Objective: The prevalence of overweight and obesity among women of reproductive age is increasing. We aimed to determine risk factors and maternal, fetal and childhood consequences of maternal obesity and excessive gestational weight gain. Design and Methods: The study was embedded in a population-based prospective cohort study among 6959 mothers and their children. The study was based in Rotterdam, The Netherlands (2001-2005. Results: Maternal lower educational level, lower household income, multiparity, and FTO risk allel were associated with an increased risk of maternal obesity, whereas maternal European ethnicity, nulliparity, higher total energy intake, and smoking during pregnancy were associated with an increased risk of excessive gestational weight gain (all p-values <0.05). As compared to normal weight, maternal obesity was associated with increased risks of gestational hypertension (OR 6.31 (95% CI 4.30, 9.26)), preeclampsia (OR (3.61, (95% CI 2.04, 6.39)), gestational diabetes (OR 6.28 (95%CI 3.01, 13.06)), caesarean delivery (OR 1.91 (95% CI 1.46, 2.50)), delivering large size for gestational age infants (OR 2.97 (95% CI 2.16, 4.08)), and childhood obesity (OR 5.02 (95% CI:2.97, 8.45)). Weaker associations of excessive gestational weight gain with maternal, fetal and childhood outcomes were observed, with the strongest effects for first trimester weight gain. Conclusions: Our study shows that maternal obesity and excessive weight gain during pregnancy are associated with socio-demographic, lifestyle, and genetic factors and with increased risks of adverse maternal, fetal and childhood outcomes. As compared to prepregnancy overweight and obesity, excessive gestational weight gain has a limited influence on adverse pregnancy outcomes.

Obesity is one of the biggest challenges facing global reproductive health. Women in the UK and USA are today more likely to be obese or overweight at booking than normal weight, and many low-and middle-income countries (LMICs) seem destined to follow suit (Poston et al. Lancet Diabetes Endocrinol 2016;4:1025-36). Understanding how, and to what extent, maternal body mass index (BMI) and weight gain during pregnancy contribute to adverse outcomes for mothers and their offspring is therefore vital to informing future health policy.In an individual participant data meta-analysis of over 265 000 births, Santos et al. (BJOG 2019;126:984-95) confirm strong correlations between pre-pregnancy maternal BMI and the risks of gestational hypertension, preeclampsia and gestational diabetes. Over one-third of such complications in the study population were considered attributable to maternal overweight and obesity. The risk of large size for gestational age (LGA) at birth increased similarly across all categories of pre-pregnancy BMI and gestational weight gain, although these data should be interpreted in the context of a continuing debate regarding the customisation of fetal growth charts. It remains uncertain how maternal height and weight influence fetal growth potential, and whether LGA babies born to mothers who are obese or mothers with excessive weight gain carry the same short-and long-term health risks as LGA babies born to mothers who are normal weight. Preterm birth was also more common among women who are obese and past literature has suggested that this association is strongest for extremely preterm delivery (Cnattingius et al. JAMA 2013;309:2362-70), whether spontaneous or iatrogenic.Whereas women who are obese or have high weight gain are consistently shown to be at greatest risk, there is clear evidence of a continuum of risk across the full BMI range, which is emphasised by the authors' use of population attributable risk (PAR). Notably, the overall burden of pregnancy complications is similar in overweight and obese groups (PAR 11.4 and 12.5%, respectively). This calls into question traditional models of care targeting women with a booking BMI above 30 kg/m 2 or even higher thresholds. Minimising gestational weight gain in these women ameliorates but does not remove the excess risk, and ultimately may have less impact on outcomes at a population level than previously hoped.The authors acknowledge that the data were derived from cohorts who were largely white; however, comparable findings have been reported in LMICs with varied ethnic populations (Rahman et al. Obes Rev 2015;16:758-70).Being healthy entails more than just not being obese, and the study also draws important attention to the risks of small size for gestational age and preterm birth, particularly amongst underweight women with inadequate weight gain during pregnancy. These findings strengthen the argument for novel public health approaches to optimise maternal health with a shift in focus towards pre-conception and interpregnancy intervent...

A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.

BackgroundMaternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact.Methods and findingsWe conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0–5.0 years), mid (5.0–10.0 years) and late childhood (10.0–18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations.ConclusionsIn this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large po...

Maternal obesity during pregnancy is an important public health problem in Western countries. Currently, obesity prevalence rates in pregnant women are estimated to be as high as 30 %. In addition, approximately 40 % of women gain an excessive amount of weight during pregnancy in Western countries. An accumulating body of evidence suggests a long-term impact of maternal obesity and excessive weight gain during pregnancy on adiposity, cardiovascular and metabolic related health outcomes in the offspring in fetal life, childhood and adulthood. In this review, we discuss results from recent studies, potential underlying mechanisms and challenges for future epidemiological studies.

Maternal obesity during pregnancy is associated with an adverse cardiometabolic risk profile in childhood and adulthood. [1][2][3][4] The mechanisms underlying these associations might involve increased placental transfer of nutrients during fetal development, which may cause permanent adaptations in appetite, energy metabolism, and neuroendocrine function in offspring, which predispose individuals to a greater risk of cardiometabolic disease in later life. 5 However, these associations might also reflect shared family-based, lifestyle-related characteristics or genetic factors. 5 Comparing the strength of associations of prepregnancy body mass index (BMI) from both mother and father with childhood outcomes could help in disentangling underlying mechanisms. 6,7 Stronger associations for maternal BMI suggest direct intrauterine mechanisms, whereas similar or stronger associations for paternal BMI suggest a role for shared family-based, lifestyle-related characteristics or genetic factors. To date, studies comparing associations of maternal and paternal BMI with childhood BMI have shown conflicting results. 5,[8][9][10][11] Also, most previous studies did not explore associations of parental BMI with detailed childhood body and abdominal fat distribution and cardiometabolic outcomes. It further remains unclear whether differences in magnitude of associations of parental BMI with childhood outcomes are present across the full range of BMI or confined to parental obesity only.Therefore, in a population-based prospective cohort study among 4871 children and their parents, we examined the associations of maternal and paternal prepregnancy BMI with childhood BMI, total body and abdominal fat distribution, and cardiometabolic risk factors. We also explored whether these associations are present across the full range of BMI and explained by pregnancy, birth, or childhood characteristics.Abstract-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<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 cardiometab...

