Collaborative Perinatal Project Research Articles

Birthweight and Childhood Cancer: Preliminary Findings from the International Childhood Cancer Cohort Consortium (I4C).

BackgroundEvidence relating childhood cancer to high birthweight is derived primarily from registry and case–control studies. We aimed to investigate this association, exploring the potential modifying roles of age at diagnosis and maternal anthropometrics, using prospectively collected data from the International Childhood Cancer Cohort Consortium.MethodsWe pooled data on infant and parental characteristics and cancer incidence from six geographically and temporally diverse member cohorts [the Avon Longitudinal Study of Parents and Children (UK), the Collaborative Perinatal Project (USA), the Danish National Birth Cohort (Denmark), the Jerusalem Perinatal Study (Israel), the Norwegian Mother and Child Cohort Study (Norway), and the Tasmanian Infant Health Survey (Australia)]. Birthweight metrics included a continuous measure, deciles, and categories (≥4.0 vs. <4.0 kilogram). Childhood cancer (377 cases diagnosed prior to age 15 years) risk was analysed by type (all sites, leukaemia, acute lymphoblastic leukaemia, and non-leukaemia) and age at diagnosis. We estimated hazard ratios (HR) and 95% confidence intervals (CI) from Cox proportional hazards models stratified by cohort.ResultsA linear relationship was noted for each kilogram increment in birthweight adjusted for gender and gestational age for all cancers [HR = 1.26; 95% CI 1.02, 1.54]. Similar trends were observed for leukaemia. There were no significant interactions with maternal pre-pregnancy overweight or pregnancy weight gain. Birthweight ≥4.0 kg was associated with non-leukaemia cancer among children diagnosed at age ≥3 years [HR = 1.62; 95% CI 1.06, 2.46], but not at younger ages [HR = 0.7; 95% CI 0.45, 1.24, P for difference = 0.02].ConclusionChildhood cancer incidence rises with increasing birthweight. In older children, cancers other than leukaemia are particularly related to high birthweight. Maternal adiposity, currently widespread, was not demonstrated to substantially modify these associations. Common factors underlying foetal growth and carcinogenesis need to be further explored.

A prospective investigation of neurodevelopmental risk factors for adult antisocial behavior combining official arrest records and self-reports

Neurodevelopmental deficits are postulated to play an important role in the etiology of persistent antisocial behavior (ASB). Yet it remains uncertain as to which particular deficits are most closely associated with ASB. We seek to advance this understanding using prospectively collected data from a birth cohort in which multiple indices of neurodevelopmental functioning and ASB were assessed. Participants (n = 2776) were members of the Providence, Rhode Island cohort of the Collaborative Perinatal Project. Information on demographic and neurodevelopmental variables was collected from pregnancy through age 7. When all offspring had reached 33 years of age an adult criminal record check was conducted. A subset of subjects also self-reported on their engagement in serious ASB. Bivariate logistic regression was used to examine the relationship between each neurodevelopmental factor and adult ASB and test whether associations varied depending on how ASB was ascertained. After controlling for background and contextual characteristics, maternal smoking during pregnancy, lower childhood verbal and performance IQ, and age 7 aggressive/impulsive behavior all significantly increased the odds of adult ASB. Associations were not modified by sex and did not depend on how ASB was assessed. However, while both males and Black participants were more likely to engage in ASB than their respective female and White counterparts, relationships were significantly stronger for official records than for self-reports. Results point to a particular subset of early neurodevelopmental risks for antisocial outcomes in adulthood. Findings also suggest that prior contradictory results are not due to the use of official records versus self-reported outcomes.

Elevated risk of nicotine dependence among sib-pairs discordant for maternal smoking during pregnancy: evidence from a 40-year longitudinal study.

