Maternal Pre-pregnancy Overweight Research Articles

Maternal gestational hypertension, smoking and pre-eclampsia are associated with metabolic dysfunction-associated fatty liver disease in overweight offspring.

Due to a steep increase in obesity, metabolic dysfunction-associated fatty liver disease (MAFLD) has also become the most common chronic hepatic condition among children and adolescents. Various maternal and pregnancy-related factors have also been implicated in the development of MAFLD, but human studies remain scarce. Comprehensive data of 460 overweight or obese children aged 2-16 years were collected and combined with data on selected maternal and pregnancy-related factors for a case-control study. MALFD was defined as alanine aminotransferase >2× upper limit of normal. Children with and without MAFLD were compared regarding to the study variables and multivariable regression analysis was utilized. Median age of the study children was 11.8 (quartiles 9.1-14.2) years; 44% were girls and 17.8% had MAFLD. Children with MAFLD were older (12.7 vs. 11.6 years, p = 0.002), while the groups did not differ age-standardized body mass index (BMI-SDS) or gender. Factors associated with MAFLD in a multivariable model considering also the offspring's present BMI-SDS, sex, and maternal prepregnancy overweight, were child's older age (odds ratio [OR] 1.16, 95% confidence interval [CI]: 1.06-1.28), maternal gestational smoking (OR 2.01, 95% CI: 1.16-3.47), gestational hypertension (OR 3.44, 95% CI: 1.08-11.0) and pre-eclampsia (OR 2.93, 95% CI: 1.15-7.45). There was no significant association between MAFLD and maternal BMI, birth anthropometrics or perinatal complications. Maternal smoking, gestational hypertension and pre-eclampsia were associated with MAFLD among overweight or obese children. Further prospective studies are needed to verify causal relationships.

Maternal pre-pregnancy overweight or obesity and risk of birth defects in offspring: Population-based cohort study.

Maternal obesity, a health condition increasingly prevalent worldwide, has been suggested to be associated with a higher risk of birth defects in offspring, whereas evidence from population-based data from China was largely lacking. Additionally, the role of gestational diabetes in the association between maternal obesity and birth defects remains unclear. We aimed to investigate the association of maternal pre-pregnancy overweight or obesity with any and different types of birth defects in offspring and the interaction between pre-pregnancy overweight or obesity and gestational diabetes. We conducted a population-based cohort study including 257 107 singletons born between 2015 and 2021 in Longgang District, Shenzhen, China, using data from the Shenzhen Maternal and Child Health Management System. Poisson regression was conducted to estimate the associations of maternal pre-pregnancy overweight or obesity, as well as the interaction between pre-pregnancy overweight or obesity and gestational diabetes, with the risk of birth defects. Models were adjusted for maternal age at delivery, educational level, type of household registration, and gravidity. Maternal pre-pregnancy overweight was associated with a higher risk of any birth defect (risk ratio [RR] 1.21, 95% confidence interval [CI] 1.12 to 1.31) as well as of congenital malformations of the circulatory system (RR 1.26, 95% CI 1.12 to 1.41), eye/ear/face/neck (RR 1.42, 95% CI 1.04 to 1.94), and musculoskeletal system (RR 1.21, 95% CI 1.01 to 1.44). Maternal pre-pregnancy obesity was associated with a higher risk of any birth defect (RR 1.38, 95% CI 1.18 to 1.63) and congenital malformations of the circulatory system (RR 1.61, 95% CI 1.30 to 1.98). Infants born to overweight or obese mothers with gestational diabetes had a higher risk of congenital malformations of the circulatory system than infants born to overweight or obese mothers without gestational diabetes. Maternal pre-pregnancy overweight or obesity was associated with a higher risk of birth defects, particularly congenital malformations of the circulatory system, in offspring. Gestational diabetes interacts additively with pre-pregnancy overweight or obesity on modifying the risk of congenital malformations of the circulatory system. The importance of improving weight management and assessment of glucose and metabolic functions was emphasized among women planning for pregnancy who are overweight or obese.

Networks in Auxology – proceedings of the 31st Aschauer Soiree, held at Aschau, Germany, June 17th 2023

