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Objective: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes.Design: Individual level meta-analysis, which reduces heterogeneity across studies.Setting: A consortium of eight population-based studies (seven European and one US) comprising 72 694 participants.Methods: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses.Main Outcome Measures: Birth weight, large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), % body fat, and ponderal index at birth.Results: Late, but not early, gestation maternal moderate to vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia, and ponderal index, without heterogeneity (all: I2  = 0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98), respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA.Conclusions: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA.Tweetable Abstract: In an individual participant meta-analysis, late pregnancy moderate to vigorous physical activity modestly reduced birth size outcomes. [ABSTRACT FROM AUTHOR]

Much remains to be understood about the socioeconomic inequalities in hypertension that continue to exist. We investigated the association of socioeconomic status with blood pressure and prehypertension in childhood. In a prospective cohort, 3024 five- to six-year-old children had blood pressure measurements and available information on potential explanatory factors, namely birth weight, gestational age, smoking during pregnancy, pregnancy-induced hypertension, familial hypertension, maternal body mass index, breastfeeding duration, domestic tobacco exposure, and body mass index. The systolic and diastolic blood pressures of children from mid-educated women were 1.0-mm Hg higher (95% CI, 0.4-1.7) and 0.9-mm Hg higher (95% CI, 0.3-1.4), and the blood pressures of children with low-educated women were 2.2-mm Hg higher (95% CI, 1.4-3.0) and 1.7-mm Hg higher (95% CI, 1.1-2.4) compared with children with high-educated women. Children with mid- (odds ratio, 1.50; 95% CI, 1.18-1.92) or low-educated mothers (odds ratio, 1.80; 95% CI, 1.35-2.42) were more likely to have prehypertension compared with children with high-educated mothers. Using path analyses, birth weight, breastfeeding duration, and body mass index were determined as having a role in the association of maternal education with offspring blood pressure and prehypertension. The socioeconomic gradient in hypertension appears to emerge from childhood as the results show a higher blood pressure and more prehypertension in children from lower socioeconomic status families. Socioeconomic disparities could be reduced by improving 3 factors in particular, namely birth weight, breastfeeding duration, and body mass index, but other factors might also play a role. [ABSTRACT FROM AUTHOR]

Low vitamin D levels during pregnancy may account for reduced fetal growth and for altered neonatal development. The present study explored the association between maternal vitamin D status measured early in pregnancy and birth weight, prevalence of small-for-gestational-age (SGA) infants and postnatal growth (weight and length), as well as the potential role of vitamin D status in explaining ethnic disparities in these outcomes. Data were derived from a large multi-ethnic cohort in The Netherlands (Amsterdam Born Children and their Development (ABCD) cohort), and included 3730 women with live-born singleton term deliveries. Maternal serum vitamin D was measured during early pregnancy (median 13 weeks, interquartile range: 12-14), and was labelled 'deficient' ( or= 50 nmol/l). Six ethnic groups were distinguished: Dutch, Surinamese, Turkish, Moroccan, other non-Western and other Western. Associations with neonatal outcomes were analysed using multivariate regression analyses. Results showed that compared with women with adequate vitamin D levels, women with deficient vitamin D levels had infants with lower birth weights ( - 114.4 g, 95% CI - 151.2, - 77.6) and a higher risk of SGA (OR 2.4, 95% CI 1.9, 3.2). Neonates born to mothers with a deficient vitamin D status showed accelerated growth in weight and length during the first year of life. Although a deficient vitamin D status influenced birth weight, SGA risk and neonatal growth, it played a limited role in explaining ethnic differences. Although vitamin D supplementation might be beneficial to those at risk of a deficient vitamin D status, more research is needed before a nationwide policy on the subject can be justified. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the association between (self-reported) maternal pre-pregnancy body mass index (pBMI), and child's weight, height and BMI at age 14 months. DESIGN: Prospective multi-ethnic community-based cohort study. SETTING: Amsterdam, The Netherlands. PARTICIPANTS: 8266 pregnant women from the Amsterdam Born Children and their Development study, filled out a questionnaire covering socio-demographic data, obstetric history, lifestyle, dietary habits and psychosocial factors, 2 weeks after their first antenatal visit. 7730 gave birth to a viable term singleton infant with information on birth weight, gender and pregnancy duration. Growth data were available for 3171 of these children. MAIN OUTCOME MEASURES: Weight (g), height (cm) and BMI (kg/m(2)) of the child at age 14 months. RESULTS: pBMI was linearly associated with weight and BMI of the child at age 14 months. One unit increase in pBMI resulted in an increment of 29 g (95% CI 19 to 39) in weight and 0.041 kg/m(2) (95% CI 0.030 to 0.053) in BMI. The effect size decreased after adjustment for birth weight (weight: beta coefficient 19 g, 95% CI 10 to 28; BMI: beta coefficient 0.034 kg/m(2), 95% CI 0.023 to 0.046) and hardly changed after adjustment for all other variables (weight: beta coefficient 21 g, 95% CI 11 to 30; BMI: beta coefficient 0.031 kg/m(2), 95% CI 0.019 to 0.043). pBMI was not related to height. CONCLUSIONS: pBMI is an independent determinant of weight and BMI of the child at age 14 months. At least one third of this effect is mediated through birth weight. [ABSTRACT FROM AUTHOR]

BACKGROUND: The objective was the evaluation of the effect of the Dutch national routine antenatal RhIG (anti-D) immunization prevention (RAADP) program comprising one single dose of 200 microg (1000 IU) of RhIG in the 30th week of pregnancy, restricted to women without a living child. STUDY DESIGN AND METHODS: A nationwide historic control study was performed. All newly detected anti-D-immunized para-1 in 1999, 2002, and 2004 were included and classified on the basis of received prophylaxis during the first pregnancy: antenatal and postnatal versus only postnatal RhIG. The numbers of D- parae-1 who delivered a D+ first child before the introduction (control group) or after the introduction (intervention group) of the RAADP were calculated from Vital Birth Statistics (8,700 and 12,000, respectively). RESULTS: Fifty-eight newly detected anti-D immunizations in the first trimester were observed in the control group and 39 in the intervention group, which resulted in a significant reduction of the prevalence of new anti-D immunizations from 0.67 percent (95% confidence interval [CI], 0.50%-0.84%) to 0.31 percent (95% CI, 0.21%-0.41%). No reduction was observed in anti-D immunizations newly detected at the 30th-week screening (0.25%). A nonsignificant risk reduction of the risk of severe hemolytic disease of the fetus and newborn (HDFN) was found (0.23% vs. 0.10%). The numbers needed to treat to prevent one anti-D-immunized pregnancy and one case of subsequent severe HDFN were 357 and 1255, respectively. CONCLUSIONS: RAADP of one single dose of 200 microg of RhIG in addition to postnatal RhIG (200 microg) halves the risk of anti-D immunization and subsequent severe HDFN. [ABSTRACT FROM AUTHOR]

BACKGROUND: Maternal n-3, n-6, and trans fatty acids are claimed to affect fetal growth, yet evidence is limited. OBJECTIVE: We investigated the association between maternal n-3, n-6, and trans fatty acids measured early in pregnancy and fetal growth. DESIGN: Amsterdam pregnant women (n = 12 373) were invited to complete a questionnaire (response 67%) and donate blood around the 12th pregnancy week for nutrient analysis. For 4336 women, fatty acid concentrations were measured in plasma phospholipids (gas-liquid chromatography). Associations of these concentrations with birth weight and small-for-gestational-age (SGA) risk were analyzed (liveborn singleton term deliveries, n = 3704). RESULTS: Low concentrations of individual n-3 fatty acids and 20:3n-6, the precursor of arachidonic acid (20:4n-6), but high concentrations of the other n-6 fatty acids and the main dietary trans fatty acid (18:1n-9t) were associated with lower birth weight (estimated difference in univariate analysis -52 to -172 g for extreme quintile compared with middle quintile). In general, SGA risk increased accordingly. After adjustment for physiologic, lifestyle-related and sociodemographic factors, low concentrations of most n-3 fatty acids and 20:3n-6 and high concentrations of 20:4n-6 remained associated with lower birth weight (-52 to -57 g), higher SGA risk, or both (odds ratios: 1.38-1.50). Infants of the 7% of women with the most adverse fatty acid profile were on average 125 g lighter and twice as likely to be small for gestational age. CONCLUSION: An adverse maternal fatty acid profile early in pregnancy is associated with reduced fetal growth, which, if confirmed, gives perspective for the dietary prevention of lower birth weight. Copyright © 2008 American Society for Nutrition [ABSTRACT FROM AUTHOR]