Compelling evidence links maternal smoking during pregnancy with elevated risk of nicotine dependence among the offspring. However, no study to date has examined the maternal smoking during pregnancy-nicotine dependence link among sibling-pairs discordant for maternal smoking during pregnancy. We tested two hypotheses that, if supported, suggest that the maternal smoking during pregnancy-nicotine dependence link may be physiologically mediated. Study participants were adult offspring of women enrolled in the Providence and Boston sites of the Collaborative Perinatal Project (1959-1966). Approximately 10% of these adult offspring (average age: 39.6 years) were enrolled in the New England Family Study (n = 1,783), a follow-up study that oversampled families with multiple siblings. Logistic regression models predicting maternal smoking during pregnancy risk on various prospectively collected smoking and marijuana use outcomes, including nicotine dependence, were fit using models that allowed between-mother effects of maternal smoking during pregnancy exposure to differ from within-mother effects. In the absence of significant effect heterogeneity, we calculated a combined estimate. Maternal smoking during pregnancy predicted progression from weekly smoking to nicotine dependence (odds ratio = 1.4 [95% confidence interval = 1.2, 1.8]), but not weekly smoking or progression to marijuana dependence. Current evidence from sibling-pairs discordant for maternal smoking during pregnancy is consistent with previous reports of a dose-response association between maternal smoking during pregnancy and nicotine dependence, as well as of up-regulation of nicotine receptors among animals exposed to maternal smoking during pregnancy. Together, they provide support for the existence of a physiologically mediated link between maternal smoking during pregnancy and nicotine dependence.

Early Childhood IQ Trajectories in Individuals Later Developing Schizophrenia and Affective Psychoses in the New England Family Studies.

Individuals who develop schizophrenia in adulthood exhibit, on average, deficits in childhood cognition relative to healthy controls. However, it remains unclear when in childhood such deficits emerge and whether they are stable across childhood or change (increase or decrease) across development. Importantly, whether the trajectory of childhood cognition differs among youth who later develop affective psychoses (AP) vs schizophrenia as adults remains unresolved. Subjects in the Collaborative Perinatal Project were administered the Stanford-Binet IQ test at age 4 and the Wechsler Intelligence Scale for Children at age 7. A total of 9809 (54.7%) participants in the New England Study sites were tested at both ages, including 37 who later developed schizophrenia spectrum psychoses (SSP) and 39 who later developed AP. Logistic regression models examined the association of level of and change in childhood IQ and later SSP or AP. Lower overall childhood IQ was associated with higher risk of SSP. Additionally, there was a small mean increase in IQ in the SSP group relative to a mean decrease in the control group from age 4 to 7 such that positive change in IQ was significantly associated with a higher risk of SSP. Neither overall level nor change in IQ was associated with risk of AP. The results are consistent with neurocognitive impairment throughout early childhood specifically for children who later develop schizophrenia, affirming the theory of atypical neurodevelopment in premorbid schizophrenia.

Choosing the Best Newborn Anthropometric Measure Associated With the Risks and Outcomes of Intrauterine Growth Restriction.

Intrauterine growth restriction (IUGR) is associated with various prenatal risks and postnatal adverse outcomes. The aim of this study is to choose the most sensitive newborn anthropometric measure, which is closely associated with IUGR-related risks and outcomes, to substitute IUGR after delivery. Data were obtained from the Collaborative Perinatal Project, a multicenter prospective cohort study in the United States from 1959 to 1976. Maternal heavy smoking and severe hypertensive disorders during pregnancy, neonatal polycythemia and hypothermia, low intelligence quotient (<70) at age 7 years were chosen as IUGR-related risks and outcomes. Eight anthropometric measures at birth were tested by logistic regression model. Birth weight-to-head circumference (W/HC) had the largest odds ratio (OR) for neonatal polycythemia (OR = 1.8, 95% confidence interval [CI] = 1.5-2.0), severe hypertensive disorders (OR = 1.9, 95% CI = 1.5-2.2), and maternal heavy smoking (OR = 1.9, 95% CI = 1.7-2.1) during pregnancy. It also had the highest summary OR (9.3). Thus, W/HC may be a good measure for IUGR.

Positing, fitting, and selecting regression models for pooled biomarker data.

Pooling biospecimens prior to performing lab assays can help reduce lab costs, preserve specimens, and reduce information loss when subject to a limit of detection. Because many biomarkers measured in epidemiological studies are positive and right-skewed, proper analysis of pooled specimens requires special methods. In this paper, we develop and compare parametric regression models for skewed outcome data subject to pooling, including a novel parameterization of the gamma distribution that takes full advantage of the gamma summation property. We also develop a Monte Carlo approximation of Akaike's Information Criterion applied to pooled data in order to guide model selection. Simulation studies and analysis of motivating data from the Collaborative Perinatal Project suggest that using Akaike's Information Criterion to select the best parametric model can help ensure valid inference and promote estimate precision.

