Maternal Alcohol Exposure Research Articles

Parental Alcohol Exposures Associate with Lasting Mitochondrial Dysfunction and Accelerated Aging in a Mouse Model.

Although detrimental changes in mitochondrial morphology and function are widely described symptoms of fetal alcohol exposure, no studies have followed these mitochondrial deficits into adult life or determined if they predispose individuals with fetal alcohol spectrum disorders (FASDs) to accelerated biological aging. Here, we used a multiplex preclinical mouse model to compare markers of cellular senescence and age-related outcomes induced by maternal, paternal, and dual-parental alcohol exposures. We find that even in middle life (postnatal day 300), the adult offspring of alcohol-exposed parents exhibited significant increases in markers of stress-induced premature cellular senescence in the brain and liver, including an upregulation of cell cycle inhibitory proteins and increased senescence-associated β-galactosidase activity. Strikingly, in the male offspring, we observe an interaction between maternal and paternal alcohol use, with histological indicators of accelerated age-related liver disease in the dual-parental offspring exceeding those induced by either maternal or paternal alcohol use alone. Our studies indicate that chronic parental alcohol use causes enduring mitochondrial dysfunction in offspring, resulting in a reduced NAD+/NAHD ratio and altered expression of the NAD+-dependent deacetylases SIRT1 and SIRT3. These observations suggest that some aspects of FASDs may be linked to accelerated aging due to programmed changes in the regulation of mitochondrial function and cellular bioenergetics.

EFFECTS OF CHRONIC MATERNAL ALCOHOLIZATION ON THE CARDIOMYOCYTE CONTRACTILITY IN RAT OFFSPRINGS

The effects of intrauterine alcohol exposure on heart development, specifically the contractile apparatus and myofibril distribution within cardiomyocytes, remain controversial. Aim: This study investigates the postnatal dynamics of myofibril ultrastructure in rat ventricular cardiomyocytes following chronic maternal alcohol exposure. Methods: We analyzed cardiac tissue from offspring of chronically alcoholized rats at various postnatal stages using transmission electron microscopy. Quantitative parameters of cardiomyocyte myofibrils in different ventricular myocardial zones were assessed. Results: Chronic maternal alcohol exposure appeared to inhibit sarcomerogenesis and reduced overall myofibril content in the hearts of newborn offspring. Furthermore, we observed increased myofibril surface area and disrupted spatial orientation in subendocardial left ventricular cardiomyocytes and intramural zones of both ventricles. Even in mature offspring, the myocardial contractile apparatus remained irreversibly damaged, exhibiting reduced myofibril density, increased surface area, and disrupted orientation.

Potentially modifiable risk and protective factors affecting mental and emotional wellness in pregnancy.

Impaired mental and emotional wellness often co-occurs with prenatal substance use, and both affect infant socio-emotional, cognitive, language, motor, and adaptive behavioral outcomes. Guided by the modified biopsychosocial framework, this study examined the role of common substance exposures during pregnancy (i.e., alcohol and cannabis), socio-cultural factors (social support during pregnancy, adverse childhood experiences), and reproductive health factors on maternal mental health (MMH). Data were obtained from a prospective cohort study-Ethanol, Neurodevelopment, Infant, and Child Health (ENRICH-2), and included 202 pregnant persons. Alcohol and cannabis exposures were assessed through repeated prospective interviews and a comprehensive battery of drug and ethanol biomarkers. MMH outcomes were evaluated during the third trimester through the Perceived Stress Scale, Edinburgh Depression Scale, Generalized Anxiety Disorders-7, and Post-traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders. Univariate and multivariable linear regression models evaluated significant predictors of MMH. Results of multivariable analysis indicate that both maternal adverse childhood experiences and alcohol exposure, even at low-to-moderate levels, during pregnancy were associated with poorer scores for most MMH measures, while higher level of social support and Spanish as the primary language at home (as a proxy of enculturation) had protective effects (all p's < 0.05). These findings highlight the importance of assessing substance use, including periconceptional alcohol exposure, and mental health in pregnant persons as closely related risk factors which cannot be addressed in isolation. Our findings also emphasize a strong protective effect of socio-cultural factors on maternal mental and emotional wellbeing-a strong precursor to maternal-infant bonding and infant neurodevelopment.

