Changes in parental smoking during pregnancy and risks of adverse birth outcomes and childhood overweight in Europe and North America: An individual participant data meta-analysis of 229,000 singleton births.

BACKGROUND: Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. METHODS AND FINDINGS: We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers' median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02-1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02-1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07-2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35-1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52-2.34] instead of OR 2.20 [95% CI 2.02-2.42] when reducing from 5-9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39-3.25] and OR 1.93 [95% CI 1.46-2.57] instead of OR 2.95 [95% CI 2.75-3.15] when reducing from ≥10 to 5-9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16-1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations. CONCLUSIONS: We observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy.

Growth patterns from birth to overweight at age 5-6 years of children with various backgrounds in socioeconomic status and country of origin: the ABCD study.

INTRODUCTION: Children from minority groups are at increased risk of overweight. This study compared BMI growth patterns from birth onwards of boys and girls with overweight at 5-6 years, according to socioeconomic status (SES) and country of origin, in order to gain more insight into the critical periods of growth to overweight. METHODS: A total of 3714 singletons of the multi-ethnic ABCD study were included. Within children with overweight at age 5-6 years (N = 487, prevalence boys: 11.6%, girls: 14.6%), BMI growth patterns from birth onwards (12.8 serial measurements; SD = 3.1) were compared between children from European (69.4%) and non-European mothers (30.6%), and between children from low (20.8%), mid (37.0%) or high SES (42.2%), based on maternal educational level. RESULTS: BMI growth to overweight did not differ between children of European or non-European mothers, but it did differ according to maternal SES. Children with overweight in the low and mid SES group had a lower BMI in the first 2 years of life, an earlier adiposity rebound and increased in BMI more rapidly after age 2, resulting in a higher BMI at age 7 years compared to children with overweight in the high SES group [∆BMI (kg/m2 ) between high and low SES: boys 1.43(95%CI:0.16;3.01) and girls 1.91(0.55;3.27)]. CONCLUSION: Children with overweight from low SES have an early adiposity rebound and accelerated growth to a higher BMI at age 5-6 years compared to children with overweight from the high SES group. These results imply that timing of critical periods for overweight development is earlier in children with a low socioeconomic background as compared to other children.

Does maternal pre-pregnancy overweight or obesity influence offspring's growth patterns from birth up to 7years? The ABCD-study.

BACKGROUND: Maternal pre-pregnancy overweight is known to program offspring for adverse health outcomes later in life. AIMS: To investigate how growth patterns of weight, height and BMI from birth to 7years differ according to maternal pre-pregnancy weight (normal weight, overweight and obesity), with specific attention for sex differences. STUDY DESIGN: Prospective multi-ethnic ABCD-study. SUBJECTS: 3805 mother-child pairs were included. Self-reported maternal pre-pregnancy body mass index was categorized into: normal weight (18.5-25kg/m2; n=3354), overweight (25-30kg/m2; n=711) and obesity (≥30kg/m2; n=241). OUTCOME MEASURES: Population-specific growth patterns were used to compute SD-scores for weight, height and BMI (on average 12.7 (SD=2.6) measurements for each child) for term born boys and girls separately. Mixed effect models were fitted to these SD-scores to determine the effect of pre-pregnancy BMI category on postnatal growth, corrected for maternal characteristics. RESULTS: Compared to children of mothers with normal weight before pregnancy, children of overweight mothers grew faster in weight and BMI (boys and girls) and children of obese mothers grew faster in height (only girls), weight and BMI (boys and girls) during the first years of life. The differences seemed to increase with age and were in general larger in girls. CONCLUSION: Maternal overweight and obesity impact on offspring's weight, height and BMI growth pattern with increasing differences when children age. Effects were in general stronger for girls. These results suggest that a healthy weight before pregnancy may be beneficial for optimal weight, height and BMI growth in the offspring.

Pre-pregnancy weight status, early pregnancy lipid profile and blood pressure course during pregnancy: The ABCD study.

