Maternal Covariates Research Articles

Contextual Factors Predictive of Social-Emotional Functioning Among Children of Mothers With and Without Low Intellectual Functioning

This study used Future of Families Child and Wellbeing Study data to examine community, family, and maternal predictors of social-emotional outcomes for kindergarten-aged children of mothers with and without low intellectual functioning. Multivariate analysis of variance and multivariate regression explored relationships between maternal intellectual functioning, covariates, and outcomes. As poverty was an important covariate, predictive of outcomes, marginal analysis was used to understand the interaction between poverty and intellectual functioning on each of the outcomes. Children whose mothers had low intellectual functioning had poorer outcomes than their peers regarding positive, anxious/depressed, and withdrawn behaviors regardless of poverty level. This research supports prioritizing these children for early social-emotional education as they enter elementary school, as well as prioritizing their families for supportive interventions in community-based settings.

Newborn adiposity is associated with cord blood DNA methylation at IGF1R and KLF7.

This study aimed to identify whether cord blood DNA methylation at specific loci is associated with neonatal adiposity, a key risk factor for childhood obesity. An epigenome-wide association study was conducted using the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study as a discovery sample. Linear regression models adjusted for maternal and offspring covariates and cell counts were used to analyze associations between neonatal adiposity as measured by sum of three skinfold thicknesses and cord blood DNA methylation. Assays were performed with Illumina EPIC arrays (791,359 CpG sites after quality control). Replication was performed in an independent cohort, Genetics of Glucose regulation in Gestation and Growth (Gen3G). In 2740 HAPO samples, significant associations were identified at 89 CpG sites after accounting for multiple testing (Bonferroni-adjusted p < 0.05). Replication analyses conducted in 139 Gen3G participants confirmed associations for seven CpG sites. These included IGF1R, which encodes a transmembrane receptor involved in cell growth and survival that binds insulin-like growth factor I and insulin, and KLF7, which encodes a regulator of cell proliferation and inhibitor of adipogenesis; both are key regulators of growth during fetal life. These findings support epigenetic mechanisms in the developmental origins of neonatal adiposity and as potential biomarkers of metabolic disease risk.

Maternal pregnancy diet quality, night eating, and offspring metabolic health: the GUSTO study.

We investigated the understudied influence of maternal diet quality, food timing, and their interactions during pregnancy on offspring metabolic health. Maternal diet at 26-28 weeks' gestation was assessed using a 24-h recall and adherence to the modified-healthy-eating-index (HEI-SGP) reflects diet quality. Predominant night-eating (PNE) was defined as consuming >50% of total daily energy intake from 19:00 to 06:59. Outcomes were offspring composite metabolic syndrome score and its components measured at age 6 years. Multivariable linear regressions adjusted for relevant maternal and child covariates assessed associations of diet quality and PNE with these outcomes. Up to 758 mother-child pairs were included. The mean(SD) maternal HEI-SGP score was 52.3(13.7) points (theoretical range: 0-100) and 15% of the mothers demonstrated PNE. Maternal diet quality showed inverse relationship with offspring HomeostaticModel AssessmentforInsulinResistance (HOMA-IR) [β(95% CI): -0.08(-0.15, -0.02) per-10-point HEI-SGP increment; P = 0.012]. Maternal PNE was associated with a higher offspring HOMA-IR [0.28(0.06, 0.50); P = 0.012], with similar estimates after adjustment for children's BMI and diet quality; the association was stronger for boys (P-interaction<0.001) and among mothers with lower diet quality (<median HEI-SGP) (P-interaction = 0.062). Maternal PNE and low dietary quality were associated with a higher level of insulin resistance in early childhood, especially among boys. We demonstrated that maternal predominant night-eating behavior and low-quality diet are associated with higher offspring insulin resistance. Maternal low-quality diet and predominant night-eating behavior synergistically interact to influence offspring insulin resistance, particularly among boys. While maternal diet quality and food timing impact the mother's health, their influence on offspring long-term health outcomes through developmental programming is not well understood. Our findings highlight the significance of maternal food timing and calls for further studies on its influence on child health through developmental programming. Targeting both dietary quality and food timing during pregnancy could be a promising intervention strategy.

