Maternal smoking, consumption of alcohol, and caffeinated beverages during pregnancy and the risk of childhood brain tumors: a meta-analysis of observational studies.

BACKGROUND: We conducted this meta-analysis to investigate the potential association between maternal smoking, alcohol and caffeinated beverages consumption during pregnancy and the risk of childhood brain tumors (CBTs). METHODS: A thorough search was carried out on PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Internet to identify pertinent articles. Fixed or random effects model was applied to meta-analyze the data. RESULTS: The results suggested a borderline statistically significant increased risk of CBTs associated with maternal smoking during pregnancy (OR 1.04, 95% CI 0.99-1.09). We found that passive smoking (OR 1.12, 95% CI 1.03-1.20), rather than active smoking (OR 1.00, 95% CI 0.93-1.07), led to an increased risk of CBTs. The results suggested a higher risk in 0-1 year old children (OR 1.21, 95% CI 0.94-1.56), followed by 0-4 years old children (OR 1.12, 95% CI 0.97-1.28) and 5-9 years old children (OR 1.11, 95% CI 0.95-1.29). This meta-analysis found no significant association between maternal alcohol consumption during pregnancy and CBTs risk (OR 1.00, 95% CI 0.80-1.24). An increased risk of CBTs was found to be associated with maternal consumption of caffeinated beverages (OR 1.16, 95% CI 1.07-1.26) during pregnancy, especially coffee (OR 1.18, 95% CI 1.00-1.38). CONCLUSIONS: Maternal passive smoking, consumption of caffeinated beverages during pregnancy should be considered as risk factors for CBTs, especially glioma. More prospective cohort studies are warranted to provide a higher level of evidence.

Maternal alcohol consumption and risk of postpartum depression: a meta-analysis of cohort studies.

OBJECTIVES: The relationship between maternal alcohol consumption and postpartum depression (PPD) is still controversial. The objective of the present study was to assess the association between maternal alcohol consumption and the risk of developing PPD by means of a meta-analysis of cohort studies. STUDY DESIGN: This was a meta-analysis. METHODS: PubMed, Web of Science, Embase, Cochrane Library, China Biology Medicine disc, Chinese National Knowledge Infrastructure, Weipu, and Wanfang databases were searched up to February 4, 2021, to identify relevant studies that evaluated the association between maternal alcohol consumption and PPD. Meta-analysis was conducted using RevMan software and Stata software. Subgroup and sensitivity analyses were performed to explore the potential heterogeneity source, and Begg's funnel plots and Begg's linear regression test were conducted to assess the potential publication bias. RESULTS: A total of 12 studies involving 50,377 participants were identified in our study. Overall, pregnant women who were exposed to alcohol were at a significantly greater risk of developing PPD compared with those who did not consume alcohol (odds ratio = 1.21; 95% confidence interval: 1.04-1.41; P = 0.020). CONCLUSIONS: Maternal alcohol consumption is significantly associated with the risk of developing PPD. These results emphasize the necessity of enhancing health awareness, improving the public health policies and regulations concerning alcohol use, and strengthening the prevention and intervention of maternal alcohol consumption to promote maternal mental health.

In Utero Exposure to Smoking and Alcohol, and Passive Smoking during Childhood: Effect on the Retinal Nerve Fibre Layer in Young Adulthood.

PURPOSE: In utero exposure to cigarette smoke has been suggested to result in thinner retinal nerve fibre layer (RNFL). However, the potential cofounding effects of in utero alcohol exposure and passive smoking during childhood had not been considered. We explored RNFL thickness in young adults in relation to these early life factors. METHODS: In 1989-1991, pregnant women completed questionnaires on their current smoking and alcohol drinking patterns. Following the birth of their offspring, information on household smokers was obtained between the 1- and 13-year follow-ups. At the 20-year follow-up, these offspring underwent an eye examination including optical coherence tomography imaging of the RNFL. RESULTS: Participants (n = 1,287) were 19-22 years old at time of eye examination. Most participants (77%) had no in utero exposure to cigarette smoke; 1.3% were initially exposed but not after 18 weeks' gestation, while 21% had continual in utero smoking exposure. Half of the mothers never consumed alcohol or only consumed alcohol once during their pregnancies. After correcting for potential confounders, including in utero alcohel exposure and childhood passive smoking, participants who had continued in utero exposure to >10 cigarettes/day and ≤10 cigarettes/day had thinner RNFLs by 6.6 (95% confidence interval [CI] = 4.4-8.7) and 3.7 µm (95%[CI] = 2.3-5.5), respectively, than those with no exposure (p < .001). In utero alcohol exposure and childhood passive smoking were not significantly associated with RNFL thickness after accounting for in utero exposure to smoking. CONCLUSIONS: In utero exposure to cigarette smoke is associated with thinner RFNL in young adulthood, independent of other early life environmental factors.

Prenatal alcohol exposure and risk of attention deficit hyperactivity disorder in offspring: A retrospective analysis of the millennium cohort study.

