Heavy Prenatal Alcohol Exposure Research Articles

Characteristics of sleep in children with heavy prenatal alcohol exposure.

Sleep plays an important role in neurodevelopment. However, the effects of prenatal alcohol exposure on sleep quality have been understudied, despite reports of sleep disturbance in infants prenatally exposed to alcohol and elevated levels of sleep problems reported by caregivers of children with fetal alcohol spectrum disorders. The current study characterizes sleep in children with prenatal alcohol exposure using both objective (actigraphy) and subjective (questionnaires, sleep diaries) methods. Participants aged 6-10 years, with and without prenatal alcohol exposure, were included in the study (alcohol-exposed [AE]: n = 35; control [CON]: n = 39). Objective sleep was measured via 24-h actigraphy for 2 weeks. Parents completed sleep diaries and sleep questionnaires (Children's Sleep Habits Questionnaire, Pediatric Sleep Questionnaire). Multivariate analysis of variance was used to characterize the sleep profile (objective, subjective) and examine group differences. There were no group differences on actigraphy metrics averaged across 2 weeks. However, the AE group showed significantly greater intraindividual variability on most actigraphy measures, particularly total sleep time, percent sleep, wake after sleep onset, and number of wake bouts. Parents reported significantly more sleep problems in the AE group than in the CON group, primarily driven by night wakings, parasomnias (e.g., sleepwalking), snoring, and daytime sleepiness. These effects were more severe in children >8.5 years of age. Despite similar 2-week average sleep outcomes, children with prenatal alcohol exposure showed greater intraindividual sleep variability and parents reported more sleep problems related to sleep behavior and snoring. These difficulties with sleep may be related to other cognitive and behavioral outcomes. Importantly, sleep is a modifiable behavior, and interventions that focus on variability in sleep, particularly in sleep duration, can impact the quality of life in children with prenatal alcohol exposure and their families.

Impact of low-level prenatal alcohol exposure and maternal stress on autonomic regulation.

Prenatal alcohol exposure (PAE) impacts the neurodevelopment of the fetus, including the infant's ability to self-regulate. Heart rate variability (HRV), that is, the beat-to-beat variability in heart rate, is a non-invasive measurement that can indicate autonomic nervous system (ANS) function/dysfunction. The study consisted of a subset of our ENRICH-2 cohort: 80 participants (32 PAE and 48 Controls) who had completed three visits during pregnancy. The participants completed a comprehensive assessment of PAE and other substances throughout pregnancy and assessments for stress, anxiety, and depression in the third trimester. At 24 h of age, infant HRV was assessed in the hospital during the clinically indicated heel lance; 3- to 5-min HRV epochs were obtained during baseline, heel lancing, and recovery episodes. Parameters of HRV differed in infants with PAE compared to Controls during the recovery phase of the heel lance (respiratory sinus arrhythmia (RSA) and high-frequency (HF), p < 0.05). Increased maternal stress was also strongly associated with abnormalities in RSA, HF, and low-frequency / high-frequency (LF/HF, p's < 0.05). Alterations in ANS regulation associated with PAE and maternal stress may reflect abnormal development of the hypothalamic-pituitary-adrenal axis and have long term implications for infant responsiveness and self-regulation. Previous studies have focused on effects of moderate to heavy prenatal alcohol exposure (PAE) on autonomic dysregulation, but little is known about the effects of lower levels of PAE on infant self-regulation and heart rate variability (HRV). Prenatal stress is another risk factor for autonomic dysregulation. Mild PAE impacts infant self-regulation, which can be assessed using HRV. However, the effect of prenatal stress is stronger than that of mild PAE or other mental health variables on autonomic dysregulation.

