Macrosomia and Childhood Growth Trajectories From Birth to 10 Years of Age: Findings From the ROLO Longitudinal Birth Cohort Study

Purpose: Obesity often aggregates within families and parental obesity has been identified as a risk factor. To examine the different effects of maternal and paternal body mass index on the prevalence rate and risk of overweight in children. Materials and Methods: A total of 1418 students, aged 12 or 13 years, were recruited for analysis. Children's body height, weight and waist and hip circumferences were obtained. Self-reported body height and weight of their parents were collected. The 85th percentile of body mass index (BMI) was used as cutoff points to identify the children being overweight. Spearman's correlation and logistic regression analysis were used to examine the parent-offspring BMI relationship. Paternal and maternal BMI were classified into four groups using the quartile categories to examine their different effects on the prevalence rate and risk of children overweight. Results: The association of children's BMI with parents' BMI was the strongest, closely followed by children's waist circumference whereas waist-hip ratio barely had any association. The Spearman's correlation coefficient of the mother-daughter association was the highest among all the parent-offspring association. Among the boys, the prevalence rate for being overweight increased significantly from 9.2% in the lowest quartile to 21.3% in the highest quartile of paternal BMI (p trend＜0.005). The effect of maternal BMI on the prevalence rate for being overweight was also noted (p trend＜0.0001). Among the girls, an increasing rate of being overweight for the increasing quartile of paternal and maternal BMI was also noted (p trend＜0.0001). Multiple logistic regression analysis revealed that maternal BMI was significantly associated with boys' overweight with the odds ratios increased from 1.0 in the lowest quartile to 2.33 in the highest quartile of maternal BMI (p＜0.001). However, the association between paternal BMI and boys' overweight was marginally significant (p=0.055). Among the girls, both maternal and paternal BMI were significantly associated with girls' overweight (p＜0.001 and p=0.001, respectively). Conclusion: Maternal BMI was an independent risk factor of overweight in both boys and girls. Paternal BMI was also associated with girls' overweight.

Prenatal exposure to phthalates and child growth trajectories in the first 24 months of life

While prenatal nutrition and maternal obesity are recognized as important contributors to epigenetic changes and childhood obesity, the role of paternal obesity in the epigenome of offspring has not been well studied. To test whether periconception paternal body mass index (BMI) is associated with DNA methylation patterns in newborns, to examine associations between maternal and paternal BMI and the epigenome of offspring, and to examine persistence of epigenetic marks at ages 3 and 7 years. Project Viva is a prebirth cohort study of mothers and children including 2128 live births that enrolled mothers from April 1999 to July 2002 and followed offspring to adolescence. This study analyzed the subset of participants with available data on paternal BMI and DNA methylation in offspring blood in the newborn period, at age 3 years, and at age 7 years. Data were analyzed from July 2017 to October 2019. The primary exposure was paternal periconception BMI; associations were adjusted for maternal prepregnancy BMI and stratified according to maternal BMI above or below 25. The primary outcome was genome-wide DNA methylation patterns in offspring blood collected at birth, age 3 years, and age 7 years. A total of 429 father-mother-infant triads were included. The mean (SD) periconception paternal BMI was 26.4 (4.0) and mean maternal prepregnancy BMI was 24.5 (5.2); 268 fathers had BMI greater than or equal to 25 (mean [SD], 28.5 [3.3]) and 161 had BMI less than 25 (mean [SD], 22.8 [1.8]). Paternal BMI greater than or equal to 25 was associated with increased offspring birth weight compared with paternal BMI less than 25 (mean [SD] z score, 0.38 [0.91] vs 0.11 [0.96]; P = .004). Cord blood DNA methylation at 9 CpG sites was associated with paternal BMI independent of maternal BMI (q < .05). Methylation at cg04763273, between TFAP2C and BMP7, decreased by 5% in cord blood with every 1-unit increase in paternal BMI (P = 3.13 × 10-8); hypomethylation at this site persisted at ages 3 years and 7 years. Paternal BMI was associated with methylation at cg01029450 in the promoter region of the ARFGAP3 gene; methylation at this site was also associated with lower infant birth weight (β = -0.0003; SD = 0.0001; P = .03) and with higher BMI z score at age 3 years. In this study, paternal BMI was associated with DNA methylation, birth weight, and childhood BMI z score in offspring.

