Abnormal mTOR Activity in Pediatric Autoimmune Neuropsychiatric and MIA-Associated Autism Spectrum Disorders.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by the early onset of communication and behavioral problems. ASD is highly heritable; however, environmental factors also play a considerable role in this disorder. A significant part of both syndromic and idiopathic autism cases could be attributed to disorders caused by mammalian target of rapamycin (mTOR)-dependent translation deregulation. This narrative review analyzes both bioinformatic and experimental evidence that connects mTOR signaling to the maternal autoantibody-related (MAR) autism spectrum and autoimmune neuropsychiatric disorders simultaneously. In addition, we reconstruct a network presenting the interactions between the mTOR signaling and eight MAR ASD genes coding for ASD-specific maternal autoantibody target proteins. The research discussed in this review demonstrates novel perspectives and validates the need for a subtyping of ASD on the grounds of pathogenic mechanisms. The utter necessity of designing ELISA-based test panels to identify all antibodies related to autism-like behavior is also considered.

Fetal Growth Restriction Before and After Birth.

Fetal growth restriction, previously called intrauterine growth restriction, is a condition in which a fetus does not achieve its full growth potential during pregnancy. Early detection and management of fetal growth restriction are essential because it has significant clinical implications in childhood. It is diagnosed by estimated fetal weight or abdominal circumference below the 10th percentile on formal ultrasonography. Early-onset fetal growth restriction is diagnosed before 32 weeks' gestation and has a higher risk of adverse fetal outcomes. There are no evidence-based measures for preventing fetal growth restriction; however, aspirin used for the prevention of preeclampsia in high-risk pregnancies may reduce the likelihood of developing it. Timing of delivery for pregnancies affected by growth restriction must be adjusted based on the risks of premature birth and ongoing gestation, and it is best determined in consultation with maternal-fetal medicine specialists. Neonates affected by fetal growth restriction are at risk of feeding difficulties, glucose instability, temperature instability, and jaundice. As these children age, they are at risk of abnormal growth patterns, as well as later cardiac, metabolic, neurodevelopmental, reproductive, and psychiatric disorders.

In-utero arsenic exposure and growth of infants from birth to 6 months of age: a prospective cohort study in rural Bangladesh.

Arsenic exposure in postnatal life impacts the growth of children, but little is known about the effect of in-utero arsenic exposure on growth very early in childhood. The aim of this study was to examine the associations between in-utero arsenic exposure and the growth of infants from birth to 6 months of age using monthly follow-up data. A prospective cohort study was conducted in rural areas of Bangladesh with 108 mother-infant pairs. This study identified a negative association between in-utero arsenic exposure and head circumference of infants 1-6 months of age (coefficient = -1.20, 95% confidence interval [CI]: -1.97, -0.42), and the effect was more pronounced in the earlier ages of 1-3 months (coefficient = -0.88, 95% CI: -1.70, -0.05). Because head circumference is considered as a surrogate of brain size, our findings suggest that in-utero arsenic exposure influences brain growth during an important developmental period.

AGORA, a data- and biobank for birth defects and childhood cancer.

BACKGROUND: Research regarding the etiology of birth defects and childhood cancer is essential to develop preventive measures, but often requires large study populations. Therefore, we established the AGORA data- and biobank in the Netherlands. In this study, we describe its rationale, design, and ongoing data collection. METHODS: Children diagnosed with and/or treated for a structural birth defect or childhood cancer and their parents are invited to participate in the AGORA data- and biobank. Controls are recruited through random sampling from municipal registries. The parents receive questionnaires about demographics, family and pregnancy history, health status, prescribed medication, lifestyle, and occupational exposures before and during the index pregnancy. In addition, blood or saliva is collected from children and parents, while medical records are reviewed for diagnostic information. RESULTS: So far, we have collected data from over 6,860 families (3,747 birth defects, 905 childhood cancers, and 2,208 controls). The types of birth defects vary widely and comprise malformations of the digestive, respiratory, and urogenital tracts as well as facial, cardiovascular, kidney, skeletal, and central nervous system anomalies. The most frequently occurring childhood cancer types are acute lymphatic leukemia, Hodgkin and non-Hodgkin lymphoma, Wilms' tumor, and brain and spinal cord tumors. Our genetic and/or epidemiologic studies have been focused on hypospadias, anorectal malformations, congenital anomalies of the kidney and urinary tract (CAKUT), and orofacial clefts. CONCLUSION: The large AGORA data- and biobank offers great opportunities for investigating genetic and nongenetic risk factors for disorders in children and is open to collaborative initiatives. Birth Defects Research (Part A) 106:675-684, 2016. © 2016 Wiley Periodicals, Inc.

The assignment of scores procedure for ordinal categorical data.

Ordinal data are the most frequently encountered type of data in the social sciences. Many statistical methods can be used to process such data. One common method is to assign scores to the data, convert them into interval data, and further perform statistical analysis. There are several authors who have recently developed assigning score methods to assign scores to ordered categorical data. This paper proposes an approach that defines an assigning score system for an ordinal categorical variable based on underlying continuous latent distribution with interpretation by using three case study examples. The results show that the proposed score system is well for skewed ordinal categorical data.

In-utero exposure to smoking, alcohol, coffee, and tea and risk of strabismus.

In a prospective, population-based cohort study, the authors investigated the effect of in-utero exposure to maternal smoking and consumption of alcohol, coffee, and tea on the risk of strabismus. They reviewed medical records for children in the Danish National Birth Cohort identified through national registers as possibly having strabismus. Relative risk estimates were adjusted for year of birth, social class, maternal smoking, maternal age at birth, and maternal coffee and tea consumption. The authors identified 1,321 cases of strabismus in a cohort of 96,842 Danish children born between 1996 and 2003. Maternal smoking was associated with a significantly elevated risk of strabismus in the child, increasing with number of cigarettes smoked per day (<5 cigarettes/day: relative risk (RR) = 0.95, 95% confidence interval (CI): 0.80, 1.14; 5-<10 cigarettes/day: RR = 1.38, 95% CI: 1.12, 1.70; > or =10 cigarettes/day: RR = 1.90, 95% CI: 1.57, 2.30). Nicotine replacement therapy was not associated with strabismus risk (RR = 1.22, 95% CI: 0.92, 1.61). Light maternal alcohol consumption was inversely associated with strabismus risk, whereas maternal coffee and tea drinking were not associated with strabismus risk. In conclusion, smoking during pregnancy is associated with an increased risk of strabismus in the offspring. Conversely, light alcohol consumption is associated with decreased risk.

A new method of prenatal alcohol classification accounting for dose, pattern and timing of exposure: improving our ability to examine fetal effects from low to moderate alcohol.

BACKGROUND: When examining the association between prenatal alcohol exposure and fetal effects, the timing and intensity of exposure have been ignored in epidemiological studies. The effect of using dose, pattern and timing of consumption ("composite" method) was investigated in this study, to examine the association between prenatal alcohol exposure and fetal effects. METHODS: The composite method resulted in six categories of exposure (abstinent, low, moderate, binge