Developmental diseases, such as birth defects, growth restriction and preterm delivery, account for >25% of infant mortality and morbidity. Several studies have shown that exposure to chemicals ...during pregnancy is associated with adverse birth outcomes. The aim of this study was to identify whether occupational exposure to various chemicals might adversely influence intrauterine growth patterns and placental weight.
METHODS
Associations between maternal occupational exposure to various chemicals and fetal growth were studied in 4680 pregnant women participating in a population-based prospective cohort study from early pregnancy onwards in the Netherlands (2002–2006), the Generation R Study. Mothers who filled out a questionnaire during mid-pregnancy (response: 77% of enrolment) were included if they conducted paid employment during pregnancy and had a spontaneously conceived singleton live born pregnancy (n = 4680). A job exposure matrix was used, linking job titles to expert judgement on exposure to chemicals in the workplace. Fetal growth characteristics were repeatedly measured by ultrasound and were used in combination with measurements at birth. Placental weight was obtained from medical records and hospital registries. Linear regression models for repeated measurements were used to study the associations between maternal occupational exposure to chemicals and intrauterine growth.
RESULTS
We observed that maternal occupational exposure to polycyclic aromatic hydrocarbons, phthalates, alkylphenolic compounds and pesticides adversely influenced several domains of fetal growth (fetal weight, fetal head circumference and fetal length). We found a significant association between pesticide and phthalate exposure with a decreased placental weight.
CONCLUSIONS
Our results suggest that maternal occupational exposure to several chemicals is associated with impaired fetal growth during pregnancy and a decreased placental weight. Further studies are needed to confirm these findings and to assess post-natal consequences.
Prenatal Maternal Stress and Child IQ Cortes Hidalgo, Andrea P.; Neumann, Alexander; Bakermans‐Kranenburg, Marian J. ...
Child development,
March/April 2020, Letnik:
91, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The evidence for negative influences of maternal stress during pregnancy on child cognition remains inconclusive. This study tested the association between maternal prenatal stress and child ...intelligence in 4,251 mother–child dyads from a multiethnic population‐based cohort in the Netherlands. A latent factor of prenatal stress was constructed, and child IQ was tested at age 6 years. In Dutch and Caribbean participants, prenatal stress was not associated with child IQ after adjustment for maternal IQ and socioeconomic status. In other ethnicities no association was found; only in the Moroccan/Turkish group a small negative association between prenatal stress and child IQ was observed. These results suggest that prenatal stress does not predict child IQ, except in children from less acculturated minority groups.
The benefits of combination anti-retroviral therapy (cART) in HIV-positive pregnant women (improved maternal health and prevention of mother to child transmission pMTCT) currently outweigh the ...adverse effects due to cART. As the variety of cART increases, however, the question arises as to which type of cART is safest for pregnant women and women of childbearing age. We studied the effect of timing and exposure to different classes of cART on adverse birth outcomes in a large HIV cohort in the Netherlands.
We included singleton HEU infants registered in the ATHENA cohort from 1997 to 2015. Multivariate logistic regression analysis for single and multiple pregnancies was used to evaluate predictors of small for gestational age (SGA, birth weight <10th percentile for gestational age), low birth weight and preterm delivery.
A total of 1392 children born to 1022 mothers were included. Of these, 331 (23.8%) children were SGA. Women starting cART before conception had an increased risk of having a SGA infant compared to women starting cART after conception (OR 1.35, 95% CI 1.03-1.77, p = 0.03). The risk for SGA was highest in women who started a protease inhibitor-(PI) based regimen prior to pregnancy, compared with women who initiated PI-based cART during pregnancy. While the association of preterm delivery and preconception cART was significant in univariate analysis, on multivariate analysis only a non-significant trend was observed (OR 1.39, 95% CI 0.94-1.92, p = 0.06) in women who had started cART before compared to after conception. In multivariate analysis, the risk of low birth weight (OR 1.34, 95% CI 0.94-1.92, p = 0.11) was not significantly increased in women who had started cART prior to conception compared to after conception.