County-Level Structural Vulnerabilities in Maternal Health and Geographic Variation in Infant Mortality

ObjectiveTo evaluate whether community factors that differentially affect the health of pregnant people contribute to geographic differences in infant mortality across the United States. Study designThis retrospective cohort study sought to characterize the association of a novel composite measure of county-level maternal structural vulnerabilities, the Maternal Vulnerability Index (MVI), with risk of infant death. We evaluated 11,456,232 singleton infants born at 22 0/7 through 44 6/7 weeks’ gestation from 2012 to 2014. Using county-level MVI, which ranges from 0-100, multivariable mixed effects logistic regression models quantified associations per 20-point increment in MVI, with odds of death clustered at the county level and adjusted for state, maternal, and infant covariates. Secondary analyses stratified by the social, physical, and health exposures that comprise the overall MVI score. Outcome was also stratified by cause of death. ResultsOdds of death were higher among infants from counties with the greatest maternal vulnerability (0.62% in highest quintile vs 0.32% in lowest quintile, [p<0.001]). Odds of death increased 6% per 20-point increment in MVI (aOR: 1.06, 95% CI 1.04, 1.07). The effect estimate was highest with theme of mental health and substance use (aOR 1.08; 95% CI 1.06, 1.09). Increasing vulnerability was associated with six of seven causes of death. ConclusionsCommunity-level social, physical, and healthcare determinants indicative of maternal vulnerability may explain some of the geographic variation in infant death, regardless of cause of death. Interventions targeted to county-specific maternal vulnerabilities may reduce infant mortality.

Maternal Characteristics and Rates of Unexpected Complications in Term Newborns by Hospital

The Joint Commission Unexpected Complications in Term Newborns measure characterizes newborn morbidity potentially associated with quality of labor and delivery care. Infant exclusions isolate relatively low-risk births, but unexpected newborn complications (UNCs) are not adjusted for maternal factors that may be associated with outcomes independently of hospital quality. To investigate the association between maternal characteristics and hospital UNC rates. This cohort study was conducted using linked 2016 to 2018 New York City birth and hospital discharge datasets among 254 259 neonates at low risk (singleton, ≥37 weeks, birthweight ≥2500 g, and without preexisting fetal conditions) at 39 hospitals. Logistic regression was used to calculate unadjusted hospital-specific UNC rates and replicated analyses adjusting for maternal covariates. Hospitals were categorized into UNC quintiles; changes in quintile ranking with maternal adjustment were examined. Data analyses were performed from December 2022 to July 2023. UNCs were classified according to Joint Commission International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) criteria. Maternal preadmission comorbidities, obstetric factors, social characteristics, and hospital characteristics were ascertained. Among 254 259 singleton births at 37 weeks or later who were at low risk (125 245 female [49.3%] and 129 014 male [50.7%]; 71 768 births [28.2%] to Hispanic, 47 226 births [18.7%] to non-Hispanic Asian, 42 682 births [16.8%] to non-Hispanic Black, and 89 845 births [35.3%] to non-Hispanic White mothers and 2738 births [1.0%] to mothers with another race or ethnicity), 148 393 births (58.4%) were covered by Medicaid and 101 633 births (40.0%) were covered by commercial insurance. The 2016 to 2018 cumulative UNC incidence in New York City hospitals was 37.1 UNCs per 1000 births. Infants of mothers with preadmission risk factors had increased UNC risk; for example, among mothers with vs without preeclampsia, there were 104.4 and 35.8 UNCs per 1000 births, respectively. Among hospitals, unadjusted UNC rates ranged from 15.6 to 215.5 UNCs per 1000 births and adjusted UNC rates ranged from 15.6 to 194.0 UNCs per 1000 births (median [IQR] change from adjustment, 1.4 [-4.7 to 1.0] UNCs/1000 births). The median (IQR) change per 1000 births for adjusted vs unadjusted rates showed that hospitals with low (<601 deliveries/year; -2.8 [-7.0 to -1.6] UNCs) to medium (601 to <954 deliveries/year; -3.9 [-7.1 to -1.9] UNCs) delivery volume, public ownership (-3.6 [-6.2 to -2.3] UNCs), or high proportions of Medicaid-insured (eg, ≥90.72%; -3.7 [-5.3 to -1.9] UNCs), Black (eg, ≥32.83%; -5.3 [-9.1 to -2.2] UNCs), or Hispanic (eg, ≥6.25%; -3.7 [-5.3 to -1.9] UNCs) patients had significantly decreased UNC rates after adjustment, while rates increased or did not change in hospitals with the highest delivery volume, private ownership, or births to predominantly White or privately insured individuals. Among all 39 hospitals, 7 hospitals (17.9%) shifted 1 quintile comparing risk-adjusted with unadjusted quintile rankings. In this study, adjustment for maternal case mix was associated with small overall changes in hospital UNC rates. These changes were associated with performance assessment for some hospitals, and these results suggest that profiling on this measure should consider the implications of small changes in rates for hospitals with higher-risk obstetric populations.