Heavy prenatal alcohol exposure and overall morbidities: a Danish nationwide cohort study from 1996 to 2018

Heavy prenatal alcohol exposure is harmful and can lead to fetal alcohol spectrum disorders. A systematic review and meta-analysis identified 428 comorbidities in individuals with fetal alcohol spectrum disorders, and reported pooled prevalence estimates. We aimed to investigate overall risk of morbidities in heavy prenatal alcohol-exposed children by estimating risk of the identified comorbidities, and previously unidentified diseases and health-related problems. Our Danish nationwide register-based cohort study included all singleton births. Individuals were followed up to age 18 years, between 1996 and 2018. Stillbirths and children of immigrants were not included in the study, and births of women who migrated within 1 year before or during pregnancy were also excluded due to loss to follow-up. Data on health and education were extracted from the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Prescription Registry, the Danish Civil Registration System, and the Population Education Register. We estimated crude and standardised risk differences of hospital diagnoses. Heavy prenatal alcohol exposure was defined by hospital contacts with alcohol-attributable diagnoses given to the mother or her child, or by maternal redeemed prescriptions for drugs to treat alcohol dependence 1 year before or during pregnancy. Of 1 407 689 identified singleton births, 219 186 were excluded for reasons including they were born to immigrants, lost to follow-up, or were stillbirths. Of the remaining 1 188 503 children, 4799 (0·4%) had heavy prenatal alcohol exposure and 1 183 704 (99·6%) were classified as non-alcohol-exposed births. 578 179 (48·6%) babies were female and 610 324 (51·4%) were male. We found 234 of 428 previously identified comorbidities in individuals with fetal alcohol spectrum disorder, of which 29 conditions had a standardised risk difference of at least 0·5%, predominantly related to brain function, behavioural disorders, infections, and neonatal conditions. The four highest standardised risk differences were found for low birthweight (4·70% [95% CI 3·70-5·71]), small for gestational age (4·63% [3·72-5·55]), delayed milestone (3·81% [2·99-4·64]), and other preterm infants (2·69% [1·71-3·68]). Of previously unidentified diseases and health-related problems, 32 of 719 had a standardised risk difference of at least 1·0%, mainly related to brain function, some injuries, substance-related conditions, and childhood adversities. Heavy prenatal alcohol exposure is associated with an overall increased risk of child morbidities and previously unrecognised alcohol-related health problems. Prenatal alcohol exposure is a key public health issue with a potential negative impact on child and adolescent health. This study urges for renewed efforts and substantiates the profound degree to which pre-conceptional care is mandatory. The Obel Family Foundation, The Health Foundation, TrygFonden, Aase and Ejnar Danielsens Foundation, The North Denmark Region Health Science and Research Foundation, Holms Memorial Foundation, Dagmar Marshalls Foundation, the A.P. Møller Foundation, King Christian X Foundation, Torben and Alice Frimodts Foundation, the Axel and Eva Kastrup-Nielsens Foundation, and the A.V. Lykfeldts Foundation.

Heavy prenatal alcohol exposure and obstetric and birth outcomes: a Danish nationwide cohort study from 1996 to 2018