Abstract Background Since July 1998 all Dutch women (± 200,000/y) are screened for red cell antibodies, other than anti-RhesusD (RhD) in the first trimester of pregnancy, to facilitate timely treatment of pregnancies at risk for hemolytic disease of the fetus and newborn (HDFN). Evidence for benefits, consequences and costs of screening for non-RhD antibodies is still under discussion. The screening program was evaluated in a nation-wide study. As a part of this evaluation study we investigated, according to the sixth criterium of Wilson and Jüngner, the acceptance by pregnant women of the screening program for non-RhD antibodies. Methods Controlled longitudinal survey, including a prenatal and a postnatal measurement by structured questionnaires. Main outcome measures: information satisfaction, anxiety during the screening process (a.o. STAI state inventory and specific questionnaire modules), overall attitude on the screening program. Univariate analysis was followed by standard multivariate analysis to identify significant predictors of the outcome measures. Participants: 233 pregnant women, distributed over five groups, according to the screening result. Results Satisfaction about the provided information was moderate in all groups. All screen- positive groups desired more supportive information. Anxiety increased in screen- positives during the screening process, but decreased to basic levels postnatally. All groups showed a strongly positive balance between perceived utility and burden of the screening program, independent on test results or background characteristics. Conclusion Women highly accept the non-RhD antibody screening program. However, satisfaction about provided information is moderate. Oral and written information should be provided by obstetric care workers themselves, especially to screen-positive women.

Background: Since July 1998 all Dutch women (+/- 200,000/y) are screened for red cell antibodies, other than anti-RhesusD (RhD) in the first trimester of pregnancy, to facilitate timely treatment of pregnancies at risk for hemolytic disease of the fetus and newborn (HDFN). Evidence for benefits, consequences and costs of screening for non-RhD antibodies is still under discussion. The screening program was evaluated in a nation-wide study. As a part of this evaluation study we investigated, according to the sixth criterium of Wilson and Jüngner, the acceptance by pregnant women of the screening program for non-RhD antibodies.Methods: Controlled longitudinal survey, including a prenatal and a postnatal measurement by structured questionnaires.Main Outcome Measures: information satisfaction, anxiety during the screening process (a.o. STAI state inventory and specific questionnaire modules), overall attitude on the screening program. Univariate analysis was followed by standard multivariate analysis to identify significant predictors of the outcome measures.Participants: 233 pregnant women, distributed over five groups, according to the screening result.Results: Satisfaction about the provided information was moderate in all groups. All screen- positive groups desired more supportive information. Anxiety increased in screen- positives during the screening process, but decreased to basic levels postnatally. All groups showed a strongly positive balance between perceived utility and burden of the screening program, independent on test results or background characteristics.Conclusion: Women highly accept the non-RhD antibody screening program. However, satisfaction about provided information is moderate. Oral and written information should be provided by obstetric care workers themselves, especially to screen-positive women. [ABSTRACT FROM AUTHOR]

Objectives: Thyroid autoimmunity is common in pregnant women and associated with thyroid dysfunction and adverse obstetric outcomes. Most studies focus on thyroid peroxidase antibodies (TPOAbs) assessed by a negative-positive dichotomy and rarely take into account thyroglobulin antibodies (TgAbs). This study aimed at determining the association of TPOAbs and TgAbs, respectively, and interdependently, with maternal thyroid function. Methods: This was a meta-analysis of individual participant cross-sectional data from 20 cohorts in the Consortium on Thyroid and Pregnancy. Women with multiple pregnancy, pregnancy by assisted reproductive technology, history of thyroid disease, or use of thyroid interfering medication were excluded. Associations of (log2) TPOAbs and TgAbs (with/without mutual adjustment) with cohort-specific z-scores of (log2) thyrotropin (TSH), free triiodothyronine (fT3), total triiodothyronine (TT3), free thyroxine (fT4), total thyroxine (TT4), or triiodothyronine:thyroxine (T3:T4) ratio were evaluated in a linear mixed model. Results: In total, 51,138 women participated (51,094 had TPOAb-data and 27,874 had TgAb-data). Isolated TPOAb positivity was present in 4.1% [95% confidence interval, CI: 3.0 to 5.2], isolated TgAb positivity in 4.8% [CI: 2.9 to 6.6], and positivity for both antibodies in 4.7% [CI: 3.1 to 6.3]. Compared with antibody-negative women, TSH was higher in women with isolated TPOAb positivity (z-score increment 0.40, CI: 0.16 to 0.64) and TgAb positivity (0.21, CI: 0.10 to 0.32), but highest in those positive for both antibodies (0.54, CI: 0.36 to 0.71). There was a dose-response effect of higher TPOAb and TgAb concentrations with higher TSH (TSH z-score increment for TPOAbs 0.12, CI: 0.09 to 0.15, TgAbs 0.08, CI: 0.02 to 0.15). When adjusting analyses for the other antibody, only the association of TPOAbs remained statistically significant. A higher TPOAb concentration was associated with lower fT4 ( p  < 0.001) and higher T3:T4 ratio (0.09, CI: 0.03 to 0.14), however, the association with fT4 was not significant when adjusting for TgAbs ( p  = 0.16). Conclusions: This individual participant data meta-analysis demonstrated an increase in TSH with isolated TPOAb positivity and TgAb positivity, respectively, which was amplified for individuals positive for both antibodies. There was a dose-dependent association of TPOAbs, but not TgAbs, with TSH when adjusting for the other antibody. This supports current practice of using TPOAbs in initial laboratory testing of pregnant women suspected of autoimmune thyroid disease. However, studies on the differences between TPOAb- and TgAb-positive women are needed to fully understand the spectrum of phenotypes.