Trade-off between double cleavage-stage embryos transfer and single blastocyst-stage embryo transfer in patients with few good quality embryos in antagonist cycles: a retrospective study using a propensity score matching analysis

ObjectiveThis study aimed to compare the per OPU clinical outcomes for transfer of Day 3 double cleavage-stage embryos (DET) and Day 5 single blastocyst-stage (SBT) in patients with five or fewer good quality embryos on day 3 per occyte pick-up cycle (OPU) in antagonist cycles with consideration of blastocyst formation failure.MethodsThis was a retrospective, observational cohort study of 2,116 cases of OPU treated with antagonist protocol in the affiliated Chenggong Hospital of Xiamen University between January 2013 and December 2020. DET was performed in 1,811cycles and SBT was performed in 305 cycles. The DET group was matched to the SBT group by propensity score (PS) matching according to multiple maternal baseline covariates. After PS matching, there were 303 ET cycles in each group. The primary outcomes were the cumulative live birth rate (CLBR), cumulative multiple pregnancy rate(CMPR)per OPU and the number of ET to achieve live birth per OPU. Secondary outcomes were the percentage of clinical pregnancy(CPR), live birth rate(LBR), multiple pregnancy rate(MPR).ResultsFollowing PS mating, the CLBR was slightly higher (48.8% versus 40.3% ; P = 0.041) and the CMPR was significantly higher in the DET group compared to SBT group(44.2% versus 7.9%, P < 0.001). The CPR, LBR and MPR per fresh transfer were higher in DET group compared to SBT group(50.2% versus 28.7%; 41.3% versus 21.5%;29.6% versus 0%, P < 0.001). The number of ET to achieve live birth per OPU in SBT group was obiviously more than in DET group(1.48 ± 0.578 versus 1.22 ± 0.557 ,P < 0.001).ConclusionWith a marginal difference cumulative live birth rate, the lower live birth rate per fresh transfer and higher number of ET per OPU in the SBT group suggested that it might take longer time to achieve a live birth with single blastocyst strategy. A trade-off decision should be made between efficiency and safety.

Preterm Birth Risk and Maternal Nativity, Ethnicity, and Race

Immigrant birthing people have lower rates of preterm birth compared with their US-born counterparts. This advantage and associated racial and ethnic disparities across the gestational age spectrum have not been examined nationally. To examine associations of maternal nativity, ethnicity, and race with preterm birth. This cohort study used birth certificates from the National Vital Statistics System to analyze in-hospital liveborn singleton births in the US between January 1, 2009, and December 31, 2018. Data were analyzed from January to June 2023. Mutually exclusive nativity, ethnicity, and race subgroups were constructed using nativity (defined as US-born or non-US-born), ethnicity (defined as Hispanic or non-Hispanic), and race (defined as American Indian or Alaska Native, Asian, Black, Native Hawaiian or Other Pacific Islander, White, or other [individuals who selected other race or more than 1 race]). The primary outcome of interest was preterm birth. Modified Poisson and multinomial logistic regression models quantified relative risk (RR) of preterm birth overall (<37 weeks' gestation) and by gestational category (late preterm: 34-36 weeks' gestation; moderately preterm: 29-33 weeks' gestation; and extremely preterm: <29 weeks' gestation) for each maternal nativity, ethnicity, and race subgroup compared with the largest group, US-born non-Hispanic White (hereafter, White) birthing people. The RR of preterm birth overall and by category was also measured within each racial and ethnic group by nativity. Models were adjusted for maternal demographic and medical covariates, birth year, and birth state. A total of 34 468 901 singleton live births of birthing people were analyzed, with a mean (SD) age at delivery of 28 (6) years. All nativity, ethnicity, and race subgroups had an increased adjusted risk of preterm birth compared with US-born White birthing people except for non-US-born White (adjusted RR, 0.85; 95% CI, 0.84-0.86) and Hispanic (adjusted RR, 0.98; 95% CI, 0.97-0.98) birthing people. All racially and ethnically minoritized groups had increased adjusted risks of extremely preterm birth compared with US-born White birthing people. Non-US-born individuals had a decreased risk of preterm birth within each subgroup except non-Hispanic Native Hawaiian or Other Pacific Islander individuals, in which immigrants had significantly increased risk of overall (adjusted RR, 1.07; 95% CI, 1.01-1.14), moderately (adjusted RR, 1.10; 95% CI, 0.92-1.30), and late (adjusted RR, 1.11; 95% CI, 1.02-1.22) preterm birth than their US-born counterparts. Results of this cohort study suggest heterogeneity of preterm birth across maternal nativity, ethnicity, and race and gestational age categories. Understanding these patterns could aid the design of targeted preterm birth interventions and policies, especially for birthing people typically underrepresented in research.