Constitutional chromosomal anomalies in children, fetal alcohol syndrome, and maternal toxicant exposures: A longitudinal cohort study

DNA alterations in gametes, which may occur either spontaneously or as a result of exposure to genotoxicants, can lead to constitutional chromosomal anomalies in the offspring. Alcohol is an established genotoxicant. The goal of this hypothesis-testing longitudinal cohort study was to evaluate the effect of significant/sustained maternal alcohol exposure on clinically diagnosed constitutional chromosomal anomalies among children diagnosed with fetal alcohol syndrome (FAS). De-identified eligibility and claim healthcare records, prospectively generated from the 1990–2012 Florida Medicaid system within the Independent Healthcare Research Database (IHRD), were analyzed. Children examined were continuously eligible with ≥ 8 outpatient office visits during the 96-month period following birth. Among these children, 377 were diagnosed with FAS and 137,135 were not. The incidence rate of chromosomal anomalies involving segregation (trisomy 13, 18, or 21, n = 625), microdeletions (microdeletion syndromes, n = 39), and point mutations (sickle-cell anemia/cystic fibrosis, n = 2570) were examined using frequency risk ratio (RR) and logistic regression (adjusted odds ratio (aOR) for sex, race, residence, socioeconomic/environmental exposure status, and birth date) models. The incidence rates of chromosomal anomalies involving segregation (RR=5.92, aOR=5.85) and microdeletions (RR=41.6, aOR=34.1) were significantly increased in the FAS cohort as compared to the non-diagnosed cohort, but there was no difference in the incidence rate of point mutations (RR=1.14, aOR=1.29). Maternal toxicant exposure should be considered in the etiology of constitutional chromosomal anomaly in offspring.

Involvement of metalloproteinase and nitric oxide synthase/nitric oxide mechanisms in early decidual angiogenesis-vascularization of normal and experimental pathological mouse placenta related to maternal alcohol exposure.

Successful pregnancy for optimal fetal growth requires adequate early angiogenesis and remodeling of decidual spiral arterioles during placentation. Prior to the initiation of invasion and endothelial replacement by trophoblasts, interactions between decidual stromal cells and maternal leukocytes, such as uterine natural killer cells and macrophages, play crucial roles in the processes of early maternal vascularization, such as proliferation, apoptosis, migration, differentiation, and matrix and vessel remodeling. These placental angiogenic events are highly dependent on the coordination of several mechanisms at the early maternal-fetal interface, and one of them is the expression and activity of matrix metalloproteinases (MMPs) and endothelial nitric oxide synthases (NOSs). Inadequate balances of MMPs and nitric oxide (NO) are involved in several placentopathies and pregnancy complications. Since alcohol consumption during gestation can affect fetal growth associated with abnormal placental development, recently, we showed, in a mouse model, that perigestational alcohol consumption up to organogenesis induces fetal malformations related to deficient growth and vascular morphogenesis of the placenta at term. In this review, we summarize the current knowledge of the early processes of maternal vascularization that lead to the formation of the definitive placenta and the roles of angiogenic MMP and NOS/NO mechanisms during normal and altered early gestation in mice. Then, we propose hypothetical defective decidual cellular and MMP and NOS/NO mechanisms involved in abnormal decidual vascularization induced by perigestational alcohol consumption in an experimental mouse model. This review highlights the important roles of decidual cells and their MMP and NOS balances in the physiological and pathophysiological early maternal angiogenesis-vascularization during placentation in mice.