Should Obese Women Gain Less Weight in Pregnancy than Recommended?

Background Previous research on inadequate gestational weight gain among obese women and adverse outcomes has been mixed. The objective of this study was to examine associations between inadequate gain among obese women and antepartum, intrapartum, and infant outcomes. Methods Obese women from the U.S. Collaborative Perinatal Project were divided into obesity classes I (30.0–34.9 kg/m2) and II/III (> 35.0 kg/m2) and three weight gain categories (inadequate: 9 kg) as defined by the U.S. Institute of Medicine. Associations between 1-kg increments of inadequate gain ( 9 kg) weight. Results Each fewer 1-kg of weight gain increased small-for-gestational age (SGA) risk and reduced large-for-gestational age (LGA) risk by similar magnitude. Compared with excessive gain, inadequate gain reduced the odds of preeclampsia (OR: 0.56, CI: 0.37, 0.84), gestational hypertension (OR: 0.66, CI: 0.47, 0.92), and LGA (OR: 0.48, CI: 0.38, 060) and increased the odds of SGA (OR: 2.26, CI: 1.52, 3.35). Inadequate gain offered fewer advantages over adequate weight gain: lower odds of LGA (OR: 0.75, CI: 0.57, 0.99); increased odds of SGA (OR: 1.86, CI: 1.18, 2.91). Most associations applied to obesity class I but not class II/III women. Conclusions Inadequate weight gain poses benefits and risks to mothers and infants, but is preferable to excessive gain. The risks and benefits apply differently to class I versus class II/III obese women, indicating the need for weight gain recommendations by obesity class.

Maternal serum paraxanthine during pregnancy and offspring body mass index at ages 4 and 7 years.

Obesity affects 18% of U.S. children. In a recent report, maternal consumption of ≥150 mg of caffeine per day during pregnancy was associated with increased odds for obesity in the offspring (odds ratio = 2.1 [95% confidence interval = 1.2-3.5]). If this association was causal, a considerable fraction of childhood obesity might be prevented by reduction of caffeine intake in pregnancy. We studied 1986 mother-child pairs who were controls from a case-control study of caffeine metabolites and spontaneous abortion nested within the Collaborative Perinatal Project. Women were pregnant during 1959-1966, and children were followed with visits at 48 and/or 84 months of age, when height and weight were measured according to a standardized protocol. Serum was drawn at <20 and ≥26 weeks' gestation and assayed for paraxanthine (caffeine's primary metabolite) by high-performance liquid chromatography. Relative risks of obesity (body mass index ≥95th percentile for age and sex) were estimated by log-binomial or Poisson regression and adjusted for maternal age, race, education, smoking, prepregnant weight, diabetes in pregnancy, and gestational age at blood draw. Obesity prevalence was 11.7% at 48 months and 6.5% at 84 months. Associations of maternal serum paraxanthine and child obesity were nonlinear, and adjustment reduced the magnitude of all associations. The maximum relative risk (approximately 1.4) was for the association of paraxanthine drawn at <20 weeks with obesity at ages 48 and 84 months. This study does not support an increased risk of childhood obesity with increasing maternal caffeine consumption during pregnancy.

Is the fetoplacental ratio a differential marker of fetal growth restriction in small for gestational age infants?

