Jens Henrichs

Maternal Thyroid Function during Early Pregnancy and Cognitive Functioning in Early Childhood: The Generation R Study

CONTEXT Thyroid hormones are essential for neurodevelopment from early pregnancy onward. Yet population-based data on the association between maternal thyroid function in early pregnancy and childrens cognitive development are sparse. OBJECTIVE Our objective was to study associations of maternal hypothyroxinemia and of early pregnancy maternal TSH and free T(4)(FT(4)) levels across the entire range with cognitive functioning in early childhood. DESIGN AND SETTING We conducted a population-based cohort in The Netherlands. PARTICIPANTS Participants included 3659 children and their mothers. MAIN MEASURES In pregnant women with normal TSH levels at 13 wk gestation (SD = 1.7), mild and severe maternal hypothyroxinemia were defined as FT(4) concentrations below the 10th and 5th percentile, respectively. Childrens expressive vocabulary at 18 months was reported by mothers using the MacArthur Communicative Development Inventory. At 30 months, mothers completed the Language Development Survey and the Parent Report of Childrens Abilities measuring verbal and nonverbal cognitive functioning. RESULTS Maternal TSH was not related to the cognitive outcomes. An increase in maternal FT(4) predicted a lower risk of expressive language delay at 30 months only. However, both mild and severe maternal hypothyroxinemia was associated with a higher risk of expressive language delay across all ages [odds ratio (OR) = 1.44; 95% confidence interval (CI) = 1.09-1.91; P = 0.010 and OR = 1.80; 95% CI = 1.24-2.61; P = 0.002, respectively]. Severe maternal hypothyroxinemia also predicted a higher risk of nonverbal cognitive delay (OR = 2.03; 95% CI = 1.22-3.39; P = 0.007). CONCLUSIONS Maternal hypothyroxinemia is a risk factor for cognitive delay in early childhood.

Maternal psychological distress and fetal growth trajectories: the Generation R Study.

BACKGROUND Previous research suggests, though not consistently, that maternal psychological distress during pregnancy leads to adverse birth outcomes. We investigated whether maternal psychological distress affects fetal growth during the period of mid-pregnancy until birth. METHOD Pregnant women (n=6313) reported levels of psychological distress using the Brief Symptom Inventory (anxious and depressive symptoms) and the Family Assessment Device (family stress) at 20.6 weeks pregnancy and had fetal ultrasound measurements in mid- and late pregnancy. Estimated fetal weight was calculated using head circumference, abdominal circumference and femur length. RESULTS In mid-pregnancy, maternal distress was not linked to fetal size. In late pregnancy, however, anxious symptoms were related to fetal size after controlling for potential confounders. Anxious symptoms were also associated with a 37.73 g [95% confidence interval (CI) -69.22 to -6.25, p=0.019] lower birth weight. When we related maternal distress to fetal growth curves using multilevel models, more consistent results emerged. Maternal symptoms of anxiety or depression were associated with impaired fetal weight gain and impaired fetal head and abdominal growth. For example, depressive symptoms reduced fetal weight gain by 2.86 g (95% CI -4.48 to -1.23, p<0.001) per week. CONCLUSIONS The study suggests that, starting in mid-pregnancy, fetal growth can be affected by different aspects of maternal distress. In particular, children of prenatally anxious mothers seem to display impaired fetal growth patterns during pregnancy. Future work should address the biological mechanisms underlying the association of maternal distress with fetal development and focus on the effects of reducing psychological distress in pregnancy.

Parental depressive and anxiety symptoms during pregnancy and attention problems in children: A cross-cohort consistency study