Abstract 6458: Maternal and paternal alcohol exposures program higher incidence of hepatocellular carcinoma in offspring

Abstract Environmental exposures during development are known to influence adult health and disease. Specifically, early developmental exposures have been shown to increase susceptibility to cancer in adults through epigenetic mechanisms. Alcohol is a potent environmental carcinogen and teratogen, causing a wide range of health problems across the life course of an individual. Current literature examining early life exposures solely focuses on maternal exposures despite recent efforts to recognize paternal epigenetic contributions. Thus, we investigated the influence of preconception paternal, maternal, and dual parental alcohol exposures on offspring’s predisposition to develop liver disease and hepatocellular carcinoma (HCC). We hypothesized that dual-parental alcohol exposure would exacerbate the incidence of liver cancer in adult offspring. Using an established mouse model, we exposed male and female adult C57BL/6J mice to control (0% EtOH) or alcohol (10% EtOH) preconception treatments. Next, we randomly assigned pups from each treatment to either a single injection of Diethylnitrosamine (DEN; 25mg/kg) to promote liver tumors, or saline control. Finally, we sacrificed offspring on postnatal day 182 and collected organs and blood for enzyme analysis. DEN-treated males display an increased liver-to-body weight ratio compared to saline males while also exhibiting lower body weight. The male progeny from the dual-parental treatment group exhibited a significant increase in tumor incidence and burden in DEN-treated males, exceeding those measured for the maternal and paternal treatments. Further, offspring from the dual-parental group had high levels of alanine transaminase (ALT) and aspartate transaminase (AST) compared to the other treatment groups. Oil Red-O and Sirius Red staining of liver sections revealed increased hepatic steatosis and fibrosis in DEN males compared to saline males. Again, the dual-parental exposed offspring exhibited the most aberrant phenotype. Blind scoring of H&amp;E-stained liver sections identified increases in steatosis, fibrosis, and HCC lesions, with the highest scores emerging in DEN-treated dual-parental offspring. These findings demonstrate that preconception paternal and gestational maternal alcohol exposures program a predisposition to adult-onset chronic diseases including alcoholic fatty liver disease, hepatic fibrosis, and HCC. These experiments not only confirm our hypothesis that dual-parental exposed offspring exhibit an exacerbated hepatic abnormality phenotype, but also highlight the importance of both maternal and paternal environmental exposures on disease risk in offspring. While the negative effects of maternal alcohol consumption have been well established, our novel finding that paternal alcohol exposure also promotes hepatocellular carcinoma in offspring has potentially profound clinical implications. Citation Format: Alison Basel, Sanat S. Bhadsavle, Kara N. Thomas, Katherine N. Zimmel, Alexis N. Roach, Matthew Gaytan, Grace Parkey, Michael C. Golding. Maternal and paternal alcohol exposures program higher incidence of hepatocellular carcinoma in offspring. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6458.

Prenatal maternal alcohol exposure: diagnosis and prevention of fetal alcohol syndrome.

Fetal alcohol syndrome (FAS) is a developmental and congenital disorder characterized by neurocognitive impairment, structural defects, and growth restriction due to prenatal alcohol exposure. The estimated global prevalence of alcohol use during pregnancy is 9.8%, and the estimated prevalence of FAS in the general population is 14.6 per 10,000 people. In Korea, the estimated prevalence of alcohol use during pregnancy is 16%, and the prevalence of FAS is 18–51 per 10,000 women, which is higher than the global prevalence. Women’s alcohol consumption rates have increased, especially in women of childbearing age. This could increase the incidence of FAS, leading to higher medical expenses and burden on society. Alcohol is the single most important teratogen that causes FAS, and there is no safe trimester to drink alcohol and no known safe amount of alcohol consumption during pregnancy. Thus, physicians should assess women’s drinking patterns in detail and provide education on FAS to women by understanding its pathophysiology. Moreover, the prevention of FAS requires long-term care with a multidisciplinary approach.

