Although microcephaly is a feature of Fetal Alcohol Syndrome, it is currently unknown whether low-to-moderate prenatal alcohol exposure affects head circumference. Small magnitude associations reported in observational studies are likely to be misleading due to confounding and misclassification biases. Alternative analytical approaches such as the use of family negative controls (e.g. comparing the effects of maternal and paternal exposure) could help disentangle causal effects. We investigated the association of maternal and paternal alcohol drinking before and early in pregnancy with infant head circumference, using data from 68,244 mother-father-offspring trios from the Norwegian Mother and Child Cohort Study (MoBa) (1999-2009). In analyses adjusted for potential confounders, we found no consistent pattern of association between maternal or paternal alcohol intake before or during pregnancy and offspring head circumference modelled as a continuous outcome. However, we found higher odds of microcephaly at birth for higher paternal, but not maternal, alcohol consumption before pregnancy, and similar but weaker effect estimates for first trimester drinking. Associations with paternal drinking before pregnancy were unexpected and should be regarded as hypothesis generating, until independently replicated, although potentially important given the absence of guidelines on safe drinking levels for men in couples trying for a pregnancy.
The adverse effects of prenatal alcohol exposure constitute a continuum of disabilities (fetal alcohol spectrum disorders [FASD]). In 1996, the Institute of Medicine established diagnostic categories delineating the spectrum but not specifying clinical criteria by which diagnoses could be assigned. In 2005, the authors published practical guidelines operationalizing the Institute of Medicine categories, allowing for standardization of FASD diagnoses in clinical settings. The purpose of the current report is to present updated diagnostic guidelines based on a thorough review of the literature and the authors' combined expertise based on the evaluation of >10 000 children for potential FASD in clinical settings and in epidemiologic studies in conjunction with National Institute on Alcohol Abuse and Alcoholism-funded studies, the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, and the Collaboration on FASD Prevalence. The guidelines were formulated through conference calls and meetings held at National Institute on Alcohol Abuse and Alcoholism offices in Rockville, MD. Specific areas addressed include the following: precise definition of documented prenatal alcohol exposure; neurobehavioral criteria for diagnosis of fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder; revised diagnostic criteria for alcohol-related birth defects; an updated comprehensive research dysmorphology scoring system; and a new lip/philtrum guide for the white population, incorporating a 45-degree view. The guidelines reflect consensus among a large and experienced cadre of FASD investigators in the fields of dysmorphology, epidemiology, neurology, psychology, developmental/behavioral pediatrics, and educational diagnostics. Their improved clarity and specificity will guide clinicians in accurate diagnosis of infants and children prenatally exposed to alcohol.
Objective: This study examined the point prevalence of neurodevelopmental disorders among predominantly low-income, African-American psychiatric patients at Jackson Park Hospital’s Family Medicine Clinic on Chicago’s South Side. Methods: Using active case ascertainment methodology, the authors assessed the records of 611 psychiatric patients visiting the clinic between May 23, 2013, and January 14, 2014, to identify those with DSM-5 neurodevelopmental disorders. Results: A total of 297 patients (49%) met criteria for a neurodevelopmental disorder during childhood. Moreover, 237 (39%) had clinical profiles consistent with neurobehavioral disorder associated with prenatal alcohol exposure, and 53 (9%) had other neurodevelopmental disorders. The authors disagreed on the specific type of neurodevelopmental disorder of seven (1% of 611) of the 297 patients with neurodevelopmental disorders. Conclusions: A high prevalence of neurodevelopmental disorders was found among low-income predominantly African-American psychiatric patients on Chicago’s South Side. If replicated, these findings should bring about substantial changes in medical practice with African-American patients.
The viviparous sea snakes (Hydrophiinae) are a young radiation of at least 62 species that display spectacular morphological diversity and high levels of local sympatry. To shed light on the mechanisms underlying sea snake diversification, we investigated recent speciation and eco-morphological differentiation in a clade of four nominal species with overlapping ranges in Southeast Asia and Australia. Analyses of morphology and stomach contents identified the presence of two distinct ecomorphs: a ‘macrocephalic’ ecomorph that reaches >2 m in length, has a large head and feeds on crevice-dwelling eels and gobies; and a ‘microcephalic’ ecomorph that rarely exceeds 1 m in length, has a small head and narrow fore-body and hunts snake eels in burrows. Mitochondrial sequences show a lack of reciprocal monophyly between ecomorphs and among putative species. However, individual assignment based on newly developed microsatellites separated co-distributed specimens into four significantly differentiated clusters corresponding to morphological species designations, indicating limited recent gene flow and progress towards speciation. A coalescent species tree (based on mitochondrial and nuclear sequences) and isolation-migration model (mitochondrial and microsatellite markers) suggest between one and three transitions between ecomorphs within the last approximately 1.2 million to approximately 840 000 years. In particular, the macrocephalic ‘eastern’ population of Hydrophis cyanocinctus and microcephalic H. melanocephalus appear to have diverged very recently and rapidly, resulting in major phenotypic differences and restriction of gene flow in sympatry. These results highlight the viviparous sea snakes as a promising system for speciation studies in the marine environment.
