Marjolein N. Kooijman

The Generation R Study: Biobank update 2015

The Generation R Study is a population-based prospective cohort study from fetal life until adulthood. The study is designed to identify early environmental and genetic causes and causal pathways leading to normal and abnormal growth, development and health from fetal life, childhood and young adulthood. In total, 9,778 mothers were enrolled in the study. Data collection in children and their parents include questionnaires, interviews, detailed physical and ultrasound examinations, behavioural observations, Magnetic Resonance Imaging and biological samples. Efforts have been conducted for collecting biological samples including blood, hair, faeces, nasal swabs, saliva and urine samples and generating genomics data on DNA, RNA and microbiome. In this paper, we give an update of the collection, processing and storage of these biological samples and available measures. Together with detailed phenotype measurements, these biological samples provide a unique resource for epidemiological studies focused on environmental exposures, genetic and genomic determinants and their interactions in relation to growth, health and development from fetal life onwards.

Correlates of physical activity in 2-year-old toddlers: the generation R study.

OBJECTIVE To describe and identify correlates of objectively measured physical activity and sedentary behavior in 2-year-old toddlers. STUDY DESIGN A total of 347 children participating in a birth cohort study wore a unaxial ActiGraph accelerometer during 1 weekday and 1 weekend day. Information on potential correlates was assessed by parent-reported questionnaires, delivery reports, and regular visits to child health centers. Univariate and multivariable linear regression analyses were conducted to examine the associations between potential correlates and the following physical activity outcomes: percentage of time spent in sedentary behavior, percentage of time spent in moderate-to-vigorous physical activity, and mean counts per minute. RESULTS A high percentage of monitored time was spent in sedentary behavior; 85.6% on weekdays and 84.5% on weekend days. Four correlates were significantly associated with at least 1 physical activity outcome in the multivariable regression models: childs sex, childs age, number of siblings, and season of measurement. The associations of gross motor development with moderate-to-vigorous physical activity and mean counts per minute approached significance. Associations of socioeconomic variables and childs body mass index z-score with physical activity outcomes were not significant. CONCLUSION Two-year-old toddlers spend most of their time in sedentary behavior. No modifiable correlates were identified. Further research on physical activity and associated health benefits among very young children is warranted.

Childhood Kidney Outcomes in Relation to Fetal Blood Flow and Kidney Size

Impaired fetal abdominal blood flow may lead to smaller kidneys and subsequent impaired kidney function in later life. In a prospective cohort study among 923 pregnant women and their children, we measured fetal growth, kidney volumes, and umbilical and cerebral artery blood flow (median gestational age of 30.3 weeks; 95% range, 28.5-32.7 weeks). We used a higher umbilical/cerebral artery pulsatility index ratio as an indicator of preferential fetal blood flow to the upper body parts at the expense of the intra-abdominal organs. At a median age of 5.9 years (95% range, 5.7-6.6 years), we measured childhood kidney volumes, creatinine and cystatin C blood levels, microalbuminuria, BP, and eGFR. A preferential fetal blood flow to the upper body parts at the expense of the intra-abdominal organs associated only with a smaller combined kidney volume in childhood. Fetal combined kidney volume positively associated with childhood combined kidney volume and eGFR, and inversely associated with childhood creatinine and cystatin C levels (all P values <0.05), but did not associate with childhood microalbuminuria and BP. Children within the highest tertile of fetal umbilical/cerebral ratio and the lowest tertile of fetal combined kidney volume had the lowest eGFR (difference, -6.36 ml/min per 1.73 m(2); 95% confidence interval, -11.78 to -0.94 compared with children within the middle tertiles). These data suggest that impaired fetal blood to the abdominal organs and smaller fetal kidney size are associated with subclinical changes in kidney outcomes in school-aged children.