Background & Aims: Specific dietary components during childhood may affect risk factors for cardiovascular disease. Whether overall higher diet quality prevents children from adverse cardiovascular outcomes remains contradictive. We aimed to examine the associations between diet quality at age 5-6 years and cardiovascular outcomes after a 6-year follow-up., Methods: We used data from the Amsterdam Born Children and their Development study, a multi-ethnic birth cohort. Dietary intake was assessed at age 5-6 using a semi-quantitative food frequency questionnaire and diet quality was ascertained with the Dietary Approaches to Stop Hypertension (DASH) score and the child diet quality score (CDQS), an index specifically developed for Dutch school-age children. Cardiovascular outcomes were examined after 6-years follow-up (age 11-12, N = 869). Outcomes were body mass index (BMI), waist circumference (WC), blood pressure (BP), lipid profile, fasting glucose and carotid intima-media thickness (CIMT). Multivariable linear and logistic regression models adjusted for baseline value were used to examine associations between diet quality and cardiovascular outcomes., Results: Higher diet quality at age 5-6 was associated with lower BMI (DASH score: Δ quintile (Q) 5 and Q1: -0.35 kg/m 2 , p for trend = 0.016), lower WC (DASH score: Δ Q5 and Q1: -1.0 cm, p for trend = 0.028), lower systolic (DASH score: Δ Q5 and Q1: -2.7 mmHg, p for trend = 0.046) and diastolic BP (DASH score: Δ Q5 and Q1: -2.4, p for trend < 0.001) and with lower plasma triglycerides (DASH score: Δ Q5 and Q1: -0.20 mmol/L, p for trend = 0.032) after 6-years follow-up. Associations of the CDQS with these outcomes showed similar trends, but less pronounced. We found no statistically significant associations between diet quality and LDL-C, HDL-C, total cholesterol, fasting glucose or CIMT., Conclusions: Higher diet quality in childhood at age 5-6 years predicted better health on some cardiovascular outcomes in preadolescence., Competing Interests: Declaration of competing interest The authors (JJAK, MN, ANN, TV, BAH, TGMV) declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Rationale: Low birth weight has been found to increase the problem behavior of children. Yet, little attention has been given to adequately account for the impact of the child's neighborhood on this relation. The residential neighborhood is a choice, based on factors that are usually not observed that may also influence birth weight and problem behavior., Objective: Using a model that accounts for such endogeneity of both neighborhood choice and birth weight, we have analyzed behavioral problems in 4210 pre-school children between the ages of 5 and 6, birth weight, and neighborhood status, simultaneously., Method: The data used are from the Amsterdam Born Children and their Development (ABCD) cohort for whom a complete prospective record of birth outcomes, pregnancy, socio-demographic characteristics, and indicators of problem behavior are available. Neighborhood data obtained from Statistics Netherlands are merged with the ABCD data file., Results: Our results suggest that ignoring endogeneity attenuates the effect of disadvantaged neighborhoods on both birth weight and problem behavior in pre-school children. Living in a disadvantaged neighborhood decreases the birth weight and increases the probability of problem behavior. Accounting for the endogeneity of neighborhood choice increases the estimated impacts (marginal effects: from -10% to -44% for birth weight and from 3% to 11% for problem behavior). Lower birth weight increases the probability of problem behavior, but it is only significant after adjusting for endogeneity. The coefficients of other factors have the expected associations with problem behavior., Conclusions: These significant effects of disadvantaged neighborhood on birth weight and problem behavior could inform policies and practices that improve neighborhood development for children born in Amsterdam., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are associated with low birthweight, but important knowledge gaps remain regarding the effect of subclinical thyroid function test abnormalities on birthweight-both in general and during the late second and third trimester of pregnancy. The aim of this study was to examine associations of maternal thyroid function with birthweight., Methods: In this systematic review and individual-participant data meta-analysis, we searched MEDLINE (Ovid), Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar from inception to Oct 15, 2019, for prospective cohort studies with data on maternal thyroid function during pregnancy and birthweight, and we issued open invitations to identify study authors to join the Consortium on Thyroid and Pregnancy. We excluded participants with multiple pregnancies, in-vitro fertilisation, pre-existing thyroid disease or thyroid medication usage, miscarriages, and stillbirths. The main outcomes assessed were small for gestational age (SGA) neonates, large for gestational age neonates, and newborn birthweight. We analysed individual-participant data using mixed-effects regression models adjusting for maternal age, BMI, ethnicity, smoking, parity, gestational age at blood sampling, fetal sex, and gestational age at birth. The study protocol was pre-registered at the International Prospective Register of Systematic Reviews, CRD42016043496., Findings: We identified 2526 published reports, from which 36 cohorts met the inclusion criteria. The study authors for 15 of these cohorts agreed to participate, and five more unpublished datasets were added, giving a study population of 48 145 mother-child pairs after exclusions, of whom 1275 (3·1%) had subclinical hypothyroidism (increased thyroid stimulating hormone [TSH] with normal free thyroxine [FT 4 ]) and 929 (2·2%) had isolated hypothyroxinaemia (decreased FT 4 with normal TSH). Maternal subclinical hypothyroidism was associated with a higher risk of SGA than was euthyroidism (11·8% vs 10·0%; adjusted risk difference 2·43%, 95% CI 0·43 to 4·81; odds ratio [OR] 1·24, 1·04 to 1·48; p=0·015) and lower mean birthweight (mean difference -38 g, -61 to -15; p=0·0015), with a higher effect estimate for measurement in the third trimester than in the first or second. Isolated hypothyroxinaemia was associated with a lower risk of SGA than was euthyroidism (7·3% vs 10·0%, adjusted risk difference -2·91, -4·49 to -0·88; OR 0·70, 0·55 to 0·91; p=0·0073) and higher mean birthweight (mean difference 45 g, 18 to 73; p=0·0012). Each 1 SD increase in maternal TSH concentration was associated with a 6 g lower birthweight (-10 to -2; p=0·0030), with higher effect estimates in women who were thyroid peroxidase antibody positive than for women who were negative (p interaction =0·10). Each 1 SD increase in FT 4 concentration was associated with a 21 g lower birthweight (-25 to -17; p<0·0001), with a higher effect estimate for measurement in the third trimester than the first or second., Interpretation: Maternal subclinical hypothyroidism in pregnancy is associated with a higher risk of SGA and lower birthweight, whereas isolated hypothyroxinaemia is associated with lower risk of SGA and higher birthweight. There was an inverse, dose-response association of maternal TSH and FT 4 (even within the normal range) with birthweight. These results advance our understanding of the complex relationships between maternal thyroid function and fetal outcomes, and they should prompt careful consideration of potential risks and benefits of levothyroxine therapy during pregnancy., Funding: Netherlands Organization for Scientific Research (grant 401.16.020)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth., Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth., Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded., Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models., Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age)., Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56])., Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.

Objective: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes., Design: Individual level meta-analysis, which reduces heterogeneity across studies., Setting: A consortium of eight population-based studies (seven European and one US) comprising 72 694 participants., Methods: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses., Main Outcome Measures: Birth weight, large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), % body fat, and ponderal index at birth., Results: Late, but not early, gestation maternal moderate to vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia, and ponderal index, without heterogeneity (all: I 2  = 0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98), respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA., Conclusions: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA., Tweetable Abstract: In an individual participant meta-analysis, late pregnancy moderate to vigorous physical activity modestly reduced birth size outcomes., (© 2018 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Objective: Inadequate maternal micronutrient status during pregnancy can lead to short- and long-term health risks for mother and offspring. The present study investigated the association between pre-pregnancy weight status and micronutrient status during pregnancy., Design: Maternal blood samples were collected during early pregnancy (median 13, interquartile range 12-15 weeks) and were assayed for serum folate, ferritin, Fe and vitamin B12. Regression modelling was used to assess the association between pre-pregnancy underweight, normal weight, overweight and obesity, and micronutrient levels, as well as the odds for deficiencies., Setting: The Amsterdam Born Children and their Development (ABCD) study, the Netherlands., Subjects: Women with singleton pregnancies without diabetes (n 4243)., Results: After adjustment for covariates, overweight women and obese women had lower (β; 95 % CI) folate (-1·2; -2·2, -0·2 and -2·3; -4·0, -0·7 nmol/l, respectively) and Fe (-1·7; -2·3, -1·1 and -3·6; -4·7, -2·6 μmol/l, respectively) levels than women with normal weight. Furthermore, overweight women had 6 % (95 % CI -9, -3 %) and obese women had 15 % (-19, -10 %), lower vitamin B12 levels, and obese women had 19 % (6, 32 %) higher ferritin levels, than normal-weight women. Obese women had higher odds (OR; 95 % CI) for folate deficiency (2·03; 1·35, 3·06), Fe deficiency (3·26; 2·09, 5·08) and vitamin B12 deficiency (2·05; 1·41, 2·99) than women with normal weight. Underweight was not associated with micronutrient status., Conclusions: During early pregnancy, women with pre-pregnancy overweight and obesity had lower serum folate, Fe and vitamin B12 status. This resulted in increased risk of serum folate, Fe and vitamin B12 deficiencies in women with obesity.