Evaluating Decadal Changes in Determinants of Early Childhood Stunting and Assessing Their Contribution to Socio-economic Disparity in Child Nutritional Status Across India

Various efforts have been made over the years to bring about reduction in child malnutrition; the latest among them involves Goal 2 of the SDGs. The SDG Target 2.2 recognizes the global dimension of the nutrition issue and aims to end all forms of malnutrition by 2030, including achieving, by 2025, (WHO, 2015). The present evidence on childhood malnutrition suggests that while improvement in maternal and child covariates have resulted in decline of childhood stunting over time. The present study aims to investigate how the effect of maternal and child covariates on early childhood malnutrition have changed over the last decade and examining the socio-economic disparity in the nutritional status of children across India. The present study utilizes data from the last two rounds of the National Family Health Survey, NFHS-3 in 2005-06 and NFHS-4 in 2015-16 of children in the age group 6-23 months for whom data on height-for-age was available from the last two rounds of the National Family Health Survey (NFHS-3 and NFHS-4). After dropping the missing and flagged cases, the total sample size was 12,507 and 68,246 children from NFHS-3 (2005-06) and NFHS-4 (2015-16), respectively. The selected indicator of childhood under nutrition for this study is stunting. The exposure variables selected for the study were child factors such as sex, age, birth order, size at birth, place of delivery, diet diversity, meal frequency and early initiation of breastfeeding. Maternal factors such as maternal education, media exposure, and mother’s BMI were taken into account. For healthcare service utilization we considered the variable of complete antenatal care. Other background characteristics like religion, caste, wealth index, place of residence and geographical region were also considered. We utilized chi-square test to test for the association of various factors with early childhood stunting followed by t-test to assess the changes in prevalence by each factor. We also carried out bivariate and multivariate logistic analysis to effect of various factors on childhood stunting. Lastly, we carried out Oaxaca decomposition to examine the contribution of the determinants of childhood stunting towards the changes in its prevalence over the last ten years. Concentration Index was calculated to examine the disparity in early childhood stunting across India for both rounds of the National Family Health Survey. The predictive probabilities were calculated for each category of the wealth index after fitting a logistic model to control for other determinants of early childhood stunting to assess the change in prevalence of stunting across each socio-economic group in the last ten years. The study reveals an overall decline in prevalence of early childhood stunting across India over the last ten years from 2005-16. However, high levels of variation continue to exist across all the states in India. The study reveals institutional delivery as the highest contributing factor for this decline. Maternal education, body mass index and complete antenatal care during pregnancy also contribute significantly to the improvement in childhood stunting

Risk of immune-related diseases in childhood after intrapartum antibiotic exposure

Intrapartum antibiotic prophylaxis is effective in preventing early-onset group B streptococcal disease in newborn infants, but it influences gut microbiota development. Gut microbiota composition is, in turn, associated with immune-related diseases in childhood. This study hypothesized that intrapartum antibiotic exposure is associated with immune-related diseases in childhood. We conducted a population-based cohort study of vaginally delivered children. We retrieved data on intrapartum antibiotic exposure from structured electronic medical records and obtained outcome data on childhood autoimmune, allergic, and obstructive airway diseases from comprehensive national registers. We used Cox regression analysis with adjustment for maternal and neonatal covariates and regarded death as a competing risk in the analyses. The study population comprised 45,575 vaginally born children of whom 9733 (21%) had been exposed to intrapartum antibiotics. Intrapartum antibiotic exposure was associated with an autoimmune disease diagnosis (adjusted hazard ratio, 1.28; 95% confidence interval, 1.02-1.62), which corresponds to 22% (95% confidence interval, 6-39) as a theoretical population-attributable fraction. Intrapartum antibiotic exposure was not associated with diagnoses of allergic (adjusted hazard ratio, 1.08; 95% confidence interval, 0.97-1.20) or obstructive airway diseases (adjusted hazard ratio, 1.04; 95% confidence interval, 0.96-1.14). Intrapartum antibiotic exposure may be associated with an increased risk for autoimmune diseases in childhood. This finding supports the efforts to develop more specific group B streptococcal disease prevention strategies in the future.

