Effects Of Prenatal Alcohol Exposure Research Articles

Effects of prenatal alcohol exposure on the olfactory system development

Fetal Alcohol Spectrum Disorders (FASD), resulting from maternal alcohol consumption during pregnancy, are a prominent non-genetic cause of physical disabilities and brain damage in children. Alongside common symptoms like distinct facial features and neurocognitive deficits, sensory anomalies, including olfactory dysfunction, are frequently noted in FASD-afflicted children. However, the precise mechanisms underpinning the olfactory abnormalities induced by prenatal alcohol exposure (PAE) remain elusive. Utilizing rodents as a model organism with varying timing, duration, dosage, and administration routes of alcohol exposure, prior studies have documented impairments in olfactory system development caused by PAE. Many reported a reduction in the olfactory bulb (OB) volume accompanied by reduced OB neuron counts, suggesting the OB is a brain region vulnerable to PAE. In contrast, no significant olfactory system defects were observed in some studies, though subtle alterations might exist. These findings suggest that the timing, duration, and extent of fetal alcohol exposure can yield diverse effects on olfactory system development. To enhance comprehension of PAE-induced olfactory dysfunctions, this review summarizes key findings from previous research on the olfactory systems of offspring prenatally exposed to alcohol.

Lower resting state functional connectivity partially mediates adverse effects of prenatal alcohol exposure on arithmetic performance in children.

Fetal alcohol spectrum disorders (FASD) include a range of neurocognitive and behavioral impairments resulting from prenatal alcohol exposure (PAE). Among the PAE-related cognitive deficits, number processing is particularly affected. This study examines alterations in number processing networks and whether changes in functional connectivity mediate the adverse effects of PAE on arithmetic performance. Magnetic resonance imaging (MRI) was acquired in 57 children (mean (SD) age = 11.3 (+0.9) yr), 38 with FASD (19 fetal alcohol syndrome (FAS) or partial FAS (PFAS), 19 heavily exposed (HE)) and 19 controls. Whole-brain correlation analyses were performed from five seeds located in regions involved in number processing. Children with FAS/PFAS showed dose-dependent reductions in resting state functional connectivity between the seed in the right (R) posterior superior parietal lobule and a cluster in the left (L) inferior frontal gyrus, and between a seed in the R horizontal intraparietal sulcus and clusters in the R precentral gyrus and L cerebellar lobule VI. HE children showed lower resting state functional connectivity in a subset of these regions. Lower functional connectivity in the two fronto-parietal connections partially mediated the adverse effects of PAE on arithmetic performance. This study demonstrates PAE-related functional connectivity impairments in functional networks involved in number processing. The weaker connectivity between the R posterior superior parietal lobule and the L inferior frontal gyrus suggests that impaired verbal processing and visuospatial working memory may play a role in number processing deficits, while weaker connectivity between the R intraparietal sulcus and the R precentral gyrus points to poorer finger-based numerical representation, which has been linked to arithmetic computational skills.

The Impact of Prenatal Alcohol Exposure on the Autonomic Nervous System and Cardiovascular System in Rats in a Sex-Specific Manner.

Fetal Alcohol Spectrum Disorder (FASD) is a consequence of prenatal alcohol exposure (PAE) associated with a range of effects, including dysmorphic features, prenatal and/or postnatal growth problems, and neurodevelopmental difficulties. Despite advances in treatment methods, there are still gaps in knowledge that highlight the need for further research. The study investigates the effect of PAE on the autonomic system, including sex differences that may aid in early FASD diagnosis, which is essential for effective interventions. During gestational days 5 to 20, five pregnant female Wistar rats were orally administered either glucose or ethanol. After 22 days, 26 offspring were born and kept with their mothers for 21 days before being isolated. Electrocardiographic recordings were taken on the 29th and 64th day. Heart rate variability (HRV) parameters were collected, including heart rate (HR), standard deviation (SD), standard deviation of normal-to-normal intervals (SDNN), and the root mean square of successive differences between normal heartbeats (RMSSD). Additionally, a biochemical analysis of basic serum parameters was performed on day 68 of the study. The study found that PAE had a significant impact on HRV. While electrolyte homeostasis remained mostly unaffected, sex differences were observed across various parameters in both control and PAE groups, highlighting the sex-specific effects of PAE. Specifically, the PAE group had lower mean heart rates, particularly among females, and higher SDNN and RMSSD values. Additionally, there was a shift towards parasympathetic activity and a reduction in heart rate entropy in the PAE group. Biochemical changes induced by PAE were also observed, including elevated levels of alanine transaminase (ALT) and aspartate aminotransferase (AST), especially in males, increased creatinine concentration in females, and alterations in lipid metabolism. PAE negatively affects the development of the autonomic nervous system, resulting in decreased heart rate and altered sympathetic activity. PAE also induces cardiovascular abnormalities with sex-specific effects, highlighting a relationship between PAE consequences and sex. Elevated liver enzymes in the PAE group may indicate direct toxic effects, while increased creatinine levels, particularly in females, may suggest an influence on nephrogenesis and vascular function. The reduced potassium content may be linked to hypothalamus-pituitary-adrenal axis overactivity.

