Mother-offspring Dyads Research Articles

Contributions of maternal prenatal infection and antibiotic exposure to offspring infection and risk for allergic respiratory conditions through age 5

ObjectivesTo determine if maternal prenatal infection increases risk of offspring postnatal infections through age 5 or diagnosis of respiratory allergy at age 5, independent of prenatal/postnatal antibiotic exposure. To evaluate if frequency of offspring infections mediates an association between prenatal infection and respiratory allergy at age 5. Study designSecondary data analyses were performed from the Child Health and Development Studies (CHDS), a prospective, longitudinal birth cohort that enrolled pregnant women from 1959 to 1966 (N = 19,044 live births). The sample included a subset of mother-offspring dyads (n = 2062) with abstracted medical record data from the prenatal period through age 5 that included information on antibiotic use, infection, and offspring respiratory allergy. ResultsSecond trimester maternal infection was associated with an increased risk of offspring infection (IRR = 1.23; 95% CI = 1.09–1.39; p = 0.001). No significant direct associations were detected between prenatal infection and diagnosis of offspring respiratory allergy. Offspring infection (OR = 1.17; 95% CI = 1.13–1.20; p < 0.001) and antibiotic exposure (OR = 1.28; 95% CI = 1.22–1.33; p < 0.001) were significantly associated with a diagnosis of offspring respiratory allergy. Respiratory allergy diagnosis risk was greater with increasing offspring infection exposure and antibiotics. There was a significant indirect effect of second trimester maternal infection on offspring respiratory allergy, due to infections and not antibiotic use, via offspring infection, indicating a partially mediated effect. ConclusionPrenatal maternal infection may contribute to increase risk for early childhood infections, which in turn, may increase risk for allergic conditions.

Intergenerational continuation of parent-child separation and 1-year telomere length attrition among mother-offspring dyads in rural China: The moderating effects of resilience

BackgroundAlthough stressor exposure early in life was known risk factor for telomere length (TL) attrition, limited literature explored it across generations. Furthermore, the effects of resilience have rarely been examined. Here, we examined whether the effects of intergenerational parent-child separation on offspring 1-year TL attrition vary by the levels of resilience. MethodIn a sample of 342 mother-child dyads living in rural China, the intergenerational continuation of parent-child separation was defined as the two generations both experiencing parent-child separation from both parents for >6 months a year early in life assessed by the parent-reported questionnaire, whereas intergenerational discontinuity refers to parent-child separation exposed in one generation only. TL was measured at baseline (from June to November 2021) and 1-year later with children's buccal mucosa swabs, with resilience polygenic risk scores (PRS) evaluated based on 4 single-nucleotide variations in 4 resilience-related genes (OXTR, FKBP5, NPY, and TNF-α). ResultsAmong 342 mother-offspring dyads, 35 (10.2 %) experienced intergenerational continuation of parent-child separation, and 139 (40.6 %) were identified as discontinuous. Remarkably, a 0.12-point reduction in TL attrition was only associated with intergenerational continuation of parent-child separation (95 % CI: 0.04, 0.21, P < 0.01) but not discontinuity. Importantly, the association between intergenerational continuation of parent-child separation with accelerated TL attrition disappeared in offspring with high resilience PRS (β = 0.07, 95%CI: −0.06, 0.21). ConclusionOur findings highlight the importance of breaking the intergenerational cycle of parent-child separation and the moderating effects of resilience on TL attrition for children exposed to adversity.

Maternal Adverse Childhood Experiences and Biological Aging During Pregnancy and in Newborns

Adverse childhood experiences (ACEs), potentially traumatic experiences occurring before the age of 18 years, are associated with epigenetic aging later in life and may be transmitted across generations. To test evidence of the transmission of biological embedding of life experience across generations by analyzing maternal ACEs and epigenetic clocks measured in mothers during pregnancy and in their children at birth. For this cross-sectional study, data from the Accessible Resource for Integrated Epigenomic Studies (ARIES) substudy of the Avon Longitudinal Study of Parents and Children (ALSPAC) were analyzed. The ALSPAC study recruited 14 541 women who gave birth in the Avon Health District in the UK between April 1, 1991, and December 31, 1992. The ARIES substudy comprised 1018 mother-offspring dyads based on the availability of DNA samples profiled in 2014. Epigenetic age was estimated using DNA methylation-based epigenetic clocks (including Horvath, Hannum, GrimAge, PhenoAge, and DunedinPACE) in mothers during pregnancy and the Knight and Bohlin cord blood epigenetic clocks in newborns. Analyses were performed between October 1, 2022, and November 30, 2023. A composite measure of maternal ACEs was the primary exposure in both maternal and offspring models; as a secondary analysis, individual ACEs were measured separately. The Edinburgh Postnatal Depression Scale (EPDS) was used to investigate depression during pregnancy as an exposure. Changes in epigenetic age acceleration (EAA) were investigated as the primary outcome in maternal models during pregnancy. Changes in epigenetic gestational age acceleration (GAA) were the primary outcome in offspring analyses. Linear regression analyses were used to determine the association between maternal ACEs and both outcomes. This study included 883 mother-child dyads. The mean (SD) maternal age at delivery was 29.8 (4.3) years. Pregnant women with higher ACE scores exhibited higher GrimAge EAA (β, 0.22 [95% CI, 0.12 to 0.33] years; P < .001). Maternal ACEs were not associated with GAA in newborns using P < .05 as a cutoff to determine statistical significance. Depression was associated with higher GrimAge EAA (β, 0.06 [95% CI, 0.02 to 0.10] years; P = .01) in mothers during pregnancy, but not in newborns, and did not mediate the association between ACEs and EAA. The findings of this study suggest that maternal ACEs may be associated with epigenetic aging later in life, including during pregnancy, supporting a role for maternal ACEs in offspring development and health later in life.