Heavy alcohol use during pregnancy can harm the fetus, but the relation to most obstetric outcomes remains unclear. We therefore aimed to describe maternal characteristics and estimate the association between heavy prenatal alcohol exposure and 22 adverse obstetric and birth outcomes. We carried out a Danish nationwide register-based historical cohort study, including all singleton births from Jan 1, 1996, to Dec 31, 2018. Births of women who had emigrated to Denmark were excluded from the study due to missing data and women who migrated within 1 year before or during pregnancy were also excluded due to loss to follow-up. Data were extracted from the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Prescription Registry, the Danish Civil Registration System, and the Population Education Register. Logistic regression models were used to estimate crude and adjusted odds ratios (ORs) of obstetric and birth outcomes. Heavy alcohol use was defined by hospital contacts for alcohol-attributable diagnoses given to the mother, her infant, or both, or maternal redeemed prescriptions for drugs to treat alcohol dependence within 1 year before or during pregnancy. Of 1 191 295 included births, 4823 (0·40%) were defined as heavily alcohol-exposed and 1 186 472 were categorised as a reference group with no identified heavy prenatal alcohol exposure. Heavy-alcohol-exposed births more often had mothers with psychiatric diagnoses (49·8% vs 9·6%), substance use (22·0% vs 0·4%), tobacco use (64·3% vs 15·8%), and low educational level (64·1% vs 17·6%) than did the reference group. For heavy-alcohol-exposed births, significantly increased adjusted ORs were found for small for gestational age (OR 2·20 [95% CI 1·97-2·45]), preterm birth (OR 1·32 [1·19-1·46]), haemorrhage in late pregnancy (OR 1·25 [1·05-1·49]), and preterm prelabour rupture of membranes (OR 1·18 [1·00-1·39]). Decreased adjusted ORs were found for postpartum haemorrhage (500-999 mL; OR 0·80 [95% CI 0·69-0·93]), gestational diabetes (OR 0·81 [0·67-0·99]), planned caesarean section (OR 0·82 [0·72-0·94]), pre-eclampsia and eclampsia (OR 0·83 [0·71-0·96]), and abnormalities of forces of labour (OR 0·92 [0·86-0·99]). Heavy prenatal alcohol exposure is associated with adverse obstetric and birth outcomes and high proportions of maternal low educational level, psychiatric disease, and lifestyle risk behaviours. These findings highlight a need for holistic public health programmes and policy attention on improving pre-conceptional care and antenatal care. The Obel Family Foundation, The Health Foundation, TrygFonden, Aase and Ejnar Danielsens Foundation, The North Denmark Region Health Science and Research Foundation, Holms Memorial Foundation, Dagmar Marshalls Foundation, the A.P. Møller Foundation, King Christian X Foundation, Torben and Alice Frimodts Foundation, the Axel and Eva Kastrup-Nielsens Foundation, the A.V. Lykfeldts Foundation.

Mediating and Moderating Effects of Iron Homeostasis Alterations on Fetal Alcohol-Related Growth and Neurobehavioral Deficits.

We have previously demonstrated prenatal alcohol exposure (PAE)-related alterations in maternal and infant iron homeostasis. Given that early iron deficiency and PAE both lead to growth restriction and deficits in recognition memory and processing speed, we hypothesized that PAE-related iron homeostasis alterations may mediate and/or moderate effects of PAE on growth and neurobehavior. We examined this hypothesis in a prenatally recruited, prospective longitudinal birth cohort [87 mother-infant pairs with heavy prenatal alcohol exposure (mean = 7.2 drinks/occasion on 1.4 days/week); 71 controls], with serial growth measures and infant neurobehavioral assessments. PAE was related to growth restriction at 2 weeks and 5 years, and, in infancy, poorer visual recognition memory, slower processing speed, lower complexity of symbolic play, and higher emotionality and shyness on a parental report temperament scale. Lower maternal hemoglobin-to-log(ferritin) ratio, which we have shown to be associated with PAE, appeared to exacerbate PAE-related 2-week head circumference reductions, and elevated maternal ferritin, which we have shown to be associated with PAE, appeared to exacerbate PAE-related visual recognition memory deficits. In causal inference analyses, PAE-related elevations in maternal ferritin and hemoglobin:log(ferritin) appeared to statistically mediate 22.6–82.3% of PAE-related growth restriction. These findings support potential mechanistic roles of iron homeostasis alterations in fetal alcohol spectrum disorders (FASD).

Heavy Prenatal Alcohol Exposure and Obstetrical Outcomes: A Danish Nationwide Cohort Study from 1996 to 2018

Heavy Prenatal Alcohol Exposure and Obstetrical Outcomes: A Danish Nationwide Cohort Study from 1996 to 2018

Heavy Prenatal Alcohol Exposure and Risk of Morbidities Not Previously Identified: A Danish Nationwide Cohort Study from 1996 to 2018

Heavy Prenatal Alcohol Exposure and Risk of Morbidities Not Previously Identified: A Danish Nationwide Cohort Study from 1996 to 2018

Development and validation of a postnatal risk score that identifies children with prenatal alcohol exposure.

