Fetal overgrowth and weight trajectories during infancy and adiposity in early childhood.

BACKGROUND: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood. Little is known about how infancy growth trajectories affect adiposity in early childhood in LGA. METHODS: In the Shanghai Birth Cohort, we followed up 259 LGA (birth weight >90th percentile) and 1673 appropriate-for-gestational age (AGA, 10th-90th percentiles) children on body composition (by InBody 770) at age 4 years. Adiposity outcomes include body fat mass (BFM), percent body fat (PBF), body mass index (BMI), overweight/obesity, and high adiposity (PBF >85th percentile). RESULTS: Three weight growth trajectories (low, mid, and high) during infancy (0-2 years) were identified in AGA and LGA subjects separately. BFM, PBF and BMI were progressively higher from low- to mid-to high-growth trajectories in both AGA and LGA children. Compared to the mid-growth trajectory, the high-growth trajectory was associated with greater increases in BFM and the odds of overweight/obesity or high adiposity in LGA than in AGA children (tests for interactions, all P < 0.05). CONCLUSIONS: Weight trajectories during infancy affect adiposity in early childhood regardless of LGA or not. The study is the first to demonstrate that high-growth weight trajectory during infancy has a greater impact on adiposity in early childhood in LGA than in AGA subjects. IMPACT: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood, but little is known about how weight trajectories during infancy affect adiposity during early childhood in LGA subjects. The study is the first to demonstrate a greater impact of high-growth weight trajectory during infancy (0-2 years) on adiposity in early childhood (at age 4 years) in subjects with fetal overgrowth (LGA) than in those with normal birth size (appropriate-for-gestational age). Weight trajectory monitoring may be a valuable tool in identifying high-risk LGA children for close follow-ups and interventions to decrease the risk of obesity.

Cord blood fatty acid binding protein 4 and lipids in infants born small- or large-for-gestational-age.

Aim: Adverse (poor or excessive) fetal growth "programs" an elevated risk of type 2 diabetes. Fatty acid binding protein 4 (FABP4) has been implicated in regulating insulin sensitivity and lipid metabolism relevant to fetal growth. We sought to determine whether FABP4 is associated with poor or excessive fetal growth and fetal lipids. Methods: In a nested case-control study in the Shanghai Birth Cohort including 60 trios of small-for-gestational-age (SGA, an indicator of poor fetal growth), large-for-gestational-age (LGA, an indicator of excessive fetal growth) and optimal-for-gestational-age (OGA, control) infants, we measured cord blood concentrations of FABP4 and lipids [high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterols, triglycerides (TG)]. Results: Adjusting for maternal and neonatal characteristics, higher cord blood FABP4 concentrations were associated with a lower odds of SGA [OR = 0.29 (0.11-0.77) per log unit increment in FABP4, P = 0.01], but were not associated with LGA (P = 0.46). Cord blood FABP4 was positively correlated with both LDL (r = 0.29, P = 0.025) and HDL (r = 0.33, P = 0.01) in LGA infants only. Conclusion: FABP4 was inversely associated with the risk of SGA. The study is the first to demonstrate LGA-specific positive correlations of cord blood FABP4 with HDL and LDL cholesterols, suggesting a role of FABP4 in fetal lipid metabolism in subjects with excessive fetal growth.

Genome-Wide Placental Gene Methylations in Gestational Diabetes Mellitus, Fetal Growth and Metabolic Health Biomarkers in Cord Blood.