Dose-response effect of prenatal alcohol exposure on perinatal outcomes.

A better understanding of the effects of lower levels of prenatal alcohol exposure (PAE), as a common exposure, is needed. The goal of this study was to examine the effects of mild-moderate PAE and episodic binge drinking on perinatal outcomes. The data were obtained from three prospective cohorts with a combined sample of 281 participants: 125 with PAE and 156 without PAE. Alcohol-related measures included the Alcohol Use Disorders Identification Test, timeline follow-back questionnaires (covering the periconceptional period, mid-gestation, and late gestation), and biomarkers. Absolute alcohol per day (AAD) and per drinking day (AADD), number of binge episodes, and maximum number of drinks in a 24-h period were estimated. Perinatal outcomes included gestational age and anthropometric measures. Data were analyzed using correlation and multivariable regression analysis. Among women with PAE, average alcohol consumption across the periconceptional period and pregnancy was 0.37 oz ± 0.74 AA/day (~5 drinks/week). After adjusting for tobacco co-exposure and sociodemographic characteristics, significant associations between all alcohol measures and gestational age at delivery were observed, including cumulative measures of AAD (β = -0.58; 95% CI: -0.98; -0.17) and AADD (β = -0.58; 95% CI: -0.90; -0.26) during pregnancy and the periconceptional period. A significant association between the maximum number of drinks in a 24-h period and birth length percentile (β = -0.70; 95% CI: -1.36; -0.04) was observed in the final model. PAE was associated with lower birth weight percentile in univariate analyses only. Results of this study demonstrate a negative association between mild-moderate PAE and episodic binge drinking with gestational age at delivery and birth length percentile after controlling for other factors. Robust negative effects of PAE, including in the periconceptional period before pregnancy recognition, on duration of gestation highlight the need for primary prevention efforts aimed at PAE in persons of reproductive age.

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.

Longitudinal effects of prenatal alcohol exposure on visual neurodevelopment over infancy.

Prenatal alcohol exposure (PAE) affects neurodevelopment in over 59 million individuals globally. Prior studies using dichotomous categorization of alcohol use and comorbid substance exposures provide limited knowledge of how prenatal alcohol specifically impacts early human neurodevelopment. In this longitudinal cohort study from Cape Town, South Africa, PAE is measured continuously-characterizing timing, dose, and drinking patterns (i.e., binge drinking). High-density electroencephalography (EEG) during a visual-evoked potential (VEP) task was collected from infants aged 8 to 52 weeks with prenatal exposure exclusively to alcohol and matched on sociodemographic factors to infants with no substance exposure in utero. First trimester alcohol exposure related to altered timing of the P1 VEP component over the first 6 months postnatally, and first trimester binge drinking exposure altered timing of the P1 VEP components such that increased exposure was associated with longer VEP latencies while increasing age was related to shorter VEP latencies (n = 108). These results suggest alcohol exposure in the first trimester may alter visual neurodevelopmental timing in early infancy. Exploratory individual-difference analysis across infants with and without PAE tested the relation between VEP latencies and myelination for a subsample of infants with usable magnetic resonance imaging (MRI) T1w and T2w scans collected at the same time point as EEG (n = 47). Decreased MRI T1w/T2w ratios (an indicator of myelin) in the primary visual cortex (n = 47) were linked to longer P1 VEP latencies. Results from these two sets of analyses suggest that prenatal alcohol and postnatal myelination may both separately impact VEP latency over infancy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Independent and Combined Effects of Prenatal Alcohol Exposure and Prenatal Stress on Fetal HPA Axis Development.