Objective: To investigate a dose dependency of thyroperoxidase antibody (TPOAb) concentrations in relation to thyroid function and premature delivery and define a population-based, pregnancy-specific, functional cutoff for TPOAb positivity., Design: Individual participant meta-analysis of three prospective birth cohorts: the Amsterdam Born Children and their Development study, and the Holistic Approach to Pregnancy., Setting: Population-based studies in the Netherlands (2002 to 2014)., Participants: A total of 11,212 pregnant women (<20 weeks' gestation)., Main Outcome Measures: Thyrotropin (TSH) and FT4 concentrations, premature delivery., Results: In all cohorts, there was a dose-dependent positive association of TPOAb concentrations with TSH concentrations, as well as a dose-dependent negative association with FT4 concentrations during early pregnancy (all P < 0.0001). There was a dose-dependent association of TPOAb concentrations with the risk of premature delivery, which was also modified by TSH concentrations. Women with TPOAb concentrations from the 92nd percentile upward had a higher TSH and a higher risk of a TSH >2.5 mU/L (range, 19.4% to 51.3%). Stratified analyses showed that women with TPOAb concentrations below manufacturer cutoffs already had a higher risk of premature delivery, especially when TSH concentrations were high or in the high-normal range., Conclusions: This study demonstrated a dose-dependent relationship between TPOAbs and thyroid function as well as the risk of premature delivery. Furthermore, our results indicate that the currently used cutoffs for TPOAb positivity may be too high. Furthermore, the use of a population-based cutoff for TPOAbs may identify women with a clinically relevant extent of thyroid autoimmunity and a higher risk of premature delivery but that would not be considered TPOAb positive or eligible for treatment otherwise., (Copyright © 2017 Endocrine Society)

Background: Psychosocial stress during pregnancy has been proposed as a major contributor of glucocorticoid-mediated programming of the fetal hypothalamic-pituitary adrenal (HPA) axis, with later adverse health consequences. However, evidence linking maternal stress to maternal cortisol values during pregnancy is inconclusive. A possible explanation for this is that other maternal factors overshadow any potential effects of stress on cortisol levels. We studied a large cohort of pregnant women with extensive data on pregnancy characteristics to determine the respective contributions of biological, environmental and psychosocial stress factors to cortisol levels in pregnancy., Methods: We used data from 3039 women from the Amsterdam Born Children and their Development-study cohort. Serum cortisol was measured in blood, collected at the first prenatal visit, at different gestational ages (median=91days, range=40-256days), and at various time points during the day (median=11:45h, range=08:00-18:30h). We assessed associations between maternal serum cortisol in pregnancy and biological factors, lifestyle factors and stress factors, including depression, anxiety, pregnancy-related anxiety, work stress, parenting stress and fatigue., Results: In multivariable analysis, variables that were associated with higher cortisol levels in pregnancy were lower maternal age [1.5nmol/l, 95%CI (0.6-2.4)], being nulliparous [21.5 nmol/l (15.9-27.1)], lower pre-pregnancy body mass index (BMI) [1.3nmol/l (0.3-2.4)], higher C-reactive protein (CRP) [1.0nmol/l (0.4-1.5)], carrying a female fetus [9.2nmol/l (1.8-16.5)], non-smoking [14.2nmol/l (0.6-27.7)], sufficient sleep [8.5nmol/l (0.9-16.1)], and being unemployed [12.7nmol/l (2.2-23.2)]. None of the psychosocial stressors was significantly associated with serum cortisol levels in pregnancy. A total of 32% of all variance in cortisol was explained by gestational age, maternal age, time of day, parity, pre-pregnancy BMI, CRP, fetal sex, smoking behavior, self-reported sleep sufficiency, and employment., Conclusions: Our data suggest that maternal cortisol during pregnancy is mainly affected by biological and lifestyle factors, but not by psychosocial factors. We suggest that psychosocial stress in pregnancy might program the fetus through other mechanisms than through altering maternal cortisol levels., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Intrauterine growth patterns are influenced by maternal thyroid function during gestation and by fetal sex. It is unknown, however, whether the relationships between maternal thyrotropin (TSH) and free thyroxine (fT4) levels in early pregnancy and fetal growth outcomes are modified by fetal sex., Design: Data were obtained from a community-based cohort study of pregnant women living in Amsterdam (Amsterdam Born Children and Their Development study). TSH and fT4 levels were determined during the first prenatal screening at median 13 weeks (interquartile range, 12 to 14). Women with live-born singletons and no overt thyroid dysfunction were included (N = 3988). Associations between these maternal hormones and birth weight, small for gestational age (SGA), and large for gestational age (LGA) were analyzed separately for each sex., Results: After adjustments, 1 pmol/L increase in maternal fT4 levels was associated with a reduction in birth weight of 33.7 g (P < 0.001) in male newborns and 16.1 g (P < 0.05) in female newborns. Increased maternal fT4 was not associated with increased odds for SGA, but was associated with a decreased odds for LGA in boys [per 1 pmol/L; odds ratio (OR), 0.79; 95% confidence interval (CI), 0.69 to 0.90]. Maternal subclinical hypothyroidism in early pregnancy (TSH > 2.5 mU/L, 7.3%) was associated with increased odds for LGA in male newborns (OR, 1.95; 95% CI, 1.22 to 3.11)., Conclusion: Maternal fT4 in early pregnancy was observed to be inversely associated with birth weight, with a stronger relationship in males. Male infants also had increased odds for LGA in mothers with subclinical hypothyroidism. Sexual dimorphism appears to be present in the relationship between maternal thyroid metabolism and fetal intrauterine growth, with stronger associations in male infants., (Copyright © 2017 by the Endocrine Society)

The onset of behavioral problems starts in early life. This study examined whether excessive infant crying (maternal ratings) is a determinant of emotional and behavioral problems at age 5-6 years. In the Amsterdam Born Children and their Development (ABCD) study, a large prospective, observational, population-based multiethnic birth cohort, excessive infant crying (crying for three or more hours per 24 h day over the past week) during the 13th week after birth (range 11-25 weeks, SD 2 weeks), maternal burden of infant care and maternal aggressive behavior (either angry speaking, or physical aggression) was assessed using a questionnaire. Children's behavioral and emotional problems at the age of 5-6 were assessed by Goodman's Strengths and Difficulties Questionnaire (SDQ), by the subscale of generalized anxiety of the preschool anxiety scale (PAS), and by the Short Mood and Feelings Questionnaire (SMFQ). Inclusion criterion was singleton birth. Exclusion criteria were preterm born babies or congenital disorders. Among 3389 children, excessive infant crying (n = 102) was associated with a twofold increased risk of the overall problem behavior, conduct problems, hyperactivity, and mood problems at the age of 5-6 [ORs between 1.75 (95 % CI 1.09-2.81) and 2.12 (95 % CI 1.30-3.46)]. This association was mediated by maternal burden of infant care (change in odds' ratio 1-17 %) and maternal aggressive behavior (change in odds' ratio 4-10 %). There was no effect modification by the child's gender or maternal parity. Excessive infant crying was not associated with general anxiety problems. Excessive infant crying doubles the risk of behavioral, hyperactivity, and mood problems at the age of 5-6, as reported by their mother. Maternal burden of infant care partially mediates the association between excessive crying and behavioral and mood problems. Special care for mothers with a high burden of care for their excessive crying infant, notwithstanding their own good health, can be a feasible strategy for possible prevention of mood and behavioral problems in their children later in life.

