Maternal Sociodemographic Factors Are Associated with Methylphenidate Initiation in Children in the Netherlands: A Population-Based Study.

Multiple factors may contribute to the decision to initiate methylphenidate treatment in children such as maternal sociodemographic factors of which relatively little is known. The objective was to investigate the association between these factors and methylphenidate initiation. The study population included 4243 children from the Generation R Study in the Netherlands. Maternal sociodemographic characteristics were tested as determinants of methylphenidate initiation through a time-dependent Cox regression analysis. Subsequently, we stratified by mother-reported ADHD symptoms (present in 4.2% of the study population). When ADHD symptoms were absent, we found that girls (adjusted HR 0.25, 95%CI 0.16-0.39) and children born to a mother with a non-western ethnicity (compared to Dutch-Caucasian) (adjusted HR 0.42, 95%CI 015-0.68) were less likely to receive methylphenidate. They were more likely to receive methylphenidate when their mother completed a low (adjusted HR 2.29, 95%CI 1.10-4.77) or secondary (adjusted HR 1.71, 95%CI 1.16-2.54) education. In conclusion, boys and children born to a mother of Dutch-Caucasian ethnicity were more likely to receive methylphenidate, irrespective of the presence of ADHD symptoms.

Maternal psychological distress during pregnancy and childhood cardio-metabolic risk factors.

BACKGROUND AND AIMS: Previous studies suggest that psychological distress during pregnancy may lead to fetal developmental adaptations, which programme cardio-metabolic disease of the offspring. We examined the associations of maternal overall psychological distress, depression and anxiety during pregnancy with cardio-metabolic risk factors in 10-year-old children and explore potential sex-specific differences. METHODS AND RESULTS: In a population-based prospective cohort study among 4,088 mothers and their children, information about overall psychological distress, including depression and anxiety was obtained through the Brief Symptom Inventory during pregnancy. We measured child blood pressure and heart rate and insulin, glucose, serum lipids and C-reactive protein blood concentrations at 10 years. Analyses were performed in the total group and in boys and girls separately. Psychological distress during pregnancy was associated with higher childhood heart rate among boys only (differences 0.34 (95% Confidence Interval (CI) 0.18, 0.50) standard deviation scores (SDS), 0.22 (95% CI 0.06, 0.38) SDS, 0.33 (95% CI 0.19, 0.48) SDS, for overall psychological distress, depression and anxiety, respectively). Maternal anxiety during pregnancy was associated with higher childhood triglycerides among girls (difference 0.35 (95% CI 0.17, 0.53) SDS). Maternal psychological distress was not associated with childhood blood pressure, cholesterol, insulin, glucose and C-reactive protein concentrations. CONCLUSIONS: Maternal psychological distress may influence their offspring heart rate and triglycerides concentrations. Further studies are needed to replicate these findings and assess the long-term cardio-metabolic consequences of maternal psychological distress.

The concordance between self-reported medication use and pharmacy records in pregnant women.

PURPOSE: Several studies have been conducted to assess determinants affecting the performance or accuracy of self-reports. These studies are often not focused on pregnant women, or medical records were used as a data source where it is unclear if medications have been dispensed. Therefore, our objective was to evaluate the concordance between self-reported medication data and pharmacy records among pregnant women and its determinants. METHODS: We conducted a population-based cohort study within the Generation R study, in 2637 pregnant women. The concordance between self-reported medication data and pharmacy records was calculated for different therapeutic classes using Yule's Y. We evaluated a number of variables as determinant of discordance between both sources through univariate and multivariate logistic regression analysis. RESULTS: The concordance between self-reports and pharmacy records was moderate to good for medications used for chronic conditions, such as selective serotonin reuptake inhibitors or anti-asthmatic medications (0.88 and 0.68, respectively). Medications that are used occasionally, such as antibiotics, had a lower concordance (0.51). Women with a Turkish or other non-Western background were more likely to demonstrate discordance between pharmacy records and self-reported data compared with women with a Dutch background (Turkish: odds ratio, 1.63; 95% confidence interval, 1.16-2.29; other non-Western: odds ratio, 1.33; 95% confidence interval, 1.03-1.71). CONCLUSIONS: Further research is needed to assess how the cultural or ethnic differences may affect the concordance or discordance between both medication sources. The results of this study showed that the use of multiple sources is needed to have a good estimation of the medication use during pregnancy.

