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Rotterdam, Netherlands

Gabriele C.,Erasmus Medical Center | Gabriele C.,Generation R Study Group | Jaddoe V.W.,Erasmus Medical Center | Jaddoe V.W.,Generation R Study Group | And 6 more authors.
European Respiratory Journal | Year: 2012

We assessed whether exhaled nitric oxide fraction (FeNO), a marker of eosinophilic airway inflammation, at 6 months was associated with the risk of wheezing during the first 2 yrs of life. In the Generation R birth cohort, pre- and post-natal risk factors for respiratory morbidity and respiratory symptoms were assessed by questionnaires at 6 and 24 months. In 428 infants, off-line mixed oral/nasal FeNO was successfullymeasured during tidal breathing at 6 months. Complete data on FeNO and respiratory symptoms within the first 6 months of life were available for 294 infants. FeNO was higher in males, was positively associated with age and was negatively associated with upper and lower respiratory symptoms within the first 6 months. Logistic regression analysis showed that for every ppb increase of FeNO measured at 6 months, infants had a 1.06 (95% confidence interval 1.01-1.11)-fold increased risk of wheezing in the second year of life. High FeNO (>17.5 ppb) showed a limited added value in predicting wheezing in the second year. We conclude that FeNO at 6 months is positively associated with the risk of wheezing, but has limited added value in predicting wheezing in the second year of life in individual children. Copyright©ERS 2012.

Duijts L.,Generation R Study Group | Duijts L.,Erasmus Medical Center | Jaddoe V.W.V.,Generation R Study Group | Jaddoe V.W.V.,Erasmus Medical Center | And 2 more authors.
Pediatrics | Year: 2010

OBJECTIVE: To examine the associations of duration of exclusive breastfeeding with infections in the upper respiratory (URTI), lower respiratory (LRTI), and gastrointestinal tracts (GI) in infancy. METHODS: This study was embedded in the Generation R Study, a population-based prospective cohort study from fetal life onward in the Netherlands. Rates of breastfeeding during the first 6 months (never; partial for <4 months, not thereafter; partial for 4-6 months; exclusive for 4 months, not thereafter; exclusive for 4 months, partial thereafter; and exclusive for 6 months) and doctor-attended infections in the URTI, LRTI, and GI until the age of 12 months were assessed by questionnaires and available for 4164 subjects. RESULTS: Compared with never-breastfed infants, those who were breastfed exclusively until the age of 4 months and partially thereafter had lower risks of infections in the URTI, LRTI, and GI until the age of 6 months (adjusted odds ratio [aOR]: 0.65 [95% confidence interval (CI): 0.51-0.83]; aOR: 0.50 [CI: 0.32-0.79]; and aOR: 0.41 [CI: 0.26-0.64], respectively) and of LRTI infections between the ages of 7 and 12 months (aOR: 0.46 [CI: 0.31-0.69]). Similar tendencies were observed for infants who were exclusively breastfed for 6 months or longer. Partial breastfeeding, even for 6 months, did not result in significantly lower risks of these infections. CONCLUSIONS: Exclusive breastfeeding until the age of 4 months and partially thereafter was associated with a significant reduction of respiratory and gastrointestinal morbidity in infants. Our findings support healthpolicy strategies to promote exclusive breastfeeding for at least 4 months, but preferably 6 months, in industrialized countries. Copyright © 2010 by the American Academy of Pediatrics.

Van Den Hooven E.H.,Generation R Study Group | Van Den Hooven E.H.,TNO | Van Den Hooven E.H.,Erasmus Medical Center | De Kluizenaar Y.,TNO | And 8 more authors.
Hypertension | Year: 2011

Exposure to air pollution is associated with elevated blood pressure and cardiovascular disease. We assessed the associations of exposure to particulate matter (PM10) and nitrogen dioxide (NO2) 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. PM10 exposure was not associated with first trimester systolic and diastolic blood pressure, but a 10-μg/m increase in PM10 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 PM10 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 NO2 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). PM10 exposure, but not NO2 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 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. © 2011 American Heart Association, Inc.