Higher placental weight relative to birthweight has been described as an adaptive mechanism to fetal hypoxia in small for gestational age (SGA) infants. However, placental weight alone may not be a good marker reflecting intrauterine growth restriction. We hypothesized that fetoplacental ratio (FPR)-the ratio between birthweight and placental weight-may serve as a good marker of SGA after adjustment for surrogates of fetal hypoxemia (maternal iron deficiency anemia, smoking and choriodecidual necrosis). We conducted a within-sibling analysis using data from the US National Collaborative Perinatal Project (1959-1966) of 1,803 women who delivered their first two (or more) consecutive infants at term (n = 3,494). We used variance-component fixed-effect linear regression models to explore the effect of observed time-varying factors on placental weight and conditional logistic regression to estimate the effects of the tertiles of FPRs (1st small, 2nd normal and 3rd large) on the odds of SGA infants. We found placental weights to be 15 g [95 % confidence interval (CI) 8, 23] higher and -7 g (95 % CI -13, -2) lower among women that had anemia and choriodecidual necrosis, respectively. After multivariable adjustment, newborns with a small FPR (1st-tertile ≤7) had twofold higher odds of being SGA (OR 2.0, 95 % CI 1.2, 3.5) than their siblings with a large FPR (3nd-tertile ≥9). A small FPR was associated with higher odds of SGA, suggesting that small FPR may serve as an indicator suggestive of adverse intrauterine environment. This observation may help to distinguish pathological from constitutional SGA.

The impact of low birth weight and maternal age on adulthood offending

PurposeThe current study examines the relationship between low birth weight and adult offending, and whether maternal age at childbirth moderates this relationship. MethodsUsing longitudinal data from mothers and offspring from the Providence sample of the Collaborative Perinatal Project, multivariate logistic regression models were used to study the relationship between low birth weight and adulthood arrest by maternal age. ResultsOffspring born at low birth weight were at an increased risk of adult arrest, but only if they were born to adolescent (and not adult) mothers. These results remained while controlling for preterm delivery, number of cigarettes smoked during pregnancy, mothers’ marital status, socioeconomic status, African American race, gender, and court contact during adolescence. ConclusionsResults highlight the importance of considering the moderating role of maternal age at childbirth, and underscore the notion that the adverse effect of a child born at low birth weight—with respect to crime—can be exacerbated if the child is born to a young mother but lessened or even ameliorated if born to an older mother. Theoretical and practical implications of these findings are discussed.

Early origins of inflammation: An examination of prenatal and childhood social adversity in a prospective cohort study

BackgroundChildren exposed to social adversity carry a greater risk of poor physical and mental health into adulthood. This increased risk is thought to be due, in part, to inflammatory processes associated with early adversity that contribute to the etiology of many adult illnesses. The current study asks whether aspects of the prenatal social environment are associated with levels of inflammation in adulthood, and whether prenatal and childhood adversity both contribute to adult inflammation. MethodsWe examined associations of prenatal and childhood adversity assessed through direct interviews of participants in the Collaborative Perinatal Project between 1959 and 1974 with blood levels of C-reactive protein in 355 offspring interviewed in adulthood (mean age=42.2 years). Linear and quantile regression models were used to estimate the effects of prenatal adversity and childhood adversity on adult inflammation, adjusting for age, sex, and race and other potential confounders. ResultsIn separate linear regression models, high levels of prenatal and childhood adversity were associated with higher CRP in adulthood. When prenatal and childhood adversity were analyzed together, our results support the presence of an effect of prenatal adversity on (log) CRP level in adulthood (β=0.73, 95% CI: 0.26, 1.20) that is independent of childhood adversity and potential confounding factors including maternal health conditions reported during pregnancy. Supplemental analyses revealed similar findings using quantile regression models and logistic regression models that used a clinically-relevant CRP threshold (>3mg/L). In a fully-adjusted model that included childhood adversity, high prenatal adversity was associated with a 3-fold elevated odds (95% CI: 1.15, 8.02) of having a CRP level in adulthood that indicates high risk of cardiovascular disease. ConclusionsSocial adversity during the prenatal period is a risk factor for elevated inflammation in adulthood independent of adversities during childhood. This evidence is consistent with studies demonstrating that adverse exposures in the maternal environment during gestation have lasting effects on development of the immune system. If these results reflect causal associations, they suggest that interventions to improve the social and environmental conditions of pregnancy would promote health over the life course. It remains necessary to identify the mechanisms that link maternal conditions during pregnancy to the development of fetal immune and other systems involved in adaptation to environmental stressors.

