Placental characteristics and risks of maternal mortality 50 years after delivery.

INTRODUCTION: Adverse pregnancy outcomes such as preterm delivery and preeclampsia are associated with a higher maternal risk for subsequent cardiovascular disease (CVD) and all-cause mortality. While such pregnancy conditions are related to abnormal placentation, little research has investigated whether pathologic placental measures could serve as a risk factor for future CVD mortality in mothers. METHODS: Longitudinal study of 33,336 women from the Collaborative Perinatal Project (CPP; 1959-1966) linked to mortality information through December 2016. Pathologists took extensive morphological and histopathological measures. Apart from assessing associations with morphological features, we derived an overall composite score and specific inflammation-related, hemorrhage-related, and hypoxia-related pathologic placenta index scores. Cox regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for mortality adjusting for covariates. RESULTS: Thirty-nine percent of women died with mean (standard deviation, SD) time to death of 39 (12) years. Mean (SD) placental weight and birthweight were 436 g (98) and 3156 g (566), respectively. Placenta-to-birthweight ratio was associated with all-cause mortality (adjusted HR 1.03: 1.01, 1.05 per SD in ratio). In cause-specific analyses, it was significantly associated with respiratory (HR 1.06), dementia (HR: 1.10) and liver (HR 1.04) related deaths. CVD, cancer, diabetes and kidney related deaths also tended to increase, whereas infection related deaths did not (HR 0.94; 0.83, 1.06). Placental measures of thickness, diameters, and histopathological measures grouped by inflammatory, hemorrhagic, or hypoxic etiology were not associated with mortality. DISCUSSION: Placental weight in relation to birthweight was associated with long-term maternal mortality but other histopathologic or morphologic features were not.

Associations of prenatal and early life dietary inflammatory potential with childhood adiposity and cardiometabolic risk in Project Viva.

BACKGROUND: Limited information exists regarding the association between early-life diet and cardiometabolic risk. OBJECTIVES: Examine associations of dietary inflammatory index (DII) in pregnancy and early childhood (3-5 years) with adiposity, blood pressure and metabolic markers in mid-childhood (6-10 years). METHODS: Among 992 mother-child pairs from Project Viva, a pre-birth cohort, we examined associations of DII scores with outcomes using multivariable linear regression adjusted for child age and sex and maternal age, BMI, education, parity, smoking, race and income. RESULTS: Mean (SD) maternal DII in pregnancy was -2.6(1.4) units and in child DII in early childhood was 0.3(0.7). Mean mid-childhood BMI z-score was 0.40(0.98) units. In boys only, DII in early childhood was associated with higher BMIz (adjusted ß = 0.16 units per unit DII, 95%CI 0.02, 0.29), waist circumference (0.93 cm; -0.07, 1.92) and skin fold thicknesses (1.12 mm; 0.01, 2.23). Dietary inflammatory index in the highest quartiles during both pregnancy and in early childhood, compared to the lowest quartiles, was associated with higher waist circumference (2.4 cm; 0.14, 4.6) in all children, and BMIz in boys (0.78 units; 0.34, 1.22). Associations with BP and metabolic markers were null. CONCLUSIONS: A pro-inflammatory diet in pregnancy and early childhood may promote the development of adiposity.

Childcare before age 6 and body mass index at age 7 years in a cohort of Danish children.