This study aimed to develop an efficient and easily calculable risk score that can be used to identify an individual's risk of having been exposed to alcohol prenatally. Data for this study were collected as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, Phases 2 and 3. Two cohorts (ages 5 to 17years) completed a comprehensive neurobehavioral battery and a standard dysmorphology exam: a development cohort (DC; n=325) and a comparative cohort (CC; n=523). Both cohorts included two groups: those with histories of heavy prenatal alcohol exposure (AE-DC, n=121; AE-CC, n=177) and a control group that included subjects with minimal or no prenatal alcohol exposure (CON-DC, n=204; CON-CC, n=346). Behavioral assessments and physical exam data were combined using regression techniques to derive a risk score indicating the likelihood of prenatal alcohol exposure. Subjects were then divided into two subgroups: (1) low risk and (2) high risk. Chi-square (χ2 ) determined classification accuracy and ROC curves were produced to assess the predictive accuracy. Correlations between risk scores and intelligence quotient and executive function scores were calculated. Subjects were accurately classified in the DC (χ2 =78.61, p<0.001) and CC (χ2 =86.63, p<0.001). The classification model also performed well in the DC (ROC=0.835 [SE=0.024, p<0.001]) and CC (ROC=0.786 [SE=0.021, p<0.001]). In the AE-CC and CON-CC, there were modest but significant associations between the risk score and executive function (AE-CC: r=-0.20, p=0.034; CON-CC: r=-0.28, p<0.001) and intelligence quotient (AE-CC: r=-0.20, p=0.034; CON-CC: r=-0.28, p<0.001). The risk score significantly distinguished alcohol-exposed from control subjects and correlated with important cognitive outcomes. It has significant clinical potential and could be easily deployed in clinical settings.

The effect of heavy prenatal alcohol exposure on adolescent body mass index and waist-to-height ratio at 12-13 years.

Growing evidence suggests that prenatal alcohol exposure (PAE) has the potential to impact on a wide range of physical outcomes in offspring, including metabolism and body composition, although the evidence to-date is primarily from preclinical studies. The current clinical study examined the association between heavy PAE and indirect measures of adiposity in adolescence. Analyses drew on data from the Longitudinal Study of Australian Children, a national prospective cohort of children and their families from birth to adolescence. Participants included children with heavy PAE (≥70 g/week; n = 46), measured via maternal self-report of alcohol use during pregnancy and a comparison group of children without any PAE (n = 782), frequency matched on sex, ethnicity and socio-economic position. Body mass index (BMI) z-scores, waist-to-height ratios and proportion overweight/obese were calculated from height, weight and waist circumference measured at age 12-13 years. Two (PAE) × two (sex) ANCOVA and logistic regression models were performed, controlling for matching variables, adolescent age, pubertal status and birthweight; maternal age at birth and smoking during pregnancy. Female adolescents with heavy PAE during late pregnancy had significantly higher BMI z-scores (M = 0.75, SD = 0.69) and proportion overweight/obese (38.5%) than females not exposed to any prenatal alcohol (M = 0.29, SD = 1.07, P = 0.04; 23.8%, P = 0.03, respectively). There was no significant effect of heavy PAE on male adolescent BMI z-scores and proportion overweight/obese or adolescent waist-to-height ratios (all P > 0.05). Heavy PAE had a sex-specific effect on measures of adiposity in early adolescence, with girls more likely to have increased BMI and overweight/obesity status. Further longitudinal follow-up of children exposed to PAE is required to confirm if maternal alcohol consumption is a risk factor for later life obesity.

Effects of ethanol-and choline-treated astrocytes on hippocampal neuron neurite outgrowth in vitro.