The Optimal Postnatal Growth Trajectory for Term Small for Gestational Age Babies: A Prospective Cohort Study

To identify an optimal growth trajectory for term small for gestational age (SGA) babies from birth to 7-years-old. Data were from the Collaborative Perinatal Project, a US multicenter prospective cohort study from 1959-1976. Five weight growth trajectories of the 1957 term SGA babies were grouped by a latent class model. We selected the optimal growth pattern based on the lowest overall risks of childhood diseases. Compared with appropriate for gestational age children, SGA babies with no catch-up growth (439, 22.4%) had higher risks of infection in infancy (aOR 1.2, 95% CI 1.0-1.6), growth restriction (11.2, 8.6-14.6), and low IQ (2.1, 1.7-2.8) at age 7 years. Those with excessive catch-up growth (176, 8.9%) had higher risks of overweight/obesity (7.5, 5.4-10.5) and elevated blood pressure (1.7, 1.1-2.4) at age 7 years. Babies with slow catch-up growth (328, 16.8%) or regression after 4 months (285, 14.6%) were associated with higher risks of low IQ (1.6, 1.2-2.1) and growth restriction (2.2, 1.5-3.2), respectively. Only babies with appropriate catch-up growth (729, 37.3%) did not have increased risk of adverse outcomes. Further, we also tested linear growth trajectories with similar findings. The optimal growth trajectory for term SGA infants may be fast catch-up growth to about the 30th percentile in the first several months, with modest catch-up growth thereafter, to be around the 50th percentile by 7-years-old.

Maternal vitamin D status and infant anthropometry in a US multi-centre cohort study

Background: Maternal vitamin D status in pregnancy is linked to foetal growth and may impact infant growth.Aim: This study examined the association between maternal vitamin D status and infant anthropometry.Subjects and methods: Data came from n = 2473 mother–child pairs from the 12-site US Collaborative Perinatal Project (1959–1965). Maternal serum 25-hydroxyvitamin D (25(OH)D) was measured at ≤ 26 weeks gestation. Multivariate-adjusted linear mixed models were used to relate maternal vitamin D status to infant z-scores for length (LAZ), head circumference (HCZ), weight (WAZ) and BMI (BMIZ), measured at birth and 4, 8 and 12 months.Results: Infants with maternal 25(OH)D ≥30 nmol/L vs <30 nmol/L had LAZ and HCZ measures 0.13 (95% CI = 0.03–0.23) and 0.20 (95% CI = 0.11–0.28) units higher, respectively, across the first year of life. Similar differences in WAZ and BMIZ at birth were resolved by 12 months of age due to interactions indicating steeper age slopes in infants with maternal 25(OH)D <30 nmol/L.Conclusion: Low maternal vitamin D status was associated with deficits at birth in infant weight and BMI that were recouped across the first year of life; associations with reduced measures of linear and skeletal growth were sustained from birth to 12 months.

Maternal complement C1q and increased odds for psychosis in adult offspring

The presence of maternal antibodies to food and infectious antigens may confer an increased risk of developing schizophrenia and psychosis in adult offspring. Complement factor C1q is an immune molecule with multiple functions including clearance of antigen–antibody complexes from circulation and mediation of synaptic pruning during fetal brain development. To determine if maternal C1q was associated with offspring schizophrenia and psychosis, we evaluated 55 matched case–control maternal serum pairs from the National Collaborative Perinatal Project. Sample pairs were composed of mothers whose offspring developed psychoses as adults and those whose offspring were free from psychiatric disease. Matching criteria for offspring included birth date, delivery hospital, race, and gender, with further matching based on mother's age. IgG markers of C1q, bovine milk casein, egg ovalbumin, and wheat gluten were measured with enzyme-linked immunosorbent assays. C1q levels were compared to food antigen IgG and to previously generated data for C-reactive protein, adenovirus, herpes simplex viruses, influenza viruses, measles virus, and Toxoplasma gondii. C1q was significantly elevated in case mothers with odds ratios of 2.66–6.31 (conditional logistic regressions, p≤0.008–0.05). In case mothers only, C1q was significantly correlated with antibodies to both food and infectious antigens: gluten (R2=0.26, p≤0.004), herpes simplex virus type 2 (R2=0.21, p≤0.02), and adenovirus (R2=0.25, p≤0.006). In conclusion, exposure to maternal C1q activity during pregnancy may be a risk factor for the development of schizophrenia and psychosis in offspring. Prenatal measurement of maternal C1q may be an important and convergent screening tool to identify potentially deleterious immune activation from multiple sources.