BACKGROUND: Previous studies show inconsistent associations between childcare and obesity. AIMS: Our prior work demonstrated that childcare in infancy was associated with higher weight in a cohort of Danish children. Here, we extend this work and examine childcare through 6 years and body mass index (BMI) at age 7 years. MATERIALS AND METHODS: We examined 24 714 children in the Danish National Birth Cohort who were also in the Childcare Database. We conducted multivariable linear regressions examining children prior to age 6, overall and by type (daycare, crèche, age-integrated and kindergarten), and BMI z-score at 7 years, stratifying on maternal socio-occupational status. RESULTS: A total of 19 760 (80.0%) children attended childcare before age 6. Childcare prior to age 6 was associated with BMI z-score at 7 years (0.004 units per each additional 6 months of care; 95% CI: 0.001, 0.008; p = 0.01). Childcare in a kindergarten was the only type of care associated with BMI (0.009 units; 95% CI: 0.003, 0.02; p = 0.01). For children of higher socio-occupational status mothers, childcare was associated with a 0.008 unit increase in BMI (95% CI: 0.004, 0.01; p > 0.001). CONCLUSIONS: Childcare was weakly associated with later BMI. This relationship was more pronounced in children from higher socio-occupational status mothers and children in kindergarten care.

Adherence to the Mediterranean diet during pregnancy and offspring adiposity and cardiometabolic traits in childhood.

BACKGROUND: In adults, adherence to the Mediterranean diet has been inversely associated with cardiovascular risk, but the extent to which diet in pregnancy is associated with offspring adiposity is unclear. We aimed to investigate the association between adherence to Mediterranean diet in pregnancy and offspring cardiometabolic traits in two pregnancy cohorts. METHODS: We studied 997 mother-child pairs from Project Viva in Massachusetts, USA, and 569 pairs from the Rhea study in Crete, Greece. We estimated adherence to the Mediterranean diet with an a priori defined score (MDS) of nine foods and nutrients (0 to 9). We measured child weight, height, waist circumference, skin-fold thicknesses, blood pressure, and blood levels of lipids, c-reactive protein and adipokines in mid-childhood (median 7.7 years) in Viva, and in early childhood (median 4.2 years) in Rhea. We calculated cohort-specific effects and pooled effects estimates with random-effects models for cohort and child age. RESULTS: In Project Viva, the mean (SD, standard deviation) MDS was 2.7 (1.6); in Rhea it was 3.8 (1.7). In the pooled analysis, for each 3-point increment in the MDS, offspring BMI z-score was lower by 0.14 units (95% CI, -0.15 to -0.13), waist circumference by 0.39 cm (95% CI, -0.64 to -0.14), and the sum of skin-fold thicknesses by 0.63 mm (95% CI, -0.98 to -0.28). We also observed lower offspring systolic (-1.03 mmHg; 95% CI, -1.65 to -0.42) and diastolic blood pressure (-0.57 mmHg; 95% CI, -0.98 to -0.16). CONCLUSION: Greater adherence to Mediterranean diet during pregnancy may protect against excess offspring cardiometabolic risk.

Prenatal and early life exposure to traffic pollution and cardiometabolic health in childhood.

BACKGROUND: Prenatal exposure to traffic pollution has been associated with faster infant weight gain, but implications for cardiometabolic health in later childhood are unknown. METHODS: Among 1418 children in Project Viva, a Boston-area pre-birth cohort, we assessed anthropometric and biochemical parameters of cardiometabolic health in early (median age 3.3 years) and mid- (median age 7.7 years) childhood. We used spatiotemporal models to estimate prenatal and early life residential PM2.5 and black carbon exposure as well as traffic density and roadway proximity. We performed linear regression analyses adjusted for sociodemographics. RESULTS: Children whose mothers lived close to a major roadway at the time of delivery had higher markers of adverse cardiometabolic risk in early and mid-childhood. For example, total fat mass was 2.1 kg (95%CI: 0.8, 3.5) higher in mid-childhood for children of mothers who lived <50 m vs. ≥200 m from a major roadway. Black carbon exposure and traffic density were generally not associated with cardiometabolic parameters, and PM2.5 exposure during the year prior was paradoxically associated with improved cardiometabolic profile. CONCLUSIONS: Infants whose mothers lived close to a major roadway at the time of delivery may be at later risk for adverse cardiometabolic health.

Association of prenatal antibiotics with foetal size and cord blood leptin and adiponectin.