In our cohort of pregnant HIV-positive women, the use of cART prior to conception, most notably a PI-based regimen, was associated with intrauterine growth restriction resulting in SGA. Data showed a non-significant trend in the risk of PTD associated with preconception use of cART compared to its use after conception. More studies are needed with regard to the mechanisms taking place in the placenta during fetal growth in pregnant HIV-positive women using cART. It will only be with this knowledge that we can begin to understand the potential impact of HIV and cART on the fetus, in order to be able to determine the optimal individualised drug regimen for HIV-infected women of childbearing age.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of the study was to investigate the relationship between serum 25(OH)D levels and axial length (AL) and myopia in 6-year-old children. A total of 2666 children aged 6 years participating in ...the birth-cohort study Generation R underwent a stepwise eye examination. First, presenting visual acuity (VA) and AL were performed. Second, automated cycloplegic refraction was measured if LogMAR VA > 0.1. Serum 25-hydroxyvitamin D 25(OH) D was determined from blood using liquid chromatography/tandem mass spectrometry. Vitamin D related SNPs were determined with a SNP array; outdoor exposure was assessed by questionnaire. The relationships between 25(OH)D and AL or myopia were investigated using linear and logistic regression analysis. Average 25(OH)D concentration was 68.8 nmol/L (SD ± 27.5; range 4-211); average AL 22.35 mm (SD ± 0.7; range 19.2-25.3); and prevalence of myopia 2.3 % (n = 62). After adjustment for covariates, 25(OH)D concentration (per 25 nmol/L) was inversely associated with AL (β -0.043; P < 0.01), and after additional adjusting for time spent outdoors (β —0.038; P < 0.01). Associations were not different between European and non-European children (β —0.037 and β —0.039 respectively). Risk of myopia (per 25 nmol/L) was OR 0.65 (95 % CI 0.46-0.92). None of the 25(OH)D related SNPs showed an association with AL or myopia. Lower 25(OH)D concentration in serum was associated with longer AL and a higher risk of myopia in these young children. This effect appeared independent of outdoor exposure and may suggest a more direct role for 25(OH)D in myopia pathogenesis.
In this study, we aim to assess the associations over time between poverty and child weight status, asthma, and health-related quality of life (HRQoL).
We analyzed data for 3968 children from the ...Generation R Study, a population-based cohort study in the Netherlands. Net household income and the number of adults and children living from this income were measured at 4 time-points (during pregnancy and at ages 2, 3, and 6). Poverty was defined on the basis of the equivalized household income being <60% of the median national income. Child health outcomes were measured at age 6 years. The association was explored by using logistic and linear regression models.
In this cohort, 9.8% of children were born into poverty and 6.0% had experienced 3 to 4 episodes of poverty. Independent of current poverty status, children born into poverty had an odds ratio (OR) of 1.68 for having overweight/obesity and a lower physical HRQoL (OR = -1.32) than those not born into poverty. Children having experienced 3 to 4 episodes of poverty had an OR of 1.94 for having asthma and a lower physical HRQoL (OR = -3.32) compared with children from never-poor families. Transition out of poverty before age 2 was associated with lower risk of asthma and a higher physical HRQoL compared with children who remained in poverty.
Being born into poverty or experiencing multiple episodes of poverty is associated with negative child health outcomes, such as having overweight, asthma, or a lower HRQoL. Support for children and families with a low household income is warranted.
Thyroid hormone is involved in the regulation of early brain development. Since the fetal thyroid gland is not fully functional until week 18-20 of pregnancy, neuronal migration and other crucial ...early stages of intrauterine brain development largely depend on the supply of maternal thyroid hormone. Current clinical practice mostly focuses on preventing the negative consequences of low thyroid hormone concentrations, but data from animal studies have shown that both low and high concentrations of thyroid hormone have negative effects on offspring brain development. We aimed to investigate the association of maternal thyroid function with child intelligence quotient (IQ) and brain morphology.
In this population-based prospective cohort study, embedded within the Generation R Study (Rotterdam, Netherlands), we investigated the association of maternal thyroid function with child IQ (assessed by non-verbal intelligence tests) and brain morphology (assessed on brain MRI scans). Eligible women were those living in the study area at their delivery date, which had to be between April 1, 2002, and Jan 1, 2006. For this study, women with available serum samples who presented in early pregnancy (<18 weeks) were included. Data for maternal thyroid-stimulating hormone, free thyroxine, thyroid peroxidase antibodies (at weeks 9-18 of pregnancy), and child IQ (assessed at a median of 6·0 years of age 95% range 5·6-7·9 years) or brain MRI scans (done at a median of 8·0 years of age 6·2-10·0) were obtained. Analyses were adjusted for potential confounders including concentrations of human chorionic gonadotropin and child thyroid-stimulating hormone and free thyroxine.
Data for child IQ were available for 3839 mother-child pairs, and MRI scans were available from 646 children. Maternal free thyroxine concentrations showed an inverted U-shaped association with child IQ (p=0·0044), child grey matter volume (p=0·0062), and cortex volume (p=0·0011). For both low and high maternal free thyroxine concentrations, this association corresponded to a 1·4-3·8 points reduction in mean child IQ. Maternal thyroid-stimulating hormone was not associated with child IQ or brain morphology. All associations remained similar after the exclusion of women with overt hypothyroidism and overt hyperthyroidism, and after adjustment for concentrations of human chorionic gonadotropin, child thyroid-stimulating hormone and free thyroxine or thyroid peroxidase antibodies (continuous or positivity).