Maternal vitamin D status, prolonged labor, cesarean delivery and instrumental delivery in an era with a low cesarean rate.

ObjectiveTo examine the association between maternal 25-hydroxyvitamin D (25(OH)D) and adverse labor and delivery outcomes.Study designWe measured serum 25(OH)D at ≤26 weeks gestation in a random subsample of vertex, singleton pregnancies in women who labored (n=2798) from the 12 site Collaborative Perinatal Project (1959–66). We used labor and delivery data to classify cases of adverse outcomes.ResultsTwenty-four percent of women were vitamin D deficient (25(OH)D <30 nmol/L) and 4.5%, 3.3%, 1.9%, and 7.5% of women had prolonged stage 1 labor, prolonged stage 2 labor, primary cesarean delivery, or indicated instrumental delivery, respectively. After adjustment for prepregnancy BMI, race, and study site, 25(OH)D concentrations were not associated with risk of prolonged stage 1 or 2, cesarean delivery, or instrumental delivery.ConclusionMaternal vitamin D status at ≤26 weeks was not associated with risk of prolonged labor or operative delivery in an era with a low cesarean rate.

Fetal Sex and Race Modify the Predictors of Fetal Growth

The objective of this study is unknown if fetal sex and race modify the impact of maternal pre-pregnancy body mass index (BMI), and smoking on fetal growth. The authors studied markers of fetal growth in singleton offspring of 8,801 primiparous, normotensive women, enrolled in the Collaborative Perinatal Project. The authors tested for departures from additivity between sex/race and each predictor. The head-to-chest circumference ratio (HCC) decreased more, while birthweight and ponderal index (PI) increased more for each 1kg/m(2) increase in pre-pregnancy BMI among term females versus males (P=0.07, P<0.01 and P=0.08, interaction respectively). For term offspring of White compared with Black women, smoking independent of "dose" was associated with larger reductions in growth (165g vs. 68g reduction in birthweight, P<0.01, interaction), greater reduction in fetal placental ratio (P<0.01, interaction), PI (P<0.01, interaction), and greater increase in HCC (P=0.02), respectively. The association of BMI and smoking with fetal size appeared to be reversed in term versus preterm infants. Our study provides evidence that the associations of pre-pregnancy BMI and smoking are not constant across sex and race. This finding may be relevant to sex and race differences in neonatal and long term health outcomes.

Childhood social disadvantage, cardiometabolic risk, and chronic disease in adulthood.

Adverse social environments in early life are hypothesized to become biologically embedded during the first few years of life, with potentially far-reaching implications for health across the life course. Using prospective data from a subset of a US birth cohort, the Collaborative Perinatal Project, started in 1959-1966 (n = 566), we examined associations of social disadvantage assessed in childhood with cardiometabolic function and chronic disease status more than 40 years later (in 2005-2007). Social disadvantage was measured with an index that combined information on adverse socioeconomic and family stability factors experienced between birth and age 7 years. Cardiometabolic risk (CMR) was assessed by combining information from 8 CMR biomarkers; an index of chronic disease status was derived by assessing 8 chronic diseases. Poisson models were used to investigate associations between social disadvantage and CMR or chronic disease scores while adjusting for childhood covariates and potential pathway variables. A high level of social disadvantage was significantly associated with both higher CMR (incident rate ratio = 1.69, 95% confidence interval: 1.19, 2.39) and with a higher number of chronic diseases (incident rate ratio = 1.39, 95% confidence interval: 1.00, 1.92) in minimally adjusted models. Associations with CMR persisted even after accounting for childhood and adult covariates.

Maternal and cord blood 25(OH)-vitamin D concentrations in relation to child development and behaviour.