The risk of depressive symptoms in offspring exposed to prenatal alcohol and tobacco use: evidence from a population-based longitudinal study

IntroductionEvidence from epidemiological studies indicated that intrauterine exposure to alcohol and tobacco is linked with a number of adverse outcomes in offspring. However, few studies have linked prenatal alcohol and tobacco exposures to offspring depressive symptoms with mixed results.ObjectivesThe objective of this study was to examine the link between maternal prenatal alcohol and tobacco exposures and depressive symptoms in offspring.MethodsUsing data from the Raine Study, a prospective multigenerational observational study, we examined the associations between maternal prenatal alcohol and tobacco use and the risk of depressive symptoms in offspring at age 17 years (N=1168). Depressive symptoms in offspring were measured using the Beck Depression Inventory for Youth. Log-binomial regression was used to estimate relative risk (RR) for associations between exposures and outcome. To better investigate the role of potential confounders, risk factors were sequentially added as adjustment variables in separate models.ResultsAfter adjustment for potential confounders, depressive symptoms in offspring remained related to maternal alcohol use of six or more standard drinks per week during the first trimester of pregnancy [RR 1.59 (95% CI: 1.11-2.26)]. Further, the risk of depressive symptoms was 50% higher for offspring exposed to prenatal tobacco use when compared to non-exposed. The Associations did not appear to be mediated by the effects of prenatal alcohol and tobacco use on adverse pregnancy outcomes.ConclusionsEarly screening and prevention of these exposures could possibly reduce depressive symptoms in offspring. Moreover, future examinations such as Mendelian Randomization that allow a stronger causal inference is warranted.DisclosureNo significant relationships.

The influence of maternal weight and alcohol exposure on infant physical characteristics and neurodevelopmental outcomes

BackgroundMothers of children with fetal alcohol spectrum disorders tend to have lower weight compared to other mothers. Yet how alcohol and maternal weight may predispose infants to poorer physical growth and neurodevelopmental trajectories is relatively unexplained. MethodsSouth African mothers (n = 406) were recruited prenatally and their offspring were provided standardized dysmorphology and neurodevelopment examinations at 6 weeks and 9 months of age. Maternal weight was obtained postpartum, and linear mixed modeling determined whether postpartum maternal weight and prenatal alcohol exposure significantly influenced infant growth, dysmorphology, and neurodevelopment within the first year of life. ResultsPostpartum maternal weight was positively associated with birth length, weight, and head circumference centile, but the rate of growth from birth to nine months was similar among all infants. Maternal weight was inversely associated with dysmorphology. Many infants in this population were performing within the borderline or extremely low range. Higher maternal weight was associated with significantly better cognitive and motor performance at 6 weeks; however, the rate of developmental growth was similar among all infants, regardless of postpartum maternal weight. ConclusionHigher postpartum maternal weight may be a protective factor but does not eliminate the adverse effects of alcohol on infant growth and dysmorphology. Regardless of maternal weight, alcohol remains a powerful teratogen and moderate to high use prenatally can result in adverse infant physical and neurocognitive development.

Maternal background alters the penetrance of growth phenotypes and sex-specific placental adaptation of offspring sired by alcohol-exposed males.

Epigenetic mechanisms of paternal inheritance are an emerging area of interest in our efforts to understand fetal alcohol spectrum disorders. In rodent models examining maternal alcohol exposures, different maternal genetic backgrounds protect or sensitize offspring to alcohol‐induced teratogenesis. However, whether maternal background can mitigate sperm‐inherited alterations in developmental programming and modify the penetrance of growth defects induced by preconception paternal alcohol exposures remains unaddressed. In our previous studies examining pure C57Bl/6J crosses, the offspring of alcohol‐exposed sires exhibited fetal growth restriction, enlarged placentas, and decreased placental efficiency. Here, we find that in contrast to our previous studies, the F1 offspring of alcohol‐exposed C57Bl/6J sires and CD‐1 dams do not exhibit fetal growth restriction, with male fetuses developing smaller placentas and increased placental efficiencies. However, in these hybrid offspring, preconception paternal alcohol exposure induces sex‐specific changes in placental morphology. Specifically, the female offspring of alcohol‐exposed sires displayed structural changes in the junctional and labyrinth zones, along with increased placental glycogen content. These changes in placental organization are accompanied by female‐specific alterations in the expression of imprinted genes Cdkn1c and H19. Although male placentae do not display overt changes in placental histology, using RNA‐sequencing, we identified programmed alterations in genes regulating oxidative phosphorylation, mitochondrial function, and Sirtuin signaling. Collectively, our data reveal that preconception paternal alcohol exposure transmits a stressor to developing offspring, that males and females exhibit distinct patterns of placental adaptation, and that maternal genetic background can modulate the effects of paternal alcohol exposure.

