Smooth and shape-constrained quantile distributed lag models.

Aim. To assess the neurological status and index of neuropsychological development in low birth weight children taking into account the FADS2 rs174583 (C/T) gene polymorphism.Materials and methods. To study the FADS2 rs174583 (C/T) gene polymorphism, 170 children were examined. The children were divided into 3 groups depending on their birth weight: group I included 53 children (birth weight was 1500–1999 g, gestation period – 33.0 [32.0; 35.0] weeks), group II included 77 children (birth weight – 2000–2499 g, gestation period – 35.0 [34.0; 36.0] weeks), group III was composed of 40 children as a control (birth weight – more than 2500 g, gestation period – 38.0 [36.0; 39.0] weeks). The genotyping was carried out using a polymerase chain reaction method.Results. The C allele and the С/Т genotype frequencies of the FADS2 rs174583 gene polymorphism in the children matched those in North-Western Europe. Seizures in the past medical history due to the nervous system disorders were most commonly occurred in children with the TT genotype (16.45 %, P < 0.05), while patients with the CC genotype had seizures in only 5.6 % of cases. Children with a birth weight of 1500–1999 g carrying the C/T heterozygous genotype and the T/T homozygous genotype of the FADS2 (rs1745683) gene polymorphism had a lower total Apgar score than children with a birth weight of more than 2000 g (P < 0.05). The coefficient of psychomotor development was the lowest in children with birth weight of 1500-1999 g and the minor homozygous T/T genotype of the FADS2 (rs1745683) gene polymorphism, at 83.0 (75.0; 83.0), which corresponded to a weak normal level of the neuropsychiatric development, while the highest index of psychomotor development (116.0 (112.0; 141.0)) and a normal high level of neuropsychiatric development were significantly registered in children with birth weight of 2500 g and the major homozygous C/C genotype.Conclusions. It is possible that the predominance of the homozygous C/C genotype and the heterozygous C/T genotype fulfils a protective function in order to reduce the negative effects of preterm birth on the nervous system.

To establish and quantify the effect of the internal armed conflict in Colombia on infant health, particularly birth weight. This document explores time differences in relation to the impact of the internal armed conflict in Colombia, measured by municipal homicide rates, on infant health, quantified as infant mortality and birth weight. Based on individual data from the 1995 and 2000 Colombian National Demographic and Health Surveys, along with annual municipal data on violence and economic performance, results obtained from two biological siblings are compared using a maternal fixed logistic regression, as one was born in a violent era and the other during a peaceful moment. Political violence negatively affected infant health outcomes during the peak of violence experienced by Colombia in the 1990s, with worse outcomes for male infants than for females. Controlling fixed maternal effects shows a three times greater probability of being born with low birth in infants born during increased violence, compared to their siblings born in more peaceful times. These results make visible all the effects of intense and long-lasting armed conflicts, as is the case of Colombia, since not only direct actors involved in conflict are affected, but also infants who show worse health outcomes. These results allows targeting policies for reducing the effects on populations in conflict or during the reconstruction period; in this case, the provision of maternal care during the gestational period and special care for newborns in areas under high violence levels should be a priority.

Serum zinc levels of cord blood: Relation to birth weight and gestational period

SummaryA total number of 125 485 single, live births with known sex and birth weight, and a gestation period estimated to be from 28.0 to 48.9 weeks, were registered in Norway in 196 and 1968. Information about these births pro vided by a national scheme of medical registration of births is used in a study of the relation between birth weight and gestation period.An almost linear relation was found to exist for gestation periods of 35 to 42 weeks. In this interval, median birth weight increased about 200 g a week. At the same gestation period male births were found to be on the average about 150 g heavier than female births. Parity also had a notable influence on birth weight. For gestation periods of 35 weeks and more, the birth weight of a first born male was found to average about 170 g less than that of a second and subsequently born. For female births the difference was 130 g.The material is suggested for use as reference for birth weight at various gestation periods and tables are included for this purpose.