OBJECTIVE: Although pre-pregnancy weight status and early pregnancy lipid profile are known to influence blood pressure course during pregnancy, little is known about how these two factors interact. The association between pre-pregnancy weight status and blood pressure course during pregnancy was assessed in the prospective ABCD study and the role (independent/mediating/moderating) of early pregnancy lipid profile in this association was determined. METHODS: We included 2500 normal weight (<25 kg/m2) and 600 overweight (≥25 kg/m2) women from the prospective ABCD-study with available measurements of non-fasting early pregnancy lipids [median (IQR): 13 (12-14) weeks of gestation] and blood pressure during pregnancy [mean (SD) = 10 (2.3)]. Lipids (triglycerides, total cholesterol, apolipoprotein A1, apolipoprotein B and free fatty acids) were divided into tertiles. Multilevel piecewise linear spline models were used to describe the course of systolic and diastolic blood pressure (SBP/DBP) in four time periods during gestation for overweight and normal weight women. RESULTS: Both SBP (5.3 mmHg) and DBP (3.9 mmHg) were higher in overweight compared to normal weight women and this difference remained the same over all four time periods. The difference in SBP and DBP was not mediated or moderated by the lipid profile. Lipid profile had an independent positive effect on both SBP (range 1.3-2.2 mmHg) and DBP (0.8-1.1 mmHg), but did not change blood pressure course. CONCLUSIONS: Both pre-pregnancy weight status and early pregnancy lipid profile independently increase blood pressure during pregnancy. Improving pre-pregnancy weight status and early pregnancy lipid profile might result in a healthier blood pressure course during pregnancy.

Maternal early pregnancy lipid profile and offspring's lipids and glycaemic control at age 5-6 years: The ABCD study.

BACKGROUND & AIMS: Maternal early pregnancy lipid profile might influence offspring's lipids and glycaemic control, through an increased offspring's fat percentage. This explorative study investigates whether maternal early pregnancy lipid profile is associated with offspring's lipids and glycaemic control independently of offspring's fat percentage and if these associations are mediated by offspring's fat percentage. Possible sex differences in these associations are also examined. METHODS: 1133 mother-child pairs of the prospective ABCD-study were included. Maternal non-fasting lipids were collected in early pregnancy: triglycerides, total cholesterol (TC), Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB) and free fatty acids (FFA). Fasting triglycerides, TC, high density lipoprotein (HDL), low density lipoprotein (LDL), glucose and C-peptide were assessed in offspring aged 5-6 years and HOMA2-IR was calculated. RESULTS: After adjustment for covariates, strongest associations were found between maternal TC and offspring's TC (boys ß(95%CI) = 0.141 (0.074-0.207); girls ß(95%CI) = 0.268 (0.200; 0.336)) and LDL (boys ß(95%CI) = 0.114 (0.052; 0.176); girls ß(95%CI) = 0.247 (0.181-0.312)), maternal ApoB and offspring's TC (boys ß(95%CI) = 0.638 (0.311-0.965); girls ß(95%CI) = 1.121 (0.766-1.475)) and LDL (boys ß(95%CI) = 0.699 (0.393-1.005); girls ß(95%CI) = 1.198 (0.868-1.529)), and maternal ApoA1 and offspring's HDL (only boys ß(95%CI) = 0.221 (0.101-0.341)). No significant association was found between maternal lipids and offspring's glycaemic control, and offspring's fat percentage played no mediating role. CONCLUSIONS: Maternal early pregnancy lipid profile is associated with offspring's lipid profile in childhood, with overall stronger associations in girls. This study provides further evidence that lowering lipid levels during pregnancy might be beneficial for the long term health of the offspring.

Is first trimester vitamin D status in nulliparous women associated with pregnancy related hypertensive disorders?