Prenatal alcohol exposure (PAE) and prenatal stress (PS) are highly prevalent conditions known to affect fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis. The objectives of this study were to assess the effect of light PAE, PS, and PAE-PS interaction on fetal HPA axis activity assessed via placental and umbilical cord blood biomarkers. Participants of the ENRICH-2 cohort were recruited during the second trimester and classified into the PAE and unexposed control groups. PS was assessed by the Perceived Stress Scale. Placental tissue was collected promptly after delivery; gene and protein analysis for 11β-HSD1, 11β-HSD2, and pCRH were conducted by qPCR and ELISA, respectively. Umbilical cord blood was analyzed for cortisone and cortisol. Pearson correlation and multivariable linear regression examined the association of PAE and PS with HPA axis biomarkers. Mean alcohol consumption in the PAE group was ~2 drinks/week. Higher PS was observed in the PAE group (p < 0.01). In multivariable modeling, PS was associated with pCRH gene expression (β = 0.006, p < 0.01), while PAE was associated with 11β-HSD2 protein expression (β = 0.56, p < 0.01). A significant alcohol-by-stress interaction was observed with respect to 11β-HSD2 protein expression (p < 0.01). Results indicate that PAE and PS may independently and in combination affect fetal programming of the HPA axis.

The Impact of Prenatal Alcohol Exposure on Longitudinal Growth, Nutritional Status, and Insulin-Like Growth Factor 1 in Early Childhood in Leyte, the Philippines

To assess the impact and potential mechanistic pathways of prenatal alcohol exposure (PAE) on longitudinal growth and nutritional status in early childhood. A cohort of 296 mother-infant dyads (32% with PAE vs 68% unexposed) were recruited in Leyte, the Philippines, and followed from early gestation through 24months of age. PAE was assessed using serum phosphatidylethanol (PEth) captured twice prenatally and in cord blood and supplemented with self-reported alcohol consumption. Linear mixed models were used to examine longitudinal effects of PAE on growth from birth through 2years including key potential mediating factors (placental histopathology, and infant serum leptin and Insulin-like Growth Factor 1 [IGF-1]). After adjusting for potential confounders, we found that PAE was significantly associated with a delayed blunting of linear growth trajectories (height-for-age z-score, body length) and weight (weight-for-age z-score, body weight) that manifested between 4 and 6months and continued through 12-24months. PAE was also associated with a decreased rate of mid-upper-arm circumference growth from birth to 12months, and a lower mean IGF-1 levels at birth and 6months. This study demonstrates a delayed impact of PAE on growth that manifested around 6months of age, underscoring the importance of routine clinical monitoring in early childhood. Furthermore, the findings supported prior animal model findings that suggest a mechanistic role for IGF-1 in PAE-induced growth delay.

Sex-specific alterations in cognitive control following moderate prenatal alcohol exposure and transient systemic hypoxia ischemia in the rat.

Prenatal alcohol exposure (PAE) continues to be a worldwide problem. Affected offspring display impaired neurodevelopment, including difficulties with executive control. Although PAE has also been associated with decreased blood flow to fetuses, the relationship between PAE and altered blood flow is not well understood. We used preclinical models of PAE, transient systemic hypoxia ischemia (TSHI), and PAE + TSHI combined to assess the effects on neurodevelopmental outcomes using translationally relevant touchscreen operant platform testing. Twenty-eight Long-Evans (Blue Spruce, Strain HsdBlu:LE) dams were randomly assigned to one of four experimental groups: Saccharin Control (Sham), 5% Ethanol (PAE), TSHI, or 5% Ethanol and TSHI (PAE + TSHI). Dams consumed either saccharin or 5% ethanol during gestation. TSHI was induced on Embryonic Day 19 (E19) during an open laparotomy where the uterine arteries were transiently occluded for 1 h. Pups were born normally and, after weaning, were separated by sex. A total of 80 offspring, 40 males and 40 females, were tested on the 5-Choice Continuous Performance paradigm (5C-CPT). Female offspring were significantly impacted by TSHI, but not PAE, with an increase in false alarms and a decrease in hit rates, omissions, accuracy, and correct choice latencies. In contrast, male offspring were mildly affected by PAE, but not TSHI, showing decreases in premature responses and increases in accuracy. No significant interactions between PAE and TSHI were detected on any measure. Transient systemic hypoxia ischemia impaired performance on the 5C-CPT in females, leading to a bias toward stimulus responsivity regardless of stimulus type. In contrast, TSHI did not affect male offspring, and only slight effects of PAE were seen. Together, these data suggest that TSHI in females may cause alterations in cortical structures that override alterations caused by moderate PAE.