Background Maternal depression and anxiety during pregnancy have been associated with offspring-attention deficit problems. Aim We explored possible intrauterine effects by comparing maternal and paternal symptoms during pregnancy, by investigating cross-cohort consistency, and by investigating whether parental symptoms in early childhood may explain any observed intrauterine effect. Methods This study was conducted in two cohorts (Generation R, n = 2,280 and ALSPAC, n = 3,442). Pregnant women and their partners completed questionnaires to assess symptoms of depression and anxiety. Child attention problems were measured in Generation R at age 3 with the Child Behavior Checklist, and in ALSPAC at age 4 with the Strengths and Difficulties Questionnaire. Results In both cohorts, antenatal maternal symptoms of depression (Generation R: OR 1.23, 95% CI 1.05–1.43; ALSPAC: OR 1.33, 95% CI 1.19–1.48) and anxiety (Generation R: OR 1.24, 95% CI 1.06–1.46; ALSPAC: OR 1.32, 95% CI 1.19–1.47) were associated with a higher risk of child attention problems. In ALSPAC, paternal depression was also associated with a higher risk of child attention problems (OR 1.11, 95% CI 1.00–1.24). After adjusting for maternal symptoms after giving birth, antenatal maternal depression and anxiety were no longer associated with child attention problems in Generation R. Moreover, there was little statistical evidence that antenatal maternal and paternal depression and anxiety had a substantially different effect on attention problems of the child. Conclusions The apparent intrauterine effect of maternal depression and anxiety on offspring-behavioural problems may be partly explained by residual confounding. There was little evidence of a difference between the strength of associations of maternal and paternal symptoms during pregnancy with offspring-attention problems. That maternal symptoms after childbirth were also associated with offspring-behavioural problems may indicate a contribution of genetic influences to the association.

Maternal hypothyroxinemia and effects on cognitive functioning in childhood : How and why?

Exposure to maternal hypothyroxinemia during pregnancy, which is characterized by low free T4 but normal thyroid‐stimulating hormone (TSH) levels, can negatively affect the foetus. This review provides an overview of present findings concerning the association between maternal hypothyroxinemia during pregnancy and childhood cognitive functioning. Possible causes of maternal hypothyroxinemia and potential mechanisms underlying this association are also discussed. Clinical and epidemiological studies suggest that maternal hypothyroxinemia in the first half of pregnancy but not later in pregnancy impairs cognitive development in infancy and childhood. Animal models confirm that the first half of pregnancy may constitute a sensitive period in which maternal hypothyroxinemia alters neurogenesis and causes neuronal migration errors in the developing foetal brain. However, observational studies in humans cannot demonstrate causality of the association between hypothyroxinemia and neurodevelopment. In the only completed randomized trial of antenatal thyroid screening and subsequent levothyroxine treatment of mild maternal subclinical thyroid dysfunction, including hypothyroxinemia, the interventions did not affect offspring intelligence quotient (IQ). More randomized trials are needed investigating whether screening for hypothyroxinemia and its treatment earlier in the first trimester of pregnancy can improve child cognitive functioning or prevent neurodevelopmental changes. Long‐term observational studies should identify molecular, neuroanatomical and neurophysiological factors involved in the association between maternal hypothyroxinemia and offspring cognitive functioning. Information on such mechanisms can be used for the development of innovative prevention and intervention studies that address maternal hypothyroxinemia and its potential consequences.

Maternal thyroid function during pregnancy and behavioral problems in the offspring: the generation R study.

Maternal thyroid function during pregnancy is implicated in the neurodevelopment of the offspring, yet little is known about the effect of maternal thyroid parameters on the behavior of children. We investigated the association of maternal thyroid function during the first half of pregnancy with parent-reported problem behavior of the offspring up to age of 3 y. In the Generation R study, a population-based cohort of 3736 children and their mothers, data on maternal thyroid function and childs behavior were examined. The degree of internalizing and externalizing problems in the children were assessed with the Child Behavior Checklist at ages 1½ and 3 y. Higher levels of maternal TSH during pregnancy predicted a higher externalizing scores in children at 1½ and 3 y (B = 0.22 per SD of TSH; 95% CI: 0.04, 0.40; B = 0.10 per SD for internalizing scores; 95% CI: −0.01, 0.21). Maternal free thyroxine (T4) and total T4 were not associated with internalizing or externalizing scores of children. The linear relationship with more externalizing scores was across the range of TSH; this implies that subtle impairments of maternal thyroid function may affect the child. The results suggest that thyroid function is crucial for fetal brain development, which determines problem behavior later in life.

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.