OBJECTIVES: this study aimed to explore if maternal vitamin D status in early pregnancy was associated with pre-eclampsia and pregnancy-induced hypertension. Relationships between vitamin D status and blood pressure at the start of pregnancy as well as the occurrence of a mid-pregnancy drop in blood pressure were also explored. This secondary analysis was completed to investigate a possible mechanism for the association between vitamin D status and pregnancy related hypertensive disorders. DESIGN AND SETTING: data were obtained from the Amsterdam Born Children and their Development study, a prospective community-based cohort study based in Amsterdam, The Netherlands. PARTICIPANTS: a total of 2074 nulliparous women without pre-existing hypertension and with a known vitamin D status before 17 weeks gestation were included in the study. Vitamin D status was categorized into four groups: "normal" (≥50nmol/L), "insufficient" (30-49.9nmol/L) "deficient" (20-29.9nmol/L) or "severely deficient" (<20nmol/L). MEASUREMENTS: logistic regression analysis was used to investigate if vitamin D status was related to the odds of experiencing pre-eclampsia or pregnancy-induced hypertension. Models were corrected for maternal age, ethnicity, pre-pregnancy BMI, smoking and socioeconomic status. χ(2) and ANOVA tests were used to investigate relationships between vitamin D status and the blood pressure parameters. FINDINGS: when compared to women with a normal vitamin D status, women who were severely deficient had an increased risk for pre-eclampsia (OR 2.08; 95% CI, 1.05-4.13), but the association was rendered non-significant after correction (OR 1.88; 95% CI 0.79-4.48). There were no associations between vitamin D status and pregnancy-induced hypertension, starting blood pressure or the occurrence of a mid-pregnancy drop in blood pressure. KEY CONCLUSIONS: no strong evidence was found for an association between first trimester vitamin D status and pregnancy related hypertensive disorders in nulliparous women. IMPLICATIONS FOR PRACTICE: at this time, vitamin D supplementation is not warranted for the specific purpose of preventing pregnancy related hypertensive disorders.

The Association between Maternal 25-Hydroxyvitamin D Concentration during Gestation and Early Childhood Cardio-metabolic Outcomes: Is There Interaction with Pre-Pregnancy BMI?

Both maternal 25-hydroxyvitamin D (25OHD) status and pre-pregnancy BMI (pBMI) may influence offspring cardio-metabolic outcomes. Lower 25OHD concentrations have been observed in women with both low and high pBMIs, but the combined influence of pBMI and 25OHD on offspring cardio-metabolic outcomes is unknown. Therefore, this study investigated the role of pBMI in the association between maternal 25OHD concentration and cardio-metabolic outcomes in 5-6 year old children. Data were obtained from the ABCD cohort study and 1882 mother-child pairs were included. The offspring outcomes investigated were systolic and diastolic blood pressure, heart rate, BMI, body fat percentage (%BF), waist-to-height ratio, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, glucose, C-peptide, and insulin resistance (HOMA2-IR). 62% of the C-peptide samples were below the detection limit and were thus imputed using survival analysis. Models were corrected for maternal and offspring covariates and tested for interaction with pBMI. Interaction with pBMI was observed in the associations with insulin resistance markers: in offspring of overweight mothers (≥25.0 kg/m2), a 10 nmol/L increase in maternal 25OHD was associated with a 0.007(99%CI:-0.01,-0.001) nmol/L decrease in C-peptide and a 0.02(99%CI:-0.03,-0.004) decrease in HOMA2-IR. When only non-imputed data were analyzed, there was a trend for interaction in the relationship but the results lost significance. Interaction with pBMI was not observed for the other outcomes. A 10 nmol/L increase in maternal 25OHD was significantly associated with a 0.13%(99%CI:-0.3,-0.003) decrease in %BF after correction for maternal and child covariates. Thus, intrauterine exposure to both low 25OHD and maternal overweight may be associated with increased insulin resistance in offspring, while exposure to low 25OHD in utero may be associated with increased offspring %BF with no interactive effects from pBMI. Due to the limitations of this study, these results are not conclusive, however the observations of this study pose important research questions for future studies to investigate.

Maternal prepregnancy BMI, offspring's early postnatal growth, and metabolic profile at age 5-6 years: the ABCD Study.