Unraveling the complex relationship between prenatal alcohol exposure, hippocampal LTP, and learning and memory.

Prenatal alcohol exposure (PAE) has been extensively studied for its profound impact on neurodevelopment, synaptic plasticity, and cognitive outcomes. While PAE, particularly at moderate levels, has long-lasting cognitive implications for the exposed individuals, there remains a substantial gap in our understanding of the precise mechanisms underlying these deficits. This review provides a framework for comprehending the neurobiological basis of learning and memory processes that are negatively impacted by PAE. Sex differences, diverse PAE protocols, and the timing of exposure are explored as potential variables influencing the diverse outcomes of PAE on long-term potentiation (LTP). Additionally, potential interventions, both pharmacological and non-pharmacological, are reviewed, offering promising avenues for mitigating the detrimental effects of PAE on cognitive processes. While significant progress has been made, further research is required to enhance our understanding of how prenatal alcohol exposure affects neural plasticity and cognitive functions and to develop effective therapeutic interventions for those impacted. Ultimately, this work aims to advance the comprehension of the consequences of PAE on the brain and cognitive functions.

Fetal Alcohol Spectrum Disorders and Inadequacy of Care: Importance of Raising Awareness in Clinical Practice.

Prenatal alcohol exposure is one of the major avoidable causes of developmental disruption and health abnormalities in children. Fetal alcohol spectrum disorders (FASDs), a significant consequence of prenatal alcohol exposure, have gained more attention recently. This review aims to provide a narrative approach to the scientific literature on the history, clinical presentation, diagnosis, and management of FASDs. A literature search in PubMed, ScienceDirect, and Google Scholar online databases was conducted. The dates of publications ranged from 2000 to 2023. FASD presentations tend to persist into adulthood, which, combined with environmental factors, potentially lead to secondary psychosocial problems and disabilities. This review covers different aspects of FASDs regarding the concept of the umbrella term and public health, somatic, and psychiatric perspectives. FASD management remains an obstacle to health professionals, and mental health problems are underestimated. Its management involves a multi-disciplinary team, which varies according to the patient's individual needs. FASD diagnosis and management have not been sufficiently established and tailored. Stigma, cultural contexts, knowledge gaps, and the heterogeneity of clinical manifestations are significant barriers to an accurate diagnostic process. Further development of early interventions and the elaboration of complex treatment approaches are needed.

Spectral-based thickness profiling of the corpus callosum enhances anomaly detection in fetal alcohol spectrum disorders.

Fetal alcohol spectrum disorders (FASD) range from fetal alcohol syndrome (FAS) to non-syndromic forms (NS-FASD). The neuroanatomical consequences of prenatal alcohol exposure are mainly the reduction in brain size, but also focal abnormalities such as those of the corpus callosum (CC). We previously showed a narrowing of the CC for brain size, using manual measurement and its usefulness to improve diagnostic certainty. Our aim was to automate these measurements of the CC and identify more recurrent abnormalities in FAS subjects, independently of brain size reduction. We developed a fast, automated, and normalization-free method based on spectral analysis to generate thicknesses of the CC continuously and at singular points (genu, body, isthmus, and splenium), and its length (LCC). We applied it on midsagittal section of the CC extracted from T1-anatomical brain MRI of 89 subjects with FASD (52 FAS, 37 NS-FASD) and 126 with typically development (6-20 y-o). After adjusting for batch effect, we compared the mean profiles and thicknesses of the singular points across the 3 groups. For each parameter, we established variations with age (growth charts) and brain size in the control group (scaling charts), then identified participants with abnormal measurements (<10th percentile). We confirmed the slimming of the posterior half of the CC in both FASD groups, and of the genu section in the FAS group, compared to the control group. We found a significant group effect for the LCC, genu, median body, isthmus, and splenium thicknesses (p < 0.05). We described a body hump whose morphology did not differ between groups. According to the growth charts, there was an excess of FASD subjects with abnormal LCC and isthmus, and of FAS subjects with abnormal genu and splenium. According to the scaling charts, this excess remained only for LCC, isthmus and splenium, undersized for brain size. We characterized size-independent anomalies of the posterior part of the CC in FASD, with an automated method, confirming and extending our previous study. Our new tool brings the use of a neuroanatomical criterion including CC damage closer to clinical practice. Our results suggest that an FAS signature identified in NS-FASD, could improve diagnosis specificity.