Prenatal maternal Inflammation, childhood cognition and adolescent depressive symptoms

BackgroundAccumulating evidence indicates that higher prenatal maternal inflammation is associated with increased depression risk in adolescent and adult-aged offspring. Prenatal maternal inflammation (PNMI) may increase the likelihood for offspring to have lower cognitive performance, which, in turn, may heighten risk for depression onset. Therefore, this study explored the potential mediating role of childhood cognitive performance in the relationship between PNMI and adolescent depressive symptoms in offspring. MethodsParticipants included 696 mother-offspring dyads from the Child Health and Development Studies (CHDS) cohort. Biomarkers of maternal inflammation [interleukin (IL)-6, IL-8, IL-1 receptor antagonist (IL-1RA) and soluble TNF receptor-II (sTNF-RII)] were assayed from first (T1) and second trimester (T2) sera. Childhood (ages 9–11) cognitive performance was assessed via standardized Peabody Picture Vocabulary Test (PPVT), a measure of receptive vocabulary correlated with general intelligence. Adolescent (ages 15–17) depressive symptoms were assessed via self-report. ResultsThere were no significant associations between T1 biomarkers and childhood PPVT or adolescent depressive symptoms. Higher T2 IL1-RA was directly associated with lower childhood PPVT (b = -0.21, SE = 0.08, t = -2.55, p = 0.01), but not with adolescent depressive symptoms. T2 IL-6 was not directly associated with childhood PPVT, but higher T2 IL-6 was directly associated at borderline significance with greater depressive symptoms in adolescence (b = 0.05, SE = 0.03, t = 1.96, p = 0.05). Lower childhood PPVT predicted significantly higher adolescent depressive symptoms (b = -0.07, SE = 0.02, t = -2.99, p < 0.01). There was a significant indirect effect of T2 IL-1RA on adolescent depressive symptoms via childhood PPVT (b = 0.03, 95 % CI = 0.002–0.03) indicating a partially mediated effect. No significant associations were found with T2 sTNF-RII nor IL-8. ConclusionsLower childhood cognitive performance, such as that indicated by a lower PPVT score, represents a potential mechanism through which prenatal maternal inflammation contributes to adolescent depression risk in offspring.

Bridging Differences in Cohort Analyses of the Relationship between Secondhand Smoke Exposure during Pregnancy and Birth Weight: The Transportability Framework in the ECHO Program.

Estimates for the effects of environmental exposures on health outcomes, including secondhand smoke (SHS) exposure, often present considerable variability across studies. Knowledge of the reasons behind these differences can aid our understanding of effects in specific populations as well as inform practices of combining data from multiple studies. This study aimed to assess the presence of effect modification by measured sociodemographic characteristics on the effect of SHS exposure during pregnancy on birth weights that may drive differences observed across cohorts. We also aimed to quantify the extent to which differences in the cohort mean effects observed across cohorts in the Environmental influences on Child Health Outcomes (ECHO) consortium are due to differing distributions of these characteristics. We assessed the presence of effect modification and transportability of effect estimates across five ECHO cohorts in a total of 6,771 mother-offspring dyads. We assessed the presence of effect modification via gradient boosting of regression trees based on the H-statistic. We estimated individual cohort effects using linear models and targeted maximum likelihood estimation (TMLE). We then estimated transported effects from one cohort to each of the remaining cohorts using a robust nonparametric estimation approach relying on TMLE estimators and compared them to the original effect estimates for these cohorts. Observed effect estimates varied across the five cohorts, ranging from significantly lower birth weight associated with exposure [; 95% confidence interval (CI): , ] to higher birth weight with wide CIs, including the null (; 95% CI: , 99.8). Transported effect estimates only minimally explained differences in the point estimates for two out of the four cohort pairs. Our findings of weak to moderate evidence of effect modification and transportability indicate that unmeasured individual-level and contextual factors and sources of bias may be responsible for differences in the effect estimates observed across ECHO cohorts. https://doi.org/10.1289/EHP13961.