Twenty-seven scientists met for the annual Auxological conference held at Aschau, Germany, to particularly discuss the interaction between social factors and human growth, and to highlight several topics of general interest to the regulation of human growth. Humans are social mammals. Humans show and share personal interests and needs, and are able to strategically adjust size according to social position, with love and hope being prime factors in the regulation of growth. In contrast to Western societies, where body size has been shown to be an important predictor of socioeconomic status, egalitarian societies without formalized hierarchy and material wealth-dependent social status do not appear to similarly integrate body size and social network. Social network structures can be modeled by Monte Carlo simulation. Modeling dominance hierarchies suggests that winner-loser effects play a pivotal role in robust self-organization that transcends the specifics of the individual. Further improvements of the St. Nicolas House analysis using re-sampling/bootstrap techniques yielded encouraging results for exploring dense networks of interacting variables. Customized pediatric growth references, and approaches towards a Digital Rare Disease Growth Chart Library were presented. First attempts with a mobile phone application were presented to investigate the associations between maternal pre-pregnancy overweight, gestational weight gain, and the child’s future motor development. Clinical contributions included growth patterns of individuals with Silver-Russell syndrome, and treatment burden in children with growth hormone deficiency. Contributions on sports highlighted the fallacy inherent in disregarding the biological maturation status when interpreting physical performance outcomes. The meeting explored the complex influence of nutrition and lifestyle on menarcheal age of Lithuanian girls and emphasized regional trends in height of Austrian recruits. Examples of the psychosocial stress caused by the forced migration of modern Kyrgyz children and Polish children after World War II were presented, as well as the effects of nutritional stress during and after World War I. The session concluded with a discussion of recent trends in gun violence affecting children and adolescents in the United States, and aspects of life history theory using the example of "Borderline Personality Disorder." The features of this disorder are consistent with the notion that it reflects a "fast" life history strategy, with higher levels of allostatic load, higher levels of aggression, and greater exposure to both childhood adversity and chronic stress. The results were discussed in light of evolutionary guided research. In all contributions presented here, written informed consent was obtained from all participants in accordance with institutional Human investigation committee guidelines in accordance with the Declaration of Helsinki amended October 2013, after information about the procedures used.

Association between maternal pre-pregnancy body mass index and offspring’s outcomes at 9 to 15 years of age

ObjectiveMaternal pre-pregnancy underweight, overweight and obesity might increase the risk for worse short- and long-term outcome in the offspring. There is a need for further study into the relationship between maternal pre-pregnancy body mass index (BMI) and the combined outcome of physical development, state of health and social behavior in children. Question: Is maternal pre-pregnancy BMI associated with the child outcome in terms of physical development, state of health and social behavior (school and leisure time behavior) at the age of 9 to 15 years?MethodsIn the population-based birth cohort study Survey of Neonates in Pomerania (SNIP) children at the age 9–15 years and their families were re-examined by questionnaire-based follow-up. 5725 mother–child pairs were invited to SNiP-follow-up. This analysis is based on the recall fraction of 24.1% (n = 1379). Based on the maternal pre-pregnancy BMI (ppBMI), 4 groups were formed: underweight (ppBMI < 19 kg/m2, n = 117), normal weight (ppBMI 19–24.99 kg/m2, n = 913, reference), overweight (ppBMI 25–30 kg). /m2, n = 237) and obesity (ppBMI > 30 kg/m2, n = 109).ResultsIn the multiple regression model, the BMI-z-score for children of mothers in the underweight group was −0.50 lower, and 0.50/1.07 higher in the overweight/obese group (p < 0.001) compared to reference at median age of 12 years. No differences were found in children of underweight mothers with regard to social behavior (interaction with friends and family), school and sports performance (coded from “very good” to “poor”), other leisure activities (watching television, using mobile phones, gaming), and health (occurrence of illnesses) compared to children of normal weight mothers. In contrast, maternal pre-pregnancy overweight and obesity were associated with lower school and sports performance, and higher screen time (smart phone, gaming, television) compared to children of normal weight mothers.ConclusionMaternal pre-pregnancy overweight and obesity but not underweight was negatively associated with school performance and leisure time behavior in the offspring at 9–15 years of age.

Association of Maternal Pre-Pregnancy Overweight and Obesity with Childhood Anthropometric Factors and Perinatal and Postnatal Outcomes: A Cross-Sectional Study.

Pre-pregnancy overweight and obesity in reproductive-aged women becomes a growing tendency in middle- and high-income populations. This study aimed to evaluate whether maternal excess body mass index (BMI) before gestation is associated with children's anthropometric characteristics, as well as perinatal and postnatal outcomes. This was a cross-sectional study performed on 5198 children aged 2-5 years old and their paired mothers, assigned from 9 different areas of Greece. Maternal and childhood anthropometric data, as well as perinatal and postnatal outcomes, were collected from medical history records or validated questionnaires. Prevalences of 24.4% and 30.6% of overweight/obesity were recorded for the enrolled children and their mothers 2-5 years postpartum. Maternal pre-pregnancy overweight/obesity was more frequently observed in older mothers and female children, and was also associated with high childbirth weight, preterm birth, high newborn ponderal index, caesarean section delivery, diabetes type 1, and childhood overweight/obesity at pre-school age. In multivariate analysis, maternal pre-pregnancy overweight/obesity was independently associated with a higher risk of childhood overweight/obesity at pre-school age, as well as with a higher increased incidence of childbirth weight, caesarean section delivery, and diabetes type 1. Maternal overweight/obesity rates before gestation were related with increased childhood weight status at birth and 2-5 years postpartum, highlighting the necessity of encouraging healthy lifestyle promotion, including healthier nutritional habits, and focusing on obesity population policies and nutritional interventions among women of reproductive age.