BACKGROUND: Early postnatal antibiotic use has been shown to promote excess weight gain, but it is unclear whether intrauterine exposure to antibiotics is associated with foetal growth and adiposity. The objective of this study was to examine associations of antibiotic prescription in each trimester of pregnancy with foetal size and adipokine levels at birth. METHODS: In 2128 pregnant women from the pre-birth Project Viva cohort, from electronic medical records, we estimated antibiotic prescribing by timing during pregnancy. Outcomes were sex-specific birth weight-for-gestational-age z-score (BW/GA-z) and levels of umbilical cord leptin and adiponectin. We used linear regression models adjusted for maternal age, pre-pregnancy body mass index, parity, race/ethnicity, education, smoking during pregnancy, household income and child sex and additionally adjusted cord blood leptin and adiponectin models for gestation length. RESULTS: Of the 2128 women in our sample, 643 (30.2%) were prescribed with oral antibiotics during pregnancy. Mean (standard deviation) BW/GA-z was 0.17 (0.97), cord blood leptin was 9.0 ng mL-1 (6.6) and cord blood adiponectin was 28.8 ng mL-1 (6.8). Overall, antibiotic prescription in pregnancy was associated with lower BW/GA-z [multivariable adjusted ß -0.11; 95% confidence interval {CI} -0.20, -0.01]. In trimester-specific analyses, only second trimester antibiotic prescription was associated with lower BW/GA-z (ß -0.23; 95% CI -0.37, -0.08). Overall, antibiotic prescription in pregnancy was not associated with cord blood leptin or adiponectin levels. However, in trimester-specific analyses, third trimester antibiotic prescription was associated with higher cord blood leptin (ß 2.28 ng mL-1 ; 95% CI 0.38, 4.17). CONCLUSIONS: Antibiotics in mid-pregnancy were associated with lower birth weight for gestational age, whereas third trimester antibiotics were associated with higher cord blood leptin.

Longitudinal study of maternal body mass index, gestational weight gain, and offspring asthma.

BACKGROUND: Sparse data are available on the relationship between prenatal exposures and asthma during later childhood. In a longitudinal study of adolescents and their mothers, we examined the association of (i) maternal prepregnancy body mass index (BMI) and (ii) gestational weight gain (GWG), with incidence of allergic and nonallergic asthma in offspring. METHODS: Analyses were conducted using data from 12 963 children aged 9-14 years at enrolment in the Growing Up Today Study, and their mothers, who are participants in the Nurses' Health Study II. Physician-diagnosed asthma and allergies were assessed by questionnaires sent regularly to participants and their mothers. Logistic regression was used to evaluate associations of maternal BMI and GWG with offspring asthma, overall and by subtype. RESULTS: Physician-diagnosed asthma during childhood or adolescence was reported by 2694 children (21%). Maternal prepregnancy overweight (OR: 1.19, 95% CI: 1.03-1.38) and obesity (1.34, 1.08-1.68) were associated with offspring asthma. In asthma subtype analyses, the association was seen only for asthma onset before age 12 years. Moreover, the association of maternal obesity with nonallergic asthma was observed in boys (2.39, 1.40-4.09) and not in girls (0.96, 0.50-1.85; Pinteraction = 0.03); the opposite pattern was suggested for allergic asthma. With regard to GWG, an association was suggested between gains of <15 lb and higher risk of offspring asthma (1.28, 0.98-1.66), without clear allergy- or sex-related patterns. CONCLUSION: The relation of several prenatal factors to risk of childhood asthma supports the early origins hypothesis for asthma. The observed allergy- and sex-specific patterns suggest multiple etiologic pathways.

The effect of antenatal lifestyle advice for women who are overweight or obese on secondary measures of neonatal body composition: the LIMIT randomised trial.