Alterations to Placental Glucocorticoid Receptor Expression with Alcohol Consumption.

Maternal alcohol consumption during pregnancy results in elevated vulnerability to intrauterine growth restriction, preterm birth, miscarriage, and stillbirth. Many of the detrimental effects of fetal alcohol exposure may be mediated through placental dysfunction; however, the exact mechanisms remain unknown. Here, we aimed to determine the effect of maternal alcohol exposure prior to and during early pregnancy on placental glucocorticoid receptor (GR) isoforms, associated GR regulated genes, and infant outcomes. Participants carrying singleton fetuses (n = 113) were recruited during early pregnancy. Amount and type of alcohol consumed over the last 12months were obtained at 18weeks of gestation. The level of drinking was separated into none (0g/day), low (< 10g/day), moderate (10-100g/day), and heavy (> 100g/day). At delivery, placental weight, infant sex, birthweight, and head circumference were recorded. Placental GR isoforms and genes involved in downstream signalling pathways were quantified. The majority of women (70.8%) consumed alcohol. Of these, most consumed low (48.8%) or moderate (37.5%) amounts. Placental weight was unaffected by alcohol consumption, but infants born to heavy drinkers tended to be lighter at birth. In female, but not male, placentae, maternal alcohol consumption resulted in increased GRαC and decreased GRαD1 cytoplasmic expression. In both female and male placentae, a dampened inflammatory response was evident with maternal alcohol consumption, involving downregulated IL6R and upregulated POU2F2 gene expression, respectively. Maternal alcohol consumption in the months prior to, and/or during early, pregnancy alters placental GR isoform and expression of some inflammatory genes in a sex-specific manner.

Prenatal alcohol and tobacco use and the risk of depression in offspring at age of 17 years: findings from the Raine Study

BackgroundPrenatal alcohol and tobacco exposures have been associated with adverse mental health consequences in offspring. The objective of this study was to test the associations between maternal prenatal alcohol and tobacco exposures and depressive symptoms in the offspring, adjusting for a wide range of potential confounders. MethodsWe used data from 1168 mother-offspring pairs from the Raine Study based in Perth, Western Australia. Depressive symptoms at age 17 years were measured using the Beck Depression Inventory for Youth (BDI-Y). Associations between prenatal alcohol and tobacco use and the risk of depressive symptoms in offspring were estimated by risk ratios (RR) derived with multivariable log-binomial regression. ResultsAmong offspring who were assessed for depressive symptoms, 5% were born to mothers who consumed six or more standard drinks of alcohol per week during pregnancy and 20% were exposed to prenatal tobacco. After adjustment for confounders, depressive symptoms at the age of 17 years remained associated with maternal alcohol use of six or more standard drinks per week [RR 1.59 (95% CI: 1.11-2.26)] and any tobacco use [RR 1.36 (95% CI: 1.05-1.79)] during the first trimester of pregnancy. ConclusionOffspring exposed to prenatal alcohol and tobacco use had greater risks of depressive symptoms compared with unexposed offspring, suggesting early screening and prevention of these exposures could possibly reduce depressive symptoms in offspring.

Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids

Maternal alcohol exposure during pregnancy can substantially impact the development of the fetus, causing a range of symptoms, known as fetal alcohol spectrum disorders (FASDs), such as cognitive dysfunction and psychiatric disorders, with the pathophysiology and mechanisms largely unknown. Recently developed human cerebral organoids from induced pluripotent stem cells are similar to fetal brains in the aspects of development and structure. These models allow more relevant in vitro systems to be developed for studying FASDs than animal models. Modeling binge drinking using human cerebral organoids, we sought to quantify the downstream toxic effects of alcohol (ethanol) on neural pathology phenotypes and signaling pathways within the organoids. The results revealed that alcohol exposure resulted in unhealthy organoids at cellular, subcellular, bioenergetic metabolism, and gene expression levels. Alcohol induced apoptosis on organoids. The apoptotic effects of alcohol on the organoids depended on the alcohol concentration and varied between cell types. Specifically, neurons were more vulnerable to alcohol-induced apoptosis than astrocytes. The alcohol-treated organoids exhibit ultrastructural changes such as disruption of mitochondria cristae, decreased intensity of mitochondrial matrix, and disorganized cytoskeleton. Alcohol exposure also resulted in mitochondrial dysfunction and metabolic stress in the organoids as evidenced by (1) decreased mitochondrial oxygen consumption rates being linked to basal respiration, ATP production, proton leak, maximal respiration and spare respiratory capacity, and (2) increase of non-mitochondrial respiration in alcohol-treated organoids compared with control groups. Furthermore, we found that alcohol treatment affected the expression of 199 genes out of 17,195 genes analyzed. Bioinformatic analyses showed the association of these dysregulated genes with 37 pathways related to clinically relevant pathologies such as psychiatric disorders, behavior, nervous system development and function, organismal injury and abnormalities, and cellular development. Notably, 187 of these genes are critically involved in neurodevelopment, and/or implicated in nervous system physiology and neurodegeneration. Furthermore, the identified genes are key regulators of multiple pathways linked in networks. This study extends for the first time animal models of binge drinking-related FASDs to a human model, allowing in-depth analyses of neurotoxicity at tissue, cellular, subcellular, metabolism, and gene levels. Hereby, we provide novel insights into alcohol-induced pathologic phenotypes, cell type-specific vulnerability, and affected signaling pathways and molecular networks, that can contribute to a better understanding of the developmental neurotoxic effects of binge drinking during pregnancy.

Associations of prenatal alcohol exposure and offspring harmful alcohol use: findings from the Raine Study

BackgroundEpidemiological evidence suggests offspring exposed to prenatal alcohol are at increased risk of alcohol use disorders in adulthood. The evidence on the risk of developing harmful alcohol use in adolescence is less clear. MethodsWe used data from the Raine Study, a multi-generational birth cohort study, to examine the association between prenatal alcohol exposure and the risk of harmful alcohol use in offspring at the age of 17 years. Log binomial regression was used to estimate the relative risks (RRs) of harmful alcohol use in offspring exposed to maternal alcohol use in the first (early) and third (late) trimesters of pregnancy. Maternal pre-pregnancy alcohol use was used as a negative control for intrauterine exposure for comparison. ResultsComplete data were available for 1200 mother-offspring pairs. After adjustment for potential confounders, we found increased RRs of harmful alcohol use in offspring born to mothers who consumed four or more standard drinks of alcohol per week during the first trimester [RR 1.45(95% CI: 1.08−1.93)], third trimester [RR 1.34 (95% CI: 1.04–1.72)] and during both trimesters of pregnancy [RR 1.86 (95% CI: 1.16−2.96)]. Maternal pre-pregnancy alcohol use was not associated with an increased risk of harmful alcohol use in offspring [RR 1.15 (95% CI: 0.89−1.48)]. ConclusionObserved associations for maternal prenatal alcohol exposure but not maternal pre-pregnancy alcohol use suggests a biological mechanism for intrauterine alcohol exposure on the risk of harmful alcohol use in the offspring.