Gestational diabetes mellitus (GDM) "program" an elevated risk of metabolic syndrome in the offspring. Epigenetic alterations are a suspected mechanism. GDM has been associated with placental DNA methylation changes in some epigenome-wide association studies. It remains unclear which genes or pathways are affected, and whether any placental differential gene methylations are correlated to fetal growth or circulating metabolic health biomarkers. In an epigenome-wide association study using the Infinium MethylationEPIC Beadchip, we sought to identify genome-wide placental differentially methylated genes and enriched pathways in GDM, and to assess the correlations with fetal growth and metabolic health biomarkers in cord blood. The study samples were 30 pairs of term placentas in GDM vs. euglycemic pregnancies (controls) matched by infant sex and gestational age at delivery in the Shanghai Birth Cohort. Cord blood metabolic health biomarkers included insulin, C-peptide, proinsulin, IGF-I, IGF-II, leptin and adiponectin. Adjusting for maternal age, pre-pregnancy BMI, parity, mode of delivery and placental cell type heterogeneity, 256 differentially methylated positions (DMPs,130 hypermethylated and 126 hypomethylated) were detected between GDM and control groups accounting for multiple tests with false discovery rate <0.05 and beta-value difference >0.05. WSCD2 was identified as a differentially methylated gene in both site- and region-level analyses. We validated 7 hypermethylated (CYP1A2, GFRA1, HDAC4, LIMS2, NAV3, PAX6, UPK1B) and 10 hypomethylated (DPP10, CPLX1, CSMD2, GPR133, NRXN1, PCSK9, PENK, PRDM16, PTPRN2, TNXB) genes reported in previous epigenome-wide association studies. We did not find any enriched pathway accounting for multiple tests. DMPs in 11 genes (CYP2D7P1, PCDHB15, ERG, SIRPB1, DKK2, RAPGEF5, CACNA2D4, PCSK9, TSNARE1, CADM2, KCNAB2) were correlated with birth weight (z score) accounting for multiple tests. There were no significant correlations between placental gene methylations and cord blood biomarkers. In conclusions, GDM was associated with DNA methylation changes in a number of placental genes, but these placental gene methylations were uncorrelated to the observed metabolic health biomarkers (fetal growth factors, leptin and adiponectin) in cord blood. We validated 17 differentially methylated placental genes in GDM, and identified 11 differentially methylated genes relevant to fetal growth.

Effectiveness of Online-Delivered Project ImPACT for Children With ASD and Their Parents: A Pilot Study During the COVID-19 Pandemic.

Objective: During the COVID-19 pandemic, face-to-face intervention services for families of children with autism spectrum disorder (ASD) were limited. This study aimed to evaluate the effectiveness of an 8-week, online-delivered Project ImPACT program for children with ASD and their parents in China during the COVID-19 pandemic. Methods: A pilot non-randomized study with a waitlist control group was conducted in 68 children with ASD and their parents in the Department of Developmental and Behavioral Pediatrics between April 15, 2020 and March 19, 2021. Participants were allocated to either the intervention (IG) or the waitlist group (WLG) according to their order of recruitment. Parents in the IG immediately received 8 weeks of the online-delivered Project ImPACT program, and the WLG received the same program with a delay when the IG had completed all sessions. Participants in both groups received treatment as usual during the research period. Results: The online-delivered Project ImPACT program significantly improved the parent-reported social communication skills of children with ASD. Furthermore, parent's involvement in the training program produced a collateral reduction in parenting stress and an increase in perceived competence in the parental role. Parents rated the program acceptable in terms of curriculum schedule, session content, homework assignments, and therapist feedback. Conclusions: The 8-week, online-delivered Project ImPACT program is a feasible and effective social skill training program for families of children with ASD in China during the COVID-19 pandemic. Due to the methodological limitations, randomized controlled studies with larger sample sizes are suggested to provide more solid evidence.

Psychological distress in parents of children with autism spectrum disorder: A cross-sectional study based on 683 mother-father dyads.

PURPOSE: This study aimed to assess psychological distress and its gender difference in parents of children with ASD. Predictive factors for parental psychological distress and interaction effects between parents were also explored. DESIGN AND METHODS: A cross-sectional study was conducted for parents of children with ASD and 683 mother-father dyads were included in the analyses. RESULTS: Mothers of children with severe autistic symptoms reported significantly higher levels of stress, anxiety, and depression than fathers. The prevalence of moderate-to-severe anxiety and depression for mothers was 13.8% and 13.1%, respectively. The corresponding prevalence for fathers was 9.9% and 8.0%, respectively. A college education or above protected against maternal stress and an only child predicted paternal stress. Child social impairment predicted maternal but not paternal psychological distress. Stress was a significant predictor of anxiety and depression for both parents. Paternal stress and anxiety moderated the relationship between child's social impairment and maternal stress, and paternal anxiety moderated the relationship between child's social impairment and maternal depression. CONCLUSIONS: The gender difference in the parental psychological distress depends on the severity of children's autistic symptoms. Child social impairment exerts significant effects on mothers' psychological distress and parental stress contributes to anxiety and depression for both parents. The psychological distress of fathers moderates the relationship between child social impairment and maternal psychological distress. IMPLICATIONS: Health-care professionals should pay special attention to parents who are susceptible to psychological distress. Social skill interventions for children and stress reduction programs for parents are recommended to promote parental psychological well-being.