Both low and high maternal free thyroxine concentrations during pregnancy were associated with lower child IQ and lower grey matter and cortex volume. The association between high maternal free thyroxine and low child IQ suggests that levothyroxine therapy during pregnancy, which is often initiated in women with subclinical hypothyroidism during pregnancy, might carry the potential risk of adverse child neurodevelopment outcomes when the aim of treatment is to achieve high-normal thyroid function test results.
The Netherlands Organisation for Health Research and Development (ZonMw) and the European Community's Seventh Framework Programme.
Please cite this paper as: Bergen N, Jaddoe V, Timmermans S, Hofman A, Lindemans J, Russcher H, Raat H, Steegers‐Theunissen R, Steegers E. Homocysteine and folate concentrations in early pregnancy ...and the risk of adverse pregnancy outcomes: the Generation R Study. BJOG 2012;119:739–751.
Objective To investigate associations between early pregnancy homocysteine, folate and vitamin B12 concentrations and placental weight, birthweight and adverse pregnancy outcomes.
Design Population‐based birth cohort study.
Setting Rotterdam, the Netherlands.
Population Cohort of 5805 pregnant women.
Methods To analyse homocysteine, folate and vitamin B12 concentrations, blood was drawn in early pregnancy. These concentrations were divided into quintiles. Information on birth outcomes was retrieved from medical records. Multivariate regression analyses were used.
Main outcome measures Placental weight, birthweight, small for gestational age at birth (SGA) (<5th centile), prematurity and pre‐eclampsia.
Results High homocysteine concentrations (highest quintile) were associated with lower placental weight (difference 30 g; P < 0.001) and birthweight (difference 110 g; P < 0.001), and increased risk of SGA odds ratio (OR) 1.7; P = 0.006 compared with lowest quintile (reference). Low folate concentrations (lowest quintile) were associated with lower placental weight (difference 26 g; P = 0.001) and birthweight (difference 125 g; P < 0.001), and increased risks of SGA (OR 1.9; P = 0.002), prematurity (OR 2.2; P = 0.002) and pre‐eclampsia (OR 2.1; P = 0.04) compared with highest quintile (reference). The risk of developing SGA and pre‐eclampsia was substantially higher in women who had higher homocysteine and lower folate concentrations. No associations were found with vitamin B12.
Conclusions Higher homocysteine and lower folate concentrations in early pregnancy are associated with lower placental weight and birthweight, and higher risk of adverse pregnancy outcomes. These findings suggest that high homocysteine and low folate concentrations in early pregnancy may adversely influence placentation and subsequently affect the success of pregnancy and birth outcomes.
We aimed to evaluate the association between family socioeconomic status and repeatedly measured child television viewing time from early childhood to the school period. We analyzed data on 3,561 ...Dutch children from the Generation R Study, a population-based study in the Netherlands. Parent-reported television viewing time for children aged 2, 3, 4, 6 and 9 years were collected by questionnaires sent from April 2004 until January 2015. Odds ratios of watching television ≥1 hour/day at each age were calculated for children of mothers with low, mid-low, mid-high and high (reference group) education and children from low, middle and high (reference group) income households. A generalized logistic mixed model was used to assess the association between family socioeconomic status and child television viewing time trajectory. The percentage of children watching television ≥1 hour/day increased from age 2 to 9 years for all children (24.2%-85.0% for children of low-educated mothers; 4.7%-61.4% for children of high-educated mothers; 17.2%-74.9% for children from low income households; 6.2%-65.1% for children from high income households). Independent socioeconomic effect in child television viewing time was found for maternal educational level. The interaction between net household income and child age in longitudinal analyses was significant (p = 0.01), indicating that the television viewing time trajectories were different in household income subgroups. However the interaction between maternal educational level and child age was not significant (p = 0.19). Inverse socioeconomic gradients in child television viewing time were found from the preschool period to the late school period. The educational differences between the various educational subgroups remained stable with increasing age, but the differences between household income groups changed over time. Intervention developers and healthcare practitioners need to raise awareness among non-highly educated parents that the socioeconomic gradient in television viewing time has a tracking effect starting from preschool age.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Phthalates are related with fetal growth restriction and preterm birth.•Phthalates may have trimester specific effects on fetal growth and birth outcomes.•Limiting prenatal phthalate exposure is ...crucial to prevent suboptimal fetal growth.