Fetal Smoke Exposure and Kidney Outcomes in School-Aged Children

BACKGROUND Fetal smoke exposure may result in developmental adaptations that permanently affect the developing kidney. In this study, the associations of maternal and paternal smoking during pregnancy with childhood kidney size and function were assessed. STUDY DESIGN Prospective cohort study from fetal life onward. SETTING & PARTICIPANTS This study was conducted in a group of 5,622 children in Rotterdam, the Netherlands. PREDICTORS Maternal and paternal smoking were assessed during pregnancy by questionnaires. OUTCOMES & MEASUREMENTS At a median age of 6.0 (5th-95th percentile, 5.6-7.9) years, we measured childhood kidney volumes, estimated glomerular filtration rate (eGFR), and albumin-creatinine ratio. RESULTS The confounder model, which included size at birth, shows that compared with children from mothers who did not smoke during pregnancy, those from mothers who continued smoking during pregnancy had smaller combined kidney volumes at the age of 6 years. The strongest effect estimate was observed for mothers who smoked 5 or more cigarettes per day during pregnancy (difference for combined kidney volume, -2.80 [95% CI, -5.15 to -0.45] cm(3)). Similarly, continued maternal smoking during pregnancy also was associated with a lower eGFR in childhood (difference, -2.25 [95% CI, -3.70 to -0.79] mL/min/1.73 m(2)). First-trimester-only smoking was associated with a higher risk of increased albumin-creatinine ratio (OR, 1.45; 95% CI, 1.05-2.01). Among mothers who did not smoke during pregnancy, paternal smoking was associated with smaller childhood combined kidney volume (difference, -1.78 [95% CI, -3.48 to -0.07] cm(3)), but not with childhood kidney function measures. LIMITATIONS Smoking behavior was measured with questionnaires. Follow-up measurements were available for only 70% of the children. CONCLUSIONS Continued maternal smoking during pregnancy is associated with smaller combined kidney volume and lower eGFR in school-aged children. Stronger effect estimates for maternal versus paternal smoking suggest that intrauterine adaptive responses may play a role as underlying mechanisms.

Third trimester fetal hemodynamics and cardiovascular outcomes in childhood: the Generation R study.

Objective: Low birth weight is associated with cardiovascular disease in adulthood. Hemodynamic adaptations related to fetal growth restriction may underlie these associations, through persistent influences on cardiovascular development. We examined the associations of third trimester fetal hemodynamics with cardiovascular outcomes in childhood. Methods: In a prospective cohort study among 917 pregnant women and their children, we measured fetal growth, and fetal arterial and cardiac hemodynamic variables with ultrasound and Doppler examinations at a gestational age of 30.3 (95% range 28.8–32.3) weeks. At the age of 6 years, we measured blood pressure, carotid-femoral pulse wave velocity, and left cardiac structures and function. Results: We observed that fetal hemodynamics were not associated with childhood blood pressure and carotid-femoral pulse wave velocity. The fetal aorta ascendens diameter and left cardiac output were positively associated with childhood aortic root diameter [0.14 standard deviation score (SDS), 95% confidence interval (CI) 0.07–0.22 and 0.08 SDS, 95% CI 0.01–0.15 per SDS change in diameter and output, respectively]. Fetal left ventricular diastolic filling pattern was inversely associated with aortic root diameter (−0.07 SDS, 95% CI −0.13 to 0.00 per SDS change in E/A ratio) at 6 years. Analyses adjusted and stratified for estimated fetal weight showed no differences in results. Conclusion: Our results suggest that third trimester fetal vascular resistance parameters do not affect blood pressure or arterial stiffness in childhood. Fetal cardiac functional and structural measures are associated with cardiac outcomes in childhood. Whether these early adaptations lead to greater risks of cardiovascular disease should be further studied.

Influence of fetal blood flow redistribution on fetal and childhood growth and fat distribution: the Generation R Study

A suboptimal intrauterine environment leads to fetal blood flow redistribution and fetal growth restriction. Not much is known about childhood growth consequences. We examined the associations of fetal blood flow redistribution with birth outcomes, and repeatedly measured fetal and childhood growth and fat mass measures.