Exposure to ethanol in utero can result in Fetal Alcohol Spectrum Disorders, which may cause long-lasting cognitive and behavioral abnormalities. Preclinical studies indicate that choline ameliorates the behavioral effects of developmental alcohol exposure in rodents, and clinical studies on the effectiveness of choline, administered early in pregnancy, showed that the adverse effects of heavy prenatal alcohol exposure on postnatal growth, and cognition in human infants were mitigated. However, little is known on the mechanisms behind the effects of choline. We have previously reported that astrocyte pre-treatment with 75 mM ethanol, in vitro, reduces neurite outgrowth in hippocampal neurons co-cultured with the pre-treated astrocytes. Our in vitro system allows us to study the effects of chemicals on astrocyte functions, able to modulate neuronal development. The main objective was to test the hypothesis that choline can ameliorate the astrocyte-mediated effects of ethanol on neurite growth. In this study, we exposed primary rat cortical astrocytes to ethanol, choline, ethanol plus choline, or control conditions for 24 h. Culture media was then removed, replaced with fresh media containing no ethanol or choline treatments and primary rat hippocampal neurons were plated on top of the astrocyte monolayer and cultured for 16 h. Neurons were then stained for β-III Tubulin and neurite outgrowth was measured. Astrocyte exposure to ethanol (25, 50, and 75 mM) decreases neurite outgrowth in co-cultured hippocampal pyramidal neurons, while astrocyte treatment with choline had no effect. Astrocyte treatment with ethanol and choline in combination, however, prevented the effect of ethanol, leading to levels of neurite outgrowth similar the control condition. Choline prevents the inhibitory effect of ethanol-treated astrocytes on neurite outgrowth while not altering normal neuronal development. These results suggest a new, astrocyte-mediated mechanism by which choline ameliorates the effects of developmental alcohol exposure.

Cognitive and Behavioural Attention in Children with Low-Moderate and Heavy Doses of Prenatal Alcohol Exposure: a Systematic Review and Meta-analysis.

Attention problems are thought to be a hallmark feature of prenatal alcohol exposure (PAE). Despite decades of research however, these findings have never been pooled to assess the association between PAE and the different domains of attention functioning. This systematic review and meta-analysis aimed to examine the relationships between low-moderate, binge and heavy PAE with domains of attention functioning (encode, focus, shift, sustain and behavioural) in children. Thirteen studies compared children with PAE to abstinent controls. A significant adverse effect of any PAE on shifting attention (Cohen's d = -0.61), and a trend towards an adverse effect of heavy PAE on encoding attention (Cohen's d = -0.79) were identified. Compared to controls, there were trends showing that low-moderate PAE (odds ratio = 1.21) was associated with greater odds of behavioural attention problems. Remaining analyses were limited by insufficient studies or were non-significant. In summary, a vulnerability of higher-level attention skills to PAE was found. Urgent investigation into the effects of low to moderate PAE is needed given the prevalence of this drinking pattern, trends towards behavioural attention problems, the lack of comprehensive and high-quality research and the known impacts of attention difficulties on academic and social development in children.

Validity and Reliability of Executive Function Measures in Children With Heavy Prenatal Alcohol Exposure: Correspondence Between Multiple Raters and Laboratory Measures.

Rating scales are designed to complement traditional performance-based measures, and both can provide useful information about the functioning of youth with histories of prenatal alcohol exposure. Few studies, however, have compared ratings from multiple informants or the relationship between these subjective rating scale scores and the objective results from laboratory performance-based scales. The current study addressed both of these questions in 3 study groups: children with histories of prenatal alcohol exposure (n = 47), attention-deficit/hyperactivity disorder (ADHD; n=41), and typically developing controls (CON; n=73). All subjects completed a standardized neuropsychological test battery, including laboratory measures of executive functioning and a self-report measure of executive function behaviors. Parents and teachers completed corresponding rating scales of executive function behaviors for each subject. This study assessed the relationship between these behavior rating scales and corresponding neuropsychological tests, and interrater agreement among the multiple informants. Weak correlations were found between the rating scales and laboratory measures, indicating poor convergent validity for the behavior rating scale. Interrater reliability was found but it differed by group. Agreement was found between parent and teacher ratings for children with prenatal alcohol exposure, whereas teacher-child agreement was found for those with ADHD. Findings from this study indicate that behavior ratings can be used to supplement laboratory measures but may not be measuring cognitive abilities regardless of whether a clinical diagnosis is present. A multimethod approach should be used when measuring skills in this domain. This was one of the first studies to examine cross-informant agreement in a sample of children with prenatal alcohol exposure. Further research is necessary to understand why interrater agreement differed for children with prenatal alcohol exposure and those with ADHD.