Ghassabian A.,Generation R Study Group | Herba C.M.,University of Quebec at Montreal | Herba C.M.,Ste Justines Hospital Research Center | Roza S.J.,Erasmus MC Sophia Childrens Hospital | And 10 more authors.
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2013

Background: Neuroimaging findings have provided evidence for a relation between variations in brain structures and Attention Deficit/Hyperactivity Disorder (ADHD). However, longitudinal neuroimaging studies are typically confined to children who have already been diagnosed with ADHD. In a population-based study, we aimed to characterize the prospective association between brain structures measured during infancy and executive function and attention deficit/hyperactivity problems assessed at preschool age. Methods: In the Generation R Study, the corpus callosum length, the gangliothalamic ovoid diameter (encompassing the basal ganglia and thalamus), and the ventricular volume were measured in 784 6-week-old children using cranial postnatal ultrasounds. Parents rated executive functioning at 4 years using the Behavior Rating Inventory of Executive Function-Preschool Version in five dimensions: inhibition, shifting, emotional control, working memory, and planning/organizing. Attention Deficit/Hyperactivity Problems were assessed at ages 3 and 5 years using the Child Behavior Checklist. Results: A smaller corpus callosum length during infancy was associated with greater deficits in executive functioning at 4 years. This was accounted for by higher problem scores on inhibition and emotional control. The corpus callosum length during infancy did not predict Attention Deficit/Hyperactivity Problem at 3 and 5 years, when controlling for the confounders. We did not find any relation between gangliothalamic ovoid diameter and executive function or Attention Deficit/Hyperactivity Problem. Conclusions: Variations in brain structures detectible in infants predicted subtle impairments in inhibition and emotional control. However, in this population-based study, we could not demonstrate that early structural brain variations precede symptoms of ADHD. © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

Roman G.C.,Methodist Neurological Institute | Roman G.C.,New York Medical College | Ghassabian A.,Generation R Study Group | Ghassabian A.,Erasmus Medical Center | And 8 more authors.
Annals of Neurology | Year: 2013

Objective Transient gestational hypothyroxinemia in rodents induces cortical neuronal migration brain lesions resembling those of autism. We investigated the association between maternal hypothyroxinemia (gestational weeks 6-18) and autistic symptoms in children. Methods The mother-and-child cohort of the Generation R Study (Rotterdam, the Netherlands) began prenatal enrollment between 2002 and 2006. At a mean gestational age of 13.4 weeks (standard deviation = 1.9, range = 5.9-17.9), maternal thyroid function tests (serum thyrotropin [TSH], free thyroxine [fT4], and thyroid peroxidase [TPO] antibodies) were assessed in 5,100 women. We defined severe maternal hypothyroxinemia as fT4 < 5th percentile with normal TSH. Six years later, parents reported behavioral and emotional symptoms in 4,039 children (79%) using the Pervasive Developmental Problems (PDP) subscale of the Child Behavior Checklist and/or the Social Responsiveness Scale (SRS). We defined a probable autistic child by a PDP score > 98th percentile and SRS score in the top 5% of the sample (n = 81, 2.0%). Results Severe maternal hypothyroxinemia (n = 136) was associated with an almost 4-fold increase in the odds of having a probable autistic child (adjusted odds ratio = 3.89, 95% confidence interval [CI] = 1.83-8.20, p < 0.001). Using PDP scores, children of mothers with severe hypothyroxinemia had higher scores of autistic symptoms by age 6 years (adjusted B = 0.23, 95% CI = 0.03-0.37); SRS results were similar. No risk was found for children of TPO-antibody-positive mothers (n = 308). Interpretation We found a consistent association between severe, early gestation maternal hypothyroxinemia and autistic symptoms in offspring. Findings are concordant with epidemiological, biological, and experimental data on autism. Although these findings cannot establish causality, they open the possibility of preventive interventions. © 2013 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of the American Neurological Association.

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