Maternal weight and its association with risk of overweight in offspring: a trajectory analysis from a birth cohort in China.

Most studies on the association of maternal pregnancy weight with offspring weight trajectory have a short follow-up time. This study aimed to explore the associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) with childhood weight trajectories in a 7-year birth cohort. A total of 946 mother-child pairs (467 boys and 479 girls) from a longitudinal birth cohort in TianjinCity, China, were included in this study, ranging from pregnancy to offspring at 7years. The outcome variable was defined as overweight or not overweight in offspring at the last round. A group-based trajectory model was applied to identify childhood BMI trajectory groups. Five discrete BMI trajectory groups were identified and characterized as constant underweight (25.2%), constant normal weight (42.8%), and high or increasing trajectory [at risk of overweight (16.9%), progressive overweight (11.0%) and progressive obesity (4.1%)]. Maternal prepregnancy overweight was associated with 1.72 (95% CI 1.14-2.60, P = 0.01) to 4.02 (95% CI 1.94-8.36, P < 0.001) times the risk of all high or increasing trajectory groups, and excessive GWG was related to groups at risk of overweight [relative risk ratio (RRR) 2.09, 95% CI 1.27-3.46, P = 0.004] and progressive obesity (RRR 3.33, 95% CI 1.13-9.79, P = 0.029). Children in all high or increasing trajectory groups were associated with greater overweight risk at the last round [risk ratios (RRs) ranged from 3.54 (95% CI 2.53-4.95, P < 0.001) to 6.18 (95% CI 4.05-9.42, P < 0.001)]. Maternal prepregnancy overweight and excessive gestational weight gain were associated with increasing or high-level childhood body mass index trajectories as well as a greater risk of overweight at 7 years.

Maternal Pre-Pregnancy BMI, Offspring Adiposity in Late Childhood, and Age of Weaning: A Causal Mediation Analysis.

Infant feeding practices have been hypothesized to influence offspring's body mass index (BMI) later in life, and women with overweight or obesity tend to wean their infants earlier than women with healthy BMI. We, therefore, aimed to investigate how much early age of weaning mediated the maternal-offspring adiposity relationship. The study included 4920 mother-child pairs from the Avon Longitudinal Study of Parents and Children birth cohort. G-computation was applied to estimate the natural direct (NDE) and indirect (NIE) effects, via the age of weaning (<3 months, 3 months, >3 months), of maternal pre-pregnancy overweight or obesity on offspring's BMI and fat mass index. The NDE of maternal overweight or obesity on offspring BMI at 17 years old was 2.63 kg/m2 (95% CI: 2.27 to 2.99). The NIE via the age of weaning was 0.02 kg/m2 (95% CI: 0.00 to 0.04), corresponding to 0.8% of the total effect. Similar results were observed for the offspring's fat mass index. The NDE and NIE were similar to the main analyses when we looked at the relationship stratified by breastfeeding status. Our study found a minimal influence of age of weaning on the pathway between maternal and offspring adiposity, indicating the age of weaning may not be a key mediator.

Abnormal birth weights for gestational age in relation to maternal characteristics in Sweden: a five year cross-sectional study

BackgroundAbnormal birth weight – small for gestational age (SGA) and large for gestational age (LGA) – are important indicators for newborn health. Due to changes in lifestyle in recent decades, it is essential to keep up-to-date with the latest information on maternal factors linked to abnormal birth weight. The aim of this study is to investigate SGA and LGA in relation to maternal individual, lifestyle and socioeconomic characteristics. .MethodsThis is a register-based cross-sectional study. Self-reported data from Sweden’s Salut Programme maternal questionnaires (2010–2014) were linked with records in the Swedish Medical Birth Register (MBR). The analytical sample comprised 5089 singleton live births. A Swedish standard method using ultrasound-based sex-specific reference curves defines the abnormality of birth weight in MBR. Univariable and multivariable logistic regressions were used to examine crude and adjusted associations between abnormal birth weights and maternal individual, lifestyle and socioeconomic characteristics. A sensitivity analysis, using alternative definitions of SGA and LGA under the percentile method, was undertaken.ResultsIn multivariable logistic regression, maternal age and parity were associated with LGA (aOR = 1.05, CI = 1.00, 1.09) and (aOR = 1.31, CI = 1.09, 1.58). Maternal overweight and obesity were strongly associated with LGA (aOR = 2.28, CI = 1.47, 3.54) and (aOR = 4.55, CI = 2.85, 7.26), respectively. As parity increased, the odds of delivering SGA babies decreased (aOR = 0.59, CI = 0.42, 0.81) and preterm deliveries were associated with SGA (aOR = 9.46, CI = 5.67, 15.79). The well-known maternal determinants of abnormal birthweight, such as unhealthy lifestyles and poor socioeconomic factors, were not statistically significant in this Swedish setting.ConclusionsThe main findings suggest that multiparity, maternal pre-pregnancy overweight and obesity are strong determinants for LGA babies. Public health interventions should address modifiable risk factors, especially maternal overweight and obesity. These findings suggest that overweight and obesity is an emerging public health threat for newborn health. This might also result in the intergenerational transfer of overweight and obesity. These are important messages for public health policy and decision making.