Cross‐Sectional Analysis of Spatial Working Memory Development in Children with Histories of Heavy Prenatal Alcohol Exposure

In children with prenatal alcohol exposure, spatial working memory is affected and brain regions important for spatial working memory performance exhibit atypical neurodevelopment. We therefore hypothesized that children with prenatal alcohol exposure may also have atypical development of spatial working memory ability. We examined the relation between spatial working memory and age using a cross-sectional developmental trajectory approach in youth with and without histories of heavy prenatal alcohol exposure. The Cambridge Neuropsychological Test Automated Battery Spatial Working Memory subtest was administered to children 5.0 to 16.9years old. While the controls and children with prenatal alcohol exposure showed similar performance at younger ages, larger group differences were observed in older children. This effect was replicated in a separate sample. The atypical brain development that has previously been reported in children with heavy prenatal alcohol exposure may have clinically relevant implications for cognitive development; however, longitudinal cognitive analyses are needed.

An investigation of the link between prenatal alcohol exposure and sleep problems across childhood

ObjectiveTo investigate the association between dose and frequency of prenatal alcohol exposure (PAE) and sleep problems in children, after controlling for established risk factors for sleep problems. MethodsData from the birth cohort of the Longitudinal Study of Australian Children (LSAC) was used. Mothers of 3447 children provided information on alcohol consumption during pregnancy, children’s sleep problems from 2- to 9-years, and potential confounders associated with sleep problems. Children were classified into PAE groups based on distinct patterns of maternal drinking during pregnancy: abstinent, occasional, low, moderate, and heavy. The effect of PAE on the number and persistence of sleep problems across childhood (2−9 years) was examined. ResultsAfter controlling for multiple covariates that impact sleep, children with heavy PAE had 1.13 more sleep problems across childhood (2−9 years) relative to children whose mothers were abstainers, in particular 0.37 more at 2- to 3-years (0.504, 95 % CI 0.053, 0.956), and 0.34 more at 6- to 7-years (0.847, 95 % CI 0.299, 1.396). Compared to children of abstainers, heavy PAE increases the probability of having persistent sleep problems from 2- to 9-years by 22.57 %. No negative associations between moderate or low PAE and sleep were observed. Parenting, family, economic, and child health factors also significantly affected child sleep. ConclusionHeavy PAE was associated with significantly more sleep problems across childhood and a higher probability of reporting persistent sleep problems, relative to children with no PAE. Implications for the understanding and management of sleep in young children with PAE and FASD are discussed.

The association of prenatal alcohol exposure on the cognitive abilities and behaviour profiles of 4-year-old children: a prospective cohort study.

To examine the association of prenatal alcohol exposure (PAE) on cognitive abilities and behaviour profiles of 4-year-old children. Prospective cohort study. Cape Town, South Africa. A cohort of 500 children. Children from the Safe Passage Study, which prospectively collected PAE, were included. Cognition and behavioural profiles were assessed. Children with and without PAE were compared. Mean scores were compared, with P≤0.05 considered significant. Results were adjusted for confounding factors. The Kaufman Assessment Battery for children measured intellectual and mental ability; the NEPSY-II instrument assessed neurocognitive performance. The caregiver completed the Preschool Child Behaviour checklist to rate the child's problem behaviours and competencies. Two hundred children had no PAE, 117 children had mild to moderate PAE (with no binge episodes), 113 children had heavy PAE (with one or two binge episodes), and 70 children had very heavy PAE (with three or more binge episodes). Women who binge drank had significantly higher rates of smoking, marijuana use, and methamphetamine use. Low to moderate PAE had no effect on cognitive ability and behaviour. Very heavy PAE was associated with problems performing simultaneous as well as sequential functions, lower scores in the language and sensorimotor domain, and more attention and pervasive developmental problems. Low to moderate PAE was not associated with cognitive processing or developmental problems. Women who had many binge drinking episodes during pregnancy were the most at risk for cognitive processing, neurocognitive, and behaviour problems in their children at 4years of age. Low to moderate prenatal alcohol use was not associated with cognitive or behavioural problems in 4-year-olds.