Atmospheric pollutants and meteorological conditions are suspected to be causes of preterm birth. We aimed to characterize their possible association with the risk of preterm birth (defined as birth occurring before 37 completed gestational weeks). We pooled individual data from 13 birth cohorts in 11 European countries (71,493 births from the period 1994-2011, European Study of Cohorts for Air Pollution Effects (ESCAPE)). City-specific meteorological data from routine monitors were averaged over time windows spanning from 1 week to the whole pregnancy. Atmospheric pollution measurements (nitrogen oxides and particulate matter) were combined with data from permanent monitors and land-use data into seasonally adjusted land-use regression models. Preterm birth risks associated with air pollution and meteorological factors were estimated using adjusted discrete-time Cox models. The frequency of preterm birth was 5.0%. Preterm birth risk tended to increase with first-trimester average atmospheric pressure (odds ratio per 5-mbar increase = 1.06, 95% confidence interval: 1.01, 1.11), which could not be distinguished from altitude. There was also some evidence of an increase in preterm birth risk with first-trimester average temperature in the -5°C to 15°C range, with a plateau afterwards (spline coding, P = 0.08). No evidence of adverse association with atmospheric pollutants was observed. Our study lends support for an increase in preterm birth risk with atmospheric pressure., (© The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Suboptimal prenatal and early postnatal growths are associated with obesity in later life, but the underlying mechanisms are unknown. The aim of this study was to systematically review the literature that reports on the longitudinal association of (i) birth size or (ii) infant growth with later (i) energy intake, (ii) eating behaviors, (iii) physical activity or (iv) sedentary behavior in humans., Methods: A comprehensive search of MEDLINE, EMBASE, PsycINFO and The Cochrane Library was conducted to identify relevant publications. We appraised the methodological quality of the studies and synthesized the extracted data through a best-evidence synthesis., Results: Data from 41 publications were included. The quality of the studies was high in three papers, moderate in 11 and low in the large majority (n = 27) of papers appraised. Our best-evidence synthesis indicates that there is no evidence for an association of birth weight with later energy intake, eating behavior, physical activity or sedentary behavior. We found moderate evidence for an association of extreme birth weights (at both ends of the spectrum) with lower physical activity levels at a later age. Evidence for the association of infant growth with energy balance-related behavior was generally insufficient., Conclusions: We conclude that current evidence does not support an association of early-life growth with energy balance-related behaviors in later life, except for an association of extreme birth weights with later physical activity., Competing Interests: The authors have declared that no competing interests exist.

Background: Migrant and ethnic minority groups constitute substantial parts of European populations. They frequently experience health disadvantages relative to the respective majority populations. Birth cohort studies can help to disentangle social and biological factors producing these health inequalities over the life course. We investigated whether birth cohorts in European countries (i) assess migration history and ethnicity in the study design; and (ii) use this information in data analyses., Methods: A scoping review was performed in which European birth cohort studies were identified using dedicated web-based registries, MEDLINE and EMBASE. Two reviewers systematically assessed all identified birth cohorts and selected those fulfilling defined inclusion criteria (e.g. enrolment after 1980). Publications and websites were screened for information on the inclusion of migrants and ethnic minorities. To obtain more detailed information, researchers of enrolled birth cohorts were contacted individually., Results: Eighty-eight birth cohorts were identified in 20 European countries, with more than 486 250 children enrolled in total. Sixty-two studies (70.5%) reported collecting data about migration history or ethnic background. Twenty-three studies (26%) used information on migration history or ethnicity for data analyses or plan to do so in future., Conclusion: The majority of European birth cohorts assessed participants' migration history or ethnic background; however, this information was seldom used for comparative analyses in trying to disentangle reasons for health inequalities. Also, heterogeneous indicators were used. Better use of data already available, as well as harmonization of data collection on migration history and ethnicity, could yield interesting insights into the production of health inequalities., (© The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Background: Low maternal thyroid function during early pregnancy is associated with various adverse outcomes including impaired neurocognitive development of the offspring, premature delivery and abnormal birthweight., Aim: To aid doctors in the risk assessment of thyroid dysfunction during pregnancy, we set out to investigate clinical risk factors and derive a prediction model based on easily obtainable clinical variables., Methods: In total, 9767 women during early pregnancy (≤18 week) were selected from two population-based prospective cohorts: the Generation R Study (N = 5985) and the ABCD study (N = 3782). We aimed to investigate the association of easily obtainable clinical subject characteristics such as maternal age, BMI, smoking status, ethnicity, parity and gestational age at blood sampling with the risk of low free thyroxine (FT4) and elevated thyroid stimulating hormone (TSH), determined according to the 2·5th-97·5th reference range in TPOAb negative women., Results: BMI, nonsmoking and ethnicity were risk factors for elevated TSH levels; however, the discriminative ability was poor (range c-statistic of 0·57-0·60). Sensitivity analysis showed that addition of TPOAbs to the model yielded a c-statistic of 0·73-0·75. Maternal age, BMI, smoking, parity and gestational age at blood sampling were risk factors for low FT4, which taken together provided adequate discrimination (range c-statistic of 0·72-0·76)., Conclusions: Elevated TSH levels depend predominantly on TPOAb levels, and prediction of elevated TSH levels is not possible with clinical characteristics only. In contrast, the validated clinical prediction model for FT4 had high discriminative value to assess the likelihood of low FT4 levels., (© 2016 John Wiley & Sons Ltd.)

Background: Studies on adult population indicate shorter sleep duration in ethnic minority groups than host populations. We examined ethnic differences in sleep duration and its relationship with overweight and blood pressure (BP) among children living in Amsterdam., Methods: Participants include 2384 children (aged 5 years) and their mothers from the Amsterdam-based longitudinal study. Sleep was categorised into short sleep (<10 h/night) and normal sleep (10-11 h/night). Linear regressions ( Β: were used to study association between sleep duration and systolic BP (SBP) and diastolic BP (DBP). Prevalence ratios (PRs) were used to study ethnic differences in sleep duration and its association with overweight and raised BP., Results: Minority groups reported shorter sleep duration compared to native Dutch, with prevalence ranging from 11.3% in Dutch to 53.1% in Ghanaians. Age-adjusted PRs ranged from 3.38 (95%CI 2.63-4.34) in Moroccans to 4.78 (95%CI 3.36-6.82) in Ghanaian compared with Dutch children. Increased prevalence of overweight was observed among children with short sleep in Dutch and Moroccans only, but this risk was no longer statistically significant after further adjustment for socioeconomic status. Short sleep was not related to SBP and DBP in all groups. No relationship was observed between short sleep and raised BP except for African Surinamese (3.65, 95% CI 1.23-10.8)., Conclusion: Like adults, children from ethnic minority populations sleep less hours than Dutch children. Efforts to improve ethnic inequalities in sleep hygiene should also include children at younger age. Associations as reported in adults with overweight and BP could not consistently be replicated in children, however., (© The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Objective: Small birth size and rapid postnatal growth have been associated with higher future blood pressure. The timing of these effects, the relative importance of weight gain and linear growth and the role of infant feeding need to be clarified., Methods: We assessed how blood pressure relates to birth weight, infant and childhood growth and infant feeding (duration of exclusive breastfeeding and timing of introduction of complementary feeding) in 2227 children aged 5 years from a prospective cohort study (Amsterdam Born Children and their Development). Postnatal growth was represented by statistically independent measures of relative weight gain (weight gain independent of height) and linear growth in four age periods during infancy (0-1 month; 1-3 months; 3-6 months; 6-12 months) and from 12 months to 5 years., Results: Lower birth weight was associated with higher childhood diastolic blood pressure (-0.38 mm Hg.SD-1; P = 0.007). Faster relative weight gain and linear growth after 1 month were positively associated with systolic and diastolic blood pressure. Associations of linear growth with systolic blood pressure ranged from 0.47 to 1.49 mm Hg.SD-1; P<0.01 for all. Coefficients were similar for different periods of infancy and also for relative weight gain and linear growth. Compared to breastfeeding <1 month, breastfeeding >1 month was associated with lower blood pressure (e.g. >6 months -1.56 mm Hg systolic blood pressure; P<0.001). Compared to >6 months, introduction of complementary feeding <6 months was associated with higher blood pressure (e.g. 4-6 months 0.91 mm Hg systolic blood pressure; P = 0.004)., Conclusions: After the age of one month faster growth in either weight or height is associated with higher childhood blood pressure. It is unknown whether faster weight gain and linear growth carry the same risk for adult hypertension and cardiovascular morbidity. Longer breastfeeding and delayed introduction of complementary feeding may be associated with lower adult blood pressure., Competing Interests: The authors have declared that no competing interests exist.

