Early respiratory morbidity in a multicultural birth cohort: the Generation R Study

Ethnic disparities in the prevalence of asthma symptoms in children have been described. We evaluated to what extent the association between ethnic background and respiratory symptoms during the first 2 years of life could be explained by the mediating effect of risk factors for respiratory morbidity. The Generation R Study is a multiethnic, population-based birth cohort study. Pre and postnatal risk factors for respiratory morbidity were prospectively assessed by questionnaires. Information about ethnicity was available for 5,684 infants. The associations between ethnic background and lower respiratory symptoms at 12 and 24 months were evaluated with log-binomial regression models. Relative risks and 95 % confidence intervals (RR [95 % CI]) were computed for Cape Verdean, Moroccan, Antillean, Surinamese and Turkish ethnicity with Dutch ethnicity as the reference category. We found an increased risk of lower respiratory symptoms at 24 months in Antillean infants (1.32 [95 % CI 1.12-1.57]) that was mediated by early postnatal exposures (pets keeping, siblings, breastfeeding, daycare attendance, smoke exposure). Turkish infants also had an increased risk of lower respiratory symptoms at 12 and 24 months (1.14 [95 % CI 1.02-1.27] and 1.21 [95 % CI 1.07-1.38], respectively), partly explained by previous morbidity (eczema, infections and upper respiratory symptoms). There were no differences for Cape Verdean, Moroccan or Surinamese, as compared to Dutch infants. Hence, ethnic background was associated with respiratory symptoms during the first 2 years of life and this association was largely explained by mediating effects of known pre and postnatal risk factors for respiratory morbidity.     

Effects of size at birth and childhood growth on the insulin resistance syndrome in elderly individuals

Aims/hypothesis: A study of 7086 men and women born in Helsinki, Finland, has shown that the development of Type II (non-insulin-dependent) diabetes mellitus is associated with low birth weight followed by accelerated gain in height and weight during childhood and with high maternal BMI but the processes which underlie these associations are largely not known. Methods: We carried out standard oral glucose tolerance tests, and measured plasma insulin and proinsulin, serum lipid concentrations and blood pressure in 474 patients from the Helsinki cohort. Results: We used four indices of insulin resistance: fasting and 2-h plasma insulin, and fasting proinsulin and 32–33 split proinsulin concentrations. These were associated with small body size at birth and during childhood, rapid growth in height and low maternal BMI. Conclusion/interpretation: Insulin resistance and Type II diabetes share common associations with retarded fetal growth and accelerated growth during childhood. They are dissimilar, however, in that insulin resistance is associated with thinness in childhood and low maternal BMI, while Type II diabetes is associated with high BMI in childhood and high maternal BMI. [Diabetologia (2002) 45: 342–348] Received: 23 August 2001 and in revised form: 2 November 2001     

Genetic variants associated with adult blood pressure and kidney function do not affect fetal kidney volume. The Generation R Study

Background

Smaller kidneys with reduced number of nephrons in early life lead to impaired kidney function and risk for hypertension and chronic kidney disease. These associations might be partly explained by common genetic variation.

Aims

To assess the associations between common genetic variants, which have recently shown to be associated with blood pressure or kidney function, with fetal kidney volume.

Study design

A prospective population based cohort study in Rotterdam, The Netherlands.

Subjects

855 children, followed from early fetal life onwards (born 2003–2005).

Predictor

Common genetic variants previously associated with blood pressure or kidney function.

Outcome measures

Combined third trimester fetal kidney volume.

Results

After taking into account multiple testing, only rs12940887 (near ZNF652) was significantly associated with fetal kidney volume (β: 0.88 (95% CI: 0.40; 1.37) cm³ per minor allele, P-value < 0.001), but the effect showed the opposite direction as expected. The remaining common genetic variants were not associated with fetal kidney volume. We also did not find associations of genetic variants previously shown to affect newborn kidney volume, with third trimester fetal kidney volume.

Conclusions

Our results suggest that common genetic variants, associated with kidney function or disease and blood pressure, do not affect the third trimester fetal kidney volume. Further studies are needed to elucidate the mechanisms underlying the associations between small kidney size and increased risks of hypertension and impaired kidney function in adulthood.     

Maternal smoking during pregnancy and child emotional problems: the relevance of maternal and child 5-HTTLPR genotype

Serotonin is involved in the development of neural circuits modulating emotional behavior. The short allele (s) of a polymorphism (5-HTTLPR) of the serotonin transporter gene is a risk factor for psychopathology in the presence of environmental stressors. Maternal smoking is associated with growth restriction of the human fetal brain and adverse effects of nicotine on the developing serotonin system have been documented. We hypothesized that maternal smoking interacts with both child and mother 5-HTTLPR genotype as a risk factor for later child emotional problems. In a sample of n?=?1,529 mother-child dyads, smoking habits were assessed by questionnaires during pregnancy. Child emotional problems were measured by the Child Behavior Checklist at the child's age of 3 years. Maternal smoking during pregnancy significantly increased the risk for emotional problems in children carrying the s-allele; β?=?0.24, P?=?0.03 (mother-report), and β?=?0.46, P?=?0.001 (father-report). In children heterozygous at 5-HTTLPR and exposed to maternal prenatal smoking (n?=?79) risk of emotional problems increased with each additional s-allele the mother carried. The associations between 5-HTTLPR and child emotional problems were not moderated by paternal prenatal smoking. These findings imply that the vulnerability for emotional problems in s-allele carriers may already originate in fetal life.     