Long-term effects of low prenatal alcohol exposure on GABAergic interneurons of the murine posterior parietal cortex.

Fetal alcohol spectrum disorders (FASDs) are characterized by a wide range of physical, cognitive, and behavioral impairments that occur throughout the lifespan. Prenatal alcohol exposure (PAE) can lead to adult impairments in cognitive control behaviors mediated by the posterior parietal cortex (PPC). The PPC plays a fundamental role in the performance of response tasks in both primates and rodents, specifically when choices between similar target and nontarget stimuli are required. Furthermore, the PPC is reciprocally connected with other cortical areas. Despite the extensive literature investigating the molecular mechanisms underlying PAE impairments in cognitive functions mediated by cortical areas, little is known regarding the long-term effects of PAE on PPC development and function. Here, we examined changes in the cellular organization of GABAergic interneurons and their function in PPC using behaviorally naïve control and PAE mice. We used a limited access model of PAE in which C57BL/6J females were exposed to a solution of 10% (w/v) ethanol and 0.066% (w/V) saccharin for 4 h/day throughout gestation. Using high-throughput fluorescent microscopy, we quantified the levels of GABAergic interneurons in the PPC of adult PAE and control offspring. In a separate cohort, we recorded spontaneous inhibitory postsynaptic currents (sIPSCs) using whole-cell patch clamp recordings from PPC layer 5 pyramidal neurons. PAE led to a significant overall reduction of parvalbumin-expressing GABAergic interneurons in PAE mice regardless of sex. Somatostatin- and calretinin-expressing GABAergic interneurons were not affected. Interestingly, PAE did not modulate sIPSC amplitude or frequency. These results suggest that impairments in cognitive control observed in FASD may be due to the significant reduction of parvalbumin-expressing GABAergic interneurons in the PPC. PAE animals may show compensatory changes in GABAergic function following developmental reduction of these interneurons.

Effects of prenatal alcohol exposure on infant lung function, wheeze, and respiratory infections in Australian children.

Prenatal alcohol exposure (PAE) is a known risk factor for a range of adverse outcomes, such as facial dysmorphism, adverse birth outcomes, and neurodevelopmental changes. Preclinical research shows that PAE also inhibits lung development, lowers surfactant protein expression, has detrimental effects on alveolar macrophages, and decreases both T and B cell numbers. However, clinical evidence of respiratory impacts from PAE is limited. This study explored whether lung function, wheeze, and incidence of respiratory infections differ in children with PAE compared with unexposed children. Data from the Barwon Infant Study (n = 1074) were examined. PAE data were extracted from maternal questionnaires at trimesters 1 and 2 (combined), and trimester 3, and included as "total standard drinks" during each trimester and total pregnancy intake, a binary yes/no for PAE, and binge drinking (>5 standard drinks in one session). Respiratory outcomes were parent-reported wheeze, lung function (measured by multiple breath washout), and parent report and medical record indicators of health service attendances for respiratory conditions. Linear and logistic regressions were performed to quantify relationships between PAE and respiratory outcomes, controlling for socioeconomic status, birthweight, sex, gestational age, and maternal smoking. Binge drinking was associated with increased health service attendance for respiratory condition(s) in the first 12 months of life (OR = 5.0, 95% CI (1.7, 20.7), p = 0.008). We did not find a relationship between binary PAE and binge drinking with lung function at 4 weeks of age or wheeze at 12 months. The number of standard drinks consumed in trimester two was associated with a lower lung clearance index (β = -0.011 turnovers, 95% CI (-0.0200, -0.0013), p = 0.03), and a small increase in functional residual capacity (β = 0.34 mL, 95% CI (0.02, 0.66), p = 0.04). We found an association between binge drinking and health service utilization for respiratory conditions in infancy, but no evidence that low-level PAE was associated with adverse respiratory outcomes.

Breastfeeding and neurodevelopment in infants with prenatal alcohol exposure.