Nutrition interventions and clinical outcomes of pregnant women with gestational diabetes mellitus: More than meets the eye.

In the retrospective study by Luo et al regarding clinical outcomes in gestational diabetes mellitus (GDM), the results are statistically significant in favour of the benefits of individualized nutrition interventions enumerated therein. The study has provided important evidence to improve maternal and child health in the Asian population. The methods, however, appear to have considerable limi-tations, wherein the time point of diagnosis of GDM, severity of GDM, selection bias, compliance to therapy, important maternal covariates, observable microvascular abnormalities and the confounding effect of added insulin have not been considered. We have provided suggestions to improve the external validity of the study, including the use of Equator Network reporting guidelines and inclusion of overweight and obese patients in future studies.

Prenatal Exposure to Air Pollution and Respiratory Distress in Term Newborns: Results from the MIREC Prospective Pregnancy Cohort.

Respiratory distress is the leading cause of neonatal morbidity and mortality worldwide, and prenatal exposure to air pollution is associated with adverse long-term respiratory outcomes; however, the impact of prenatal air pollution exposure on neonatal respiratory distress has not been well studied. We examined associations between prenatal exposures to fine particular matter () and nitrogen dioxide () with respiratory distress and related neonatal outcomes. We used data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a prospective pregnancy cohort () recruited in the first trimester from 10 Canadian cities. Prenatal exposures to () and () were estimated using land-use regression and satellite-derived models coupled with ground-level monitoring and linked to participants based on residential location at birth. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between air pollution and physician-diagnosed respiratory distress in term neonates in hierarchical logistic regression models adjusting for detailed maternal and infant covariates. Approximately of newborns experienced respiratory distress. Neonates received clinical interventions including oxygen therapy (6%), assisted ventilation (2%), and systemic antibiotics (3%). Two percent received multiple interventions and 4% were admitted to the neonatal intensive care unit (NICU). Median and concentrations during pregnancy were and , respectively. Prenatal exposures to air pollution were not associated with physician-diagnosed respiratory distress, oxygen therapy, or NICU admissions. However, exposures were strongly associated with assisted ventilation (OR per increase in ; 95% CI: 1.02, 1.35), multiple clinical interventions (OR per increase in ; 95% CI: 1.07, 1.26), and systemic antibiotics, (OR per increase in ; 95% CI: 1.04, 1.21). These associations were consistent across exposure periods-that is, during prepregnancy, individual trimesters, and total pregnancy-and robust to model specification. exposure was associated with administration of systemic antibiotics (OR per 1-ppb increase in ; 95% CI: 1.00, 1.06). Prenatal exposures to increased the risk of severe respiratory distress among term newborns. These findings support the development and prioritization of public health and prenatal care strategies to increase awareness and minimize prenatal exposures to air pollution. https://doi.org/10.1289/EHP12880.

Critical windows of greenness exposure during preconception and gestational periods in association with birthweight outcomes

Few studies have examined the association between greenness exposure and birth outcomes. This study aims to identify critical exposure time windows during preconception and pregnancy for the association between greenness exposure and birth weight. A cohort of 13 890 pregnant women and newborns in Shanghai, China from 2016–2019 were included in the study. We assessed greenness exposure using Normalized Difference Vegetation Index (NDVI) during the preconception and gestational periods, and evaluated the association with term birthweight, birthweight z-score, small-for-gestational age, and large-for-gestational age using linear and logistic regressions adjusting for key maternal and newborn covariates. Ambient temperature, relative humidity, ambient levels of fine particles (PM2.5) and nitrogen dioxide (NO2) assessed during the same period were adjusted for as sensitivity analyses. Furthermore, we explored the potential different effects by urbanicity and park accessibility through stratified analysis. We found that higher greenness exposure at the second trimester of pregnancy and averaged exposure during the entire pregnancy were associated with higher birthweight and birthweight Z-score. Specifically, a 0.1 unit increase in second trimester averaged NDVI value was associated with an increase in birthweight of 10.2 g (95% CI: 1.8–18.5 g) and in birthweight Z-score of 0.024 (0.003–0.045). A 0.1 unit increase in an averaged NDVI during the entire pregnancy was associated with 10.1 g (95% CI: 1.0–19.2 g) increase in birthweight and 0.025 (0.001–0.048) increase in birthweight Z-score. Moreover, the associations were larger in effect size among urban residents than suburban residents and among residents without park accessibility within 500 m compared to those with park accessibility within 500 m. Our findings suggest that increased greenness exposure, particularly during the second trimester, may be beneficial to birth weight in a metropolitan area.

