Manon van Eijsden

Ambient air pollution and low birthweight: a European cohort study (ESCAPE)

BACKGROUND Ambient air pollution has been associated with restricted fetal growth, which is linked with adverse respiratory health in childhood. We assessed the effect of maternal exposure to low concentrations of ambient air pollution on birthweight. METHODS We pooled data from 14 population-based mother-child cohort studies in 12 European countries. Overall, the study population included 74 178 women who had singleton deliveries between Feb 11, 1994, and June 2, 2011, and for whom information about infant birthweight, gestational age, and sex was available. The primary outcome of interest was low birthweight at term (weight <2500 g at birth after 37 weeks of gestation). Mean concentrations of particulate matter with an aerodynamic diameter of less than 2·5 μm (PM2·5), less than 10 μm (PM10), and between 2·5 μm and 10 μm during pregnancy were estimated at maternal home addresses with temporally adjusted land-use regression models, as was PM2·5 absorbance and concentrations of nitrogen dioxide (NO2) and nitrogen oxides. We also investigated traffic density on the nearest road and total traffic load. We calculated pooled effect estimates with random-effects models. FINDINGS A 5 μg/m(3) increase in concentration of PM2·5 during pregnancy was associated with an increased risk of low birthweight at term (adjusted odds ratio [OR] 1·18, 95% CI 1·06-1·33). An increased risk was also recorded for pregnancy concentrations lower than the present European Union annual PM2·5 limit of 25 μg/m(3) (OR for 5 μg/m(3) increase in participants exposed to concentrations of less than 20 μg/m(3) 1·41, 95% CI 1·20-1·65). PM10 (OR for 10 μg/m(3) increase 1·16, 95% CI 1·00-1·35), NO2 (OR for 10 μg/m(3) increase 1·09, 1·00-1·19), and traffic density on nearest street (OR for increase of 5000 vehicles per day 1·06, 1·01-1·11) were also associated with increased risk of low birthweight at term. The population attributable risk estimated for a reduction in PM2·5 concentration to 10 μg/m(3) during pregnancy corresponded to a decrease of 22% (95% CI 8-33%) in cases of low birthweight at term. INTERPRETATION Exposure to ambient air pollutants and traffic during pregnancy is associated with restricted fetal growth. A substantial proportion of cases of low birthweight at term could be prevented in Europe if urban air pollution was reduced. FUNDING The European Union.

Pregnancy and Birth Cohort Resources in Europe: a Large Opportunity for Aetiological Child Health Research

BACKGROUND During the past 25 years, many pregnancy and birth cohorts have been established. Each cohort provides unique opportunities for examining associations of early-life exposures with child development and health. However, to fully exploit the large amount of available resources and to facilitate cross-cohort collaboration, it is necessary to have accessible information on each cohort and its individual characteristics. The aim of this work was to provide an overview of European pregnancy and birth cohorts registered in a freely accessible database located at http://www.birthcohorts.net. METHODS European pregnancy and birth cohorts initiated in 1980 or later with at least 300 mother-child pairs enrolled during pregnancy or at birth, and with postnatal data, were eligible for inclusion. Eligible cohorts were invited to provide information on the data and biological samples collected, as well as the timing of data collection. RESULTS In total, 70 cohorts were identified. Of these, 56 fulfilled the inclusion criteria encompassing a total of more than 500,000 live-born European children. The cohorts represented 19 countries with the majority of cohorts located in Northern and Western Europe. Some cohorts were general with multiple aims, whilst others focused on specific health or exposure-related research questions. CONCLUSION This work demonstrates a great potential for cross-cohort collaboration addressing important aspects of child health. The web site, http://www.birthcohorts.net, proved to be a useful tool for accessing information on European pregnancy and birth cohorts and their characteristics.