Few studies have evaluated the differential benefits of breastfeeding on infant neurodevelopment at varying levels of prenatal alcohol exposure (PAE). This study examined whether the association between breastfeeding and neurodevelopment is modified by prenatal drinking pattern. The study included 385 infants from Ukraine born to women prospectively enrolled in a cohort study during pregnancy. Neurodevelopment was assessed at six and 12 months using the Bayley Scales of Infant Development II (BSID-II) Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI). Linear regression modeling with interaction terms and stratification by PAE group was used to determine the relationship between breastfeeding, PAE, and neurodevelopment. A significant interaction between PAE and breastfeeding was observed for the MDI and PDI at six and 12 months. Infants with high PAE who were breastfed at least four months had BSID-II scores 14 or more points higher compared to those never breastfed. Counterintuitively, those with moderate PAE had poorer performance on the BSID-II at 12 months when breastfed longer. There was a significant joint effect of PAE and breastfeeding on infant neurodevelopment at six and 12 months. Breastfeeding may provide distinct benefits to infants exposed to high levels of PAE. We found a positive effect of breastfeeding on infant neurodevelopment among infants with prenatal alcohol exposure (PAE), particularly those exposed to higher levels during gestation. This study is one of the first to evaluate whether breastfeeding mitigates harm caused by PAE. Breastfeeding may provide distinct benefits to infants with higher levels of PAE.

Increased incidence of renal and urinary tract anomalies among individuals with fetal alcohol spectrum disorders (FASD).

Fetal alcohol spectrum disorders (FASD) in a spectrum of neurodevelopmental conditions resulting from prenatal alcohol exposure (PAE). Animal models have confirmed the toxic effects of PAE on the kidneys and urinary tract, yet the evidence from human studies is contradictory. The purpose of this study was to establish the incidence of renal and urinary tract anomalies (RUTA), impaired kidney function, and hypertension among patients with FASD. Children from the FASD Diagnostic Center with FASD diagnosis (FAS, pFAS, or ARND) were offered participation in the study. The control group consisted of patients from the Gastroenterology Department of the same hospital. The patients underwent renal and urinary tract ultrasound examination. The serum creatinine level was also evaluated and the blood pressure was taken twice. Polish OLAF charts were used to determine the percentiles of blood pressure. The incidence of kidney and urinary tract defects in the study group was significantly higher than in the control group (OR: 2.64 [1.60-4.34]). The kidney size among FASD patients was significantly lower (73 mm [60-83] vs. 83 mm [70-96]; p < .001) when compared to the control group. No differences were observed in the estimated glomerular filtration rate. In the study group, significantly lower systolic blood, diastolic blood pressure, percentile of systolic pressure, and diastolic pressure were observed. RUTA occurred more frequently among patients with FASD compared to the control group, and decreased kidney size was also demonstrated among patients with FASD. However, impaired kidney function and the risk of hypertension were not observed.

Examining the effects of prenatal alcohol exposure on performance of the sustained attention to response task in children with an FASD.

Prenatal alcohol exposure (PAE), the leading known cause of childhood developmental disability, has long-lasting effects extending throughout the lifespan. It is well documented that children prenatally exposed to alcohol have difficulties inhibiting behavior and sustaining attention. Thus, the Sustained Attention to Response Task (SART), a Go/No-go paradigm, is especially well suited to assess the behavioral and neural functioning characteristics of children with PAE. In this study, we utilized neuropsychological assessment, parent/guardian questionnaires, and magnetoencephalography during SART random and fixed orders to assess characteristics of children 8-12 years old prenatally exposed to alcohol compared to typically developing children. Compared to neurotypical control children, children with a Fetal Alcohol Spectrum Disorder (FASD) diagnosis had significantly decreased performance on neuropsychological measures, had deficiencies in task-based performance, were rated as having increased Attention-Deficit/Hyperactivity Disorder (ADHD) behaviors and as having lower cognitive functioning by their caretakers, and had decreased peak amplitudes in Broadmann's Area 44 (BA44) during SART. Further, MEG peak amplitude in BA44 was found to be significantly associated with neuropsychological test results, parent/guardian questionnaires, and task-based performance such that decreased amplitude was associated with poorer performance. In exploratory analyses, we also found significant correlations between total cortical volume and MEG peak amplitude indicating that the reduced amplitude is likely related in part to reduced overall brain volume often reported in children with PAE. These findings show that children 8-12 years old with an FASD diagnosis have decreased amplitudes in BA44 during SART random order, and that these deficits are associated with multiple behavioral measures.