Relation of Maternal Pre-Pregnancy Factors and Childhood Asthma: A Cross-Sectional Survey in Pre-School Children Aged 2–5 Years Old

Background and Objectives: Asthma constitutes a constant, prolonged, inflammation-related pulmonary disorder in childhood with serious public health concerns. Several maternal risk factors can enhance the prevalence of its development in this stage of life; however, the currently available data remain contradictory and/or inconsistent. We aim to evaluate the potential impacts of mothers' sociodemographic, anthropometric and prenatal and perinatal factors on the prevalence of developing asthma in pre-school children. Materials and Methods: This is a retrospective cross-sectional survey, which includes 5133 women and their matched pre-school children. Childhood asthma was diagnosed using validated questionnaires. Statistical analysis was accomplished to evaluate whether maternal sociodemographic, anthropometric and prenatal and perinatal factors can increase the probability of childhood asthma in pre-school age. Results: A prevalence of 4.5% of childhood asthma was recorded in pre-school age. Maternal age and pre-pregnancy overweight and obesity, caesarean section, gestational diabetes and hypertension and not breastfeeding were associated with childhood asthma after adjustment for multiple confounding factors. Conclusion: Our research showed that several maternal factors increase the prevalence of childhood asthma in pre-school age. Suitable and effective health policies and strategies should be taken into account to confront the predominant maternal factors that increase its prevalence in pre-school age.

Maternal pre-pregnancy obesity and offspring hyperactivity-inattention symptoms at 5 years in preterm and term children: a multi-cohort analysis

The objective of this study was to determine the relationship between maternal pre-pregnancy body mass index (BMI) and child hyperactivity-inattention symptoms (HIS) at 5 years, including preterm and term-born children, and to determine whether this association varied with gestational age. Maternal pre-pregnancy BMI and offspring HIS were assessed in 10,898 participants born ≥ 33 weeks of gestation from the ELFE cohort and 2646 children born between 23 and 34 weeks from the EPIPAGE 2 cohort. Reported pre-pregnancy weight (kg) and measured height (m) were collected from mothers at inclusion and used to classify BMI (kg/m2). Child HIS were evaluated using the Strengths and Difficulties Questionnaire around 5 years of age. Logistic regression estimated odds ratios (OR) of a high HIS score (≥ 90th percentile) in the ELFE cohort and generalized estimated equations were used in EPIPAGE 2 to account for non-independence of multiple births. As a negative control, paternal BMI was also considered as an exposure of interest in sensitivity analyses. Maternal pre-pregnancy obesity and overweight were associated with child HIS at 5 years in ELFE (adjusted OR [aOR] for obesity 1.27 [1.06, 1.53]; overweight aOR 1.16 [1.00, 1.36]) and pre-pregnancy obesity was associated with high HIS scores in preterm infants of EPIPAGE 2 (aOR 1.48 [1.06, 2.08]). In ELFE, the magnitude of the association increased with decreasing gestational age (interaction p = 0.02). High maternal pre-pregnancy BMI is associated with greater likelihood of high HIS scores in both at-term and preterm children at 5 years of age.

Effect of an antenatal diet and lifestyle intervention and maternal BMI on cord blood DNA methylation in infants of overweight and obese women: The LIMIT Randomised Controlled Trial.

To investigate the effect of an antenatal diet and lifestyle intervention, and maternal pre-pregnancy overweight or obesity, on infant cord blood DNA methylation. We measured DNA methylation in 645 cord blood samples from participants in the LIMIT study (an antenatal diet and lifestyle intervention for women with early pregnancy BMI ≥25.0 kg/m2) using the Illumina 450K BeadChip array, and tested for any differential methylation related to the intervention, and to maternal early pregnancy BMI. We also analysed differential methylation in relation to selected candidate genes. No CpG sites were significantly differentially methylated in relation to either the diet and lifestyle intervention, or with maternal early pregnancy BMI. There was no significant differential methylation in any of the selected genes related to the intervention, or to maternal BMI. We found no evidence of an effect of either antenatal diet and lifestyle, or of maternal early pregnancy BMI, on cord blood DNA methylation. ACTRN12607000161426.