Sex-Specific Pathways From Prenatal Maternal Inflammation to Adolescent Depressive Symptoms

Prenatal maternal inflammation has been associated with major depressive disorder in offspring in adulthood as well as with internalizing and externalizing symptoms in childhood; however, the association between prenatal inflammation and offspring depression in adolescence has yet to be examined. To determine whether maternal levels of inflammatory biomarkers during pregnancy are associated with depressive symptomatology in adolescent-aged offspring and to examine how gestational timing, offspring sex, and childhood psychiatric symptoms impact these associations. This was an observational study of a population-based birth cohort from the Child Health and Development Studies (CHDS), which recruited almost all mothers receiving obstetric care from the Kaiser Foundation Health Plan (KFHP) in Alameda County, California, between June 1959 and September 1966. Pregnancy data and blood sera were collected from mothers, and offspring psychiatric symptom data were collected in childhood (ages 9-11 years) and adolescence (ages 15-17 years). Mother-offspring dyads with available maternal prenatal inflammatory biomarkers during first and/or second trimesters and offspring depressive symptom data at adolescent follow-up were included. Data analyses took place between March 2020 and June 2023. Levels of inflammatory biomarkers (interleukin 6 [IL-6], IL-8, IL-1 receptor antagonist [IL-1RA], and soluble tumor necrosis factor receptor-II) assayed from maternal sera in the first and second trimesters of pregnancy. Self-reported depressive symptoms at adolescent follow-up. A total of 674 mothers (mean [SD] age, 28.1 [5.9] years) and their offspring (350 male and 325 female) were included in this study. Higher second trimester IL-6 was significantly associated with greater depressive symptoms in offspring during adolescence (b, 0.57; SE, 0.26); P = .03). Moderated mediation analyses showed that childhood externalizing symptoms significantly mediated the association between first trimester IL-6 and adolescent depressive symptoms in male offspring (b, 0.18; 95% CI, 0.02-0.47), while childhood internalizing symptoms mediated the association between second trimester IL-1RA and adolescent depressive symptoms in female offspring (b, 0.80; 95% CI, 0.19-1.75). In this study, prenatal maternal inflammation was associated with depressive symptoms in adolescent-aged offspring. The findings of the study suggest that pathways to adolescent depressive symptomatology from prenatal risk factors may differ based on both the timing of exposure to prenatal inflammation and offspring sex.

Maternal Prenatal Depressive Symptoms and Fetal Growth During the Critical Rapid Growth Stage

Fetal growth in the critical rapid growth stage (CRGS) before delivery, approximately between 30 to 37 gestational weeks, carries significant implications for subsequent overweight, obesity, and arterial health. Previous evidence has demonstrated the association between maternal depressive symptoms and fetal growth trajectories from early to late pregnancy, but there remains limited understanding of the association of these symptoms with the longitudinal fetal growth change within the CRGS. To investigate the association between maternal depressive symptoms and fetal growth during the CRGS before delivery. This prospective birth cohort study was conducted from January 2018 to December 2020. Volunteer pregnant women were enrolled in their first trimester of prenatal visits. Women with severe disease before pregnancy and multiple births, fetuses with congenital anomalies, and preterm or postterm births were excluded. This multicenter study was based in 13 hospitals covering 81 counties across 12 cities in Sichuan Province, China. Follow-up visits were performed at the second trimester, the third trimester, and 24 hours after delivery. The analysis was conducted from January to May 2023. Maternal depressive symptoms, as a continuous variable, measured by the Edinburgh Postpartum Depression Scale (EPDS) at a median gestational week of 24 (range, 14 to 27) weeks of gestation. A higher score on the EPDS indicates worse depressive symptoms. The main outcomes included ultrasonography-measured biparietal diameter (BPD), femur length (FL), and abdominal circumference (AC), along with calculated estimated fetal weight (EFW). These parameters were evaluated longitudinally at a median gestational week of 30 (range, 28 to 32) and 37 (range, 35 to 39) weeks. Linear mixed models were used to estimate the associations between maternal depressive symptoms and fetal growth parameters. A total of 2676 mother-offspring dyads were included, in which the mean (SD) age of mothers was 28.0 (4.4) years, and 1294 (48.4%) of the offspring were female. The median (IQR) maternal EPDS score was 5.0 (4.0 to 9.0). After adjustment for confounders, a significant correlation was found between a higher score of depressive symptoms in mothers and a slower rate of fetal growth across FL (β = -0.40; 95% CI, -0.58 to -0.22), AC (β = -1.97; 95% CI, -2.90 to -1.03), and EFW (β = -50.11; 95% CI, -68.46 to -31.75). These associations were stronger in female fetuses or those with better family socioeconomic conditions. In this prospective cohort study, maternal depressive symptoms were associated with slower fetal growth rate in the CRGS before delivery. Early screening for depressive disorders in pregnant women appears to be essential for fetal growth and later health.

