Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n=321,223) and offspring birth weight (n=230,069 mothers), we identified 190 independent association signals (129 novel). We used structural equation modelling to decompose the contributions of direct fetal and indirect maternal genetic effects, and then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of those alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

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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...

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...

Introduction: Dietary intake of specific nutrients or food groups during pregnancy could play a role in the risk of asthma and atopy in offspring, but specific dietary patterns have not been implicated. The authors evaluated the impact of maternal (during pregnancy) and child adherence to a Mediterranean diet on asthma and atopy in childhood. Methods: Women presenting for antenatal care at all general practices in Menorca, a Mediterranean island in Spain, over a 12 month period starting in mid-1997 were recruited. 460 children were included in the analysis after 6.5 years of follow-up. Maternal dietary intake during pregnancy and children's dietary intake at age 6.5 years were assessed by food frequency questionnaires, and adherence to a Mediterranean diet was evaluated by a priori defined scores. During follow-up, parents completed questionnaires on the child's respiratory and allergic symptoms. Children underwent skin prick tests with six common aeroallergens. Results: The prevalence rates of persistent wheeze, atopic wheeze and atopy at age 6.5 years were 13.2%, 5.8% and 17.0%, respectively. One-third (36.1%) of mothers had a low quality Mediterranean diet during pregnancy according to the Mediterranean Diet Score, while the rest had a high score. A high Mediterranean Diet Score during pregnancy (at two levels, using ''low'' score as the reference) was found to be protective for persistent wheeze (OR 0.22; 95% CI 0.08 to 0.58), atopic wheeze (OR 0.30; 95% CI 0.10 to 0.90) and atopy (OR 0.55; 95% CI 0.31 to 0.97) at age 6.5 years after adjusting for potential confounders. Childhood adherence to a Mediterranean diet was negatively associated with persistent wheeze and atopy although the associations did not reach statistical significance. Conclusion: These results support a protective effect of a high level of adherence to a Mediterranean diet during pregnancy against asthma-like symptoms and atopy in childhood.

BackgroundPreterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results.ObjectivesWe performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years).MethodsFirst, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age <37 weeks) and low birth weight (<2500 g) with childhood asthma outcomes.ResultsYounger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P < .05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27).ConclusionYounger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth.

Background: Atopy is not uncommon among children living in rural Crete, but wheeze and rhinitis are rare. A study was undertaken to examine whether this discrepancy could be attributed to a high consumption of fresh fruit and vegetables or adherence to a traditional Mediterranean diet. Methods: A cross-sectional survey was performed in 690 children aged 7-18 years in rural Crete. Parents completed a questionnaire on their child's respiratory and allergic symptoms and a 58-item food frequency questionnaire. Adherence to a Mediterranean diet was measured using a scale with 12 dietary items. Children underwent skin prick tests with 10 common aeroallergens. Results: 80% of children ate fresh fruit (and 68% vegetables) at least twice a day. The intake of grapes, oranges, apples, and fresh tomatoes-the main local products in Crete-had no association with atopy but was protective for wheezing and rhinitis. A high consumption of nuts was found to be inversely associated with wheezing (OR 0.46; 95% CI 0.20 to 0.98), whereas margarine increased the risk of both wheeze (OR 2.19; 95% CI 1.01 to 4.82) and allergic rhinitis (OR 2.10; 95% CI 1.31 to 3.37). A high level of adherence to the Mediterranean diet was protective for allergic rhinitis (OR 0.34; 95% CI 0.18 to 0.64) while a more modest protection was observed for wheezing and atopy. Conclusion: The results of this study suggest a beneficial effect of commonly consumed fruits, vegetables and nuts, and of a high adherence to a traditional Mediterranean diet during childhood on symptoms of asthma and rhinitis. Diet may explain the relative lack of allergic symptoms in this population.

High TSH levels and thyroid autoimmunity in early pregnancy may detrimentally affect pregnancy and birth outcomes.