Background: An infant’s birth weight is a reliable index of intrauterine growth and a sensitive predictor of newborn chances of survival, growth and long-term physical and psychosocial development. Low birth weight has been defined as birth weight <2.5 kg regardless of gestational age. The incidence of low birth weight (LBW) in India varies between 25–30% and of which 60–65% are because of intrauterine growth retardation. Aim & Objective: To determine the incidence and various determinants of low birth weight among babies delivered at rural tertiary care hospitals in central Uttar Pradesh. Methods and Material: The study was conducted at UPUMS, Saifai, Etawah, among pregnant women who delivered babies from 1st January 2018 to 31st December 2018. Details regarding age of the mother, gravida, parity, gestation period, presence of complications, the procedure for delivery and birth weight of the newborn were recorded and analyzed using SPSS software (version 23) Results: A total of 7615 deliveries were conducted (53.2% were males, 46.8% were females). The mean birth weight of babies was 2.65 Kg with S.D ± 0.52. Preterm babies were 32% while 67% were term babies and 23% of babies were low birth weight. There was a statistically significant association between birth weight of babies and factors like age of mother, parity of mother, gestation period, and presence of complications during the antenatal period. Conclusions: Prompt identification of high-risk factors, prevention of premature delivery, increasing the use of health services during pregnancy and management of the risk factors would reduce the incidence of low birth weight.

Evidence supports an association between maternal exposure to air pollution during pregnancy and children's health outcomes. Recent interest has focused on identifying critical windows of vulnerability. An analysis based on a distributed lag model (DLM) can yield estimates of a critical window that are different from those from an analysis that regresses the outcome on each of the 3 trimester-average exposures (TAEs). Using a simulation study, we assessed bias in estimates of critical windows obtained using 3 regression approaches: 1) 3 separate models to estimate the association with each of the 3 TAEs; 2) a single model to jointly estimate the association between the outcome and all 3 TAEs; and 3) a DLM. We used weekly fine-particulate-matter exposure data for 238 births in a birth cohort in and around Boston, Massachusetts, and a simulated outcome and time-varying exposure effect. Estimates using separate models for each TAE were biased and identified incorrect windows. This bias arose from seasonal trends in particulate matter that induced correlation between TAEs. Including all TAEs in a single model reduced bias. DLM produced unbiased estimates and added flexibility to identify windows. Analysis of body mass index z score and fat mass in the same cohort highlighted inconsistent estimates from the 3 methods.

BackgroundFew studies have assessed air pollution exposure association with birthweight during both preconception and gestational periods.MethodsLeveraging a preconception cohort consisting of 14220 pregnant women and newborn children in Shanghai, China during 2016–2018, we aim to assess associations of NO2 and PM2.5 exposure, derived from high-resolution spatial-temporal models, during preconception and gestational periods with outcomes including term birthweight, birthweight Z-score, small-for-gestational age (SGA) and large-for-gestational age (LGA). Linear and logistic regressions were used to estimate 3-month preconception and trimester-averaged air pollution exposure associations; and distributed lag models (DLM) were used to identify critical exposure windows at the weekly resolution from preconception to delivery. Two-pollutant models and children’s sex-specific associations were explored.ResultsAfter controlling for covariates, one standard deviation (SD) (11.5 μg/m3, equivalent to 6.1 ppb) increase in NO2 exposure during the second and the third trimester was associated with 13% (95% confidence interval: 2 – 26%) and 14% (95% CI: 1 – 29%) increase in SGA, respectively; and one SD (9.6 μg/m3) increase in PM2.5 exposure during the third trimester was associated with 15% (95% CI: 1 – 31%) increase in SGA. No association have been found for outcomes of birthweight, birthweight Z-score and LGA. DLM found that gestational weeks 22–32 were a critical window, when NO2 exposure had strongest associations with SGA. The associations of air pollution exposure tended to be stronger in female newborns than in male newborns. However, no significant associations of air pollution exposure during preconception period on birthweight outcomes were found.ConclusionConsistent with previous studies, we found that air pollution exposure during mid-to-late pregnancy was associated with adverse birthweight outcomes.

Maternal exposure to ambient particulate matter on the growth of twin fetuses after in vitro fertilization