Maternal Lipid Profile During Early Pregnancy and Pregnancy Complications and Outcomes: The ABCD Study

CONTEXT Elevated lipid levels during late pregnancy are associated with complications and adverse outcome for both mother and newborn. However, it is inconclusive whether a disturbed lipid profile during early pregnancy has similar negative associations. OBJECTIVE Our objective was to investigate whether nonfasting maternal total cholesterol and triglyceride levels during early pregnancy are associated with six major adverse pregnancy outcomes. METHODS Data were derived from the Amsterdam Born Children and Their Development (ABCD) cohort study. Random blood samples of nonfasting total cholesterol and triglyceride levels were determined during early gestation (median = 13, interquartile range = 12-14 wk). Outcome measures were pregnancy-induced hypertension (PIH), preeclampsia, preterm birth, small/large for gestational age (SGA/LGA), and child loss. Only nondiabetic women with singleton deliveries were included; the baseline sample consisted of 4008 women. Analysis for PIH and preeclampsia were performed in nulliparous women only (n = 2037). RESULTS Mean (sd) triglyceride and total cholesterol levels were 1.33 (0.55) and 4.98 (0.87) mmol/liter, respectively. The incidence of pregnancy complications and perinatal outcomes were as follows: PIH, 4.9%; preeclampsia, 3.7%; preterm birth, 5.3%; SGA, 9.3%; LGA, 9.3%; and child loss, 1.4%. After adjustments, every unit increase in triglycerides was linearly associated with an increased risk of PIH [odds ratio (OR) = 1.60, P = 0.021], preeclampsia (OR = 1.69, P = 0.018), LGA (OR = 1.48, P < 0.001), and induced preterm delivery (OR = 1.69, P = 0.006). No associations were found for SGA or child loss. Total cholesterol was not associated with any of the outcome measures. CONCLUSIONS Elevated maternal triglyceride levels measured during early pregnancy are associated with pregnancy complications and adverse pregnancy outcomes. These results suggest that future lifestyle programs in women of reproductive age with a focus on lowering triglyceride levels (i.e. diet, weight reduction, and physical activity) may help to prevent hypertensive complications during pregnancy and adverse birth outcomes.

Fish intake during pregnancy, fetal growth, and gestational length in 19 European birth cohort studies.

BACKGROUND Fish is a rich source of essential nutrients for fetal development, but in contrast, it is also a well-known route of exposure to environmental pollutants. OBJECTIVE We assessed whether fish intake during pregnancy is associated with fetal growth and the length of gestation in a panel of European birth cohort studies. DESIGN The study sample of 151,880 mother-child pairs was derived from 19 population-based European birth cohort studies. Individual data from cohorts were pooled and harmonized. Adjusted cohort-specific effect estimates were combined by using a random- and fixed-effects meta-analysis. RESULTS Women who ate fish >1 time/wk during pregnancy had lower risk of preterm birth than did women who rarely ate fish (≤ 1 time/wk); the adjusted RR of fish intake >1 but <3 times/wk was 0.87 (95% CI: 0.82, 0.92), and for intake ≥ 3 times/wk, the adjusted RR was 0.89 (95% CI: 0.84, 0.96). Women with a higher intake of fish during pregnancy gave birth to neonates with a higher birth weight by 8.9 g (95% CI: 3.3, 14.6 g) for >1 but <3 times/wk and 15.2 g (95% CI: 8.9, 21.5 g) for ≥ 3 times/wk independent of gestational age. The association was greater in smokers and in overweight or obese women. Findings were consistent across cohorts. CONCLUSION This large, international study indicates that moderate fish intake during pregnancy is associated with lower risk of preterm birth and a small but significant increase in birth weight.

Stress and Emotional Problems During Pregnancy and Excessive Infant Crying

Objective: There is evidence that stress and emotional problems during pregnancy are related to adverse health outcomes of the child at birth and in later life. The aim of this study was to determine the association between stress and emotional problems during pregnancy and excessive infant crying. Methods: From an initial sample of 8266 pregnant women, a follow-up sample of 4976 women and their 3- to 6-month-old babies was examined. Depressive symptoms, pregnancy related anxiety, parenting stress, and job strain during pregnancy were all univariately and multivariately associated with excessive infant crying (adjusted odds ratios between 1.69 and 2.23). Results: Women with three or four of these antenatal risks were more likely to have an infant who cries excessively than women with no antenatal risks (adjusted odds ratio of 4.89). Conclusion: In conclusion, stress and emotional problems during pregnancy increase the chances of having an excessively crying baby. Women with multiple antenatal risk factors are at particular risk.