OBJECTIVE: To evaluate the effect of providing antenatal dietary and lifestyle advice on neonatal anthropometry, and to determine the inter-observer variability in obtaining anthropometric measurements. DESIGN: Randomised controlled trial. SETTING: Public maternity hospitals across metropolitan Adelaide, South Australia. POPULATION: Pregnant women with a singleton gestation between 10(+0) and 20(+0) weeks, and body mass index (BMI) ≥25 kg/m(2). METHODS: Women were randomised to either Lifestyle Advice (comprehensive dietary and lifestyle intervention over the course of pregnancy including dietary, exercise and behavioural strategies, delivered by a research dietician and research assistants) or continued Standard Care. Analyses were conducted using intention-to-treat principles. MAIN OUTCOME MEASURES: Secondary outcome measures for the trial included assessment of infant body composition using body circumference and skinfold thickness measurements (SFTM), percentage body fat, and bio-impedance analysis of fat-free mass. RESULTS: Anthropometric measurements were obtained from 970 neonates (488 Lifestyle Advice Group, and 482 Standard Care Group). In 394 of these neonates (215 Lifestyle Advice Group, and 179 Standard Care Group) bio-impedance analysis was also obtained. There were no statistically significant differences identified between those neonates born to women receiving Lifestyle Advice and those receiving Standard Care, in terms of body circumference measures, SFTM, percentage body fat, fat mass, or fat-free mass. The intra-class correlation coefficient for SFTM was moderate to excellent (0.55-0.88). CONCLUSIONS: Among neonates born to women who are overweight or obese, anthropometric measures of body composition were not modified by an antenatal dietary and lifestyle intervention.

Leisure time physical activity before and during mid-pregnancy and offspring adiposity in mid-childhood.

BACKGROUND: Effects of maternal leisure time physical activity (LTPA) on paediatric obesity are unknown. The objective of this study was to examine associations of maternal LTPA with offspring overall and central adiposity in mid-childhood. METHODS: We analysed data from 802 mother-child dyads from Project Viva, a prospective pre-birth cohort study. Women reported average weekly LTPA before and during mid-pregnancy. At age 7-10 years, we measured fat, truncal fat and lean mass with dual-energy X-ray absorptiometry. Using multivariable linear regression, we examined associations of maternal LTPA with offspring adiposity, adjusting for child age and sex, maternal race/ethnicity, education, age, pre-pregnancy body mass index, marital status and smoking status. RESULTS: Mean (standard deviation) of LTPA before and during mid-pregnancy were 9.5 (8.1) and 7.1 (7.0) h week(-1) . At mean age 7.8 (0.8) years, childhood fat, truncal fat and lean mass indices were 4.3 (1.8), 1.4 (0.8) and 12.9 (1.4) kg m(-2) . We did not find that higher maternal LTPA was associated with lower child adiposity outcomes. For example, compared with 0-3 h week(-1) of LTPA during mid-pregnancy, children of mothers with +8 h week(-1) had fat mass index 0.07 kg m(-2) (95% confidence interval: -0.22, 0.36). In analyses of within-person LTPA change from before to mid-pregnancy, compared with +2 h week(-1) decrease in LTPA, increased LTPA (2 ± h week(-1) ) was associated with a 0.09 kg m(-2) fat mass index (-0.25, 0.43). CONCLUSIONS: Contrary to our hypothesis, higher LTPA before and during mid-pregnancy, and the change between them, were not associated with lower adiposity in mid-childhood.

Associations of cord blood metabolites with early childhood obesity risk.