Cortical thickness and inattention/hyperactivity symptoms in young children: a population-based study.

BACKGROUND: While many neuroimaging studies have investigated the neurobiological basis of attention deficit hyperactivity disorder (ADHD), few have studied the neurobiology of attention problems in the general population. The ability to pay attention falls along a continuum within the population, with children with ADHD at one extreme of the spectrum and, therefore, a dimensional perspective of evaluating attention problems has an added value to the existing literature. Our goal was to investigate the relationship between cortical thickness and inattention and hyperactivity symptoms in a large population of young children. METHOD: This study is embedded within the Generation R Study and includes 6- to 8-year-old children (n = 444) with parent-reported attention and hyperactivity measures and high-resolution structural imaging data. We investigated the relationship between cortical thickness across the entire brain and the Child Behavior Checklist Attention Deficit Hyperactivity Problems score. RESULTS: We found that greater attention problems and hyperactivity were associated with a thinner right and left postcentral gyrus. When correcting for potential confounding factors and multiple testing, these associations remained significant. CONCLUSIONS: In a large, population-based sample we showed that young (6- to 8-year-old) children who show more attention problems and hyperactivity have a thinner cortex in the region of the right and left postcentral gyrus. The postcentral gyrus, being the primary somatosensory cortex, reaches its peak growth early in development. Therefore, the thinner cortex in this region may reflect either a deviation in cortical maturation or a failure to reach the same peak cortical thickness compared with children without attention or hyperactivity problems.

Maternal smoking during pregnancy, fetal arterial resistance adaptations and cardiovascular function in childhood.

OBJECTIVE: To unravel the mechanisms underlying the previously demonstrated associations between low birthweight and cardiovascular disease in adulthood, we examined whether maternal smoking during pregnancy leads to fetal arterial resistance adaptations, and subsequently to fetal growth retardation and changes in postnatal blood pressure and cardiac development. DESIGN: Prospective cohort study from early fetal life onwards. SETTING: Academic hospital. POPULATION: Analyses were based on 1120 children aged 2 years. METHODS: Maternal smoking during pregnancy [non-smoking, first trimester smoking, continued smoking (< 5 and ≥ 5 cigarettes/day)] was assessed by questionnaire. MAIN OUTCOME MEASURES: Third trimester placental and fetal arterial resistance indices and fetal growth were assessed by ultrasound and Doppler measurements. Postnatal blood pressure and cardiac structures (aortic root diameter, left atrial diameter, left ventricular mass) were measured at 2 years of age. RESULTS: First trimester smoking was not associated with third trimester placental and fetal blood flow adaptations. Continued smoking of ≥ 5 cigarettes/day was associated with an increased resistance in uterine, umbilical and middle cerebral arteries, and with a decreased flow and diameter of the ascending aorta. Among mothers who continued to smoke, the third trimester estimated fetal weights and birthweights were most affected in children with the highest umbilical artery resistance. Fetal arterial resistance indices were also associated with aortic root diameter and left atrial diameter. CONCLUSIONS: Fetal arterial resistance adaptations may be involved in the pathways leading from maternal smoking during pregnancy to low birthweight and cardiovascular developmental changes in childhood in the offspring.

Agreement between maternal cannabis use during pregnancy according to self-report and urinalysis in a population-based cohort: the Generation R Study.

AIM: To verify self-reported information on prenatal drug use in urine because reporting in pregnancy is sensitive to stigma and might lead to misclassification. METHODS: Using semiquantitative immunochemical analysis, the presence of the urinary metabolite (11-nor-Δ9-tetrahydrocannabinol- 9-carboxylic acid) was compared to self-reported prenatal cannabis use. Sensitivity and specificity for self-report and urinalysis outcomes were calculated and Yule's Y was used as an agreement measure. RESULTS: Urine samples were available for 3,997 pregnant women. Of these women, 92 reported having used cannabis during pregnancy (2.3%) and 71 had positive urine screens (1.8%). In total 35% of the 92 women with self-reported cannabis use also had a positive urine screen. Positive urines were relatively frequent in women reporting cannabis use before pregnancy only (7.6%) and in women with missing information (2.6%). Sensitivity and specificity of urinalysis compared to self-report were 0.46 and 0.98. Sensitivity and specificity of self-report compared to urinalysis were 0.36 and 0.99. Yule's Y amounted to 0.77, indicating substantial agreement between the measures. CONCLUSIONS: Our findings illustrate the difficulties in obtaining valid information on prenatal cannabis use. To improve the quality of cannabis use data, we suggest a 2-step approach starting with self-report.