Study Objectives: Low or excessive sleep duration has been associated with multiple outcomes, but the biology behind these associations remains elusive. Specifically, genetic studies in children are scarce. In this study, we aimed to: (1) estimate the proportion of genetic variance of sleep duration in children attributed to common single nucleotide polymorphisms (SNPs), (2) identify novel SNPs associated with sleep duration in children, and (3) investigate the genetic overlap of sleep duration in children and related metabolic and psychiatric traits., Methods: We performed a population-based molecular genetic study, using data form the EArly Genetics and Life course Epidemiology (EAGLE) Consortium. 10,554 children of European ancestry were included in the discovery, and 1,250 children in the replication phase., Results: We found evidence of significant but modest SNP heritability of sleep duration in children (SNP h 2 0.14, 95% CI [0.05, 0.23]) using the LD score regression method. A novel region at chromosome 11q13.4 (top SNP: rs74506765, P = 2.27e-08) was associated with sleep duration in children, but this was not replicated in independent studies. Nominally significant genetic overlap was only found ( rG = 0.23, P = 0.05) between sleep duration in children and type 2 diabetes in adults, supporting the hypothesis of a common pathogenic mechanism., Conclusions: The significant SNP heritability of sleep duration in children and the suggestive genetic overlap with type 2 diabetes support the search for genetic mechanisms linking sleep duration in children to multiple outcomes in health and disease., (© 2016 Associated Professional Sleep Societies, LLC.)

Background: The purpose of this study was to examine the association of birth weight and infant growth with childhood autonomic nervous system (ANS) activity and to assess whether ANS activity mediates the associations of birth weight and infant growth with energy-balance-related behaviours, including energy intake, satiety response, physical activity and screen time., Methods: In 2089 children, we prospectively collected birth weight, infant growth defined as conditional weight and height gain between birth and 12 months and-at 5 years-indices of cardiac ANS activity and parent-reported energy-balance-related behaviours. A mediation analysis was conducted, based on MacKinnon's multivariate extension of the product-of-coefficients strategy., Results: Birth weight and infant height gain were inversely associated with sympathetic, but not parasympathetic, activity at age 5. Infant weight gain was not associated with childhood ANS activity. Infant weight gain was predictive of increased childhood screen time and infant height gain of diminished childhood energy intake, but sympathetic activity did not mediate these associations., Conclusions: Low-birth-weight children have higher sympathetic activity, which is considered a risk factor for cardiovascular disease. Height gain in infancy seems to be beneficial for childhood sympathetic activity. However, sympathetic activity was no mediator of the associations of infant growth with childhood energy-balance-related behaviours. As individual differences in ANS activity predict increased risk of cardiovascular disease, these differences may offer insight into the early-life origins of chronic diseases and provide further basis for public health strategies to optimize birth weight and infant growth., (© The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

This study aimed at analysing the association between socioeconomic status (SES) and psychosocial problems in preterm- and term-born children. Scores of mothers and teachers on the Strengths and Difficulties Questionnaire (SDQ) regarding 217 preterm-born children (<37 weeks' gestation, mean 34 weeks) were compared with 4336 term-born children in the Amsterdam Born Children and their Development (ABCD) cohort at age 5-6 years. Associations between SDQ scores and SES (maternal education and perceived income adequacy) were examined with multivariate linear regression analysis. The mean mother-reported total difficulties score was significantly higher for preterm children (6.1 ± 4.7) than for term children (5.2 ± 4.1). After covariate adjustment, this difference was 0.5 (95 % CI 0.0-1.0). For preterm children 16.1 % of the mothers reported psychosocial problems compared with 10.1 % for term children. Lower maternal education and lower income adequacy were significantly related to higher SDQ scores of mothers and teachers. Differences in mothers' SDQ score between preterm and term children were larger in the high-education (Δ0.9, 95 % CI 0.2-1.5) and high-income group (Δ0.9, 95 % CI 0.3-1.6). No significant differences were found between preterm and term children in the SDQ scores reported by teachers. Low level of maternal education and inadequate income showed a much stronger association with psychosocial problems than preterm birth. No combined effect of low SES and preterm birth was found. This study corroborates the evidence for the strength of the disadvantageous effects of low SES on early psychosocial development.

Background: Comparable evidence on adiposity inequalities in early life is lacking across a range of European countries. This study investigates whether low maternal education is associated with overweight and obesity risk in children from distinct European settings during early childhood., Methods: Prospective data of 45 413 children from 11 European cohorts were used. Children's height and weight obtained at ages 4-7 years were used to assess prevalent overweight and obesity according to the International Obesity Task Force definition. The Relative/Slope Indices of Inequality (RII/SII) were estimated within each cohort and by gender to investigate adiposity risk among children born to mothers with low education as compared to counterparts born to mothers with high education. Individual-data meta-analyses were conducted to obtain aggregate estimates and to assess heterogeneity between cohorts., Results: Low maternal education yielded a substantial risk of early childhood adiposity across 11 European countries. Low maternal education yielded a mean risk ratio of 1.58 (95% confidence interval (CI) 1.34, 1.85) and a mean risk difference of 7.78% (5.34, 10.22) in early childhood overweight, respectively, measured by the RII and SII. Early childhood obesity risk by low maternal education was as substantial for all cohorts combined (RII = 2.61 (2.10, 3.23)) and (SII = 4.01% (3.14, 4.88)). Inequalities in early childhood adiposity were consistent among boys, but varied among girls in a few cohorts., Conclusions: Considerable inequalities in overweight and obesity are evident among European children in early life. Tackling early childhood adiposity is necessary to promote children's immediate health and well-being and throughout the life course., (© 2016 John Wiley & Sons Ltd.)

Objective: Thyroid dysfunction has been described as a possible risk factor for having an abnormal fetal position at birth. In this study we aim to determine the association between thyroid function in early pregnancy and breech presentation at term., Study Design: We used data from the Amsterdam Born Children and their Development (ABCD) cohort. 3347 pregnant women were included between January 2003 and March 2004 in Amsterdam, the Netherlands. Thyroid function tests were performed between 5 and 37 weeks gestational age (median 12.9 weeks). The main outcome measure was the association between thyroid function in early pregnancy and breech presentation at term. Univariate and multivariate analysis were performed to determine the association between thyroid function and breech presentation., Results: Increased TSH in pregnancy, defined as thyroid stimulating hormone (TSH) >97.5th percentile (>3.53mIU/L), was associated with a higher risk for breech presentation at term (aOR 2.32, CI 1.1-4.8, p=0.02) compared to euthyroidism (TSH between 2.5th and 97.5th percentile). After exclusion of overt hypothyroidism and hyperthyroidism the aOR was 2.34 (CI 1.1-5.0, p=0.03). Trimester specific analysis showed a significant association of increased TSH levels (>3.68mIU/L) in the second trimester with breech presentation (aOR 3.7, CI 1.7-7.8, p=0.001). In the second trimester low free thyroxine (FT4) <2.5th percentile (<6.7pmol/L) was also associated with breech presentation (aOR 2.5, CI 1.0-6.3, p=0.04)., Conclusions: Increased TSH and decreased FT4 in the second trimester of pregnancy are associated with an increased risk for breech presentation at term. The association of abnormal thyroid parameters in the first of third trimester is still unclear., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Importance: Maternal fish intake in pregnancy has been shown to influence fetal growth. The extent to which fish intake affects childhood growth and obesity remains unclear., Objective: To examine whether fish intake in pregnancy is associated with offspring growth and the risk of childhood overweight and obesity., Design, Setting, and Participants: Multicenter, population-based birth cohort study of singleton deliveries from 1996 to 2011 in Belgium, France, Greece, Ireland, Italy, the Netherlands, Norway, Poland, Portugal, Spain, and Massachusetts. A total of 26,184 pregnant women and their children were followed up at 2-year intervals until the age of 6 years., Exposures: Consumption of fish during pregnancy., Main Outcomes and Measures: We estimated offspring body mass index percentile trajectories from 3 months after birth to 6 years of age. We defined rapid infant growth as a weight gain z score greater than 0.67 from birth to 2 years and childhood overweight/obesity at 4 and 6 years as body mass index in the 85th percentile or higher for age and sex. We calculated cohort-specific effect estimates and combined them by random-effects meta-analysis., Results: This multicenter, population-based birth cohort study included the 26,184 pregnant women and their children. The median fish intake during pregnancy ranged from 0.5 times/week in Belgium to 4.45 times/week in Spain. Women who ate fish more than 3 times/week during pregnancy gave birth to offspring with higher body mass index values from infancy through middle childhood compared with women with lower fish intake (3 times/week or less). High fish intake during pregnancy (>3 times/week) was associated with increased risk of rapid infant growth, with an adjusted odds ratio (aOR) of 1.22 (95% CI, 1.05-1.42) and increased risk of offspring overweight/obesity at 4 years (aOR, 1.14 [95% CI, 0.99-1.32]) and 6 years (aOR, 1.22 [95% CI, 1.01-1.47]) compared with an intake of once per week or less. Interaction analysis showed that the effect of high fish intake during pregnancy on rapid infant growth was greater among girls (aOR, 1.31 [95% CI, 1.08-1.59]) than among boys (aOR, 1.11 [95% CI, 0.92-1.34]; P = .02 for interaction)., Conclusions and Relevance: High maternal fish intake during pregnancy was associated with increased risk of rapid growth in infancy and childhood obesity. Our findings are in line with the fish intake limit proposed by the US Food and Drug Administration and Environmental Protection Agency., Competing Interests: Disclosures: None reported.