Human Brain Abnormalities Associated With Prenatal Alcohol Exposure and Fetal Alcohol Spectrum Disorder
- Journal of neuropathology and experimental neurology
- Published over 3 years ago
Fetal alcohol spectrum disorder (FASD) is a common neurodevelopmental problem, but neuropathologic descriptions are rare and focused on the extreme abnormalities. We conducted a retrospective survey (1980-2016) of autopsies on 174 individuals with prenatal alcohol exposure or an FASD diagnosis. Epidemiologic details and neuropathologic findings were categorized into 5 age groups. Alcohol exposure was difficult to quantify. When documented, almost all mothers smoked tobacco, many abused other substances, and prenatal care was poor or nonexistent. Placental abnormalities were common (68%) in fetal cases. We identified micrencephaly (brain weight <5th percentile) in 31, neural tube defects in 5, isolated hydrocephalus in 6, corpus callosum defects in 6 (including some with complex anomalies), probable prenatal ischemic lesions in 5 (excluding complications of prematurity), minor subarachnoid heterotopias in 4, holoprosencephaly in 1, lissencephaly in 1, and cardiac anomalies in 26 cases. The brain abnormalities associated with prenatal alcohol exposure are varied; cause-effect relationships cannot be determined. FASD is likely not a monotoxic disorder. The animal experimental literature, which emphasizes controlled exposure to ethanol alone, is therefore inadequate. Prevention must be the main societal goal, however, a clear understanding of the neuropathology is necessary for provision of care to individuals already affected.
An investigation of intra-individual variability in children with fetal alcohol spectrum disorder (FASD)
- Child neuropsychology : a journal on normal and abnormal development in childhood and adolescence
- Published almost 4 years ago
Intra-individual variability (IIV) is defined as systematic within-person variation in performance either across test sessions (e.g., test/retest performance on the same task) or in one session (e.g., variations in performance on multiple trials of a single task). Higher levels of IIV have been noted as a characteristic of neurodevelopmental disorders such as attention deficit/hyperactivity disorder (ADHD), but IIV is yet to be investigated in fetal alcohol spectrum disorder (FASD). FASD is a term used to describe a range of conditions resulting from prenatal exposure to alcohol. As part of a comprehensive neuropsychological battery, four study groups (1. fetal alcohol syndrome/partial fetal alcohol syndrome; 2. static encephalopathy/alcohol exposed; 3. neurobehavioral disorder/alcohol exposed as diagnosed using the University of Washington FASD 4-Digit Code; 4. typically-developing (TD) age-matched children with no prenatal alcohol exposure) were administered measures of motor response and inhibitory control, attention, and adaptive behavior. The results indicate increased levels of IIV in those with FASD compared to the TD controls. It was found that IIV uniquely contributes to predicting adaptive behavior above and beyond attention, while attention partially mediates the relationship between IIV and adaptive behavior. This is the first study to the authors' knowledge to show the presence of increased IIV in children with FASD. It additionally provides evidence that IIV measures some inherent variability in performance independent of poor attention in children with FASD.
Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5-19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol exposure, but raise concerns about the predictive value of this metric at an individual-subject level.
- Archives of disease in childhood. Education and practice edition
- Published over 7 years ago
An infant with a large head (2.5 SDs above normal for weight and gender or above 99.6th centile for age) is a common clinical presentation. Usually, it is due to benign isolated macrocephaly or familial macrocephaly (FM) where some close family members are similarly affected1; neither condition requires any further intervention. However, there are a few important underlying causes the clinician needs to actively consider and investigate when indicated before reassuring parents. These considerations include whether there is any associated developmental disorder or suggestion of a syndromic association or evidence of raised intracranial pressure (ICP).
Autosomal recessive intellectual disability (ARID) is vastly heterogeneous. Truncating mutations of TRAPPC9 were reported in 8 ARID families. Autosomal recessive primary microcephaly (MCPH) represents another subgroup of ARID, itself very heterogeneous, where the size of the brain is very small since birth. MCPH1 plays a role at the centrosome via a BRCT1 domain, and in DNA Damage Repair (DDR) via BRCT2 and BRCT3, and it is not clear which of these two mechanisms causes MCPH in man.
Comparison of Alcohol-Related Neurodevelopmental Disorders and Neurodevelopmental Disorders Associated with Prenatal Alcohol Exposure Diagnostic Criteria
- Journal of developmental and behavioral pediatrics : JDBP
- Published over 3 years ago
Recently, increased attention has been focused on the diagnosis of the most prevalent category of fetal alcohol spectrum disorders, alcohol-related neurodevelopmental disorders (ARNDs). In 2013, proposed criteria for neurodevelopmental disorders associated with prenatal alcohol exposure (ND-PAE) were included in the appendix of the latest revision of the Diagnostic and Statistical Manual of Mental Disorders. The concordance of the 2 sets of criteria is unknown. This study examines the overlap in diagnostic criteria for ND-PAE and the ARND Behavioral Checklist in children.