To examine the association between parental body mass index (BMI) and their offspring's body composition, physical fitness and lifestyle factors (that is, sedentary time, physical activity and diet). A total of 307 preschoolers (4.5±0.1 years) and their parents (fathers: 38.1±5.1 years and mothers: 35.6±4.2 years) participated in this study. Parental BMI was calculated using self-reported weight and height. Preschoolers body composition was assessed using: BMI, fat mass percentage, fat mass index, fat-free mass index (measured via air-displacement plethysmography) and waist circumference. Physical fitness was assessed by the PREFIT fitness battery. Lifestyle factors were assessed using the ActiGraph wGT3x-BT (sedentary time and physical activity), and the mobile-phone based tool for energy balance in children (diet). Parental BMI were positively associated with their offspring's BMI (paternal BMI: standardised beta, β=0.233, P<0.001; maternal BMI: β=0.186, P=0.001), fat mass index (paternal BMI: β=0.130, P=0.026; maternal BMI: β=0.163, P=0.005), fat-free mass index (paternal BMI: β=0.214, P<0.001; maternal BMI: β=0.119, P=0.036) and waist circumference (paternal BMI: β=0.178, P=0.001; maternal BMI: β=0.179, P=0.001). A negative association was found between maternal BMI and their offspring's standing long jump test (β=-0.132, P=0.022). Paternal BMI was associated with their offspring's sedentary time (β=0.100, P=0.026), whereas parental BMI was not associated with neither physical activity nor diet (all P⩾0.104). Parental BMI was positively associated with their offspring's BMI, fat as well as fat-free mass index and waist circumference. Moreover, a higher paternal and maternal BMI were related to higher levels of sedentary time and a lower performance in the standing long jump test of their offspring, respectively.

ObjectiveTo explore the associations of maternal smoking during pregnancy with offspring trajectories of height, weight and adiposity and to compare these with associations with paternal smoking to determine whether any...

Multigenerational smoking during pregnancy and risk of stillbirth: a population-based 3-generation cohort study.

High early pregnancy body mass index is associated with alterations in first- and second-trimester angiogenic biomarkers

Identifying prenatal environmental factors that have genuinely causal effects on psychopathology is an important research priority, but it is crucial to select an appropriate research design. In this review we explain why and what sorts of designs are preferable and focus on genetically informed/sensitive designs. In the field of developmental psychopathology, causal inferences about prenatal risks have not always been based on evidence generated from appropriate designs. We focus on reported links between maternal smoking during pregnancy and offspring attention-deficit/hyperactivity disorder or conduct problems. Undertaking a systematic review of findings from genetically informed designs and "triangulating" evidence from studies with different patterns of bias, we conclude that at present findings suggest it is unlikely that there is a substantial causal effect of maternal smoking in pregnancy on either attention-deficit/hyperactivity disorder or conduct problems. In contrast, for offspring birth weight (which serves as a positive control) findings strongly support a negative causal effect of maternal smoking in pregnancy. For maternal pregnancy stress, too few studies use genetically sensitive designs to draw firm conclusions, but continuity with postnatal stress seems important. We highlight the importance of moving beyond observational designs, for systematic evaluation of the breadth of available evidence and choosing innovative designs. We conclude that a broader set of prenatal risk factors should be examined, including those relevant in low- and middle-income contexts. Future directions include a greater use of molecular genetically informed designs such as Mendelian randomization to test causal hypotheses about prenatal exposure and offspring outcome.

Background/ObjectivePrevious studies have consistently demonstrated that maternal weight status both before and during pregnancy is associated with infant birthweight. However, a fundamental limitation across this literature remains that previous studies have not evaluated the concomitant impact of paternal weight at conception, owing to the paucity of studies in which fathers were assessed prior to pregnancy. Thus, we established a cohort of preconception couples to prospectively evaluate the associations of maternal and paternal weight prior to pregnancy with infant birthweight at delivery.MethodsIn this prospective observational cohort study, 1292 newly-married women and their partners in Liuyang, China, were assessed at median of 23.3 weeks before a singleton pregnancy, thereby enabling concomitant assessment of preconception maternal and paternal body mass index (BMI) in relation to infant birthweight.ResultsMean birthweight was 3294 ± 450 g with 147 neonates (11.4%) born large-for-gestational-age (LGA) and 94 (7.3%) small-for-gestational-age (SGA). After adjustment for maternal and paternal factors prior to conception (age, education, smoking, BMI, household income), length of gestation, total gestational weight gain, gestational diabetes, preeclampsia, and infant sex, it was noted that infant birthweight increased by 42.2 g (95% CI 29.5–54.8; p < 0.0001) per unit increase in maternal pregravid BMI and 10.7 g (95% CI 0.5–20.9; p = 0.04) per unit increase in paternal pregravid BMI. Maternal pregravid BMI explained 6.2% of the variance in birthweight whereas paternal BMI explained only 0.7%. Independent predictors of LGA delivery were maternal pregravid BMI (aOR = 1.91, 95% CI 1.50–2.44), maternal age (aOR = 1.48, 95% CI 1.09–2.00), and gestational weight gain (aOR = 1.80, 95% CI 1.40–2.30). Paternal pregravid BMI was not independently associated with LGA or SGA.ConclusionPaternal BMI prior to conception is associated with infant birthweight but only modestly so, in contrast to the dominant impact of maternal weight.