BACKGROUND/OBJECTIVE: Rapid postnatal weight gain is a potentially modifiable risk factor for obesity and metabolic syndrome. To identify markers of rapid infancy weight gain and childhood obesity, we analyzed the metabolome in cord blood from infants differing in their postnatal weight trajectories. METHODS: We performed a nested case-control study within Project Viva, a longitudinal cohort of mothers and children. We selected cases (n=26) based on top quartile of change in weight-for-age 0-6 months and body mass index (BMI) >85th percentile in mid-childhood (median 7.7 years). Controls (n=26) were age and sex matched, had normal postnatal weight gain (2nd or 3rd quartile of change in weight-for-age 0-6 months) and normal mid-childhood weight (BMI 25th-75th percentile). Cord blood metabolites were measured using untargeted liquid chromatography-mass spectrometry; individual metabolites and pathways differing between cases and controls were compared in categorical analyses. We adjusted metabolites for maternal age, maternal BMI and breastfeeding duration (linear regression), and assessed whether metabolites improved the ability to predict case-control status (logistic regression). RESULTS: Of 415 detected metabolites, 16 were altered in cases versus controls (t-test, nominal P<0.05). Three metabolites were related to tryptophan: serotonin, tryptophan betaine and tryptophyl leucine (46%, 48% and 26% lower in cases, respectively, P<0.05). Mean levels of two methyl donors, dimethylglycine and N-acetylmethionine, were also lower in cases (18% and 16%, respectively, P=0.01). Moreover, the glutamine:glutamate ratio was reduced by 33% (P<0.05) in cases. Levels of serotonin, tryptophyl leucine and N-acetylmethionine remained significantly different after adjustment for maternal BMI, age and breastfeeding. Adding metabolite levels to logistic regression models including only clinical covariates improved the ability to predict case versus control status. CONCLUSIONS: Several cord blood metabolites are associated with rapid postnatal weight gain. Whether these patterns are causally linked to childhood obesity is not clear from this cross-sectional analysis, but will require further study.

Developmental determinants in non-communicable chronic diseases and ageing.

Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.

Metabolomics in the developmental origins of obesity and its cardiometabolic consequences.

In this review, we discuss the potential role of metabolomics to enhance understanding of obesity-related developmental origins of health and disease (DOHaD). We first provide an overview of common techniques and analytical approaches to help interested investigators dive into this relatively novel field. Next, we describe how metabolomics may capture exposures that are notoriously difficult to quantify, and help to further refine phenotypes associated with excess adiposity and related metabolic sequelae over the life course. Together, these data can ultimately help to elucidate mechanisms that underlie fetal metabolic programming. Finally, we review current gaps in knowledge and identify areas where the field of metabolomics is likely to provide insights into mechanisms linked to DOHaD in human populations.

Early child care and obesity at 12 months of age in the Danish National Birth Cohort.

BACKGROUND/OBJECTIVES: Evidence suggests that the child care environment may be more obesogenic than the family home, and previous studies have found that child care use may be associated with obesity in children. Few studies, however, have focused on child care during infancy, which may be an especially vulnerable period. This study examined child care use in infancy and weight status at 12 months of age in a country where paid maternity leave is common and early child care is not as prevalent as in other developed countries. SUBJECTS/METHODS: We studied 27,821 children born to mothers participating in the Danish National Birth Cohort, a longitudinal study of pregnant women enrolled between 1997 and 2002, who were also included in the Childcare Database, a national record of child care use in Denmark. The exposure was days in child care from birth to 12 months. The outcomes were sex-specific body mass index (BMI) z-score and overweight/obesity (BMI ⩾ 85th percentile based on the World Health Organization classification) at 12 months. We conducted multivariable linear and logistic regression analyses examining child care use and weight outcomes. RESULTS: A total of 17,721 (63.7%) children attended child care during their first year of life. After adjustment for potential confounders, a 30-day increment of child care was associated with a modestly higher BMI z-score at 12 months (0.03 units; 95% confidence interval (CI) = 0.01, 0.05; P=0.003). Similarly, child care use was associated with increased odds of being overweight/obese at 12 months of age (odds ratio = 1.05; 95% CI = 1.01, 1.10; P=0.047). CONCLUSION: Child care in the first year of life was associated with slightly higher weight at 12 months, suggesting that child care settings may be important targets for obesity prevention in infancy.

Paternal physical and sedentary activities in relation to semen quality and reproductive outcomes among couples from a fertility center.