Maternal prenatal social experiences and offspring epigenetic age acceleration from birth to mid-childhood

PurposeInvestigate associations of maternal social experiences with offspring epigenetic age acceleration (EAA) from birth through mid-childhood among 205 mother-offspring dyads of minoritized racial and ethnic groups. MethodsWe used linear regression to examine associations of maternal experiences of racial bias or discrimination (0 = none, 1–2 = intermediate, or 3+ = high), social support (tertile 1 = low, 2 = intermediate, 3 = high), and socioeconomic status index (tertile 1 = low, 2 = intermediate, 3 = high) during the prenatal period with offspring EAA according to Horvath’s Pan-Tissue, Horvath’s Skin and Blood, and Intrinsic EAA clocks at birth, 3 years, and 7 years. ResultsIn comparison to children of women who did not experience any racial bias or discrimination, those whose mothers reported highest levels of racial bias or discrimination had lower Pan-Tissue clock EAA in early (−0.50 years; 90% CI: −0.91, −0.09) and mid-childhood (−0.75 years; −1.41, −0.08). We observed similar associations for the Skin and Blood clock and Intrinsic EAA. Maternal experiences of discrimination were not associated with Pan-Tissue EAA at birth. Neither maternal social support nor socioeconomic status predicted offspring EAA. ConclusionsChildren whose mothers experienced higher racial bias or discrimination exhibited slower EAA. Future studies are warranted to confirm these findings and establish associations of early-life EAA with long-term health outcomes.

No effect of multi-strain probiotic supplementation on metabolic and inflammatory markers and newborn body composition in pregnant women with obesity: Results from a randomized, double-blind placebo-controlled study

Background and aimsModulation of the gut microbiome composition with probiotics may have beneficial metabolic effects in pregnant women with obesity. The aim was to investigate the effect of probiotic supplementation during pregnancy on metabolic and inflammatory markers and the body composition of the offspring. Methods and resultsA randomized double-blind trial in 50 pregnant women (pre-pregnancy BMI ≥30 and < 35 kg/m2) comparing multi-strain probiotics (Vivomixx®; 450 billion CFU/d) versus placebo from 14 to 20 weeks of gestation until delivery was carried out. Participants were followed with two predelivery visits at gestational week 27–30 and 36–37 and with one postdelivery visit. All visits included fasting blood samples (C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin, C-peptide, glucose, glucagon, and glucagon-like peptide-1 (GLP-1)). At delivery, umbilical cord blood samples were collected (GLP-1 and glucagon). At the postdelivery visit, a dual-energy X-ray absorptiometry (DXA) scan of the newborn was performed.Forty-nine of 50 participants completed the study until delivery, and 36 mother-offspring dyads underwent postdelivery examinations including a DXA scan. There were no significant differences in changes in measured biomarkers between the probiotic versus the placebo group. No differences were found in newborn body composition or GLP-1 and glucagon. GLP-1 measured in umbilical blood samples was positively correlated to fat percent in offspring from the probiotic group. ConclusionIn this study of pregnant women with obesity and their newborns, there was no effect of probiotic supplementation in mothers or babies on metabolic or inflammatory biomarkers or on body composition of offspring.This study was registered at clinicaltrials.gov as NCT02508844.

What Do Your Neighbors Think About You? How Perceived Neighbor Attitudes Toward Latinos Influence Mental Health Among a Pregnant Latina Cohort

Latina women living in the USA experience disproportionately higher rates of psychological distress compared to their non-Latina White counterparts. Poor maternal mental health during pregnancy can contribute to intergenerational mental health disparities. Through this pathway, mothers’ experiences, environments, and exposures (henceforth “exposures”) during pregnancy become biologically embodied and can negatively affect the fetus and life-long developmental trajectories of her child. One of the exposures that can affect mother–offspring dyads is the neighborhood. With the goal of integrating anthropological and sociological theories to explain mental health disparities among pregnant Latina women, we explored how perceptions of neighbor attitudes may influence mental health during pregnancy. We analyzed self-reported responses from 239 pregnant Latina women in Southern California (131 foreign-born, 108 US-born) on their mental health and perceived attitudes of their neighbors using multiple linear regression models. Among foreign-born Latina women, living in neighborhoods with more favorable views of Latinos was associated with lower depression scores (pooled β = − .70, SE = .29, p = .019) and lower pregnancy-related anxiety scores (pooled β = − .11, SE = .05, p = .021), but greater state anxiety scores (pooled β = .09, SE = .04, p = .021). Among US-born women, there were no associations between neighbor attitudes and mental health. Overall, results suggest that social environments are correlated with mental health and that foreign-born and US-born Latinas have varied mental health experiences in the USA. Our findings highlight the importance of improving aspects of neighborhood cohesion as part of maternal–fetal care management.