Criminal Victimisation in People with Severe Mental Illness : A Multi-Site Prevalence and Incidence Survey in the Netherlands

Background Although crime victimisation is as prevalent in psychiatric patients as crime perpetration (and possibly more so), few European figures for it are available. We therefore assessed its one-year prevalence and incident rates in Dutch severely mentally ill outpatients, and compared the results with victimisation rates in the general population. Method This multisite epidemiological survey included a random sample of 956 adult severely mentally ill outpatients. Data on victimisation were obtained using the victimisation scale of the Dutch Crime and Victimisation Survey, which assesses crime victimisation over the preceding 12 months. Comparison data were derived from the nationwide survey on safety and victimisation in the Netherlands. Prevalence and incident rates were weighted for sex, age, ethnicity and socioeconomic status, and compared with a general population sample matched by region (N = 38,227). Results In the past year, almost half of the severely mentally ill outpatients (47%) had been victim of a crime. After control for demographic differences, prevalence rates of overall and specific victimisation measures were significantly higher in severely mentally ill outpatients than in the general population. The relative rates were especially high for personal crimes such as violent threats (RR = 2.12, 95% CI: 1.72–2.61), physical assaults (RR = 4.85, 95% CI: 3.69–6.39) and sexual harassment and assaults (RR = 3.94, 95% CI: 3.05–5.09). In concordance, severely mentally ill outpatients reported almost 14 times more personal crime incidents than persons from the general population (IRR = 13.68, 95% CI: 12.85–14.56). Conclusion Crime victimisation is a serious problem in Dutch severely mentally ill outpatients. Mental-healthcare institutions and clinicians should become aware of their patients’ victimisation risk, and should implement structural measures to detect and prevent (re-)victimisation.

Maternal mindfulness during pregnancy and infant socio-emotional development and temperament: The mediating role of maternal anxiety

BACKGROUND Accumulating evidence shows that maternal anxiety during pregnancy adversely affects child outcomes. The positive effects of maternal psychosocial factors during pregnancy on child outcomes are not yet studied. This prospective study addresses the association between maternal mindfulness during pregnancy and socio-emotional development and temperament in 10months-old infants. We also investigated whether this association was mediated by maternal anxiety. METHOD Mothers (N=90) provided information about mindfulness and anxiety at the beginning of the second trimester of pregnancy. Infant socio-emotional development (Ages and Stages Questionnaire: Social Emotional; ASQ:SE) and temperament (Infant Behaviour Questionnaire-Revised; IBQ-R) were assessed at age 10months. RESULTS Higher maternal mindfulness during pregnancy was associated with less infant self-regulation problems and less infant negative affectivity. Mediation analysis showed that maternal anxiety mediated the association between infant self-regulation problems and maternal mindfulness. CONCLUSION These results suggest that maternal mindfulness during pregnancy may have positive effects on infant development. This association may be mediated by reduced anxiety symptoms in pregnant women who score high on mindfulness. Additional replication studies are needed using objective measures of infant behavioural/emotional outcomes and mindfulness of the mother during child development.

Long-term Outcome and Quality of Life after Arterial Switch Operation: A Prospective Study with a Historical Comparison

AIM.: The study aims to describe the long-term cardiological and psychological results of our first surgical cohort of arterial switch operation (ASO) patients and compare the results with our earlier series of Mustard patients. METHODS.: Twenty-four survivors of ASO operated in our center (1985-1990) were evaluated by electrocardiography, echocardiography, magnetic resonance imaging, exercise testing, 24-hour Holter-monitoring, and health-related quality of life questionnaire. The results were compared with 58 adult Mustard patients who were evaluated in 2001 using the same study protocol. RESULTS.: Arterial switch operation was performed at a median age of 13 days and Mustard operation at 2 years. Median follow-up was 22 years (range 20-25) and 25 years (22-29), respectively. After ASO, survival was better (P =.04). The event-free survival after 22 years was 77% after ASO vs. 44% after Mustard (P =.03). Good systemic ventricular function was present in 93% after ASO vs. 6% after Mustard (P <.01). Exercise capacity in ASO was 85% of predicted, compared with 72% in Mustard patients (P =.01). Aortic regurgitation was found in 21% of ASO patients vs. 16% in Mustard patients. Arterial switch patients vs. Mustard patients reported significantly better quality of life and less somatic complaints. CONCLUSION.: The progression made in surgical treatment for transposition of the great arteries from Mustard to ASO has had a positive impact on survival, cardiac function, exercise capacity, and also self-reported quality of life and somatic complaints. Longer follow-up is warranted to monitor aortic regurgitation.

Fetal growth from mid- to late pregnancy is associated with infant development: the Generation R Study

Aim  The aim of this study was to investigate within a population‐based cohort of 4384 infants (2182 males, 2202 females) whether fetal growth from early pregnancy onwards is related to infant development and whether this potential relationship is independent of postnatal growth.