Bayesian modelling of effects of prenatal alcohol exposure on child cognition based on data from multiple cohorts

SummaryHigh levels of prenatal alcohol exposure (PAE) result in significant cognitive deficits in children, but the exact nature of the dose‐response relationship is less well understood. To investigate this relationship, data were assembled from six longitudinal birth cohort studies examining the effects of PAE on cognitive outcomes from early school age through adolescence. Structural equation models (SEMs) are a natural approach to consider, because of the way they conceptualise multiple observed outcomes as relating to an underlying latent variable of interest, which can then be modelled as a function of exposure and other predictors of interest. However, conventional SEMs could not be fitted in this context because slightly different outcome measures were used in the six studies. In this paper we propose a multi‐group Bayesian SEM that maps the unobserved cognition variable to a broad range of observed outcomes. The relation between these variables and PAE is then examined while controlling for potential confounders via propensity score adjustment. By examining different possible dose‐response functions, the proposed framework is used to investigate whether there is a threshold PAE level that results in minimal cognitive deficit.

Prenatal alcohol exposure and cognition at midlife: Evidence of fluid cognition deficits in two cohorts.

Prenatal alcohol exposure (PAE) impacts cognition in childhood and early adulthood. Here we evaluate the cognitive abilities of middle-aged adults with and without a history of PAE. Participants (N = 200) were recruited from longitudinal cohorts in the Atlanta and Seattle metropolitan areas and completed measures comprising the National Institutes of Health Toolbox's Fluid Cognition Composite. We found that individuals with PAE had lower Fluid Cognition Summary scores and lower Dimensional Change Card Sort and Flanker task subtest scores than non-PAE controls, after accounting for both potentially confounding demographic variables using propensity scores and the effects of study site. When we evaluated the effects of PAE with and without dysmorphic physical features, we found that middle-aged adults in both groups had lower fluid cognition scores than non-PAE controls. However, only the presence of PAE with dysmorphic features was associated with lower performance on the Dimensional Change Card Sort Test and Flanker tasks. While all participants with PAE had lower fluid cognition, those with PAE and dysmorphic features also exhibited specific deficits in their performance on measures of inhibition, attention, and cognitive flexibility. Thus, PAE is associated with ongoing cognitive deficits in middle adulthood, which can be observed most clearly among individuals with dysmorphic features.

Prenatal Alcohol Exposure Impairs the Placenta-Cortex Transcriptomic Signature, Leading to Dysregulation of Angiogenic Pathways.

Although alcohol consumption during pregnancy is a major cause of behavioral and learning disabilities, most FASD infants are late- or even misdiagnosed due to clinician's difficulties achieving early detection of alcohol-induced neurodevelopmental impairments. Neuroplacentology has emerged as a new field of research focusing on the role of the placenta in fetal brain development. Several studies have reported that prenatal alcohol exposure (PAE) dysregulates a functional placenta-cortex axis, which is involved in the control of angiogenesis and leads to neurovascular-related defects. However, these studies were focused on PlGF, a pro-angiogenic factor. The aim of the present study is to provide the first transcriptomic "placenta-cortex" signature of the effects of PAE on fetal angiogenesis. Whole mouse genome microarrays of paired placentas and cortices were performed to establish the transcriptomic inter-organ "placenta-cortex" signature in control and PAE groups at gestational day 20. Genespring comparison of the control and PAE signatures revealed that 895 and 1501 genes were only detected in one of two placenta-cortex expression profiles, respectively. Gene ontology analysis indicated that 107 of these genes were associated with vascular development, and String protein-protein interaction analysis showed that they were associated with three functional clusters. PANTHER functional classification analysis indicated that "intercellular communication" was a significantly enriched biological process, and 27 genes were encoded for neuroactive ligand/receptors interactors. Protein validation experiments involving Western blot for one ligand-receptor couple (Agt/AGTR1/2) confirmed the transcriptomic data, and Pearson statistical analysis of paired placentas and fetal cortices revealed a negative correlation between placental Atg and cortical AGTR1, which was significantly impacted by PAE. In humans, a comparison of a 38WG control placenta with a 36WG alcohol-exposed placenta revealed low Agt immunolabeling in the syncytiotrophoblast layer of the alcohol case. In conclusion, this study establishes the first transcriptomic placenta-cortex signature of a developing mouse. The data show that PAE markedly unbalances this inter-organ signature; in particular, several ligands and/or receptors involved in the control of angiogenesis. These data support that PAE modifies the existing communication between the two organs and opens new research avenues regarding the impact of placental dysfunction on the neurovascular development of fetuses. Such a signature would present a clinical value for early diagnosis of brain defects in FASD.