Effect of Air Pollution on Low Birth Weight in Seoul of Korea, 1999–2003

Preterm infants are obviously born lighter and shorter, with smaller head circumferences than normal birth weight term born neonates. They also have a different body composition. Compromised growth is associated with adverse health outcomes. Both growth retardation and accelerated growth are suggested to cause metabolic, cardiovascular, and renal complications. Reviews regarding growth and body composition in preterm infants often do not differentiate between birth weight and gestational age. The purpose of this systematic review is to assemble growth data, specific in extremely low birth weight children. Different databases were searched for studies regarding growth and body composition in former extremely low birth weight infants until adulthood. We compared height, weight, head circumference, body mass index, fat mass, lean mass, fat distribution, and body water to matched normal birth weight controls and the World Health Organization growth charts. Studies consistently reported that former extremely low birth weight neonates experience a period of accelerated postnatal growth, but they achieve lower anthropometric parameters than normal birth weight children. There is no consensus about differences in body composition and how to measure this.Conclusion: Although extremely low birth weight infants exhibit a period of catch-up growth, their growth remains retarded later in life. Further research is needed to investigate body composition and the associated risk of cardiovascular diseases or metabolic syndrome.What is Known:• Extremely low birth weight infants have lower anthropometric parameters and a different body composition at birth and term-corrected age than normal birth weight infants.• Former extremely low birth weight infants also have a higher risk on adverse cardiovascular health outcomes in later life.What is New:• After hospital discharge, extremely low birth weight neonates remain smaller and probably also lighter, with smaller head circumferences at each corrected age throughout childhood and adolescence when compared to normal birth weight infants or the World Health Organization growth charts. It is not clear whether extremely low birth weight infants reach a lower or similar body mass index score as normal birth weight infants.• There is a lack of (long-term) information on body composition in extremely low birth weight infants.

Purpose of ReviewThe developmental origins of health and disease (DOHaD) hypothesis posits that the perinatal environment can impact fetal and later life health. The placenta is uniquely situated to assess prenatal exposures in the context of DOHaD because it is an essential ephemeral fetal organ that manages the transport of oxygen, nutrients, waste, and endocrine signals between the mother and fetus. The purpose of this review is to summarize recent studies that evaluated the DOHaD hypothesis in human placentas using epigenomics, including DNA methylation and transcriptomic studies of mRNA, lncRNA, and microRNAs.Recent FindingsBetween 2016 and 2021, 28 articles evaluated associations between prenatal exposures and placental epigenomics across broad exposure categories including maternal smoking, psychosocial stressors, chemicals, air pollution, and metals. Sixteen of these studies connected exposures to health outcome such as birth weight, fetal growth, or infant neurobehavior through mediation analysis, identification of shared associations between exposure and outcome, or network analysis. These aspects of infant and childhood health serve as a foundation for future studies that aim to use placental epigenetics to understand relationships between the prenatal environment and perinatal complications (such as preterm birth or fetal growth restriction) or later life childhood health.SummaryPlacental DNA methylation and RNA expression have been linked to numerous prenatal exposures, such as PM2.5 air pollution, metals, and maternal smoking, as well as infant and childhood health outcomes, including fetal growth and birth weight. Placental epigenomics provides a unique opportunity to expand the DOHaD premise, particularly if research applies novel methodologies such as multi-omics analysis, sequencing of non-coding RNAs, mixtures analysis, and assessment of health outcomes beyond early childhood.

BackgroundVitamins B12 and folate participate in the one-carbon metabolism cycle and hence regulate fetal growth. Though vitamin B12 deficiency is widely prevalent, the current public health policy in India is to supplement only iron and folic acid for the prevention of anaemia. Prompted by our research findings of the importance of maternal vitamin B12 status for a healthy pregnancy, birth and offspring health outcomes, we evaluated available literature evidence using a systematic review approach, to inform policy.MethodsA systematic search was performed for relevant Indian studies in the MEDLINE/PubMed and IndMed databases. We selected studies reporting maternal vitamin B12 status (dietary intake or blood concentrations), and/or metabolic markers of vitamin B12 deficiency (homocysteine, methylmalonic acid) or haematological indices during pregnancy and their associations with outcomes of pregnancy, infancy or in later life. Intervention trials of vitamin B12 during pregnancy were also included. Quality of evidence was assessed on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.ResultsOf the 635 articles identified, 46 studies met the inclusion criteria (cohort studies-26, case-control studies-13, RCT’s -7). There is a high prevalence of vitamin B12 deficiency in Indian women during pregnancy (40-70%) (3 studies). Observational studies support associations (adjusted for potential sociodemographic confounders, maternal body size, postnatal factors) of lower maternal B12, higher homocysteine or an imbalance between vitamin B12-folate status with a higher risk of NTDs (6 studies), pregnancy complications (recurrent pregnancy losses, gestational diabetes, pre-eclampsia) (9 studies), lower birth weight (10 studies) and adverse longer-term health outcomes in the offspring (cognitive functions, adiposity, insulin resistance) (11 studies). Vitamin B12 supplementation (7 RCT’s) in pregnancy showed a beneficial effect on offspring neurocognitive development and an effect on birth weight was inconclusive. There is a high quality evidence to support the role of low maternal vitamin B12 in higher risk for NTD and low birth weight and moderate-quality evidence for higher risk of gestational diabetes and later life adverse health outcomes (cognitive functions, risk for diabetes) in offspring.ConclusionIn the Indian population low maternal vitaminB12 status, is associated with adverse maternal and child health outcomes. The level of evidence supports adding vitamin B12 to existing nutritional programs in India for extended benefits on outcomes in pregnancy and offspring health besides control of anaemia.Systematic Review Registration[website], identifier [registration number]