Mother’s Age and Social Integration Modulate Sex-biased Maternal Investment in Wild Spider Monkeys (Ateles geoffroyi)

In many mammal species, mothers are crucial for the survival and development of young offspring. In primates, maternal investment may ensure immatures’ survival and also foster their social integration in the group, providing long-term fitness benefits. In this study, we analysed maternal investment in a wild group (N = 49) of male philopatric spider monkeys (Ateles geoffroyi). We assessed whether maternal investment is biased toward sons (compared with daughters) and which factors modulate this relation. We studied 20 mother–offspring dyads, measuring the time mothers spent in body contact, nursing, carrying, grooming, and playing with their offspring, for a total of 359 focal samples from February to July 2022. We then ran generalized linear mixed models to assess how these responses varied depending on the two-way interactions of offspring sex with offspring age, maternal age, and maternal centrality. Our results showed that mothers were more likely to nurse, carry, and have body contact with younger than older offspring, regardless of their sex. However, we also found that mothers invested more in male than female offspring; differences were mediated by mothers’ age and social integration in the group. Older mothers, in particular, were more likely to carry sons than daughters, whereas the contrary was true for younger mothers. Moreover, socially more central mothers were more likely to be in body contact with sons than daughters. Overall, our study shows that some maternal behaviours are sex-biased in male-philopatric species, although maternal experience and social integration may modulate this relation.

Can maternal postpartum testosterone and estradiol retrospectively predict the offspring's sex at birth? A cross-sectional study in Ghana.

The selection of X- or Y-bearing spermatozoa during fertilization may depend on maternal circulating sex hormones. The zona pellucida of the developing oocyte is adapted to be selective for the Y-bearing spermatozoa when maternal circulating androgens are relatively high. This study sought to determine whether maternal postpartum testosterone and estradiol can retrospectively predict the offspring sex at birth. The study was cross-sectional from December 2020 to April 2021 at the Reproductive and Child Health unit in Tamale. The participants were part of a previous study and comprised 178 mother-offspring dyads (mother-daughter = 90, mother-son = 88). The mothers were between the ages of 18 and 35 years and had a median (interquartile range-IQR) postpartum interval of 111 (60-187) days. A single venous blood sample was drawn from the mothers between 8.00 am and 12.00 pm local time on each day to reduce diurnal variation. Postpartum serum estradiol, testosterone, and sex hormone-binding globulin were assayed using the ELISA technique. The serum total testosterone and the testosterone-to-estradiol ratio (TT: E2 ) were higher in mothers with sons while estradiol was higher in mothers with daughters (p < 0.050). The total testosterone and TT: E2 did not markedly differ by their area under the curve (AUC: 0.91 and 0.99, respectively) but both were higher than the AUC of estradiol (0.72). The Sensitivity was 97.7%, 97.7%, and 94.5% and specificity, 88.9%, 40.0%, and 95.5% at cutoff points of >1.659 nmol/L, ≤141.862 pmol/L, and > 31.5, respectively for total testosterone, estradiol, and TT: E2 . The maternal testosterone-to-estradiol ratio may be more predictive of offspring sex at birth than either testosterone or estradiol alone.

Chimpanzees communicate to coordinate a cultural practice.

Human culture thrives by virtue of communication, yet whether communication plays an influential role in the cultural lives of other animals remains understudied. Here, we investigated whether chimpanzees use communication to engage in a cultural practice by analysing grooming handclasp (GHC) interactions-a socio-cultural behaviour requiring interindividual coordination for successful execution. Previous accounts attributed GHC initiations to behavioural shaping, whereby the initiator physically moulds the partner's arm into the desired GHC posture. Using frame-by-frame analysis and matched-control methodology, we find that chimpanzees do not only shape their partner's posture (22%), but also use gestural communication to initiate GHC (44%), which requires an active and synchronized response from the partner. Moreover, in a third (34%) of the GHC initiations, the requisite coordination was achieved by seemingly effortless synchrony. Lastly, using a longitudinal approach, we find that for GHC initiations, communication occurs more frequently than shaping in experienced dyads and less in mother-offspring dyads. These findings are consistent with ontogenetic ritualization, thereby reflecting first documentation of chimpanzees communicating to coordinate a cultural practice. We conclude that chimpanzees show interactional flexibility in the socio-cultural domain, opening the possibility that the interplay between communication and culture is rooted in our deep evolutionary history.