Maternal pre-pregnancy overweight and neonatal gut bacterial colonization are associated with cognitive development and gut microbiota composition in pre-school-age offspring

Maternal gestational obesity is a risk factor for offspring’s neurodevelopment and later neuro-cognitive disorders. Altered gut microbiota composition has been found in patients with neurocognitive disorders, and in relation to maternal metabolic health. We explored the associations between gut microbiota and cognitive development during infancy, and their link with maternal obesity.In groups of children from the Pisa birth Cohort (PISAC), we analysed faecal microbiota composition by 16S rRNA marker gene sequencing of first-pass meconium samples and of faecal samples collected at age 3, 6, 12, 24, 36 months, and its relationship with maternal gestational obesity or diabetes, and with cognitive development, as measured from 6 to 60 months of age by the Griffith’s Mental Development Scales.Gut microbiota composition in the first phases of life is dominated by Bifidobacteria (Actinobacteria phylum), with contribution of Escherichia/Shigella and Klebsiella genera (Proteobacteria phylum), whereas Firmicutes become more dominant at 36 months of age. Maternal overweight leads to lower abundance of Bifidobacterium, Blautia and Ruminococcus, and lower practical reasoning scores in the offspring at the age of 36 months. In the whole population, microbiota in the first-pass meconium samples shows much higher alpha diversity compared to later samples, and its composition, particularly Bifidobacterium and Veillonella abundances, correlates with practical reasoning scores at 60 months of age.Maternal overweight correlates with bacterial colonization and with the development of reasoning skills at pre-school age. Associations between neonatal gut colonization and later cognitive function provide new perspectives of primary (antenatal) prevention of neurodevelopmental disorders.

The mediating role of gestational diabetes mellitus in the associations of maternal prepregnancy body mass index with neonatal birth weight.

BackgroundBoth prepregnancy obesity and gestational diabetes mellitus (GDM) have been linked to adverse neonatal birth weight. However, the mediating role of GDM between prepregnancy obesity and neonatal birth weight is unclear.MethodThe cohort study included 17 260 singleton pregnant women and their newborns. Participants' demographic characteristics, disease history, family history of the disease, and the perinatal outcomes were recorded. The association between maternal prepregnancy body mass index (BMI) status and small for gestational age (SGA) or large for gestational age (LGA) neonates was analyzed using logistic regressions, before and after adjusting for covariates and GDM. The potential mediation of GDM on the association between prepregnancy BMI and adverse birth weight was examined.ResultMultivariate logistic regression demonstrated that prepregnancy underweight women were more likely to deliver SGA neonates compared to those who had normal weights, whereas prepregnancy obese pregnant women were more likely to have LGA neonates. The RMediation analyses illustrated that the mediation effect of GDM on the maternal prepregnancy BMI (continuous variable) and the risk of SGA was not significant, whereas the association between prepregnancy BMI and LGA was statistically mediated by GDM (95%CI of a*b: 0.009‐0.051). The Iacobacci (2012) method indicated that the impact of maternal prepregnancy overweight (Zmediation = 2.418, P = .015) and obesity (Zmediation = 2.165, P = .030) on LGA was partially mediated by GDM, with an indirect effect of 16.3% and 13.1%, respectively.ConclusionPrepregnancy BMI was observed to be associated with SGA and LGA. The association of prepregnancy overweight and obesity with LGA was found to be partially mediated by GDM.

Gestational diabetes mellitus, pre-pregnancy body mass index and gestational weight gain predicts fetal growth and neonatal outcomes.