STUDY QUESTION: Is paternal physical activity associated with semen quality parameters and with outcomes of infertility treatment? SUMMARY ANSWER: Among men presenting for infertility treatment, weightlifting and outdoor activities were associated with higher sperm concentrations but not with greater reproductive success. WHAT IS ALREADY KNOWN: Higher physical activity is related to better semen quality but no studies to date have investigated whether it predicts greater reproductive success. STUDY DESIGN, SIZE, DURATION: The Environment and Reproductive Health (EARTH) Study is an on-going prospective cohort study which enrolls subfertile couples presenting at Massachusetts General Hospital (2005-2013). In total, 231 men provided 433 semen samples and 163 couples underwent 421 IVF or intrauterine insemination cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: Leisure time spent in physical and sedentary activities over the past year was self-reported using a validated questionnaire. We used mixed models to analyze the association of physical and sedentary activities with semen quality and with clinical pregnancy and live birth rates. MAIN RESULTS AND THE ROLE OF CHANCE: Men in this cohort engaged in a median of 3.2 h/week of moderate-to-vigorous activities. Men in the highest quartile of moderate-to-vigorous activity had 43% (95% confidence interval (CI) 9, 87%) higher sperm concentrations than men in the lowest quartile (P-trend = 0.04). Men in the highest category of outdoor activity (≥1.5 h/week) and weightlifting (≥2 h/week) had 42% (95% CI 10, 84%) and 25% (95% CI -10, 74%) higher sperm concentrations, respectively, compared with men in the lowest category (0 h/week) (P-trend = 0.04 and 0.02). Conversely, men who reported bicycling ≥1.5 h/week had 34% (95% CI 4, 55%) lower sperm concentrations compared with men who reported no bicycling (P-trend = 0.05). Paternal physical and sedentary activities were not related to clinical pregnancy or live birth rates following infertility treatment. LIMITATIONS, REASONS FOR CAUTION: The generalizability of the findings on live birth rates to populations not undergoing infertility treatment is limited. WIDER IMPLICATIONS OF THE FINDINGS: Certain types of physical activity, specifically weightlifting and outdoor activities, may improve semen quality but may not lead to improved success of infertility treatments. Further research is needed in other non-clinical populations. STUDY FUNDING/COMPETING INTERESTS: The authors are supported by NIH grants R01-ES009718, ES000002, P30-DK046200, T32-DK007703-16 and ES022955 T32-HD060454. None of the authors has any conflicts of interest to declare.

A comparison of confounding adjustment methods with an application to early life determinants of childhood obesity.

We implemented six confounding adjustment methods: (1) covariate-adjusted regression, (2) propensity score (PS) regression, (3) PS stratification, (4) PS matching with two calipers, (5) inverse probability weighting and (6) doubly robust estimation to examine the associations between the body mass index (BMI) z-score at 3 years and two separate dichotomous exposure measures: exclusive breastfeeding v. formula only (n=437) and cesarean section v. vaginal delivery (n=1236). Data were drawn from a prospective pre-birth cohort study, Project Viva. The goal is to demonstrate the necessity and usefulness, and approaches for multiple confounding adjustment methods to analyze observational data. Unadjusted (univariate) and covariate-adjusted linear regression associations of breastfeeding with BMI z-score were -0.33 (95% CI -0.53, -0.13) and -0.24 (-0.46, -0.02), respectively. The other approaches resulted in smaller n (204-276) because of poor overlap of covariates, but CIs were of similar width except for inverse probability weighting (75% wider) and PS matching with a wider caliper (76% wider). Point estimates ranged widely, however, from -0.01 to -0.38. For cesarean section, because of better covariate overlap, the covariate-adjusted regression estimate (0.20) was remarkably robust to all adjustment methods, and the widths of the 95% CIs differed less than in the breastfeeding example. Choice of covariate adjustment method can matter. Lack of overlap in covariate structure between exposed and unexposed participants in observational studies can lead to erroneous covariate-adjusted estimates and confidence intervals. We recommend inspecting covariate overlap and using multiple confounding adjustment methods. Similar results bring reassurance. Contradictory results suggest issues with either the data or the analytic method.