Inflammatory Conditions During Pregnancy and Risk of Autism and Other Neurodevelopmental Disorders

BackgroundMaternal inflammation can result from immune dysregulation and metabolic perturbations during pregnancy. Whether conditions associated with inflammation during pregnancy increase the likelihood of autism spectrum disorder (ASD) or other neurodevelopmental disorders (DDs) is not well understood. MethodsWe conducted a case-control study among children born in California from 2011 to 2016 to investigate maternal immune-mediated and cardiometabolic conditions during pregnancy and risk of ASD (n = 311) and DDs (n = 1291) compared with children from the general population (n = 967). Data on maternal conditions and covariates were retrieved from electronic health records. Maternal genetic data were used to assess a causal relationship. ResultsUsing multivariable logistic regression, we found that mothers with asthma were more likely to deliver infants later diagnosed with ASD (odds ratio [OR] = 1.62, 95% CI: 1.15–2.29) or DDs (OR = 1.30, 95% CI: 1.02–1.64). Maternal obesity was also associated with child ASD (OR = 1.51, 95% CI: 1.07–2.13). Mothers with both asthma and extreme obesity had the greatest odds of delivering an infant later diagnosed with ASD (OR = 16.9, 95% CI: 5.13–55.71). These increased ASD odds were observed among female children only. Polygenic risk scores for obesity, asthma, and their combination showed no association with ASD risk. Mendelian randomization did not support a causal relationship between maternal conditions and ASD. ConclusionsInflammatory conditions during pregnancy are associated with risk for neurodevelopmental disorders in children. These risks do not seem to be due to shared genetic risk; rather, inflammatory conditions may share nongenetic risk factors with neurodevelopmental disorders. Children whose mothers have both asthma and obesity during pregnancy may benefit from earlier screening and intervention.

Polycystic Ovary Syndrome, Gestational Diabetes Mellitus, and the Mediating Role of Obesity: A Population-Based Cohort Study

This population-based cohort study in Ontario, Canada evaluated the association between polycystic ovary syndrome (PCOS) and gestational diabetes mellitus, and the mediating effect of obesity. The study included 1 268 901 pregnancies between 2006 and 2018; 387 748 with maternal PCOS and 881 153 without PCOS. Modified Poisson regression generated relative risks adjusted for maternal covariates. Causal mediation analyses accounted for the indirect effect of obesity. Relative to individuals without PCOS, those with PCOS had a slightly higher rate (6.0% vs. 4.9%) and adjusted relative risk (1.05; 95% CI 1.03–1.06) of gestational diabetes mellitus. Obesity mediated a significant proportion (90%) of this association. Preconception counselling and future research should include strategies to support weight optimization in patients with PCOS.

IgG Seroreactivites to Viral Capsid Protein VP1 of JC and BK Polyomaviruses in Children at Early Ages with Special Reference to Parental Cofactors.

BK (BKPyV) and JC (JCPyV) polyomaviruses are widespread in humans. Transmission at an early age and the role of parents in spreading these viruses through the family are incompletely understood. Our aim was to determine the seroprevalence of BKPyV and JCPyV in infants at the age of 1, 2, 6, 12, 24, and 36 months and to assess the frequency of BKPyV and JCPyV seroconversion. A variety of maternal and paternal covariates were also tested as potential predictors of these early childhood infections. We used multiplex serology to analyze antibodies to BKPyV and JCPyV from baseline to 3-year follow-up visits. We observed that there was nearly perfect correlation in BKPyV and JCPyV serum IgG antibody levels between the mother-infant pairs during the first year of the infant's life. No correlation among BKPyV antibody titers were found in father-child pairs, whereas JCPyV antibody levels of the father and child had a significant correlation at the 2-year follow-up visit. BKPyV infection may be associated with a child's predisposition to allergy. In conclusion, after the decay of maternal antibodies, children start to develop their own immunity toward BKPyV and JCPyV, and horizontal transmission of infection in the family can occur.

Maternal Thyroid Function During Pregnancy and Offspring White Matter Microstructure in Early Adulthood: A Prospective Birth Cohort Study.