Gestational diabetes mellitus (GDM), body mass index (BMI) and gestational weight gain (GWG) are salient predictors of pregnancy-outcomes. However, findings on the association between GDM, BMI, and GWG with fetal growth measures are limited. The aim of this study was to investigate the effect of GDM on fetal growth measures and birth outcomes. All participants came from Tongji Maternal and Child health cohort, in which pregnant women were enrolled before 16 weeks of gestation and had their weights measured regularly during antenatal visits. GDM was diagnosed by oral glucose tolerance test (OGTT) during 24-28 weeks of gestation. Ultrasound measurements of fetal bi-parietal diameters (BPD), head circumferences (HC), abdominal circumferences (AC) and femur length (FL) before birth were collected and neonate outcomes were obtained from the hospital records. Odds ratios were calculated using logistic regression to assess the association of GDM, pre-pregnancy BMI, and GWG with fetal growth measures of ultrasound and birth outcomes, while controlling confounding. Of 3253 singleton pregnant women, 293 (9.0%) were diagnosed with GDM, 357 (11.0%) were overweight before pregnancy, and 1995 (61.3%) had excessive GWG. GDM was associated with decreased intrauterine fetal growth measurements including BPD and AC. Maternal pre-pregnancy overweight was associated with increased fetal HC and neonatal birth weight and length, women gained excessive GWG had increased fetal growth measurements of BPD, HC, AC, FL, neonatal birth weight and length. Offspring of GDM women had increased odds of cesarean section 1.31 (1.03, 1.66) and preterm birth 2.02 (1.05, 3.91) in unadjusted models, but these associations disappeared after adjustment. Compared with neonate born to mothers with normal pre-pregnancy weight, those born to underweight mother had higher risk of SGA, and lower risk of cesarean section, LGA and macrosamia, whereas those born to overweight mother had increased risk of cesarean section, LGA and macrosamia. Compared with neonate born to mothers of adequate GWG, neonate of women with excessive GWG had elevated risk of cesarean section, LGA and macrosamia, but lower risk of preterm birth and SGA. Pre-pregnancy BMI, GWG and GDM all associated with fetal growth and birth outcomes. The effect of GDM decreased after adjusting pre-pregnancy BMI and GWG. Early screening and management of GDM, preventing excessive GWG could help protect fetuses of GDM mothers from adverse birth outcomes.

Associations Between Infant Developmental Delays and Secondhand Smoke Exposure Modified by Maternal Prepregnancy Overweight and Obesity Status.

Secondhand smoke exposure during pregnancy has long been associated with adverse health outcomes in children, but only a few studies have examined its effect modifiers. In this study, we applied effect modification analysis for maternal prepregnancy weight status on detrimental neurodevelopmental effect of secondhand smoke exposure during pregnancy and infancy in a nationwide representative population. Term singleton mother-infant pairs with nonsmoking mothers were included for main analysis (N = 15 987) from the Taiwan Birth Cohort Study (TBCS), and were further matched with propensity score (n = 5434). We extracted secondhand smoke exposure during pregnancy and infancy, and eight neurodevelopmental milestones from the responses in the baseline visit at 6 months, and 18-month follow-up of TBCS. The associations between secondhand smoke exposure and neurodevelopmental achievement were analyzed with multivariable logistic regression and Cox model. Propensity score weighting and matching were applied for high-versus-low analysis, and relative excess risk due to interaction were used to estimate effect modification. Higher secondhand smoke exposure was associated with increased likelihood of delayed milestone achievement across gross motor, fine motor, language-related, and social-related domains. The associations in fine motor domains remained observable in propensity score-weighted and -matched models. We identified additive interaction with self-reported maternal overweight and obesity status before pregnancy in milestone development for walking with support, scribbling, and waving goodbye. Secondhand smoke exposure during pregnancy and infancy were associated with delayed neurodevelopmental milestone achievement at 18 months, and the associations were modified by maternal prepregnancy overweight and obesity status. The study results suggested the association between maternal secondhand smoke exposure during pregnancy and infancy and delayed fine motor and language-related milestone achievement at 18 months in multivariable, propensity score weighting, and matching populations. The results of positive effect modifications for maternal prepregnancy overweight and obesity status suggested the importance of concurrent interventions on smoke-free environment and maternal health during pregnancy.

Association between maternal prepregnancy body mass index and risk of preterm birth in more than 1 million Asian American mothers.

Asian Americans are among the fastest growing subpopulations in the United States. However, evidence about maternal prepregnancy body mass index (BMI) and preterm birth among Asian Americans is lacking. This population-based study used nationwide birth certificate data from the US National Vital Statistics System 2014 to 2018. All Asian American mothers who had a singleton live birth were included. According to Asian-specific cutoffs, maternal prepregnancy BMI was classified into underweight (BMI < 18.5 kg/m2 ), normal weight (BMI 18.5-22.9 kg/m2 ), overweight (BMI 23.0-27.4 kg/m2 ), class I obesity (BMI 27.5-32.4 kg/m2 ), class II obesity (BMI 32.5-37.4 kg/m2 ), and class III obesity (BMI ≥37.5 kg/m2 ). Preterm birth was defined as gestational age less than 37 weeks. Multivariable logistic regression models were used to estimate the odds ratio (OR) of preterm birth. We included 1 081 341 Asian American mother-infant pairs. The rate of preterm birth was 6.51% (n = 70 434). The rate of maternal prepregnancy overweight and obesity was 46.80% (n = 506 042). Compared with mothers with normal weight, the adjusted OR of preterm delivery was 1.04 (95% CI, 1.01-1.07) for underweight mothers, 1.18 (95% CI, 1.16-1.20) for overweight mothers, 1.41 (95% CI, 1.37-1.44) for mothers with class I obesity, 1.69 (95% CI, 1.63-1.76) for mothers with class II obesity, and 1.78 (95% CI, 1.66-1.90) for mothers with class III obesity. Similar patterns of associations were observed in Asian American mothers across different country origins. Among Asian American mothers, maternal prepregnancy overweight or obesity, defined by Asian-specific, lower BMI cutoffs, was significantly associated with an increased risk of preterm birth. The risk of preterm birth increased with increasing obesity severity. These findings highlight the importance of using Asian-specific BMI cutoffs in assessing risk of preterm birth among Asian American mothers.