CONTEXT: Maternal prepregnancy body mass index (pBMI) and offspring's accelerated postnatal growth have adverse consequences for later cardiometabolic health, but it is unknown how these two factors interact. OBJECTIVE: To assess the association between maternal pBMI and offspring's metabolic profile at age 5-6 years and determine the role (independent/mediating/moderating) of offspring's postnatal growth in this association. DESIGN/PARTICIPANTS: In total, 1459 mother-child pairs from the prospective ABCD study with known maternal pBMI, offspring postnatal growth (weight and weight-for-length gain) between age 1-3 months (Δ SD score). MAIN OUTCOME MEASURES: We analyzed metabolic components of offspring at age 5-6 years, including waist-to-height-ratio (WHtR), systolic/diastolic blood pressure (SBP/DBP), fasting glucose, triglycerides, and high-density lipoprotein-cholesterol values, both individually (Z-scores) and combined (sum Z-scores; metabolic score). RESULTS: Maternal pBMI was positively associated with offspring's WHtR (ß = 0.025; 95% confidence interval [CI], 0.010-0.039), SBP (ß = 0.020; 95% CI, 0.005-0.0035), DBP (ß = 0.016; 95% CI, 0.000-0.031), and metabolic score (ß = 0.078; 95% CI, 0.039-0.118) after adjusting. Adding postnatal growth had no relevant impact on these effect sizes. Postnatal weight gain was independently associated with WHtR (ß = 0.199; 95% CI, 0.097-0.300), fasting glucose values (ß = 0.117; 95% CI, 0.008-0.227), metabolic score (ß = 0.405; 95% CI, 0.128-0.682). Postnatal weight-for-length gain was independently associated with WHtR (ß = 0.145; 95% CI, 0.080-0.211), and metabolic score (ß = 0.301; 95% CI, 0.125-0.477). An interaction between maternal pBMI and postnatal weight gain was present in the association with SBP (P = .021) and metabolic score (P = .047), and between maternal pBMI and postnatal weight-for-length gain in the association with triglycerides (P = .022) and metabolic score (P = .042). CONCLUSIONS: Both high maternal pBMI and postnatal accelerated growth are associated with adverse metabolic components in early childhood. No evidence was found for a mediating role of postnatal growth. The combination of high maternal pBMI and postnatal accelerated growth amplified individual effects.

Maternal prepregancy BMI and lipid profile during early pregnancy are independently associated with offspring's body composition at age 5-6 years: the ABCD study.

BACKGROUND: There is growing evidence that disturbances in maternal metabolism and, subsequently, intrauterine conditions affect foetal metabolism. Whether this has metabolic consequences in offspring later in life is not fully elucidated. We investigated whether maternal pre-pregnancy body mass index (pBMI) is associated with offspring's adiposity at age 5-6 years and whether this association is mediated by the mother's lipid profile during early pregnancy. METHODS: Data were derived from a multi-ethnic birth cohort, the Amsterdam Born Children and their Development (ABCD) study (inclusion 2003-2004). During early gestation mothers completed a questionnaire during pregnancy (pBMI) and random non-fasting blood samples were analysed for total cholesterol (TC), triglycerides (TG), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and total free fatty acids (FFA) in early gestation. At age 5-6 years, child's BMI, waist-to-height-ratio (WHtR) and fat% were assessed. RESULTS: Only non-diabetic mothers with at term-born children were included (n = 1727). Of all women, 15.1% were overweight(BMI: 25-29.9 kg/m2) and 4.3% were obese (BMI≥30 kg/m2). After adjustments for confounders, every unit increase in pBMI was linearly associated with various offspring variables: BMI (ß 0.10; 95% CI 0.08-0.12), WHtR*100 (ß 0.13; 95% CI 0.09-0.17), fat% (ß 0.21; 95% CI 0.13-0.29) and increased risk for overweight (OR:1.15; 95% CI 1.10-1.20). No convincing proof for mediation by maternal lipid profile during early gestation was found. Moreover, maternal FFA was associated with the child's fat percentage, BMI and risk for overweight. Maternal ApoB and TC were positively associated with the offspring's fat percentage and maternal TG was positively associated with their children's WHtR. CONCLUSIONS: Both pBMI and maternal lipids during early pregnancy are independently related to offspring adiposity.