OBJECTIVE: To investigate the relationship between prenatal maternal alcohol consumption and the risk of attention deficit hyperactivity disorder (ADHD), the strengths and difficulties questionnaire (SDQ) score and abnormal hyperactivity score in seven-year-old children. METHODS: This study is a retrospective analysis of the Millennium Cohort Study (MCS). Questionnaires were used to gather data on gestational alcohol consumption when children were 9 months old and neurodevelopmental outcomes in offspring at 7 years of age (N = 13,004). Alcohol consumption was classified into never, light, moderate and heavy. Crude and adjusted logistic regression models were used for data analysis. RESULTS: The total number of women who reported drinking alcohol in pregnancy (the light, moderate and heavy drinking group) was 3916 (30.1%). No significant association was found between light, moderate or heavy gestational alcohol consumption and ADHD (adjusted odds ratio [aOR] for light = 0.80, 95% confidence interval [CI] = [0.53,1.22], aOR for moderate = 0.83, [0.40, 1.74]; aOR for heavy = 1.27, [0.54, 2.98]); for abnormal SDQ score (aOR for light = 0.94, [0.78,1.13], aOR for moderate = 0.70, [0.49,1.00]; aOR for heavy = 1.08, [0.70, 1.66]); for abnormal Hyperactivity score (aOR for light = 1.02, [0.89,1.17]; aOR for moderate = 1.05, [0.82, 1.34]; aOR for heavy = 0.90, [0.62, 1.32]), in offspring. CONCLUSION: Light, moderate or heavy antenatal alcohol consumption was not associated with an increased susceptibility to ADHD or behavioural outcomes in this study. However, due to the limited number of cases we cannot rule out an increased risk of ADHD in relation to heavy alcohol consumption.

Korean mothers' alcohol consumption trajectories from childbirth to 6 years postpartum and children's executive function difficulties at first grade.

PURPOSE: This study aims to identify Korean mothers' alcohol consumption trajectories during early parenthood (from birth to 6 years postpartum) and to examine associations between these trajectories and their children's executive function difficulties at first grade (age 7). METHODS: Participants were 1010 mothers and their children, a subset of the Panel Study of Korean Children. Mothers' postpartum alcohol consumption trajectories were identified using growth mixture modeling. Children's executive function difficulties by the trajectories were examined using factorial analysis of covariance. RESULTS: Korean mothers' alcohol consumption trajectories during early parenthood were heterogeneous. Mothers developed one of four alcohol consumption patterns: stable low use (49.9%), increasing use (25.0%), chronic modest use (18.3%), and chronic high use (6.8%). Children's executive function difficulties as evaluated by first grade teachers differed by mothers' postpartum alcohol consumption trajectories. Children of chronic high users displayed more difficulties in planning-organization, behavioral control, and attention-concentration than did children of the other groups of mothers. CONCLUSIONS: Mothers' chronic and excessive postpartum alcohol consumption during early parenthood can be a significant risk factor for difficulties in children's early executive function development. Early screening for mothers with unhealthy alcohol consumption habits is critical. Special attention and support should be afforded to their children's development and school adjustment.

A longitudinal, observational study of women who persisted in smoking in successive pregnancies.

BACKGROUND: This longitudinal study examined the profile and pregnancy-related behaviours of women who reported smoking in two successive pregnancies when they presented for prenatal care in a large maternity hospital. METHODS: Using the hospital electronic medical records, women who delivered two successive singleton pregnancies during the years 2011-15 were analyzed. Standardized data were computerized by a midwife at the first prenatal visit, following delivery and before discharge. RESULTS: Over the 5 years, 6647 women delivered twice. Overall 5754 (86.6%) were persistent non-smokers in both pregnancies, 609 (9.2%) were persistent smokers in both pregnancies and between pregnancies 202 (3.0%) quit and 82 (1.2%) started smoking. Compared with persistent non-smokers, persistent smokers had higher rates of reported illicit drug use, alcohol consumption and psychological problems and lower rates of planned pregnancy, folic acid supplementation and breastfeeding in both pregnancies (all P < 0.001). In persistent smokers, folic acid supplementation practices deteriorated and illicit drug use increased in the subsequent pregnancy. CONCLUSIONS: We found that approximately one in 10 women smoked in two consecutive pregnancies. Furthermore, compared with non-smokers, persistent smokers were more likely to report other health behaviours associated with adverse pregnancy outcomes and may require additional multidisciplinary support.

Prenatal Alcohol Screening During Pregnancy by Midwives and Nurses.