Associations of breast milk extracellular vesicle microRNAs with perfluoroalkyl substances in a mother-infant cohort from the Faroe Islands

Background/Aims: Early life exposures to perfluoroalkyl substances (PFASs) can adversely impact child health. Breast milk (BM) contains extracellular vesicles (EVs) that can transport biologically relevant cargo from mother to infant, including microRNAs (miRNAs), and may mediate in part the effect of PFAS on child health outcomes. However, the effect of PFASs on miRNA expression in BMEVS is unexplored. We therefore examined the associations between prenatal PFAS exposures and BMEV miRNA expression.Methods: We isolated EV RNA from 347 BM samples collected at two weeks post anticipated term from a Faroese birth cohort born in 1997-2000, and sequenced 2,083 miRNAs with the HTG Molecular Whole miRNA Transcriptome Assay. Major PFASs (perfluorooctanesulfonic acid [PFOS], perfluorooctanoic acid, perfluorononanoic acid, perfluorodecanoic acid, and perfluorohexanesulfonate) were measured in maternal serum at 34 weeks gestation with HPLC-MS. We ran robust negative binomial regression models to estimate associations between individual PFASs and 420 reliably expressed miRNAs. We examined effect modification by maternal pre-pregnancy overweight (i.e. a body mass index [BMI] ≥ 25 kg/m2). Models were adjusted for maternal education, age, parity, smoking during pregnancy and technical batch.Results: We identified no associations between PFASs and miRNA expression after correction for false discovery rate (FDR), however, we observed nominal associations between PFASs and 92 different miRNAs, 18 of which were associated with multiple PFASs. We observed effect modification by maternal overweight on associations between PFOS and 10 miRNAs (miR-1225-5p, miR-324-5p, miR-4534, miR-6126, miR-658, miR-6771-5p, miR-6780b-5p, miR-6800-5p, miR-6845-5p, and miR-6851-5p) (FDR &lt;0.20). Nine of 10 miRNAs were inversely associated with PFOS in mothers with normal BMI and positively associated with PFOS in overweight mothers.Conclusions: Our findings underscore the utility of BMEV-miRNAs as promising environmental biomarkers, particularly in subpopulations of overweight individuals. Future studies are needed to elucidate the role of BMEV-miRNAs in child health following pollutant exposure.

Environmental risk factors, protective factors, and peripheral biomarkers for ADHD: an umbrella review

Many potential environmental risk factors, environmental protective factors, and peripheral biomarkers for ADHD have been investigated, but the consistency and magnitude of their effects are unclear. We aimed to systematically appraise the published evidence of association between potential risk factors, protective factors, or peripheral biomarkers, and ADHD. In this umbrella review of meta-analyses, we searched PubMed including MEDLINE, Embase, and the Cochrane Database of Systematic Reviews, from database inception to Oct 31, 2019, and screened the references of relevant articles. We included systematic reviews that provided meta-analyses of observational studies that examined associations of potential environmental risk factors, environmental protective factors, or peripheral biomarkers with diagnosis of ADHD. We included meta-analyses that used categorical ADHD diagnosis criteria according to DSM, hyperkinetic disorder according to ICD, or criteria that were less rigorous than DSM or ICD, such as self-report. We excluded articles that did not examine environmental risk factors, environmental protective factors, or peripheral biomarkers of ADHD; articles that did not include a meta-analysis; and articles that did not present enough data for re-analysis. We excluded non-human studies, primary studies, genetic studies, and conference abstracts. We calculated summary effect estimates (odds ratio [OR], relative risk [RR], weighted mean difference [WMD], Cohen's d, and Hedges' g), 95% CI, heterogeneity I2 statistic, 95% prediction interval, small study effects, and excess significance biases. We did analyses under credibility ceilings, and assessed the quality of the meta-analyses with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). This study is registered with PROSPERO, number CRD42019145032. We identified 1839 articles, of which 35 were eligible for inclusion. These 35 articles yielded 63 meta-analyses encompassing 40 environmental risk factors and environmental protective factors (median cases 16 850, median population 91 954) and 23 peripheral biomarkers (median cases 175, median controls 187). Evidence of association was convincing (class I) for maternal pre-pregnancy obesity (OR 1·63, 95% CI 1·49 to 1·77), childhood eczema (1·31, 1·20 to 1·44), hypertensive disorders during pregnancy (1·29, 1·22 to 1·36), pre-eclampsia (1·28, 1·21 to 1·35), and maternal acetaminophen exposure during pregnancy (RR 1·25, 95% CI 1·17 to 1·34). Evidence of association was highly suggestive (class II) for maternal smoking during pregnancy (OR 1·6, 95% CI 1·45 to 1·76), childhood asthma (1·51, 1·4 to 1·63), maternal pre-pregnancy overweight (1·28, 1·21 to 1·35), and serum vitamin D (WMD -6·93, 95% CI -9·34 to -4·51). Maternal pre-pregnancy obesity and overweight; pre-eclampsia, hypertension, acetaminophen exposure, and smoking during pregnancy; and childhood atopic diseases were strongly associated with ADHD. Previous familial studies suggest that maternal pre-pregnancy obesity, overweight, and smoking during pregnancy are confounded by familial or genetic factors, and further high-quality studies are therefore required to establish causality. None.