Prospective associations of parental smoking, alcohol use, marital status, maternal satisfaction, and parental and childhood body mass index at 6.5 years with later problematic eating attitudes.

BACKGROUND: Few studies have prospectively investigated whether early-life exposures are associated with pre-adolescent eating attitudes. OBJECTIVE: The objective of this study is to prospectively investigate associations of parental smoking, alcohol use, marital status, measures of maternal satisfaction, self-reported parental body mass index (BMI) and clinically measured childhood BMI, assessed between birth and 6.5 years, with problematic eating attitudes at 11.5 years. METHODS: Observational cohort analysis nested within the Promotion of Breastfeeding Intervention Trial, a cluster-randomised trial conducted in 31 maternity hospitals and affiliated polyclinics in Belarus. Our primary outcome was a Children's Eating Attitudes Test (ChEAT) score 22.5 (85th percentile), an indicator of problematic eating attitudes. We employed multivariable mixed logistic regression models, which allow inference at the individual level. We also performed instrumental variable (IV) analysis using parents' BMIs as instruments for the child's BMI, to assess whether associations could be explained by residual confounding or reverse causation. SUBJECTS: Of the 17 046 infants enrolled between 1996 and 1997 across Belarus, 13 751 (80.7%) completed the ChEAT test at 11.5 years. RESULTS: In fully adjusted models, overweight children at age 6.5 years had a 2.14-fold (95% confidence interval (CI): 1.82, 2.52) increased odds of having ChEAT scores 85th percentile at age 11.5 years, and those who were obese had a 3.89-fold (95% CI: 2.95, 5.14) increased odds compared with normal-weight children. Children of mothers or fathers who were themselves overweight or obese were more likely to score 85th percentile (P for trend 0.001). IV analysis was consistent with a child's BMI causally affecting future eating attitudes. There was little evidence that parental smoking, alcohol use, or marital status or maternal satisfaction were associated with eating attitudes. CONCLUSION: In our large, prospective cohort in Belarus, both parental and childhood overweight and obesity at 6.5 years were associated with pre-adolescent problematic eating attitudes 5 years later.

Prenatal and perinatal predictors of blood pressure at school age in former preterm, low birth weight infants.

OBJECTIVE: The objective of this study is to investigate prenatal and perinatal determinants of school age blood pressure (BP) in former preterm, low birth weight infants. STUDY DESIGN: We studied 694 participants in the Infant Health and Development Program, an eight-center longitudinal study of children born ≤ 37 weeks and ≤ 2500 g. We obtained information about prenatal and perinatal factors by interview and medical record review, and measured BP three times at age 6.5 years. RESULT: Adjusting for sex, age, sociodemographic variables and height Z-score; for each Z-score birth weight for gestational age-which represents fetal growth-systolic BP at 6.5 years was 0.7 mm Hg higher (95% confidence interval -0.1, 1.6). Maternal age, pre-pregnancy weight, gestational weight gain, smoking, preeclampsia, gestational diabetes, and child gestational age and neonatal complications were also not associated with BP. CONCLUSION: In contrast to full-term infants, slower fetal growth was not associated with higher BP in former preterm, low birth weight infants.

Maternal experiences of racial discrimination and child weight status in the first 3 years of life.