Objective To examine whether first trimester fetal growth restriction correlates with cardiovascular outcomes in childhood.Design Population based prospective cohort study.Setting City of Rotterdam, the Netherlands.Participants 1184 children with first trimester fetal crown to rump length measurements, whose mothers had a reliable first day of their last menstrual period and a regular menstrual cycle. Main outcomes measuresBody mass index, total and abdominal fat distribution, blood pressure, and blood concentrations of cholesterol, triglycerides, insulin, and C peptide at the median age of 6.0 (90% range 5.7-6.8) years. Clustering of cardiovascular risk factors was defined as having three or more of: high android fat mass; high systolic or diastolic blood pressure; low high density lipoprotein cholesterol or high triglycerides concentrations; and high insulin concentrations.Results One standard deviation score greater first trimester fetal crown to rump length was associated with a lower total fat mass (−0.30%, 95% confidence interval −0.57% to −0.03%), android fat mass (−0.07%, −0.12% to −0.02%), android/gynoid fat mass ratio (−0.53, −0.89 to −0.17), diastolic blood pressure (−0.43, −0.84 to −0.01, mm Hg), total cholesterol (−0.05, −0.10 to 0, mmol/L), low density lipoprotein cholesterol (−0.04, −0.09 to 0, mmol/L), and risk of clustering of cardiovascular risk factors (relative risk 0.81, 0.66 to 1.00) in childhood. Additional adjustment for gestational age and weight at birth changed these effect estimates only slightly. Childhood body mass index fully explained the associations of first trimester fetal crown to rump length with childhood total fat mass. First trimester fetal growth was not associated with other cardiovascular outcomes. Longitudinal growth analyses showed that compared with school age children without clustering of cardiovascular risk factors, those with clustering had a smaller first trimester fetal crown to rump length and lower second and third trimester estimated fetal weight but higher weight growth from the age of 6 months onwards.Conclusions Impaired first trimester fetal growth is associated with an adverse cardiovascular risk profile in school age children. Early fetal life might be a critical period for cardiovascular health in later life. IntroductionFetal developmental adaptations in response to adverse environmental exposures may permanently affect the structure and function of cardiovascular organs.1 These adaptations may lead to increased risks of cardiovascular disease in adulthood. 1Human development rates are highest during the first trimester of pregnancy.2 This period includes the embryonic phase and is essential for development of fetal cardiovascular and metabolic organs.3 Therefore, the first trimester of pregnancy may be a critical period for cardiovascular health in childhood and adulthood.In obstetric care practice, first trimester fetal crown to rump length is commonly used for dating pregnancy, assuming no growth variation.3 However, among pregnant women w...

IMPORTANCE Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges. OBJECTIVES To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories. DESIGN, SETTING, AND PARTICIPANTS Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample). Optimal gestational weight gain ranges were estimated for each prepregnancy body mass index (BMI) category by selecting the range of gestational weight gain that was associated with lower risk for any adverse outcome. Individual participant-level data from 3505 participants within 4 separate hospital-based cohorts were used as a validation sample. Data were collected between 1989 and 2015. The final date of follow-up was December 2015. EXPOSURES Gestational weight gain. MAIN OUTCOMES AND MEASURES The main outcome termed any adverse outcome was defined as the presence of 1 or more of the following outcomes: preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, preterm birth, and small or large size for gestational age at birth. RESULTS Of the 196 670 women (median age, 30.0 years [quartile 1 and 3, 27.0 and 33.0 years] and 40 937 were white) included in the main sample, 7809 (4.0%) were categorized at baseline as underweight (BMI <18.5); 133 788 (68.0%), normal weight (BMI, 18.5-24.9); 38 828 (19.7%), overweight (BMI, 25.0-29.9); 11 992 (6.1%), obesity grade 1 (BMI, 30.0-34.9); 3284 (1.7%), obesity grade 2 (BMI, 35.0-39.9); and 969 (0.5%), obesity grade 3 (BMI, Ն40.0). Overall, any adverse outcome occurred in 37.2% (n = 73 161) of women, ranging from 34.7% (2706 of 7809) among women categorized as underweight to 61.1% (592 of 969) among women categorized as obesity grade 3. Optimal gestational weight gain ranges were 14.0 kg to less than 16.0 kg for women categorized as underweight; 10.0 kg to less than 18.0 kg for normal weight; 2.0 kg to less than 16.0 kg for overweight; 2.0 kg to less than 6.0 kg for obesity grade 1; weight loss or gain of 0 kg to less than 4.0 kg for obesity grade 2; and weight gain of 0 kg to less than 6.0 kg for obesity grade 3. These gestational weight gain ranges were associated with low to moderate discrimination between those with and those without adverse outcomes (range for area under the receiver operating characteristic curve, 0.55-0.76). Results for discriminative performance in the validation sample were similar to the corresponding results in the main study sample (range for area under the receiver operating characteristic curve, 0.51-0.79). CONCLUSIONS AND RELEVANCE In this meta-analysis of pooled individual participant data from 25 cohort studies, the risk for adverse maternal and infant outcomes varied by gestational wei...