex technology. Concentrations were adjusted for gestational age at sampling, experimental factors, year of sampling, and covariates (maternal age at sampling, parity (nulliparous/multiparous), smoking at first prenatal visit, and in vitro fertilization). Cox regression analysis of the entire cohort was performed to explore possible associations between protein concentrations and gestational duration. This was followed by Cox regression analysis censored at 259 days or longer, to investigate whether associations were detectable in women with spontaneous preterm delivery (n = 47). Finally, linear regression models were performed to analyze associations between protein concentrations and gestational duration in women with spontaneous onset of labor at term (n = 784). HMG-1, IGFBP-1, IL-18, MIP-1α, MIP-1β, S100A8, and thrombospondin-1 were significantly associated with gestational duration at term, but not preterm. Increased concentrations of thrombospondin-1, MIP-1β, and S100A8, respectively, were significantly associated with decreased gestational duration after the Holm-Bonferroni correction in women with spontaneous onset of labor at term. This adds to the concept of a pregnancy clock, where our findings suggest that such a clock is also reflected in the amniotic fluid at early mid-trimester, but further research is needed to confirm this.