Animal studies have linked in utero vitamin D exposure to various aspects of offspring brain development. Limited research has translated these findings to humans, and none have employed cord blood to measure exposure late in gestation. Our objective was to examine the associations between maternal 25(OH)D measured at ≤26 weeks' gestation or cord blood 25(OH)D and offspring global development, IQ, achievement, and behaviour in the US Collaborative Perinatal Project (1959-73). This was a secondary analysis of data from a case-cohort study, with 3896 women and children who participated in at least one outcome assessment. Psychologists assessed global development at 8 months, IQ and behaviour at 4 and 7 years, and achievement at 7 years. Multiple linear and logistic regression was used to examine the associations between 25(OH)D and child outcomes, controlling for maternal education, age, parity, race, maternal body mass index, marital status, smoking, gestational age and month of blood draw, and study site. Positive associations for many outcomes were greatly attenuated upon adjustment for confounders and were generally null. Only IQ at age 7 was associated with both maternal and cord blood 25(OH)D, but the effect estimates were very small (β for 5 nmol/L increment of maternal 25(OH)D = 0.10; [95% CI 0.00, 0.19]). We observed very little indication that maternal or cord blood 25(OH)D are associated with cognitive development, achievement, and behaviour between 8 months and 7 years of age.

Maternal prepregnancy obesity is associated with higher risk of placental pathological lesions

IntroductionPrepregnancy obesity is associated with increased morbidity and mortality for mother and offspring. The objective of our study is to estimate the effect of maternal prepregnancy weight on placental pathological lesions.. MethodsData used for this study were from the U.S. Collaborative Perinatal Project, a large prospective cohort study. It consisted of 54390 women giving a singleton birth from 1959 to 1966. More than 84% of women had both detailed placental pathological examinations and anthropometric measurements. Logistic regression models were used to test the associations between maternal prepregnancy body mass index (BMI) and placental pathological lesions adjusting for potential confounders. Spline smoothing was applied to describe the relation of prepregnancy BMI and placenta weight-to-birthweight ratio. ResultsThe prepregnancy obese women (BMI ≥ 30 kg/m2) showed a higher rate of maternal origin vascular lesions, maternal origin villous lesions, fetal neutrophilic infiltration, and meconium of fetal membrane compared with the normal-weight women (18.5 ≤ BMI < 24.9). The odds ratios ranged from 1.18 to 1.97 after adjusting for potential confounders. These higher odds were consistent in prepregnancy obese women without obstetric complications. Furthermore, placenta weight-to-birthweight ratio, the proxy for placenta insufficiency, was positively associated with maternal prepregnancy BMI.. ConclusionsOur study provides evidence that prepregnancy obesity exerts its adverse in-utero influence on placental pathology. These influences may have impact on maternal and fetal health. With obesity rising steadily, these results appear to raise serious public health concerns of prepregnancy obesity.

Maternal prepregnancy obesity and child neurodevelopment in the Collaborative Perinatal Project

To examine the association between maternal prepregnancy weight and child neurodevelopment, and the effect of gestational weight gain. Using the U.S. Collaborative Perinatal Project data, 1959-76, a total of 30,212 women with a calculable prepregnancy body mass index (BMI) and gestational weight gain, and term singleton children followed up for more than 7 years were included in this study. Intelligence quotient (IQ) was measured at 7 years of age by Wechsler Intelligence Scales. Maternal prepregnancy BMI displayed inverted U-shaped associations with child IQ after adjustment for maternal age, maternal education levels, maternal race, marital status, socioeconomic status, smoking during pregnancy, parity and study center. Women with BMI at around 20 kg/m2 appeared to have the highest offspring IQ scores. After controlling for familial factors in the siblings' sample, maternal obesity (BMI≥30.0 kg/m2) was associated with lower Full-scale IQ (adjusted ß=-2.0, 95% confidence interval -3.5 to -0.5), and Verbal scale IQ (adjusted ß=-2.5, 95% confidence interval -4.0 to -1.0), using BMI of 18.5-24.9 kg/m2 as the reference category. Compared with children born to normal-weight women who gained 21-25 lb. during pregnancy, those born to obese women who gained more than 40 lb. had 6.5 points deficit in IQ after adjustment for potential confounders. Maternal prepregnancy obesity was associated with lower child IQ, and excessive weight gain accelerated the association. With obesity rising steadily, these results appear to raise serious public health concerns.