Maternal Triglyceride Levels during Early Pregnancy are Associated with Birth Weight and Postnatal Growth

OBJECTIVE To investigate whether randomly sampled maternal total cholesterol (TC) and triglycerides (TG) levels during early pregnancy are associated with birth weight (BW) and postnatal growth. STUDY DESIGN Data were derived from the prospective Amsterdam Born Children and their Development cohort study. Randomly sampled TC and TG levels were determined in early gestation (median, 13; IQR, 12-14 weeks). Outcome measures were BW SDS and weight-for-gestational age; postnatal outcome measures were SDS in weight, length, and body mass index during the first year of life (total n = 2502). RESULTS The highest TG level was associated with a higher BW SDS (differences 0.20 ± 0.06 between highest and middle quintile; P = .002) and with a higher prevalence (13%) of an infant large for gestational age compared with middle quintile (9%; P = .04). Infants from mothers in the lowest TG quintile had lower SDS in weight, length, and body mass index until age 3 months, and displayed accelerated postnatal growth patterns. Maternal TC was not associated with BW or postnatal growth. CONCLUSION High maternal TG levels in the first term of pregnancy were associated with higher BWs and subsequently a higher occurrence of infants large for gestational age, whereas low TG levels were associated with accelerated postnatal growth.

Traffic-related air pollution and pregnancy outcomes in the Dutch ABCD birth cohort study

Objectives There is growing evidence for an adverse effect of maternal exposure to air pollution on pregnancy outcomes. As European data on this topic are limited, the aim of this study was to evaluate the impact of maternal exposure to traffic-related air pollution during different periods of pregnancy on preterm birth and fetal growth. Methods We estimated maternal residential exposure to NO2 during pregnancy (entire pregnancy and trimesters) for 7600 singleton births participating in the Amsterdam Born Children and their Development (ABCD) prospective birth cohort study by means of a temporally adjusted land-use regression model. Associations between air pollution concentrations and preterm birth and fetal growth (expressed as small for gestational age and term birth weight) were analysed by means of logistic and linear regression models with and without adjustment for maternal physiological, lifestyle and sociodemographic characteristics. Results There was no indication of an increase in preterm birth among highly exposed women. Children of mothers with NO2 levels in the highest exposure category on average had the highest term birth weight of all children and were among those with the lowest risk of being small for gestational age with little indication of a dose–response relationship. Conclusions In this study, there is no evidence for a harmful effect of estimated maternal exposure to traffic-related air pollution during pregnancy on pregnancy outcomes such as preterm birth, small for gestational age and term birth weight.

Maternal early-pregnancy vitamin D status is associated with maternal depressive symptoms in the Amsterdam Born Children and Their Development cohort.

Objective To examine low maternal vitamin D status as a potential risk factor for high levels of depressive symptoms in a pregnant population. Methods In the Amsterdam Born Children and Their Development cohort, maternal serum vitamin D (n = 4236) was measured during early pregnancy (median, 13 weeks) and labeled “deficient” (⩽29.9 nM), “insufficient” (30–49.9 nM), “sufficient” (50–79.9 nM), and “normal” (≥80 nM). Maternal depressive symptoms were measured by the Center for Epidemiological Studies Depression Scale at 16-week gestation. The association of vitamin D status with high levels of depressive symptoms (Center for Epidemiological Studies Depression score ≥16) was assessed by multivariate logistic regression (final sample, 4101). Results Overall, 23% of women had vitamin D deficiency, and 21% of women had vitamin D insufficiency. Women with high levels of depressive symptoms (28%) had lower vitamin D concentrations than women with low levels of depressive symptoms (p < .001). After adjustment for constitutional factors, life-style and psychosocial covariates, and sociodemographic factors, vitamin D deficiency (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.13–1.95) and insufficiency (OR, 1.44; 95% CI, 1.12–1.85) were significantly associated with high levels of depressive symptoms. Additional analyses revealed a linear trend, with an OR of 1.05 (95% CI, 1.02–1.08) for each 10-nM decrease in vitamin D status. Conclusions In this study, low early-pregnancy vitamin D status was associated with elevated depressive symptoms in pregnancy. Further research, using a randomized controlled design, would be required to confirm the causality of this association and the potential benefits of higher vitamin D intake for psychosocial health.