Explore associations between modifiable maternal pregnancy exposures: pre-pregnancy body mass index (BMI), pregnancy smoking and alcohol consumption with offspring molar-incisor hypomineralisation (MIH) and use negative control analyses to explore for the presence of confounding. Using data from a prospective UK birth cohort, Avon Longitudinal Study of Parents and Children, we performed logistic regression to explore confounder adjusted associations between maternal pre-pregnancy BMI and smoking and alcohol consumption during pregnancy with MIH. We compared these with negative control exposure (paternal BMI, smoking and alcohol) and outcome (offspring dental trauma) analyses. 5,536 mother/offspring pairs were included (297 (5.4%) MIH cases). We found a weak, positive association between maternal mean BMI and offspring MIH (Odds Ratio (OR) per 1-kg/m2 difference in BMI: 1.04, 95% confidence interval (CI): 1.00, 1.08). Results of subsequent analyses suggested this effect was non-linear and being driven by women in the highest BMI quintile (OR for women in the highest BMI quintile versus the lowest: 1.61 95%CI: 1.02, 2.60). Negative control analyses showed no evidence of an association between paternal BMI and offspring MIH (OR: 0.94, 95%CI: 0.89,1.00) and maternal BMI and offspring dental trauma (OR: 0.99, 95%CI: 0.96, 1.02). There was no clear evidence of an association for maternal smoking (OR: 0.76, 95%CI: 0.46,1.22) or alcohol consumption (OR: 0.79, 95%CI: 0.56, 1.21) with offspring MIH with results imprecisely estimated. We found a possible intrauterine effect for high maternal pre-pregnancy BMI on offspring MIH, but no robust evidence of an intrauterine effect for maternal pregnancy smoking or alcohol consumption. A key limitation includes possible misclassification of MIH. Replication of these results is warranted.

Parental body size and early weight and height growth velocities in their offspring

BackgroundThe association of low socioeconomic status (SES) with childhood and adolescent obesity has been reported. It is unknown whether low SES affects body mass index (BMI) growth trajectory in the first 12 mo of life. Moreover, accelerated growth as a compensatory mechanism for low birth weight (LBW) during infancy, is an important predictor of later obesity. The aim of the present study was to examine the association of low SES with infancy BMI growth rate and trajectory for LBW and normal birth weight (NBW) infants.MethodsFrom September 2012 to October 2014, a total of 387 infants in this longitudinal study was subjected to repeated measures of weight and length from birth to 12 mo in Hefei. Generalized growth mixture modeling was used to classify the infancy BMI growth trajectories. Differences in infancy BMI z score (zBMI) and BMI growth rate between low SES and high SES were estimated based on linear regression after adjusting for several confounders including maternal age, pregnancy BMI, physical activity during pregnancy, paternal BMI as well as alcohol use, paternal smoking status, breastfeeding duration and delivery mode.ResultsInfancy BMI trajectories in this study were classified into three categories: rapid growth (class 1), normal growth (class 2) and slow growth (class 3). Low SES infants had the higher zBMI than high SES infants for LBW group at age 6 mo [zBMI difference with 95% CI at 6 mo: 0.28(0.03, 0.53); at 12 mo: 0.21(0.01, 0.43)]. Low SES infants had more rapid zBMI growth rate than those with high SES for low birth weight between 0 and 6 months. Controlling for the confounders, these associations remained robust. We found the lower SES in the rapid growth group.ConclusionsThese findings highlighted the impact of low SES on increasing BMI and accelerated growth during early infancy. Health care and relatively optimal family environment in the first 12 mo of life, especially for LBW infants, are benefit to shape the better infancy growth trajectory.