CDT reference values for monitoring chronic alcohol abuse in pregnancy

Introduction and aimCarbohydrate Deficient Transferrin (CDT) is one of the most used biomarkers for monitoring alcohol use in pregnancy. However, its effective application in this context is hampered by the demonstrated physiological progressive increase during pregnancy (even in abstinent women) of CDT values, which in the third trimester can reach values close or exceeding the cut-offs usually adopted in clinical and forensic diagnostics.The present work was aimed at the re-assessment of CDT reference values in pregnancy. Materials and methodsThe CDT analysis was performed by a validated HPLC-UV Vis method on 284 serum samples of women with a physiological pregnancy and on 370 sera of non-pregnant woman from the general population (control group). All the samples were tested also for GGT for excluding alcohol abuse. The statistical analysis was performed using the MedCalc® Statistical Software. ResultsThe re-definition of the specific reference concentrations was carried out according to the Horn and Pesce Robust Method. The resulting CDT upper reference values were 1.45%, 2.01% and 2.05% in the first, second, and third trimester, respectively. ConclusionsIn order to prevent the development of maternal and fetal prenatal alcohol exposure complications, the use of alcohol biomarkers, including CDT, has been proposed. However, this biomarker, in the monitoring of alcohol use in pregnancy, has so far been applied adopting the same cut-off used for general population without taking into consideration the progressive physiological increase of its value throughout the pregnancy. In the present study, a specific re-assessment of the CDT reference concentrations of each trimester is reported.

Determining maternal risk factors for gastroschisis using colorado's birth registry database

Aim of StudyGastroschisis is a congenital abdominal wall defect which results in herniation of abdominal contents. The objective of this study was to determine the maternal risk factors for gastroschisis in Colorado. MethodsA case–control study was performed using the Birth Registry database from 2007 to 2016. The outcome was gastroschisis, and the main variable was maternal age which was divided into <21, 21–30, and >30 years of age. Descriptive analysis, bivariate analysis, and logistic regression was performed. ResultsThere were 236 cases of gastroschisis compared to 944 controls. Maternal age did vary significantly between groups (23.4 ± 5 years (cases) vs. 28.7 ± 5.9 years (controls); p < 0.0001). Unadjusted analysis demonstrated that those with young maternal age (<21 years of age) had a 14.14 (95% CI 8.44–23.67) higher odds of gastroschisis compared to those >30 years of age. Independent risk factors for gastroschisis were exposure to prenatal and first trimester cigarettes, prenatal and first trimester alcohol, and chlamydia infection. The odds (4.41, 95% CI 1.36–14.26) of gastroschisis were highest in those with first trimester cigarette exposure and young maternal age (p = 0.03). ConclusionsYoung maternal age, cigarette exposure, alcohol exposure, and chlamydia infection increase the odds of gastroschisis. The interaction between young maternal age and first trimester cigarette exposure significantly increases the odds of gastroschisis. Type of StudyPrognosis Study. Level of EvidenceLevel III.

NGF and BDNF Alterations by Prenatal Alcohol Exposure.

BackgroundIt is now widely established that the devastating effects of prenatal alcohol exposure on the embryo and fetus development cause marked cognitive and neurobiological deficits in the newborns. The negative effects of the gestational alcohol use have been well documented and known for some time. However, also the subtle role of alcohol consumption by fathers prior to mating is drawing special attention.ObjectiveBoth paternal and maternal alcohol exposure has been shown to affect the neurotrophins' signalling pathways in the brain and in target organs of ethanol intoxication. Neurotrophins, in particular nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), are molecules playing a pivotal role in the survival, development and function of the peripheral and central nervous systems but also in the pathogenesis of developmental defects caused by alcohol exposure.MethodsNew researches from the available literature and experimental data from our laboratory are presented in this review to offer the most recent findings regarding the effects of maternal and paternal prenatal ethanol exposure especially on the neurotrophins' signalling pathways.ResultsNGF and BDNF changes play a subtle role in short- and long-lasting effects of alcohol in ethanol target tissues, including neuronal cell death and severe cognitive and physiological deficits in the newborns.ConclusionThe review suggests a possible therapeutic intervention based on the use of specific molecules with antioxidant properties in order to induce a potential prevention of the harmful effects of the paternal and/or maternal alcohol exposure.