Background: The fetus is fully dependent on maternal thyroid hormones until mid-gestation and suboptimal maternal thyroid function has been associated with alterations in the neurodevelopment of the offspring. We used maternal free thyroxine (fT4) and thyrotropin (TSH) levels in early gestation to study the association of maternal thyroid function during early pregnancy and offspring brain white matter (WM) integrity in early adulthood. Methods: Our study population consisted of a total of 292 mother-child pairs. Maternal fT4 and TSH were used as predictors and offspring multimodal imaging measures of fractional anisotropy, mean diffusivity, and magnetization transfer ratio (FA, MD, and MTR) as dependent variables. First, as Global analysis, all analyzed 14 WM tracts were studied simultaneously using linear-mixed effect models. Second, if a global effect was detected, a post hoc Tract-wise analysis was carried out using linear models individually in each WM tract. Study population was stratified by sex. Results: We found a positive association between maternal fT4 and offspring Global FA in males when adjusted for all maternal and offspring covariates (n = 114; β = 0.154; confidence interval = 0.045-0.263; p = 0.006). The finding was observed to be driven by multiple WM tracts, of which three projection fiber tracts and the forceps minor survived correcting for multiple comparisons in Tract-wise analysis. Conclusions: Maternal thyroid function in early pregnancy was observed to be associated with WM microstructure in male offspring in early adulthood. Our results suggest that maternal fT4 levels in early pregnancy may modulate axonal characteristics, with a long-term effect on offspring WM development.

Maternal mental illness and child atopy: a UK population-based, primary care cohort study.

The number of children exposed to maternal mental illness is rapidly increasing and little is known about the effects of maternal mental illness on childhood atopy. To investigate the association between maternal mental illness and risk of atopy among offspring. Retrospective cohort study using a UK primary care database (674 general practices). In total, 590 778 children (born 1 January 1993 to 30 November 2017) were followed until their 18th birthday, with 359 611 linked to their hospital records. Time-varying exposure was captured for common (depression and anxiety), serious (psychosis), addiction (alcohol and substance misuse), and other (eating and personality disorder) maternal mental illness from 6 months before pregnancy. Using Cox regression models, incidence rates of atopy were calculated and compared for the exposed and unexposed children in primary (asthma, eczema, allergic rhinitis, and food allergies) and secondary (asthma and food allergies) care, adjusted for maternal (age, atopy history, smoking, and antibiotic use), child (sex, ethnicity, and birth year/season), and area covariates (deprivation and region). Children exposed to common maternal mental illness were at highest risk of developing asthma (adjusted hazard ratio [aHR] 1.17, 95% confidence interval [CI] = 1.15 to 1.20) and allergic rhinitis (aHR 1.17, 95% CI = 1.13 to 1.21), as well as a hospital admission for asthma (aHR 1.29, 95% CI = 1.20 to 1.38). Children exposed to addiction disorders were 9% less likely to develop eczema (aHR 0.91, 95% CI = 0.85 to 0.97) and 35% less likely to develop food allergies (aHR 0.65, 95% CI = 0.45 to 0.93). The finding that risk of atopy varies by type of maternal mental illness prompts important aetiological questions. The link between common mental illness and childhood atopy requires GPs and policymakers to act and support vulnerable women to access preventive (for example, smoking cessation) services earlier.

Health-related quality of life of mothers and developmental characteristics of very low birth weight children at 2.5 years of age: results from the Japan Environment and Children’s Study (JECS)

BackgroundThe level of child development may be associated with the risk of poor maternal health-related quality of life (HRQoL). The objective of this study was to describe the developmental characteristics of very low birth weight (VLBW) children at 2.5 years of age and to examine associations between maternal HRQoL and the degree of child development based on the Japanese version of Ages and Stages Questionnaire (J-ASQ-3).MethodsA cross-sectional study was performed using the data from a nationwide prospective birth cohort study in Japan. Among a total of 104,062 fetal records, the VLBW infants (birth weight ≤ 1500 g) were analyzed using linear regression models, adjusted for potential covariates. Subgroup analysis was also conducted to assess the association between social connection or cooperation of the partner and maternal HRQoL by the level of child development.ResultsThe final study subjects included 357 VLBW children and mothers. The suspected developmental delays (SDDs) in at least two domains was significantly associated with lower maternal mental HRQoL regression coefficient –2.314 (95%CI: –4.065 to –0.564). There was no association between the status of child development and maternal physical HRQoL. After adjusting for child and maternal covariates, the maternal HRQoL was not significantly associated with child development. Amongst women who indicated having some social support, having a child with a SDD in two or more domains was negatively associated with mental HRQoL compared with women whose child was less developmental delay, regression coefficient –2.337 (95%CI: –3.961 to –0.714). Amongst women who indicated having partner’s cooperation to child-rearing, having a child with a SDD in two or more domains was negatively associated with mental HRQoL compared with women whose child was less developmental delay, regression coefficient –3.785 (95%CI: –6.647 to –0.924).ConclusionsOur findings indicate that the lower maternal mental HRQoL was independently associated with the SDDs evaluated by the J-ASQ-3, whereas there was no association after adjusting for covariates. Further research is warranted to elucidate the impact of social connection and partner’s cooperation on maternal HRQoL and child development. This study urges that particular attention should be paid to mothers of VLBW children with SDDs and also to provide early intervention and continued support.