Background High-dimensional mediation analysis is an extension of unidimensional mediation analysis that includes multiple mediators, and is increasingly used in environmental epidemiology to evaluate the indirect epigenetic effects of environmental exposures on health outcomes. However, analyses involving high-dimensional mediators raise several statistical issues. While many methods have recently been developed to tackle those issues, no consensus has been reached about the optimal combination of approaches. Methods We developed HDMAX2, a new multi-step approach to mediation that combines latent factor regression models for epigenome-wide association studies with max-squared tests for mediation, and considers CpGs and aggregated mediator regions (AMR). HDMAX2 was carefully evaluated on simulated data, and compared to state-of-the- art multi-dimensional epigenetic mediation methods. Then it was applied to assess the indirect effects of exposure to maternal smoking (MS) on term birth weight (BW) and gestational age (GA) at delivery in a study of 470 women from the EDEN cohort. Results HDMAX2 resulted in increased power compared to state-of-the-art multi-dimensional mediation methods, and identified several AMRs not identified in previous mediation analyses of exposure to MS on BW and GA. The results provided evidence for a polygenic architecture of the causal pathway with an overall indirect effect of CpGs and AMRs of 44.5g lower BW (32.1% of the total effect size). HDMAX2 also identified AMRs having simultaneous effects both on GA and BW. Among the top hits of both GA and BW analyses, regions located in COASY, BLCAP and ESRP2 also mediated the relationship between GA on BW, suggesting a reverse causality in the relationship between GA and the methylome. Discussion This study brought up several statistical improvements of high-dimensional mediation analyses, which revealed an unsuspected complexity of the causal relationships between exposure to MS and BW at the epigenome-wide level. Mediation; high dimension; causal inference; epigenetics; DNA methylation; pregnancy

SummaryEpidemiological evidence supports an association between exposure to air pollution during pregnancy and birth and child health outcomes. Typically, such associations are estimated by regressing an outcome on daily or weekly measures of exposure during pregnancy using a distributed lag model. However, these associations may be modified by multiple factors. We propose a distributed lag interaction model with index modification that allows for effect modification of a functional predictor by a weighted average of multiple modifiers. Our model allows for simultaneous estimation of modifier index weights and the exposure–time–response function via a spline cross-basis in a Bayesian hierarchical framework. Through simulations, we showed that our model out-performs competing methods when there are multiple modifiers of unknown importance. We applied our proposed method to a Colorado birth cohort to estimate the association between birth weight and air pollution modified by a neighborhood-vulnerability index and to a Mexican birth cohort to estimate the association between birthing-parent cardio-metabolic endpoints and air pollution modified by a birthing-parent lifetime stress index.

Maternal exposure to air pollution during pregnancy has a substantial public health impact. Epidemiological evidence supports an association between maternal exposure to air pollution and low birth weight. A popular method to estimate this association while identifying windows of susceptibility is a distributed lag model (DLM), which regresses an outcome onto exposure history observed at multiple time points. However, the standard DLM framework does not allow for modification of the association between repeated measures of exposure and the outcome. We propose a distributed lag interaction model that allows modification of the exposure-time-response associations across individuals by including an interaction between a continuous modifying variable and the exposure history. Our model framework is an extension of a standard DLM that uses a cross-basis, or bi-dimensional function space, to simultaneously describe both the modification of the exposure-response relationship and the temporal structure of the exposure data. Through simulations, we showed that our model with penalization out-performs a standard DLM when the true exposure-time-response associations vary by a continuous variable. Using a Colorado, USA birth cohort, we estimated the association between birth weight and ambient fine particulate matter air pollution modified by an area-level metric of health and social adversities from Colorado EnviroScreen.