Faculty Bibliography

The rare but deleterious effects of severe iodine deficiency during pregnancy on cognitive functioning of children are well known. Reports on possible associations between mild-to-moderate maternal iodine deficiency and child development, however, are scarce. In a population-based cohort we examined the association between maternal urinary iodine during early pregnancy and executive functioning in children at 4 y of age. In addition, we investigated the modification of this association by maternal diet and thyroid function. During pregnancy, we measured urinary iodine and thyroid hormone concentrations in 1156 women. In 692 of their children impairment of executive functioning was assessed by the Behavior Rating Inventory of Executive Function. Five hundred mothers of Dutch national origin completed an FFQ. Analyses were performed by using regression models. The children of mothers with low urinary iodine showed higher scores on the problem scales of inhibition [beta = 0.05 (95% CI: 0.01, 0.10), P = 0.03] and working memory [beta = 0.07 (95% CI: 0.02, 0.12), P = 0.003]. Although maternal dietary intake and thyroid hormone concentration did not significantly modify these associations, the associations between urinary iodine and problems of inhibition were attenuated after adjustment for maternal psychological symptoms. In addition, the consumption of bread [beta = 0.61 (95% CI: 0.27, 0.95), P < 0.001] and eggs (beta = 1.87 (95% CI: 0.13, 3.62), P = 0.04] was associated with higher urinary iodine. Thus, low maternal urinary iodine during pregnancy is associated with impaired executive functioning in children. Because these symptoms were subclinical and occurred at an early age, future studies are needed to show whether these children are more vulnerable to develop later clinical disorders.

Severe maternal thyroid dysfunction during pregnancy affects fetal brain growth and corticogenesis. This study focused on the effect of maternal hypothyroxinemia during early pregnancy on growth of the fetal and infant head. In a population-based birth cohort, we assessed thyroid status in early pregnancy (median 13.4, 90% range 10.8-17.2), in 4894 women, and measured the prenatal and postnatal head size of their children at 5 time points. Hypothyroxinemia was defined as normal thyroid-stimulating hormone levels and free thyroxine-4 concentrations below the 10th percentile. Statistical analysis was performed using linear generalized estimating equation. Maternal hypothyroxinemia was associated with larger fetal and infant head size (overall estimate beta: 1.38, 95% confidence interval 0.56; 2.19, P = .001). In conclusion, in the general population, even small variations in maternal thyroid function during pregnancy may affect the developing head of the young child.

During the past decades, observational studies have demonstrated a relationship between thyroid dysfunction in pregnancy and a range of adverse outcomes in both mother and offspring. However, results from the few randomized trials of screening for thyroid dysfunction in pregnant women have not shown any benefit for women or their children. Before implementing screening in pregnant women at population level, randomized trials are needed to show that screening with subsequent intervention is effective for mothers or children. Here, we review the literature and argue that the findings from existing trials are not conclusive. Until such conclusive evidence from randomized trials is available, the best advice to the clinician is to screen only high-risk pregnant women. Such women, for example those with symptoms or a history of thyroid problems, should be screened using trimester-specific reference ranges for thyroid stimulating hormone (TSH) levels. We recommend new prospective randomized trials that combine different thyroid parameters as the screening tool, apply trimester-specific ranges for thyroid hormones and examine whether screening and intervention during the first trimester of pregnancy will improve neuropsychological outcomes in the offspring.

AIM: General developmental outcome is known to be good in school-aged children who experienced febrile seizures. We examined cognitive and behavioural outcomes in preschool children with febrile seizures, including language and executive functioning outcomes. METHOD: This work was performed in the Generation R Study, a population-based cohort study in Rotterdam from early fetal life onwards. Information about the occurrence of febrile seizures was collected by questionnaires at the ages of 1, 2, and 3 years. At the age of 3 years, behaviour and emotion were assessed using the Child Behavior Checklist. Information on expressive language development was obtained by the Language Development Survey at the age of 2 years 6 months. To assess executive functioning, parents completed the Behaviour Rating Inventory of Executive Function - Preschool Version when their children were 4 years old. Final analyses were based on 3157 children. RESULTS: No associations were found between febrile seizures and the risk of behavioural problems or executive functioning. In contrast to single febrile seizures, recurrent febrile seizures were significantly associated with an increased risk of delayed vocabulary development (odds ratio 3.22, [95% confidence interval 1.30-7.94]). INTERPRETATION: Febrile seizures are not associated with problem behaviour or executive functioning in preschool children, but the results suggest that children with recurrent febrile seizures might be at risk for delayed language development.

INTRODUCTION: Epidemiological studies on all types of illicit drug use among athletes are essential for both the sport community and drug control achievements. Here, we investigated the prevalence and associated factors of amphetamine use in body builders in Tehran, Iran, 2007. MATERIAL AND METHODS: This study is a secondary analysis of a substance use survey done in 103 randomly selected gymnasia in Tehran (capital city of Iran). The survey was conducted from November 2007 to January 2008 and included 843 randomly selected bodybuilders (aged 40 years or less). By interviews via questionnaires the following data were obtained: age, job, marital status, education level, housing status, average monthly family income, number of family members, gymnasium area (m(2)), number of trainers, number of gymnasium members, initiation time (months), weekly duration of the sporting activity (h), monthly cost of the sporting activity, purpose of participating in sporting activity, and history of anabolic steroid and amphetamine use. RESULTS: One hundred twenty (13.3%) body builders reported a history of amphetamine use. According to the results of regression analysis, being married (risk ratio - RR = 0.540), and participating in body building to enhance self-esteem (RR = 0.423) or to enhance sport performance (RR = 0.545) had protective effects on amphetamine use. However, having university qualifications (RR = 1.843), using anabolic steroids (RR = 1.803) and participating in sport to maintain fitness (RR = 2.472) were linked to increased risk of amphetamine use. CONCLUSIONS: Well-educated bodybuilders were more likely to use amphetamines, and why this is so needs to be discovered. If further studies show that they are not aware of the dangers associated with amphetamine use, providing them with information should be considered.