Maternal psychological distress during pregnancy and childhood health outcomes: a narrative review.

Maternal psychological distress is common in pregnancy and may influence the risk of adverse outcomes in children. Psychological distress may cause a suboptimal intrauterine environment leading to growth and developmental adaptations of the fetus and child. In this narrative review, we examined the influence of maternal psychological distress during pregnancy on fetal outcomes and child cardiometabolic, respiratory, atopic and neurodevelopment-related health outcomes. We discussed these findings from an epidemiological and life course perspective and provided recommendations for future studies. The literature in the field of maternal psychological distress and child health outcomes is extensive and shows that exposure to stress during pregnancy is associated with multiple adverse child health outcomes. Because maternal psychological distress is an important and potential modifiable factor during pregnancy, it should be a target for prevention strategies in order to optimize fetal and child health. Future studies should use innovative designs and strategies in order to address the issue of causality.

Stuttering and gray matter morphometry: A population-based neuroimaging study in young children.

Stuttering is a developmental speech disorder originating in early childhood. We aimed to replicate the association of stuttering and structural morphometry using a large, population-based prospective cohort, the Generation R Study, and explore the neurobiological mechanism of stuttering in children. Twenty-six children with a history of stuttering and 489 fluent speaking peers (ages 6-9) were included in the MRI sub-study. Cortical and subcortical regions of interest were analyzed using linear regression models. Compared to fluent speakers, children with a history of stuttering had less gray matter volume in the left inferior frontal gyrus and supplementary motor area. Exploratory surface-based brain analysis showed thinner cortex in the left inferior frontal gyrus, and in bilateral frontal and parietal areas. These findings corroborate previous studies that reported aberrant brain morphometry in speech motor and auditory regions in children who stutter. Future research is needed to explore the causal nature of this association.

Prenatal maternal psychopathology and stress and offspring HPA axis function at 6 years.

OBJECTIVE: Intrauterine exposures such as maternal psychopathology and stress are known to influence the physical and mental health of the offspring. One of the proposed pathways underlying these associations is dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity in the offspring. This study examined the relation of perinatal maternal symptoms of psychopathology and stress with offspring HPA axis activity at 6 years as measured by hair cortisol and cortisone concentrations. METHODS: The study was part of the population-based Generation R Study, a prospective population-based cohort from fetal life onwards. 2546 children and their mothers formed the study population. Perinatal maternal psychopathology and stress were assessed by questionnaires in the second and third trimester. Principal components for both psychopathology and stress were created to reduce the number of explanatory variables. Child hair samples for cortisol and cortisone measurements were collected at the age of 6. Linear regression analysis, adjusted for covariates, was used to examine associations between maternal psychopathology and stress and child hair cortisol and cortisone levels. RESULTS: The maternal psychopathology principal component was associated with higher child hair cortisone (adjusted B = 0.24, 95%CI 0.08;0.40, p-value < 0.01). Effect estimates of the individual dimensions ranged from 0.97 (95%CI 0.21;1.73, p-value = 0.01) for interpersonal sensitivity to 1.67 (95%CI 0.86;2.47, p-value < 0.01) for paranoid ideation. In addition, children exposed to intrauterine stress, as measured by the principal component, had higher hair cortisone levels (adjusted B = 0.54, 95%CI 0.21;0.88, p-value < 0.01). Exposure to maternal psychopathology and stress was not associated with offspring hair cortisol. Stratification by child sex resulted in associations between maternal symptoms of psychopathology during pregnancy and child hair cortisone levels in boys and associations between maternal symptoms of stress during pregnancy and child hair cortisone levels in girls. CONCLUSION: Our results suggest that maternal psychopathology and stress during pregnancy are associated with long-term HPA axis activity of the offspring. The association of maternal psychopathology and stress during pregnancy with offspring hair cortisone levels is a novel finding. Future studies should examine whether these psychophysiological differences between exposed and non-exposed children underlie offspring morbidity associated with maternal psychopathology and stress during pregnancy.