Adverse Health Outcomes in Offspring Associated With Fetal Alcohol Exposure: A Systematic Review of Clinical and Preclinical Studies With a Focus on Metabolic and Body Composition Outcomes.

Prenatal alcohol exposure (PAE) results in well-characterized neurological, behavioral, and cognitive deficits in offspring. However, the effects on other health outcomes have not been comprehensively described. We used a systematic review methodology to survey published clinical and preclinical studies investigating a broad range of health outcomes in offspring with PAE. This study specifically reports on outcomes related to metabolism and body composition. The literature was systematically searched across 4 electronic databases (PubMed, CINAHL, Embase, and Web of Science), resulting in 3,230 articles following duplicate removal. Titles and abstracts were reviewed against specific inclusion/exclusion criteria, with 242 articles meeting the criteria for full-text assessment of eligibility. Articles with ineligible study type were removed (127) and articles added from reference lists (15) and an updated search closer to submission (9) for a total of 139 studies. Although 5 health domains were identified, here we focus on metabolism and body composition. Details of alcohol exposure, offspring demographics, and sample sizes were tabulated and quality of reporting assessed. Findings were summarized for body composition (percentage fat mass), physiological and molecular outcomes related to glucose metabolism, and outcomes related to lipid metabolism. There were 32 included studies (2 case-control, 1 prospective longitudinal cohort, and 29 preclinical). Studies had a range of alcohol exposures, both dosage and timing, although all clinical studies had heavy PAE and/or evidence of fetal alcohol syndrome in offspring. The preclinical studies provided evidence of glucose intolerance and/or insulin resistance; dyslipidemia and/or hypercholesterolemia; and increased adiposity in offspring with PAE. Due to the paucity of clinical studies, we recommend further studies be conducted to obtain a complete assessment of long-term metabolic health outcomes in children and adults with PAE, particularly in those diagnosed with fetal alcohol spectrum disorder.

Prenatal alcohol exposure and infant gross motor development: a prospective cohort study

BackgroundMaternal alcohol consumption in pregnancy may have adverse effects on child gross motor (GM) development. There have been few human studies on this topic, particularly ones examining low exposure. This study examined the association between prenatal alcohol exposure (PAE) and infant GM development at 12-months of age.MethodsParticipants were 1324 women recruited from antenatal clinics in Sydney and Perth, Australia. Maternal and paternal alcohol use was assessed in pregnancy via interview; offspring GM development was measured at 12-months with the Bayley Scales of Infant Development (BSID-III).ResultsAny alcohol use in pregnancy was common: 56.1%, of pregnant women drank early in Trimester one (0–6 weeks), however this reduced to 27.9% on average thereafter and at predominantly low levels. However, infant BSID GM scale scores were not found to differ significantly as a function of PAE in the first 6-weeks (low, moderate, binge or heavy PAE), nor with low PAE across pregnancy.ConclusionsWe found no evidence to suggest that low PAE is associated with measurable impairment in infant GM development at 12-months. Further research is needed to examine potential PAE impacts on GM development in heavier exposure groups and through the childhood years when subtle GM deficits may be more detectable.

Relation Between Oppositional/Conduct Behaviors and Executive Function Among Youth with Histories of Heavy Prenatal Alcohol Exposure.