Nontargeted metabolomics reveals the potential mechanism underlying the association between birthweight and metabolic disturbances

AimsThe aim of this study was to characterize the metabolites associated with small- and large-gestational-age newborns in maternal and cord blood, and to investigate potential mechanisms underlying the association between birthweight and metabolic disturbances.Research design and methodsWe recorded detailed anthropometric data of mother-offspring dyads. Untargeted metabolomic assays were performed on 67 pairs of cord blood and maternal fasting plasma samples including 16 pairs of small-for-gestational (SGA, < 10th percentile) dyads, 28 pairs of appropriate-for-gestational (AGA, approximate 50 percentile) dyads, and 23 pairs of large-for-gestational (LGA, > 90th percentile) dyads. The association of metabolites with newborn birthweight was conducted to screen for metabolites with U-shaped and line-shaped distributions. The association of metabolites with maternal and fetal phenotypes was also performed.ResultsWe found 2 types of metabolites that changed in different patterns according to newborn birthweight. One type of metabolite exhibited a “U-shaped” trend of abundance fluctuation in the SGA-AGA-LGA groups. The results demonstrated that cuminaldehyde level was lower in the SGA and LGA groups, and its abundance in cord blood was negatively correlated with maternal BMI (r = -0.352 p = 0.009) and weight gain (r = -0.267 p = 0.043). 2-Methoxy-estradiol-17b 3-glucuronide, which showed enrichment in the SGA and LGA groups, was positively correlated with homocysteine (r = 0.44, p < 0.001) and free fatty acid (r = 0.42, p < 0.001) in maternal blood. Serotonin and 13(S)-HODE were the second type of metabolites, denoted as “line-shaped”, which both showed increasing trends in the SGA-AGA-LGA groups in both maternal and cord blood and were both significantly positively correlated with maternal BMI before pregnancy. Moreover, cuminaldehyde, serotonin, 13(S)-HODE and some lipid metabolites showed a strong correlation between maternal and cord blood.ConclusionsThese investigations demonstrate broad-scale metabolomic differences associated with newborn birthweight in both pregnant women and their newborns. The U-shaped metabolites associated with both the SGA and LGA groups might explain the U-shaped association between birthweight and metabolic dysregulation. The line-shaped metabolites might participate in intrauterine growth regulation. These observations might help to provide new insights into the insulin resistance and the risk of metabolic disturbance of SGA and LGA babies in adulthood and might identify potential new markers for adverse newborn outcomes in pregnant women.

A Prospective Cohort Study on the Intergenerational Transmission of Childhood Adversity and Subsequent Risk of Psychotic Experiences in Adolescence.

Previous studies have shown a robust relationship between childhood adversity and subsequent psychotic symptoms. However, the role of familial risk factors underlying this relationship remains largely unclear. Here, we tested whether offspring childhood adversity and postnatal maternal psychopathology mediated the relationship between maternal childhood adversity and offspring psychotic experiences. N = 3068 mother-offspring dyads were included. Maternal history of childhood adversity was retrospectively assessed using the Childhood Trauma Questionnaire during pregnancy. Maternal psychopathology was assessed during and after pregnancy. Twenty-four offspring childhood adversities were assessed by maternal interview when the child was 10 years old. Offspring psychotic experiences were examined using self-report at 14 years. Structural equation mediation models were conducted to explore whether maternal postnatal psychopathology and offspring childhood adversities sequentially mediated the relationship between maternal childhood adversity and offspring psychotic experiences. Analyses were adjusted for sociodemographic confounders. Maternal history of childhood adversity was associated with offspring childhood adversities (β = 0.12, 95% CI: 0.09 to 0.16). Offspring childhood adversity mediated the association of maternal childhood adversity with offspring hallucinations (βindirect effect = 0.008, 95% CI: 0.002 to 0.014, proportion mediated = 16.3%) and delusions (βindirect effect = 0.006, 95% CI: 0.000 to 0.012, proportion mediated = 13.1%). Intergenerational transmission of childhood adversity can be considered of relevance in the etiology of psychosis vulnerability and can potentially serve as a modifiable risk factor.

Intergenerational continuity of parent-child separation among mother-offspring dyads: Implication for child cognitive development in rural China

The labor migration in China often leads to parent-child separation. Research to date has primarily focused on understanding mental and cognitive outcomes for children exposed to parent-child separation, with little consideration for the cumulative effects of intergenerational continuity of parent-child separation. A total of 2729 children between the ages of 4 and 6, along with one parent (primarily mothers, 86.2%) and/or one primary caregiver (if the child is separated from both parents), were recruited in the rural area of Anhui Province, China. A unique subsample of children (n = 249) with persistent experience of parent-child separation or whose mother reported being left behind by her parents during early childhood were enrolled for cognitive assessment. A total of 239 age-, gender- and residence-matched children without any parent-child separation experience were selected as the control group. Child cognitive performance was examined with the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence, Fourth edition (WPPSI-IV). The association between intergenerational continuity of parent-child separation and child cognition was described using multivariate OLS regression models. Compared to mother-offspring dyads without any history of parent-child separation, girls (n = 236/450, 52.4%) who experienced the intergenerational continuity of parent-child separation showed a significant decrease of 5.73 points (95% CI: −9.83, −1.62; p = 0.006) on full-scale intelligence quotient (FSIQ) and a decrease of 5.71 points (95% CI: −9.80, 1.63; p = 0.006) on verbal comprehension index. No similar result was observed in boys. The cumulative effects of parent-child separation among mother-offspring dyads on child cognitive development highlight the need for effective early intervention to break the intergenerational cycle of disadvantage. Sex differences and possible epigenetic mechanisms underlying the intergenerational effects of parent-child separation warrant further investigation.