Background: Low and high birth weight and accelerated postnatal weight gain are associated with an increased risk of obesity. Perinatal effects on energy intake and eating behavior have been proposed as underlying mechanisms. This study aimed to examine the independent associations of birth weight and postnatal weight and height gain with childhood energy intake and satiety response., Methods: In a birth cohort study, we used data from 2227 children (52% male), mean age 5.6 (±0.4) years. Mean daily energy intake and satiety response were parent-reported through validated questionnaires. Exposures were birth weight z-score and conditional weight and height gain between 0-1, 1-3, 3-6, 6-12 months and 12 months to 5 years. Conditional weight and height are residuals of current weight and height regressed on prior growth data, to represent deviations from expected growth. Analyses were adjusted for a set of potential confounding variables., Results: Conditional weight gain between 1-3, 3-6 months and 12 months to 5 years was significantly associated with energy intake, with 29.7 (95%-CI: 4.6; 54.8), 24.0 (1.8; 46.1) and 79.5 (29.4; 129.7) kcal/day more intake for each Z-score conditional weight gain between 1-3, 3-6 months and 12 months to 5 years, respectively. Conditional height gain between 0-1, 1-3 months and 12 months to 5 years was negatively associated with energy intake (β: -42.0 [66.6; -17.4] for 0-1 months, -35.1 [-58.4; -11.8] for 1-3 months and -37.4 [-72.4; -2.3] for 12 months to 5 years). Conditional weight gain in all periods was negatively associated with satiety response, with effect sizes from - 0.03 (-0.06; -0.002) in early infancy to -0.12 (-0.19; -0.06) in childhood. Birth weight was not associated with energy intake or satiety response., Conclusions: Our findings suggest that accelerated infant and childhood weight gain are associated with increased energy intake and diminished satiety response at 5 years. Accelerated height gain seems to be beneficial for childhood energy intake. This perinatal 'programming' of energy intake and eating behavior provide a potential mechanism linking early life influences with later obesity and cardiovascular disease.

Objective: To explore whether maternal vitamin B12 and folate status during early pregnancy are associated with cardiometabolic risk factors in the offspring at age 5-6., Design: Prospective multi-ethnic birth cohort, the Amsterdam Born Children and their Development study (ABCD)., Setting: 12,373 pregnant women living in Amsterdam were approached between 2003 and 2004 for participation in the study., Population: Mother-child pairs for whom information on maternal vitamin B12 or folate status in early gestation and health at age 5-6 years was available (n = 1950)., Methods: Vitamin B12 and folate concentrations were determined in maternal serum at intake in early pregnancy (median 13 weeks' gestation). Anthropometric measurements, blood pressure and fasting blood samples were collected during a health check of children aged 5-6 years. Multiple linear regression was performed to investigate the association between maternal serum concentrations and children's outcomes, corrected for confounders., Main Outcome Measures: Gestational age at birth, birthweight, body mass index (BMI), glucose levels, triglyceride levels, blood pressure and heart rate of the offspring at age 5-6., Results: Low maternal folate levels during early pregnancy were associated with slightly higher BMI in the offspring [decrease per 10 units: β 0.07 kg/m(2), 95% confidence interval (CI) 0.01, 0.13]. Low maternal vitamin B12 concentrations were associated with higher heart rates (decrease per 100 units: β 0.49 beats/min, 95% CI 0.11, 0.87)., Conclusion: This study provides further evidence that maternal nutrition in early pregnancy may possibly program cardiometabolic health of the offspring., Tweetable Abstract: Low folate and vitamin B12 levels during pregnancy are associated with higher BMI and heart rate in offspring., (© 2015 Royal College of Obstetricians and Gynaecologists.)

Background: The health effects of suspended particulate matter (PM) may depend on its chemical composition. Associations between maternal exposure to chemical constituents of PM and newborn's size have been little examined., Objective: We aimed to investigate the associations of exposure to elemental constituents of PM with term low birth weight (LBW; weight < 2,500 g among births after 37 weeks of gestation), mean birth weight, and head circumference, relying on standardized fine-scale exposure assessment and with extensive control for potential confounders., Methods: We pooled data from eight European cohorts comprising 34,923 singleton births in 1994-2008. Annual average concentrations of elemental constituents of PM ≤ 2.5 and ≤ 10 μm (PM2.5 and PM10) at maternal home addresses during pregnancy were estimated using land-use regression models. Adjusted associations between each birth measurement and concentrations of eight elements (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) were calculated using random-effects regression on pooled data., Results: A 200-ng/m3 increase in sulfur in PM2.5 was associated with an increased risk of LBW (adjusted odds ratio = 1.36; 95% confidence interval: 1.17, 1.58). Increased nickel and zinc in PM2.5 concentrations were also associated with an increased risk of LBW. Head circumference was reduced at higher exposure to all elements except potassium. All associations with sulfur were most robust to adjustment for PM2.5 mass concentration. All results were similar for PM10., Conclusion: Sulfur, reflecting secondary combustion particles in this study, may adversely affect LBW and head circumference, independently of particle mass., Citation: Pedersen M, Gehring U, Beelen R, Wang M, Giorgis-Allemand L, Andersen AM, Basagaña X, Bernard C, Cirach M, Forastiere F, de Hoogh K, Gražulevičienė R, Gruzieva O, Hoek G, Jedynska A, Klümper C, Kooter IM, Krämer U, Kukkonen J, Porta D, Postma DS, Raaschou-Nielsen O, van Rossem L, Sunyer J, Sørensen M, Tsai MY, Vrijkotte TG, Wilhelm M, Nieuwenhuijsen MJ, Pershagen G, Brunekreef B, Kogevinas M, Slama R. 2016. Elemental constituents of particulate matter and newborn's size in eight European cohorts. Environ Health Perspect 124:141-150; http://dx.doi.org/10.1289/ehp.1409546.