Analysis of maternal and perinatal determinants of allergic sensitization in childhood

BackgroundNon-communicable diseases, such as allergies, are influenced by both genetic and epigenetic factors. Perinatal determinants conceivably modify the epigenetic makeup of the developing fetal immune system preventing or predisposing the development of allergies. The aim of this study therefore was to identify independent perinatal factors associated with allergic sensitization in childhood.MethodsIn a single center retrospective case-cohort study electronic obstetric medical records and available skin prick testing results of children were analyzed. For the analysis 286 skin prick test positive (sensitized) children [median (IQR): 3.47 (1.70–7.34) years] were compared with data from all remaining live births in the obstetric cohort (n = 66,583).ResultsSensitized children more frequently had a mother born in Asia (19.1% vs. 10.2%; P < 10–6). Applying backward elimination logistic regression, seven out of 23 initially entered perinatal factors remained in the model. High maternal age (> 35 years; OR: 1.912; P < 0.001), male offspring sex (OR: 1.423; P < 0.01) and assisted conception (OR: 1.771; P < 0.05) increased the risk for allergic sensitization. In contrast, maternal smoking (OR: 0.469; P < 0.005), increasing parity (OR: 0.881; P < 0.05), maternal pre-pregnancy overweight (OR: 0.742; P < 0.005) and preterm birth (OR: 0.484; P < 0.05) decreased the risk for allergic sensitization.ConclusionsIn addition to supporting previous findings, this study is first to report an increased risk of allergic sensitization after assisted conception. Beyond this finding’s potential implementation in preventative strategies, exploration of this association could further pathophysiological understanding of allergic disease.

Maternal pre-pregnancy overweight and gestational diabetes and dietary intakes among young adult offspring

Background/ObjectivesMaternal pre-pregnancy overweight/obesity and gestational diabetes (GDM) are associated with increased fat deposition in adult offspring. The purpose of this study was to identify if maternal pre-pregnancy overweight (body mass index (BMI) ≥ 25 kg/m2) or GDM are associated with dietary quality or intake in adult offspring.Subjects/MethodsParticipants (n = 882) from two longitudinal cohort studies (ESTER Maternal Pregnancy Disorders Study and the Arvo Ylppö Longitudinal Study) completed a validated food-frequency questionnaire at a mean age of 24.2 years (SD 1.3). Diet quality was evaluated by a Recommended Finnish Diet Index (RDI). The study sample included offspring of normoglycaemic mothers with pre-pregnancy overweight/obesity (ONO = 155), offspring of mothers with GDM regardless of BMI (OGDM = 190) and offspring of mothers with normal weight and no GDM (controls; n = 537).ResultsAmong men, daily energy and macronutrient intakes were similar in ONO and controls. However, after adjusting for current offspring characteristics, including BMI, daily carbohydrate intake relative to total energy intake was higher in ONO-men [2.2 percentages of total energy intake (95% confidence interval 0.4, 4.0)]. In ONO-women, macronutrient intakes relative to total energy intake were similar with controls, while total daily energy intake seemed lower [−587.2 kJ/day (−1192.0, 4.4)]. After adjusting for confounders, this difference was attenuated. Adherence to a healthy diet, as measured by RDI, was similar in ONO and controls [mean difference: men 0.40 (−0.38, 1.18); women 0.25 (−0.50, 1.00)]. In OGDM vs. controls, total energy and macronutrient intakes were similar for both men and women. Also adherence to a healthy diet was similar [RDI: men 0.09 (−0.62, 0.80); women −0.17 (−0.93, 0.59)].ConclusionsOur study suggested higher daily carbohydrate intake in male offspring exposed to maternal pre-pregnancy overweight/obesity, compared with controls. Prenatal exposure to GDM was not associated with adult offspring dietary intakes.