Bridging differences across cohorts in the relationship between prenatal secondhand smoke exposure and birth weight: Transportability of effect estimates in the ECHO consortium

Background and Aim: Transportability of effect estimates in epidemiology can potentially help investigators explain the differences in effect estimates for the same exposure-outcome relationships observed across different cohorts. In this study we aim to explain potential differences in the relationship between prenatal secondhand smoke exposure (SHS) and birth weight across different cohorts of the Environmental influences on Child Health Outcomes (ECHO) consortium that may be due to population differences in sociodemographic characteristics. Methods: We assessed transportability of effect estimates across 5 different cohorts in the ECHO consortium consisting of 6582 mother-offspring dyads. We first estimated individual cohort effects using Targeted Maximum Likelihood Estimation adjusting for several sociodemographic covariates. We then proceeded to estimate transported effects from one cohort to each of the remaining cohorts using a robust non-parametric estimation approach. We compared the transported effect estimates to the original effect estimates for these cohorts with any decrease in differences between cohort-specific estimates potentially attributable to different sociodemographic variable distributions. Results: Individual cohort effects associated with SHS exposure varied across the 5 cohorts with a range of strongly suggestive results for harmful effects of exposure (149.0 gram decrease in birthweight (95% confidence interval (CI): -254.4, -43.5), to results on the protective side of the null albeit with very wide confidence intervals. Transported effect estimates partially explained differences in 3 out of the 4 cohort pairs, explaining 7% to 97% of the differences in the effect point estimates. Conclusion: Differences in sociodemographic characteristics across different populations may partially explain differences observed in the relationship between prenatal SHS exposure and birth weight across cohorts in the ECHO consortium. This framework could have broader implications in in multi-cohort consortiums by aiding in the comparability of cross-cohort results. Keywords: transportability, causal inference, machine learning, secondhand smoke, birth outcomes

Population-based plasma lipidomics reveals developmental changes in metabolism and signatures of obesity risk: a mother-offspring cohort study

BackgroundLipids play a vital role in health and disease, but changes to their circulating levels and the link with obesity remain poorly characterized in expecting mothers and their offspring in early childhood.MethodsLC-MS/MS-based quantitation of 480 lipid species was performed on 2491 plasma samples collected at 4 time points in the mother-offspring Asian cohort GUSTO (Growing Up in Singapore Towards healthy Outcomes). These 4 time points constituted samples collected from mothers at 26–28 weeks of gestation (n=752) and 4–5 years postpartum (n=650), and their offspring at birth (n=751) and 6 years of age (n=338). Linear regression models were used to identify the pregnancy and developmental age-specific variations in the plasma lipidomic profiles, and their association with obesity risk. An independent birth cohort (n=1935), the Barwon Infant Study (BIS), comprising mother-offspring dyads of Caucasian origin was used for validation.ResultsLevels of 36% of the profiled lipids were significantly higher (absolute fold change > 1.5 and Padj < 0.05) in antenatal maternal circulation as compared to the postnatal phase, with phosphatidylethanolamine levels changing the most. Compared to antenatal maternal lipids, cord blood showed lower concentrations of most lipid species (79%) except lysophospholipids and acylcarnitines. Changes in lipid concentrations from birth to 6 years of age were much higher in magnitude (log2FC=−2.10 to 6.25) than the changes observed between a 6-year-old child and an adult (postnatal mother) (log2FC=−0.68 to 1.18). Associations of cord blood lipidomic profiles with birth weight displayed distinct trends compared to the lipidomic profiles associated with child BMI at 6 years. Comparison of the results between the child and adult BMI identified similarities in association with consistent trends (R2=0.75). However, large number of lipids were associated with BMI in adults (67%) compared to the children (29%). Pre-pregnancy BMI was specifically associated with decrease in the levels of phospholipids, sphingomyelin, and several triacylglycerol species in pregnancy.ConclusionsIn summary, our study provides a detailed landscape of the in utero lipid environment provided by the gestating mother to the growing fetus, and the magnitude of changes in plasma lipidomic profiles from birth to early childhood. We identified the effects of adiposity on the circulating lipid levels in pregnant and non-pregnant women as well as offspring at birth and at 6 years of age. Additionally, the pediatric vs maternal overlap of the circulating lipid phenotype of obesity risk provides intergenerational insights and early opportunities to track and intervene the onset of metabolic adversities.Clinical trial registrationThis birth cohort is a prospective observational study, which was registered on 1 July 2010 under the identifier NCT01174875.