Among US racial/ethnic minority women, we examined associations between maternal experiences of racial discrimination and child growth in the first 3 years of life. We analyzed data from Project Viva, a pre-birth cohort study. We restricted analyses to 539 mother-infant pairs; 294 were Black, 127 Hispanic, 110 Asian and 8 from additional racial/ethnic groups. During pregnancy, mothers completed the Experiences of Discrimination survey that measured lifetime experiences of racial discrimination in diverse domains. We categorized responses as 0, 1-2 or ≥3 domains. Main outcomes were birth weight for gestational age z-score; weight for age (WFA) z-score at 6 months of age; and at 3 years of age, body mass index (BMI) z-score. In multivariable analyses, we adjusted for maternal race/ethnicity, nativity, education, age, pre-pregnancy BMI, household income and child sex and age. Among this cohort of mostly (58.2%) US-born and economically non-impoverished mothers, 33% reported 0 domains of discrimination, 33% reported discrimination in 1-2 domains and 35% reported discrimination in ≥3 domains. Compared with children whose mothers reported no discrimination, those whose mothers reported ≥3 domains had lower birth weight for gestational age z-score (ß -0.25; 95% CI: -0.45, -0.04), lower 6 month WFA z-score (ß -0.34; 95% CI: -0.65, -0.03) and lower 3-year BMI z-score (ß -0.33; 95% CI: -0.66, 0.00). In conclusion, we found that among this cohort of US racial/ethnic minority women, mothers' report of experiencing lifetime discrimination in ⩾ 3 domains was associated with lower fetal growth, weight at 6 months and 3-year BMI among their offspring.

Sex-specific impact of maternal-fetal risk factors on depression and cardiovascular risk 40 years later.

Major depressive disorder (MDD) and cardiovascular disease (CVD) represent leading causes of morbidity and mortality worldwide. We tested the hypothesis that growth restriction and preeclampsia (referred to as fetal risk) are significant predictors of these conditions, with women at higher risk in adulthood. Adult offspring exposed to fetal risk factors and their discordant siblings were from two prenatal cohorts, whose mothers were followed through pregnancy and whom we recruited as adults 40 years later (n = 538; 250 males and 288 females). Subjects were psychiatrically diagnosed and underwent a stress challenge during which parasympathetic regulation was assessed by electrocardiogram, operationalized as high-frequency R-R interval variability (HF-RRV). Linear mixed models and generalized estimating equations were used to examine the relationship of fetal risk on HF-RRV, MDD and comorbidity of low HF-RRV (lowest 25th percentile) and MDD, including interactions with sex and socioeconomic status (SES). Fetal risk was significantly associated with low HF-RRV response (F = 3.64, P = 0.05), particularly among low SES (interaction: F = 4.31, P < 0.04). When stratified by MDD, the fetal risk impact was three times greater among MDD compared with non-MDD subjects (effect size: 0.21 v. 0.06). Females had a significantly higher risk for the comorbidity of MDD and low HF-RRV than males (relative risk (RR) = 1.36, 95% CI: 1.07-1.73), an association only seen among those exposed to fetal risk (RR = 1.38, 95% CI: 1.04-1.83). Findings suggest that these are shared fetal antecedents to the comorbidity of MDD and CVD risk 40 years later, an association stronger in females than in males.

The Early Determinants of Adult Health Study.

This issue of the Journal features collaborative follow-up studies of two unique pregnancy cohorts recruited during 1959-1966 in the United States. Here we introduce the Early Determinants of Adult Health (EDAH) study. EDAH was designed to compare health outcomes in midlife (age 40s) for same-sex siblings discordant on birthweight for gestational age. A sufficient sample of discordant siblings could only be obtained by combining these two cohorts in a single follow-up study. All of the subsequent six papers are either based upon the EDAH sample or are related to it in various ways. For example, three papers report results from studies that significantly extended the 'core' EDAH sample to address specific questions. We first present the overall design of and rationale for the EDAH study. Then we offer a synopsis of past work with the two cohorts to provide a context for both EDAH and the related studies. Next, we describe the recruitment and assessment procedures for the core EDAH sample. This includes the process of sampling and recruitment of potential participants; a comparison of those who were assessed and not assessed based on archived data; the methods used in the adult follow-up assessment; and the characteristics at follow-up of those who were assessed. We provide online supplementary tables with much further detail. Finally, we note further work in progress on EDAH and related studies, and draw attention to the broader implications of this endeavor.