Maternal obesity has been implicated in the origins of childhood obesity through a suboptimal environment in-utero. We examined relationships of maternal early pregnancy body mass index (BMI), overweight/obesity, and plasma biomarkers of obesity, inflammation, insulin resistance, and placental function with measures of childhood BMI and adiposity. BMI z-score, sum of skinfold thicknesses (SST), body fat percentage (BFP, by bioelectrical impedance), and waist, arm, and hip circumferences were measured in 1173 6-year-old children of nulliparous pregnant women in the Screening for Pregnancy Endpoints (SCOPE) study, New Zealand. Relationships of maternal early pregnancy (15weeks' gestation) BMI and biomarkers with these childhood anthropometric measures were assessed by linear regression, with appropriate adjustment. 28.1% of mothers were classified as overweight and 10.1% with obesity; compared with normal weight mothers, the BFP of their children were 5.3% higher (0.16 SD [95% CI, 0.04-0.29] p=.01) and 7.8% higher (0.27 [0.08-0.47] p=.006) with comparable values for BMI z-score and arm, waist, and hip circumferences. Early pregnancy maternal BMI and plasma placental growth factor (PlGF) were associated with higher child's SST, BMI z-score, hip circumference, and BFP. None of the metabolic or inflammatory maternal biomarkers were associated with childhood obesity. In this contemporary large prospective cohort study with extensive maternal/childhood phenotyping and a high prevalence of maternal overweight/obesity, we found independent relationships of maternal early pregnancy BMI with childhood BMI and adiposity; similar associations were observed with PlGF, which may imply a role for placenta function in the developmental programming of childhood obesity risk.

Maternal prepregnancy obesity is associated with impaired cardiometabolic health in offspring. Whether these associations reflect direct intrauterine causal mechanisms remains unclear. In a population-based prospective cohort study among 4871 mothers, fathers, and their children, we examined the associations of both maternal and paternal prepregnancy body mass index (BMI) with childhood body fat distribution and cardiometabolic outcomes and explored whether any association was explained by pregnancy, birth, and childhood factors. We measured childhood BMI, total body and abdominal fat distribution, blood pressure, and blood levels of lipids, insulin, and C-peptide at the age of 6 years. We observed that higher maternal and paternal prepregnancy BMI were associated with higher childhood BMI, total body and abdominal fat mass measures, systolic blood pressure, and insulin levels and lower high-density lipoprotein cholesterol levels ( P &lt;0.05). Stronger associations were present for maternal than paternal BMI, with statistical support for heterogeneity between these associations. The associations for childhood fat mass and cardiometabolic outcomes attenuated after adjustment for childhood current BMI. Compared with children from normal-weight mothers, those from obese mothers had increased risks of childhood overweight (odds ratio, 3.84 [95% confidence interval, 3.01–4.90]) and clustering of cardiometabolic risk factors (odds ratio, 3.00 [95% confidence interval, 2.09–4.34]). Smaller effect estimates for these outcomes were observed for paternal obesity. In conclusion, higher maternal and paternal prepregnancy BMI were associated with an adverse cardiometabolic profile in offspring, with stronger associations present for maternal prepregnancy BMI. These findings suggest that maternal prepregnancy BMI may influence the cardiometabolic health of offspring through direct intrauterine mechanisms.

To assess the effect of maternal age, height, early pregnancy body mass index (BMI) and ethnicity on birth weight. A cross-sectional study was conducted on more than 42,000 newborns. Ethnicity was defined by maternal country of birth or, when missing (<0.6% of records), by citizenship. The effect of maternal characteristics on birth weight was evaluated with general linear models. Maternal height and BMI, although not age, significantly affected birth weight. Among Italian babies, 4.7% of newborns were classified as appropriate-for-gestational age (AGA) (birth weight between the 10th and the 90th centile) according to the country-specific Italian Neonatal Study (INeS) charts and were re-classified as either large-(LGA) (birth weight >90th centile) or small-(SGA) (birth weight <10th centile) for gestational age (GA) after adjustment for maternal characteristics. On the contrary, 1.6% of Italian newborns were classified as SGA or LGA according to the INeS charts and re-classified as AGA after adjustment. Maternal ethnicity had a significant impact on birth weight. Specifically, babies born to Senegalese mothers were the lightest, whilst babies born to Chinese mothers were the heaviest. Maternal height and early pregnancy BMI, should be considered in the evaluation of birth weight. The effect of ethnicity suggests the appropriateness of ethnic-specific charts. Further studies are necessary to determine if changes in birth weight classification, may translate into improved detection of subjects at risk of adverse outcomes.