Cardio-metabolic risk in 5-year-old children prenatally exposed to maternal psychosocial stress: the ABCD study

BackgroundRecent evidence, both animal and human, suggests that modifiable factors during fetal and infant development predispose for cardiovascular disease in adult life and that they may become possible future targets for prevention. One of these factors is maternal psychosocial stress, but so far, few prospective studies have been able to investigate the longer-term effects of stress in detail, i.e. effects in childhood. Therefore, our general aim is to study whether prenatal maternal psychosocial stress is associated with an adverse cardio-metabolic risk profile in the child at age five.Methods/designData are available from the Amsterdam Born Children and their Development (ABCD) study, a prospective birth cohort in the Netherlands. Between 2003-2004, 8,266 pregnant women filled out a questionnaire including instruments to determine anxiety (STAI), pregnancy related anxiety (PRAQ), depressive symptoms (CES-D), parenting stress (PDH scale) and work stress (Job Content Questionnaire).Outcome measures in the offspring (age 5-7) are currently collected. These include lipid profile, blood glucose, insulin sensitivity, body composition (body mass index, waist circumference and bioelectrical impedance analysis), autonomic nervous system activity (parasympathetic and sympathetic measures) and blood pressure.Potential mediators are maternal serum cortisol, gestational age and birth weight for gestational age (intrauterine growth restriction). Possible gender differences in programming are also studied.DiscussionMain strengths of the proposed study are the longitudinal measurements during three important periods (pregnancy, infancy and childhood), the extensive measurement of maternal psychosocial stress with validated questionnaires and the thorough measurement of the childrens cardio-metabolic profile. The availability of several confounding factors will give us the opportunity to quantify the independent contribution of maternal stress during pregnancy to the cardio-metabolic risk profile of her offspring. Moreover, the mediating role of maternal cortisol, intrauterine growth, gestational age and potential gender differences can be explored extensively. If prenatal psychosocial stress is indeed found to be associated with the offsprings cardio-metabolic risk, these results support the statement that primary prevention of cardiovascular disease may start even before birth by reducing maternal stress during pregnancy.

Educational Inequalities in Perinatal Outcomes: The Mediating Effect of Smoking and Environmental Tobacco Exposure

Objective Socioeconomic status (SES) is adversely associated with perinatal outcomes. This association is likely to be mediated by tobacco exposure. However, previous studies were limited to single perinatal outcomes and devoted no attention to environmental tobacco exposure. Therefore, this study aimed firstly to explain the role of maternal smoking in the association between maternal education and preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA), and secondly to explain whether environmental tobacco smoke mediates these associations further. Study Design This study was nested in a population-based cohort study in the Netherlands, the Amsterdam Born Children and their Development (ABCD) study. Analyses were done in a sample of 3821 pregnant women of Dutch origin, using logistic regression analysis. Results Least educated women, who were more often smoking and exposed to environmental tobacco smoke, had a significantly higher risk of PTB (OR 1.95 [95% CI: 1.19–3.20]), LBW (OR 2.41 [95% CI: 1.36–4.27]) and SGA (OR 1.90 [95% CI 1.32–2.74]) than highly educated women. The mediating effect of smoking in the least educated women was 43% for PTB, 55% for LBW and 66% for SGA. Environmental tobacco smoke did not explain these associations further. After adjustment for maternal smoking, the association between lower maternal education and pregnancy outcomes was no longer significant. Conclusions Smoking explains to a considerable extent the association between lower maternal education and adverse perinatal outcomes. Therefore, tobacco-interventions in lower educated women should be primarily focussed on maternal smoking to reduce PTB, LBW, and SGA. Additional attention to environmental tobacco exposure does not seem to reduce educational inequalities in perinatal outcomes.