Dynamics and determinants of Staphylococcus aureus carriage in infancy: the Generation R Study

Serial nasal swabs were collected at the ages of 1.5, 6, and 14 months from 443 infants in the Generation R Study. The objective was to study the dynamics and determinants of Staphylococcus aureus nasal carriage in the first year of life. The prevalence of S. aureus carriage decreased in the first year of life, from 52.1% at the age of 1.5 months to 12.9% at 14 months. Persistent carriage, defined as continuous carriage of the same S. aureus strain at the three sampling moments, was rarely detected in early infancy.     

Maternal fish consumption, fetal growth and the risks of neonatal complications: the Generation R Study

Maternal fish consumption during pregnancy has been suggested to affect birth outcomes. Previous studies mainly focused on birth outcomes and did not study fetal growth during pregnancy. In a prospective cohort study from early pregnancy onwards in The Netherlands, we assessed the associations of first-trimester maternal total-fish, lean-fish, fatty-fish and shellfish consumption with fetal growth characteristics in the second and third trimesters, growth characteristics at birth and the risks of neonatal complications, including pre-term birth, low birth weight and small for gestational age. In total, 3380 mothers completed a 293-item semi-quantitative FFQ to obtain information about fish consumption during the first trimester of pregnancy. Head circumference, femur length and fetal weight were estimated in the second and third trimesters by ultrasound. Information about birth anthropometrics and neonatal complications was available from hospital and midwife registries. Maternal older age, higher educational level, folic acid supplement use, alcohol use and not smoking were associated with higher fish consumption (P < 0·01). After adjustment, we observed no consistent associations of maternal total-fish consumption or specific consumption of lean fish, fatty fish or shellfish with fetal growth characteristics in the second and third trimesters and at birth. Likewise, total-fish consumption or specific consumption of any type of fish was not consistently associated with the risks of neonatal complications. These findings suggest that in a population with a relatively low fish intake, consumption of lean fish, fatty fish or shellfish in the first trimester is not associated with fetal growth or the risks of neonatal complications.     

Breast-feeding and growth in children until the age of 3 years: the Generation R Study

Breast-feeding has been suggested to be associated with lower risks of obesity in older children and adults. We assessed whether the duration and exclusiveness of breast-feeding are associated with early postnatal growth rates and the risks of overweight and obesity in preschool children. The present study was embedded in a population-based prospective cohort study from early fetal life onwards, among 5047 children and their mothers in The Netherlands. Compared with children who were breast-fed, those who were never breast-fed had a lower weight at birth (difference 134 (95 % CI - 190, - 77) g). No associations between breast-feeding duration and exclusivity with growth rates before the age of 3 months were observed. Shorter breast-feeding duration was associated with an increased gain in age- and sex-adjusted standard deviation scores for length, weight and BMI (P for trend < 0·05) between 3 and 6 months of age. Similar tendencies were observed for the associations of breast-feeding exclusivity with change in length, weight and BMI. Breast-feeding duration and exclusivity were not consistently associated with the risks of overweight and obesity at the ages of 1, 2 and 3 years. In conclusion, shorter breast-feeding duration and exclusivity during the first 6 months tended to be associated with increased growth rates for length, weight and BMI between the age of 3 and 6 months but not with the risks of overweight and obesity until the age of 3 years.     

Air pollution, blood pressure, and the risk of hypertensive complications during pregnancy: the generation R study

Exposure to air pollution is associated with elevated blood pressure and cardiovascular disease. We assessed the associations of exposure to particulate matter (PM(10)) and nitrogen dioxide (NO(2)) levels with blood pressure measured in each trimester of pregnancy and the risks of pregnancy-induced hypertension and preeclampsia in 7006 women participating in a prospective cohort study in the Netherlands. Information on gestational hypertensive disorders was obtained from medical records. PM(10) exposure was not associated with first trimester systolic and diastolic blood pressure, but a 10-μg/m(3) increase in PM(10) levels was associated with a 1.11-mm Hg (95% confidence interval [CI] 0.43 to 1.79) and 2.11-mm Hg (95% CI 1.34 to 2.89) increase in systolic blood pressure in the second and third trimester, respectively. Longitudinal analyses showed that elevated PM(10) exposure levels were associated with a steeper increase in systolic blood pressure throughout pregnancy (P<0.01), but not with diastolic blood pressure patterns. Elevated NO(2) exposure was associated with higher systolic blood pressure levels in the first, second, and third trimester (P<0.05), and with a more gradual increase when analyzed longitudinally (P<0.01). PM(10) exposure, but not NO(2) exposure, was associated with an increased risk of pregnancy-induced hypertension (odds ratio 1.72 [95% CI 1.12 to 2.63] per 10-μg/m(3) increase). In conclusion, our results suggest that air pollution may affect maternal cardiovascular health during pregnancy. The effects might be small but relevant on a population level.