BACKGROUND: Maternal thyroid status and autoimmunity during pregnancy have been associated with impaired development of the offspring in animal and human studies. Our objective was to examine whether elevated titers of maternal thyroid peroxidase antibodies (TPOAbs) in early pregnancy increased the risk of cognitive impairment and problem behavior in preschool children. Second, we aimed at exploring to what extent any effect on child behavior was mediated by maternal thyroid parameters during pregnancy. METHODS: In the Generation R Study, a population-based cohort of 3139 children and their mothers, we measured maternal thyroid parameters (thyrotropin [TSH], free Thyroxine, and TPOAbs) at 13.5+/-1.8 weeks of gestation. Children's verbal and nonverbal cognitive functioning was measured at 2.5 years using the Language Development Survey and the Parent Report of Children Abilities. At 3 years, children's behavior was assessed using the Child Behavior Checklist. RESULTS: Elevated titers of TPOAbs during pregnancy did not predict the verbal and nonverbal cognitive functioning of the children. However, elevated titers of TPOAbs in mothers were associated with externalizing problems in children (odds ratio [OR]=1.64, 95% confidence interval [CI]: 1.17-2.29, p=0.004). In particular, children of TPOAb-positive mothers were at a higher risk of attention deficit/hyperactivity problems (OR=1.77, 95% CI: 1.15-2.72, p=0.01). To explore whether the effect of maternal TPOAbs on child problem behavior was mediated by maternal thyroid parameters, we added maternal TSH to the model. After correcting for TSH, the effect of TPOAbs on externalizing problems was attenuated slightly but remained significant (OR=1.56, 95% CI: 1.14, 2.14, p=0.005). CONCLUSIONS: Our findings imply that the elevated titers of TPOAbs during pregnancy impact children's risk of problem behavior, in particular, attention deficit/hyperactivity. The observed effect is only partially explained by maternal TSH levels. These findings may point to a specific mechanism of Attention Deficit/Hyperactivity Disorder in children. Nevertheless, we can only speculate about public health implication of the study, as there is no specific treatment for TPOAb-positive pregnant women with normal thyroid function. Further investigation is needed to explore whether TPOAb-positive pregnant women and their children can benefit from close monitoring and early detection of developmental delay in populations at risk.

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 child's behavior were examined. The degree of internalizing and externalizing problems in the children were assessed with the Child Behavior Checklist at ages 1(1/2) and 3 y. Higher levels of maternal TSH during pregnancy predicted a higher externalizing scores in children at 1(1/2) 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.

BACKGROUND: Although for asymptomatic hepatic hemangiomas conservative management is generally recommended, factors affecting the disease course are still not very well understood. AIM: To determine disease characteristics of cavernous hemangioma and factors affecting its progression in patients from a general hepatology clinic in Tehran, Iran. METHODS: We reviewed medical records of 198 patients with cavernous hemangioma of the liver visiting a large private hepatology clinic in Tehran from 1997 to 2007. Of a total of 198 cases, 129 could be followed up for a period of 3.2 +/- 2.5 years, and 80 of these had 1-5 repeated sonographies. RESULTS: Patients were between 27 and 84 years old (mean age: 44.3 +/- 10.9 years), and 131 (66.2%) were female. Thirty-six patients (18.2%) had giant hemangiomas. Abdominal pain was the primary reason for evaluation in 100 (50.5%) patients. Abdominal pain at the beginning of the follow-up was significantly associated with having irritable bowel syndrome [odds ratio (OR)=8.3; 95% confidence interval (CI): 3.1-28.7] or other gastrointestinal diseases (OR=3.9; 95% CI: 2.6-10.2), but not with hemangioma size, number, or location. During follow-up, having a single giant lesion at the time of diagnosis, adjusted for age, sex, and presence of irritable bowel syndrome, was a strong predictor of persistent pain during follow-up (OR=11.1; 95% CI: 3.2-38.6). In repeated sonographies, 35% showed an increased size, which was significantly associated only with having a single lesion (P=0.04). CONCLUSION: Many symptoms in hepatic hemangioma are attributable to accompanying gastrointestinal diseases. Patients with a single giant lesion are more likely to have persistent pain, and single lesions are more likely to grow in size.

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 children's 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. Children's 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 Children's 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.

INTRODUCTION: Information regarding gender differences in drug use of adolescents is essential for designing gender-specific drug prevention policies. This study was conducted in high school students in Tehran, Iran, in 2007. Here, we report the gender differences in lifetime prevalence as well as psychosocial associates of drug use. MATERIAL AND METHODS: This was a gender analysis of the data collected in a drug use survey conducted in a random sample of high school adolescents (573 boys and 551 girls) in Tehran, Iran, 2007. Demographic characteristics, parental and peers' substance use, school performance, religious beliefs, attachment, self-esteem and emotional intelligence (EI) were entered in logistic regression analyses to predict the lifetime illicit drug use in boy and girls, separately. RESULTS: Boys were more likely to report lifetime illicit drug use than girls (10.1% vs. 6.4%, p = 0.023). Differences in the risk profile associated with lifetime illicit drug use by gender included history of substance use in the family, higher score of attachment, and having an employed mother as predictors of substance use in boys, but not girls. CONCLUSIONS: Understanding this gender difference in predictors of lifetime use of illicit drugs in high school adolescents facilitates the design of gender-sensitive drug use preventive programmes. It seems that family variables may have more value in prevention of illicit drug use in male adolescents.