Youth with heavy prenatal alcohol exposure have high rates of behavioral concerns and psychopathology, including increased oppositional and conduct behaviors. The relation between those concerns and executive function (EF) deficits is unknown. We investigated the association of oppositional and conduct behavior and EF in adolescents to inform targeted intervention. Subjects (N=267) ages 10 to 17years comprised 3 groups: alcohol-exposed with oppositional/conduct behaviors (AE+), alcohol-exposed without oppositional/conduct behaviors (AE-), and controls (CON). Group differences on direct neuropsychological (Delis-Kaplan Executive Function System [D-KEFS]) and indirect parent-report (Behavior Rating Inventory of Executive Function [BRIEF]) EF measures were tested with multivariate analysis of covariances, followed by univariate analysis of variances and pairwise comparisons. The contribution of attention-deficit/hyperactivity disorder (ADHD) within the AE groups was assessed in secondary analyses. On the D-KEFS, there was an omnibus main effect of group, with significant main effects on 3 of 6 variables (CON>AE+, AE-). Within the AE groups, ADHD did not alter the results. On the BRIEF, there was an omnibus significant main effect of group, with significant main effects on all scales (CON<AE-<AE+). Within the AE groups, the AE+ group had higher BRIEF scores (i.e., more difficulty) than the AE- group on 4 of 8 subscales when accounting for presence of ADHD. EF deficits in youth with histories of prenatal alcohol exposure were confirmed using direct and indirect measures. Oppositional/conduct behaviors related to EF deficits on indirect but not direct EF measures. Greater understanding of the contribution of concurrent psychopathology to long-term outcomes for alcohol-exposed youth requires further investigation.

Effects of prenatal alcohol exposure on language, speech and communication outcomes: a review longitudinal studies.

The aim of this paper was to provide a systematic review and update on the available longitudinal studies on the impact of prenatal alcohol exposure (PAE) on language, speech and communication development, as well as associated potential environmental confounders during the preschool period. A literature search was restricted to English, full-text, peer-reviewed, longitudinal studies in from 1970 until present: PUBMed, Scopus, Web of Science {C-e Collection, Biological Abstracts, KCI-Kean Journal Database, Russian Science Citation Index, SciELO Citation Index, Zoological Rec-d}, Academic Search Premier (Africa-Wide Information, CINAHL, MEDLINE, PsycINFO. Keywords included: prenatal alcohol exposure (PAE); speech or language or communication outcomes; neurocognitive or neurodevelopment or neurobehavioral or neurobehavioural; infant or baby or toddler or preschooler; longitudinal or follow-up. The inclusion criteria included (i) longitudinal cohorts with at least 2 time-points; (ii) association of light, moderate or heavy PAE on language, speech or communication delay, development or disorder; (iii) environmental confounders; (iv) infants up to preschool age. Six studies satisfied the threshold for inclusion. Three studies reported that PAE was significantly associated with receptive or expressive delay. These studies demonstrated lower scores on either receptive or expressive communication in the alcohol group in comparison to the non-alcohol group, even after controlling for environmental factors up to 36 months. Evidence from the longitudinal studies reviewed suggest that PAE influenced delays in receptive and expressive communication up to 36 months. Contextual risk factors played a significant role in language development over time and especially as children approached school age.

Executive Functioning Correlates With Communication Ability in Youth With Histories of Heavy Prenatal Alcohol Exposure.

Caregivers of youth with heavy prenatal alcohol exposure report impaired communication, which can significantly impact quality of life. Using data collected as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), we examined whether cognitive variables predict communication ability of youth with histories of heavy prenatal alcohol exposure. Subjects (ages 10-16 years) comprised two groups: adolescents with heavy prenatal alcohol exposure (AE) and non-exposed controls (CON). Selected measures of executive function (NEPSY, Delis-Kaplan Executive Function System), working memory (CANTAB), and language were tested in the child, while parents completed communication ratings (Vineland Adaptive Behavior Scales - Second Edition). Separate multiple regression analyses determined which cognitive domains predicted communication ability. A final, global model of communication comprised the three cognitive models. Spatial Working Memory and Inhibition significantly contributed to communication ability across groups. Twenty Questions performance related to communication ability in the CON group only while Word Generation performance related to communication ability in the AE group only. Effects remained significant in the global model, with the exception of Spatial Working Memory. Both groups displayed a relation between communication and Spatial Working Memory and Inhibition. Stronger communication ability related to stronger verbal fluency in the AE group and Twenty Questions performance in the CON group. These findings suggest that alcohol-exposed adolescents may rely more heavily on learned verbal storage or fluency for daily communication while non-exposed adolescents may rely more heavily on abstract thinking and verbal efficiency. Interventions aimed at aspects of executive function may be most effective at improving communication ability of these individuals. (JINS, 2018, 24, 1026-1037).