Faculty Bibliography

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.

OBJECTIVE: To determine clinical characteristics, demographics and short-term outcomes of neonates diagnosed with fetomaternal haemorrhage (FMH). DESIGN: The authors analysed the Nationwide Inpatient Sample, 1993 to 2008. Singleton births diagnosed with FMH were identified by International Classification of Diseases (ICD-9) code 762.3. Descriptive, univariate and multivariable regression analyses were performed to determine the national annual incidence of FMH over time as well as demographics and clinical characteristics of neonates with FMH. RESULTS: FMH was identified in 12 116 singleton births. Newborns with FMH required high intensity of care: 26.3% received mechanical ventilation, 22.4% received blood product transfusion and 27.8% underwent central line placement. Preterm birth (OR 3.7), placental abruption (OR 9.8) and umbilical cord anomaly (OR 11.4) were risk factors for FMH. Higher patient income was associated with increased likelihood of FMH diagnosis (OR 1.2), and Whites were more likely to be diagnosed than ethnic minorities (OR 1.9). There was reduced frequency of diagnosis in the Southern USA (OR 0.8 vs the Northeastern USA). CONCLUSIONS: Diagnosis of FMH is associated with significant morbidity as well as regional, socioeconomic and racial disparity. Further study is needed to distinguish between diagnostic coding bias and true epidemiology of the disease. This is the first report of socioeconomic and racial/ethnic disparities in FMH, which may represent disparities in detection that require national attention.

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.

Congenital fibrosarcoma (CFS) is a rare fibrous tissue malignancy that usually presents in the first few years of life. It is unique among human sarcomas in that it has an excellent prognosis. We describe a temporal clustering of a number of cases of CFS and investigate the possible associated prenatal risk factors. The Pediatric Environmental History, a questionnaire developed in our clinic that is instrumental in determining environmental risk factors for tumor-related disease, was essential in documenting the presence or absence of risk factors considered as human carcinogens. We found a history of exposure to petroleum products in four cases of CFS that occurred at a greater than expected rate in a short time frame-an apparent cancer cluster. We call attention to the possibility that exposure to petroleum products raises the risk of developing CFS. While future studies should focus on systematic investigation of CFS and its underlying mechanisms, this report suggests the need for proactive measures to avoid exposure to solvents and petroleum products during pregnancy.

CONTEXT: Bisphenol A (BPA), a manufactured chemical, is found in canned food, polycarbonate-bottled liquids, and other consumer products. In adults, elevated urinary BPA concentrations are associated with obesity and incident coronary artery disease. BPA exposure is plausibly linked to childhood obesity, but evidence is lacking to date. OBJECTIVE: To examine associations between urinary BPA concentration and body mass outcomes in children. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis of a nationally representative subsample of 2838 participants aged 6 through 19 years randomly selected for measurement of urinary BPA concentration in the 2003-2008 National Health and Nutrition Examination Surveys. MAIN OUTCOME MEASURES: Body mass index (BMI), converted to sex- and age-standardized z scores and used to classify participants as overweight (BMI >/=85th percentile for age/sex) or obese (BMI >/=95th percentile). RESULTS: Median urinary BPA concentration was 2.8 ng/mL (interquartile range, 1.5-5.6). Of the participants, 1047 (34.1% [SE, 1.5%]) were overweight and 590 (17.8% [SE, 1.3%]) were obese. Controlling for race/ethnicity, age, caregiver education, poverty to income ratio, sex, serum cotinine level, caloric intake, television watching, and urinary creatinine level, children in the lowest urinary BPA quartile had a lower estimated prevalence of obesity (10.3% [95% CI, 7.5%-13.1%]) than those in quartiles 2 (20.1% [95% CI, 14.5%-25.6%]), 3 (19.0% [95% CI, 13.7%-24.2%]), and 4 (22.3% [95% CI, 16.6%-27.9%]). Similar patterns of association were found in multivariable analyses examining the association between quartiled urinary BPA concentration and BMI z score and in analyses that examined the logarithm of urinary BPA concentration and the prevalence of obesity. Obesity was not associated with exposure to other environmental phenols commonly used in other consumer products, such as sunscreens and soaps. In stratified analysis, significant associations between urinary BPA concentrations and obesity were found among whites (P < .001) but not among blacks or Hispanics. CONCLUSIONS: Urinary BPA concentration was significantly associated with obesity in this cross-sectional study of children and adolescents. Explanations of the association cannot rule out the possibility that obese children ingest food with higher BPA content or have greater adipose stores of BPA.

BACKGROUND: The WHO Multiple Exposures Multiple Effects (MEME) framework identifies community contextual variables as central to the study of childhood health. Here we identify multiple domains of neighborhood context, and key variables describing the dimensions of these domains, for use in the National Children's Study (NCS) site in Queens. We test whether the neighborhoods selected for NCS recruitment, are representative of the whole of Queens County, and whether there is sufficient variability across neighborhoods for meaningful studies of contextual variables. METHODS: Nine domains (demographic, socioeconomic, households, birth rated, transit, playground/greenspace, safety and social disorder, land use, and pollution sources) and 53 indicator measures of the domains were identified. Geographic information systems were used to create community-level indicators for US Census tracts containing the 18 study neighborhoods in Queens selected for recruitment, using US Census, New York City Vital Statistics, and other sources of community-level information. Mean and inter-quartile range values for each indicator were compared for Tracts in recruitment and non-recruitment neighborhoods in Queens. RESULTS: Across the nine domains, except in a very few instances, the NCS segment-containing tracts (N=43) were not statistically different from those 597 populated tracts in Queens not containing portions of NCS segments; variability in most indicators was comparable in tracts containing and not containing segments. CONCLUSIONS: In a diverse urban setting, the NCS segment selection process succeeded in identifying recruitment areas that are, as a whole, representative of Queens County, for a broad range of community-level variables.

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.

The obesity epidemic has transformed children's healthcare, such that diabetes, hypertension and the metabolic syndrome are phrases more commonly used by child health providers than ever before. This article reviews the economic consequences of this epidemic for healthcare delivery systems, both in the short term when obesity has been associated with increased utilization, and in the long term where increased likelihood of adult obesity and cardiovascular disease is well documented. Large investments through research and prevention are needed and are likely to provide strong returns in cost savings, and would optimally emerge through a cooperative effort between private and government payers alike

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.

OBJECTIVE: To determine the effect of mild fluid restriction on the hospital course of neonates with transient tachypnea of the newborn (TTN). STUDY DESIGN: In this pilot prospective randomized controlled trial of 64 late preterm and term neonates diagnosed with TTN at a single tertiary care hospital in the United States, patients were randomized to receive standard fluid management or mild fluid restriction. The primary outcome was duration of respiratory support. Secondary outcomes were duration of admission to the intensive care unit, time to first enteral feed, and total and composite hospital costs. Results were analyzed by t-test, chi(2) test, Kaplan-Meier estimation, and proportional hazards regression. RESULTS: Fluid restriction did not cause adverse events or unsafe dehydration. Fluid management strategy did not affect primary or secondary outcomes in the total study population. Fluid restriction significantly reduced the duration of respiratory support (P = .008) and hospitalization costs (P = .017) in neonates with severe TTN. CONCLUSION: Mild fluid restriction appears to be safe in late preterm and term neonates with uncomplicated TTN. Fluid restriction may be of benefit in decreasing the duration of respiratory support and reducing hospitalization costs in term and late preterm neonates with uncomplicated severe TTN