Objective: To investigate the consequences of weight loss in pregnancy on pregnancy outcomes and cardiometabolic profile in childhood., Design: Prospective birth cohort (ABCD study)., Setting: Between 2003 and 2004, all pregnant women in Amsterdam were approached for study participation., Population: 7818 pregnant women were included, of which 3165 consented to having their children examined at 5-6 years of age. In 1956 children fasting capillary blood samples were also taken., Methods: At antenatal booking, women answered questions about their pregnancy and whether they suffered from severe weight loss (SWL; >5 kg). Pregnancy details and outcomes were available through the obstetric caregiver., Main Outcome Measures: At birth main outcome measures were prematurity (<37 weeks) and birthweight. At follow-up, body mass index (BMI), blood pressure, glucose and lipids were assessed., Results: SWL occurred in 6.8% of cases. Women with SWL had similar preterm birth rates compared with women without these complaints (adjusted OR 1.1, 95%CI 0.7, 1.7). Birthweight (adjusted difference - 31 g, 95%CI -76, 15) and BMI at 5-6 years of age (adjusted difference 0.2 kg/m(2) , 95%CI 0.0, 0.5) were similar in children born to mothers with SWL and without SWL, but blood pressure was increased. For diastolic blood pressure this association was independent of confounders (adjusted difference 1.4 mmHg, 95%CI 0.4, 2.4). Lipid and glucose levels were not significantly different between these groups., Conclusion: Early pregnancy weight loss, usually occurring as a manifestation of hyperemesis gravidarum, could have long-term consequences for offspring health., (© 2014 Royal College of Obstetricians and Gynaecologists.)

Objective: Overt hypothyroidism in pregnant women is associated with a lower intelligence quotient in their children. More recently, subtle decreases in maternal thyroid function have also been associated with neurodevelopmental impairment in offspring. We tested the effect of hypothyroxinaemia during early pregnancy on school performance., Design: This was a longitudinal study that included the data of 1196 mother-child pairs from the Amsterdam Born Children and Their Development study., Methods: Maternal serum free thyroxine (T4) and TSH were obtained at a median gestational age of 12.9 (interquartile range: 11.9-14.3) weeks. School performance was assessed at age 5 years and based on scores obtained in arithmetic and language tests from the national monitoring and evaluation system. Poor school performance was defined as a test result <25th percentile and subnormal school performance as a result <50th percentile of the norm population. To estimate the impact of possible non-response bias, we conducted inverse-probability weighted analyses., Results: Maternal hypothyroxinaemia (i.e., a maternal free T4 in the lowest 10% of distribution) was associated with a 1.61 (95% CI: 1.05-2.47) -fold increased odds of subnormal arithmetic performance after adjustment for confounders (P=0.03). However, the odds ratio dropped to 1.48 (95% CI: 0.94-2.32) after inverse-probability weighting (P=0.09). No such relations were found with TSH., Conclusions: Maternal hypothyroxinaemia at the end of the first trimester was associated with reduced performance in an arithmetic test, but not in a language test, in 5-year-old offspring. However, our results should be interpreted carefully because of possible non-response bias., (© 2015 European Society of Endocrinology.)

Background: A causal relationship between maternal obesity and offspring asthma is hypothesized to begin during early development, but no underlying mechanism for the found association is identified. We quantitatively examined mediation by offspring body mass index (BMI) in the association of maternal pre-pregnancy BMI on risk of asthma and wheezing during the first 7-8 years of life in a large Amsterdam born birth cohort., Methods: For 3185 mother-child pairs, mothers reported maternal pre-pregnancy BMI and offspring outcomes "ever being diagnosed with asthma" and "wheezing in the past 12 months" on questionnaires. We measured offspring height and weight at age 5-6 years. We performed a multivariate log linear regression comparing outcomes in offspring of mothers with different BMI categories. For each category we quantified and tested mediation by offspring BMI and also investigated interaction by parental asthma., Results: At the age of 7-8 years, 8% of the offspring ever had asthma and 7% had current wheezing. Maternal pre-pregnancy obesity was associated with higher risks of asthma (adjusted RR 2.32 (95% CI: 1.49-3.61) and wheezing (adjusted RR 2.16 (95% CI: 1.28-3.64). Offspring BMI was a mediator in the association between maternal BMI and offspring wheezing, but not for asthma. There was no interaction by parental asthma., Conclusions: Maternal pre-pregnancy obesity was associated with higher risks of offspring asthma and wheezing. The association between maternal obesity and offspring wheezing was both direct and indirect (mediated) through the child's own BMI.

Background and Objective: Several early life determinants play a role in childhood obesity. Rapid weight gain and overweight in infancy increases the risk while breast feeding seems to protect against childhood overweight. However, should we worry about exclusively breastfed overweight infants? The aim of the study is to examine the association of feeding type (exclusive breast feeding (EBF), formula feeding or mixed feeding) and overweight at the age of 6 months with the risk of overweight at the age of 5-6 years., Methods: The Amsterdam Born Children and their Development study is a large prospective population-based birth cohort study conducted in Amsterdam, the Netherlands. Children with complete information pertaining to feeding type and weight status at the age of 6 months and 5-6 years were included (N=3367). EBF was defined as receiving only breast feeding for at least 3 months. Overweight at the ages of 6 months and 5-6 years were defined by the WHO child growth standards and the International Obesity Task Force guidelines, respectively. The association of feeding type and overweight at 6 months with overweight at 5-6 years was assessed using logistic regression analyses., Results: Overweight infants have a 4.10-fold (95% CI 2.91 to 5.78) higher odds of childhood overweight compared with those who were not overweight, independent of feeding type. EBF did not affect the association between infant overweight and childhood overweight., Conclusions: Overweight in infancy increases the odds of childhood overweight, equally for exclusively breastfed and formula fed infants. Overweight prevention should start before or at birth and applies to formula fed children as well as exclusively breastfed children., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: In adults, increased sympathetic and decreased parasympathetic nervous system activity are associated with a less favorable metabolic profile. Whether this is already determined at early age is unknown. Therefore, we aimed to assess the association between autonomic nervous system activation and metabolic profile and its components in children at age of 5-6 years., Methods: Cross-sectional data from an apparently healthy population (within the ABCD study) were collected at age 5-6 years in 1540 children. Heart rate (HR), respiratory sinus arrhythmia (RSA; parasympathetic activity) and pre-ejection period (PEP; sympathetic activity) were assessed during rest. Metabolic components were waist-height ratio (WHtR), systolic blood pressure (SBP), fasting triglycerides, glucose and HDL-cholesterol. Individual components, as well as a cumulative metabolic score, were analyzed., Results: In analysis adjusted for child's physical activity, sleep, anxiety score and other potential confounders, increased HR and decreased RSA were associated with higher WHtR (P< 0.01), higher SBP (p<0.001) and a higher cumulative metabolic score (HR: p < 0.001; RSA: p < 0.01). Lower PEP was only associated with higher SBP (p <0.05). Of all children, 5.6% had 3 or more (out of 5) adverse metabolic components; only higher HR was associated with this risk (per 10 bpm increase: OR = 1.56; p < 0.001)., Conclusions: This study shows that decreased parasympathetic activity is associated with central adiposity and higher SBP, indicative of increased metabolic risk, already at age 5-6 years.

Background: A healthy start to life is a major priority in efforts to reduce health inequalities across Europe, with important implications for the health of future generations. There is limited combined evidence on inequalities in health among newborns across a range of European countries., Methods: Prospective cohort data of 75 296 newborns from 12 European countries were used. Maternal education, preterm and small for gestational age births were determined at baseline along with covariate data. Regression models were estimated within each cohort and meta-analyses were conducted to compare and measure heterogeneity between cohorts., Results: Mother's education was linked to an appreciable risk of preterm and small for gestational age (SGA) births across 12 European countries. The excess risk of preterm births associated with low maternal education was 1.48 (1.29 to 1.69) and 1.84 (0.99 to 2.69) in relative and absolute terms (Relative/Slope Index of Inequality, RII/SII) for all cohorts combined. Similar effects were found for SGA births, but absolute inequalities were greater, with an SII score of 3.64 (1.74 to 5.54). Inequalities at birth were strong in the Netherlands, the UK, Sweden and Spain and marginal in other countries studied., Conclusions: This study highlights the value of comparative cohort analysis to better understand the relationship between maternal education and markers of fetal growth in different settings across Europe., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)