Prevalence of Fetal Alcohol Exposure by Analysis of Meconium Fatty Acid Ethyl Esters; A National Canadian Study

Our study aimed to estimate the prevalence of heavy fetal alcohol exposure through the analysis of meconium FAEEs as an objective biomarker of fetal exposure. We conducted a study on meconium samples collected nationwide through the Maternal-Infant Research on Environmental Chemicals (MIREC) Study Group. FAEE in meconium was quantified by an established headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (SPME GC-MS). Out of 1315 samples collected in 10 Canadian obstetric units coast to coast between 2008-2011, the estimated prevalence of positive meconium FAEE ranged between 1.16% and 2.40%, translating into at least 1800 new cases of FASD in Canada each year. Positive maternal self- reports of heavy alcohol use were tenfold lower (0.24%). Use of meconium FAEE revealed tenfold more cases of heavy exposure to maternal drinking than did maternal reports. The use of objective measures of maternal alcohol exposure is critical in accurately estimating risks and in monitoring effective prevention of FASD.

Maternal alcohol consumption during pregnancy and its association with offspring renal function at 30 years: Observation from a birth cohort study.

Prenatal exposure to alcohol has adverse ramifications on foetal development resulting in developmental abnormalities and major congenital anomalies. Experimental studies have documented effects on kidney structure and function among offspring exposed to alcohol during foetal life; however, human evidence is scarce. Thus, the present study aimed to determine the development of CKD among a cohort of 30-year-old Australian offspring whose mothers reported consumption of alcohol during pregnancy. The study sample comprised 1626 offspring of the Australia cohort study (MUSP) whose serum creatinine was assessed at 30 years of age and CKD was categorized from stage 1 to stage 5 based on their level of eGFR following the CKD-EPI definition. Seven percent (n = 111) of offspring had mild (stage 2) CKD at 30 years. The overall adjusted odds of CKD were 2.10 (95% CI 1.02 to 4.33) for offspring of moderate to heavy drinking mothers in late pregnancy, 1.59 (0.69 to 3.66) for early pregnancy and 1.23 (0.75 to 2.04) for pre-pregnancy. The association was higher for female offspring-2.84 (1.07 to 7.54) for late pregnancy and 2.94 (1.10 to 7.88) for early pregnancy. Higher but insignificant odds were found for male offspring at late pregnancy 1.51 (0.49 to 4.73) only. Maternal alcohol exposure during early and late pregnancy is associated with development of mild CKD in their offspring at 30 years. This association is stronger for female than male offspring.

Quantitation of Ethyl-β-D-Glucuronide in Human Umbilical Cord Tissue by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS).

In utero exposure to alcohol may adversely affect the development of the embryo or fetus and result in adverse outcomes known as fetal alcohol spectrum disorders (FASD) which encompass a range of physical, behavioral, and cognitive impairments in the newborn. Since maternal self-reports are often unreliable, biomarkers of gestational alcohol consumption are necessary for accurate identification of exposed newborns at risk. Ethyl-β-D-glucuronide (EtG) is a minor phase II metabolite of ethyl alcohol (ethanol), formed by enzymatic conjugation of ethanol with glucuronic acid in the liver. As a direct biomarker for alcohol, detection of EtG in neonatal biological matrices provides accurate identification of maternal alcohol consumption and fetal alcohol exposure during pregnancy. This chapter describes the quantitation of EtG in human umbilical cord tissue by liquid chromatography tandem mass spectrometry (LC-MS/MS).