Exposure to phthalates may affect fetal growth, but previous studies are inconsistent and have not explored the trimester-specific effects of phthalates on repeated measures of fetal growth.
To assess the associations of maternal phthalate metabolites urine concentrations with fetal growth measures and birth outcomes and identify potential windows of vulnerability to exposure.
Population-based prospective cohort study, the Generation R Study (2002–2006). Data analysis was performed from November 2019 to June 2020.
Rotterdam, the Netherlands.
1379 pregnant women.
Maternal phthalate metabolites urine concentrations in first, second and third trimester.
Fetal head circumference, length and weight measured in the second and third trimester by ultrasound and at birth and preterm birth and small size for gestational age at birth.
Higher pregnancy-averaged phthalic acid, low molecular weight phthalate (LMWP), high molecular weight phthalate (HMWP) and di-2-ethylhexylphthalate (DEHP) concentrations tended to be associated with lower fetal weight SDS across gestation. The associations of phthalic acid and LMWP with fetal weight became stronger as pregnancy progressed (differences −0.08 (95% CI −0.14 to −0.02) SDS and −0.09 (95% CI −0.16 to −0.02) SDS at 40 weeks per interquartile range increase in phthalic acid and LMWP, respectively). Higher concentrations of specific LMWP, HMWP and DEHP metabolites were also associated with smaller head circumference and lower length SDS at birth and an increased risk of preterm birth and small size for gestational age at birth (p-values < 0.05). We observed differences by timing of exposure in these associations.
Higher maternal phthalate metabolites urine concentrations seem to be related with fetal growth restriction and preterm birth. Phthalates may have trimester specific effects on fetal growth and birth outcomes. Further studies are needed to explore the underlying mechanisms and long-term consequences.
CONTEXT Adverse environmental exposures lead to developmental adaptations in fetal life. The influences of maternal physical characteristics and lifestyle habits on first-trimester fetal adaptations ...and the postnatal consequences are not known. OBJECTIVE To determine the risk factors and outcomes associated with first-trimester growth restriction. DESIGN, SETTING, AND PARTICIPANTS Prospective evaluation of the associations of maternal physical characteristics and lifestyle habits with first-trimester fetal crown to rump length in 1631 mothers with a known and reliable first day of their last menstrual period and a regular menstrual cycle. Subsequently, we assessed the associations of first-trimester fetal growth restriction with the risks of adverse birth outcomes and postnatal growth acceleration until the age of 2 years. The study was based in Rotterdam, the Netherlands. Mothers were enrolled between 2001 and 2005. MAIN OUTCOME MEASURES First-trimester fetal growth was measured as fetal crown to rump length by ultrasound between the gestational age of 10 weeks 0 days and 13 weeks 6 days. Main birth outcomes were preterm birth (gestational age <37 weeks), low birth weight (<2500 g), and small size for gestational age (lowest fifth birth centile). Postnatal growth was measured until the age of 2 years. RESULTS In the multivariate analysis, maternal age was positively associated with first-trimester fetal crown to rump length (difference per maternal year of age, 0.79 mm; 95% confidence interval CI, 0.41 to 1.18 per standard deviation score increase). Higher diastolic blood pressure and higher hematocrit levels were associated with a shorter crown to rump length (differences, −0.40 mm; 95% CI, −0.74 to −0.06 and −0.52 mm; 95% CI, −0.90 to −0.14 per standard deviation increase, respectively). Compared with mothers who were nonsmokers and optimal users of folic acid supplements, those who both smoked and did not use folic acid supplements had shorter fetal crown to rump lengths (difference, −3.84 mm; 95% CI, −5.71 to −1.98). Compared with normal first-trimester fetal growth, first-trimester growth restriction was associated with increased risks of preterm birth (4.0% vs 7.2%; adjusted odds ratio OR, 2.12; 95% CI, 1.24 to 3.61), low birth weight (3.5% vs 7.5%; adjusted OR, 2.42; 95% CI, 1.41 to 4.16), and small size for gestational age at birth (4.0% vs 10.6%; adjusted OR, 2.64; 95% CI, 1.64 to 4.25). Each standard deviation decrease in first-trimester fetal crown to rump length was associated with a postnatal growth acceleration until the age of 2 years (standard deviation score increase, 0.139 per 2 years; 95% CI, 0.097 to 0.181). CONCLUSIONS Maternal physical characteristics and lifestyle habits were independently associated with early fetal growth. First-trimester fetal growth restriction was associated with an increased risk of adverse birth outcomes and growth acceleration in early childhood.
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