Associations of maternal and foetoplacental factors with prehypertension/hypertension in early childhood.

To evaluate whether characterization of maternal and foetoplacental factors beyond birthweight can enable early identification of children at risk of developing prehypertension/hypertension. We recruited 693 mother-offspring dyads from the GUSTO prospective mother-offspring cohort. Prehypertension/hypertension at age 6 years was identified using the simplified paediatric threshold of 110/70 mmHg. We evaluated the associations of pregnancy complications (gestational diabetes, excessive/inadequate gestational weight gain, hypertensive disorders of pregnancy), foetal growth deceleration (decline in foetal abdominal circumference at least 0.67 standard deviations between second and third trimesters), high foetoplacental vascular resistance (third trimester umbilical artery systolic-to-diastolic ratio ≥90th centile), preterm birth, small-for-gestational age and neonatal kidney volumes with risk of prehypertension/hypertension at age 6 years, after adjusting for sex, ethnicity, maternal education and prepregnancy BMI. Pregnancy complications, small-for-gestational age, preterm birth, and low neonatal kidney volume were not associated with an increased risk of prehypertension/hypertension at age 6 years. In contrast, foetal growth deceleration was associated with a 72% higher risk [risk ratio (RR) = 1.72, 95% confidence interval (CI) 1.18-2.52]. High foetoplacental vascular resistance was associated with a 58% higher risk (RR = 1.58, 95% CI 0.96-2.62). Having both these characteristics, relative to having neither, was associated with over two-fold higher risk (RR = 2.55, 95% CI 1.26-5.16). Over 85% of the foetuses with either of these characteristics were born appropriate or large for gestational age. Foetal growth deceleration and high foetoplacental vascular resistance may be helpful in prioritizing high-risk children for regular blood pressure monitoring and preventive interventions, across the birthweight spectrum.

Association Between Screen Time Trajectory and Early Childhood Development in Children in China

Screen time has become an integral part of children's daily lives. Nevertheless, the developmental consequences of screen exposure in young children remain unclear. To investigate the screen time trajectory from 6 to 72 months of age and its association with children's development at age 72 months in a prospective birth cohort. Women in Shanghai, China, who were at 34 to 36 gestational weeks and had an expected delivery date between May 2012 and July 2013 were recruited for this cohort study. Their children were followed up at 6, 9, 12, 18, 24, 36, 48, and 72 months of age. Children's screen time was classified into 3 groups at age 6 months: continued low (ie, stable amount of screen time), late increasing (ie, sharp increase in screen time at age 36 months), and early increasing (ie, large amount of screen time in early stages that remained stable after age 36 months). Cognitive development was assessed by specially trained research staff in a research clinic. Of 262 eligible mother-offspring pairs, 152 dyads had complete data regarding all variables of interest and were included in the analyses. Data were analyzed from September 2019 to November 2021. Mothers reported screen times of children at 6, 9, 12, 18, 24, 36, 48, and 72 months of age. The cognitive development of children was evaluated using the Wechsler Intelligence Scale for Children, 4th edition, at age 72 months. Social-emotional development was measured by the Strengths and Difficulties Questionnaire, which was completed by the child's mother. The study described demographic characteristics, maternal mental health, child's temperament at age 6 months, and mental development at age 12 months by subgroups clustered by a group-based trajectory model. Group difference was examined by analysis of variance. A total of 152 mother-offspring dyads were included in this study, including 77 girls (50.7%) and 75 boys (49.3%) (mean [SD] age of the mothers was 29.7 [3.3] years). Children's screen time trajectory from age 6 to 72 months was classified into 3 groups: continued low (110 [72.4%]), late increasing (17 [11.2%]), and early increasing (25 [16.4%]). Compared with the continued low group, the late increasing group had lower scores on the Full-Scale Intelligence Quotient (β coefficient, -8.23; 95% CI, -15.16 to -1.30; P < .05) and the General Ability Index (β coefficient, -6.42; 95% CI, -13.70 to 0.86; P = .08); the early increasing group presented with lower scores on the Full-Scale Intelligence Quotient (β coefficient, -6.68; 95% CI, -12.35 to -1.02; P < .05) and the Cognitive Proficiency Index (β coefficient, -10.56; 95% CI, -17.23 to -3.90; P < .01) and a higher total difficulties score (β coefficient, 2.62; 95% CI, 0.49-4.76; P < .05). This cohort study found that excessive screen time in early years was associated with poor cognitive and social-emotional development. This finding may be helpful in encouraging awareness among parents of the importance of onset and duration of children's screen time.