45-OR: Newborn Adiposity and Cord Blood DNA Methylation—An Epigenome-Wide Association Study in HAPO with Validation in Gen3G

Differential cord blood DNA methylation (cb DNAm) in response to hyperglycemia in pregnancy may be associated with neonatal adiposity, a risk factor for childhood obesity. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study enrolled a multiethnic cohort to evaluate glycemia in pregnancy and newborn adiposity measured by skinfold thicknesses. We conducted an epigenome-wide association study using HAPO as a discovery sample and performed a replication study in an independent cohort, Gen3G. We analyzed cb DNAm with Illumina EPIC arrays (791,359 CpG sites after QC) on 2712 HAPO samples. We assessed the association between sum of 3 skinfolds and cb DNAm using linear regression models adjusted for maternal and offspring covariates and cell counts. We identified 90 CpG sites after accounting for multiple testing (Bonferroni-adjusted p&amp;lt;0.05). Using these sites identified in HAPO, we conducted similar regression analyses in 139 Gen3G cb DNAm samples to replicate findings. Similar associations at 7 CpG sites were identified including loci near KLF7, which encodes a regulator of cell proliferation and inhibitor of adipogenesis, and IGF1R, which encodes a transmembrane receptor involved in cell growth and survival that binds IGF1 and insulin, the latter especially during fetal life. These findings support epigenetic mechanisms in the developmental origins of neonatal adiposity. Disclosure J.L.Josefson: None. A.Kuang: None. D.Scholtens: None. C.Allard: None. W.Lowe: None. M.Hivert: None. Funding National Institutes of Health (R01HD034243, R01DK118403)

1097-P: Association between Adipokines and Glycemia in Children under Age 8—The PROGRESS Cohort of Mexico

Background: The increased incidence of type 2 diabetes is closely linked to obesity, in which an accumulation of adipocytes leads to the dysregulated production of adipokines. In adults, several adipokines contribute to the development of glycemic dysregulation, however, the role of adipokines on childhood glycemia is poorly understood. We examine the longitudinal association between adipokines and glycemia using multiple timepoint data from children in Mexico City. Methods: Children from the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) cohort (948 children, 52% male) were followed longitudinally after birth. Leptin, adiponectin, glucose, and HbA1c were measured at 4, 6, and 8 years, and fasting insulin at 8 years. Adiponectin to leptin ratio (ALR) and HOMA2 (B/IR/S) indices were computed. Longitudinal association between adipokines and each of glucose and HbA1c was examined by linear mixed models. Association between adipokines and insulin and the HOMAs at age 8 was examined by multivariable linear regression. All models were adjusted for maternal and child covariates. Results: Between ages 4 and 8 years, average levels of leptin dropped from 15.7 to 13.7 ug/mL; adiponectin increased from 3.1 to 10.8 ng/mL; and ALR dropped from 9.1 to 3.1 ug/ng. Longitudinally, across timepoints 4, 6, and 8 years after birth, there was no association between adipokines and glycemia. However, the cross-sectional analysis at age 8 years found an association between leptin and insulin (1.03, 95% CI: 1.00, 1.07), HOMA2-B (1.02, 95% CI: 1.00, 1.04), HOMA2-IR (1.03, 95% CI: 1.00, 1.07), and HOMA2-S (0.97, 95% CI: 0.94, 0.99). Similar associations were observed in males and females. Conclusion: In this prepubertal cohort, leptin was associated with insulin and with HOMA indices at age 8. Further investigation is needed to understand the role of adipokines in the development of T2DM in children and the risk factors that may alter adipokine metabolism. Disclosure Y.S.Beyh: None. R.O.Wright: None. M.M.Tellez-rojo: None. A.Baccarelli: None. H.Wu: None. K.Narayan: None. L.R.Staimez: None. U.Ramakrishnan: None. M.K.Bhasin: None. M.Tolentino dolores: None. G.Estrada-gutierrez: None. M.Yitshak sade: None. Funding National Institute of Environmental Health Sciences (R01ES032242, R01ES021357, R01ES013744, P30ES009089)