BACKGROUND: Alcohol use during pregnancy can have a variety of harmful consequences on the fetus. Lifelong effects include growth restriction, characteristic facial anomalies, and neurobehavioral dysfunction. This range of effects is known as fetal alcohol spectrum disorders (FASD). There is no amount, pattern, or timing of alcohol use during pregnancy proven safe for a developing embryo or fetus. Therefore, it is important to screen patients for alcohol use, inform them about alcohol's potential effects during pregnancy, encourage abstinence, and refer for intervention if necessary. However, how and how often nurses and midwives inquire about alcohol drinking during pregnancy or use recommended screening tools and barriers they perceive to alcohol screening has not been well established. METHODS: This survey was sent to about 6,000 American midwives, nurse practitioners, and nurses who provide prenatal care about their knowledge of the effects of prenatal alcohol exposure, the prevalence of alcohol use during pregnancy, and practices for screening patients' alcohol use. Participants were recruited by e-mail from the entire membership roster of the American College of Nurse-Midwives. RESULTS: There were 578 valid surveys returned (about 9.6%). Analyses showed that 37.7% of the respondents believe drinking alcohol is safe during at least one trimester of pregnancy. Only 35.2% of respondents reported screening to assess patient alcohol use. Only 23.3% reported using a specific screening tool, and few of those were validated screens recommended for use in pregnant women. Respondents who believe alcohol is safe at some point in pregnancy were significantly less likely to screen their patients. CONCLUSIONS: Respondents who reported that pregnancy alcohol use is unsafe felt more prepared to educate and intervene with patients regarding alcohol use during pregnancy and FASD than respondents who reported drinking in pregnancy was safe. Perceived alcohol safety and perceived barriers to screening appeared to influence screening practices. Improving prenatal care provider knowledge about the effects of prenatal alcohol exposure and the availability of valid alcohol screening tools will improve detection of drinking during pregnancy, provide more opportunities for meaningful intervention, and ultimately reduce the incidence of FASD.

Gestational Age-Dependent Interplay between Endocannabinoid Receptors and Alcohol in Fetal Cerebral Arteries.

Alcohol (ethanol) is one of the most widely consumed drugs. Alcohol consumption by pregnant women may result in a range of fetal abnormalities termed fetal alcohol spectrum disorders (FASDs). The cerebrovascular system is emerging as a critical target of alcohol in the developing brain. We recently showed that three episodes of prenatal alcohol exposure resulting in 80 mg/dL alcohol in maternal blood during mid-pregnancy up-regulated anandamide-induced dilation of fetal cerebral arteries. Moreover, ethanol dilated fetal cerebral arteries via cannabinoid (CB) receptors. Whether a critical role of fetal cerebral artery CB system in responses to alcohol was maintained throughout the gestation, remains unknow. MAIN METHODS: Pregnant baboons (second trimester equivalent) were subjected to three episodes of either alcohol or control drink infusion via gavage. Cerebral arteries from mothers and near-term female fetuses were in vitro pressurized for diameter monitoring. KEY FINDINGS: Near-term fetal and maternal arteries exhibited similar ability to develop myogenic tone, to constrict in presence of 60 mM KCl, and to respond to 10 µM anandamide. Fetal and maternal arteries largely failed to dilate in presence of 63 mM ethanol. No differences were detected between arteries from control and alcohol-exposed baboon donors. Therefore, previously observed ethanol-induced dilation of fetal cerebral arteries and up-regulation of CB components in response to fetal alcohol exposure during mid-pregnancy was transient and disappeared by near-term.

Maternal Alcohol Consumption During Pregnancy and the Risk of Autism Spectrum Disorders in Offspring: A Retrospective Analysis of the Millennium Cohort Study.

The objective of this retrospective analysis of the longitudinal Millennium Cohort Study was to examine whether maternal alcohol consumption in pregnancy (MACP) is associated with the development of childhood autism spectrum disorders (ASD). Data on MACP and ASD were obtained from parental questionnaires. There were 18,168 singleton mother-child pairs with data on MACP, and 12,595 answered the question on ASD when the children were 11 years old. No statistically significant association was found between MACP and ASD for light (OR 0.78, 95% CI 0.48-1.29), moderate (OR 0.89, 95% CI 0.35-2.27), or heavy (OR 1.54, 95% CI 0.56-4.21) MACP. Alcohol consumption during pregnancy was not associated with the risk of developing ASD in this study cohort.

Gender Difference in Offspring's Alcohol Use Disorder by 21 Years: A Longitudinal Study of Maternal Influences.

AIMS: There is little known about the extent to which maternal alcohol consumption influences offspring's alcohol use disorder. This study aims to examine whether different maternal alcohol consumption trajectories predict gender difference in adolescent alcohol use disorder at child age 21 years. METHODS: Data are from a prospective cohort, the Mater-University of Queensland Study of Pregnancy (MUSP) and its outcomes. The study involves 2531 mother-child pairs for whom data are available at the 21-year follow-up survey. Maternal alcohol consumption trajectories were determined by group-based trajectory modelling. Offspring's lifetime ever alcohol use disorder was assessed using DSM-IV diagnostic criteria. RESULTS: Over 14 years of follow-up after the birth of a child, three distinct alcohol consumption trajectories were identified (abstainer, low-stable. and moderate-escalating drinker). A maternal trajectory of moderate-escalating alcohol consumption independently predicted offspring's lifetime ever alcohol use disorder at 21 years after adjustment for a range of potential confounders. "Cross-gender influence" is observed in the study. CONCLUSIONS: A maternal life course pattern of alcohol consumption may have an independent effect on offspring alcohol consumption, with male offspring being more vulnerable to the effects of maternal alcohol use than are female offspring. Programs intended to address alcohol consumption by adolescents and young adults need to focus on the behaviors of both parents but acknowledging that maternal patterns of alcohol consumption may be particularly important for male offspring.

Maternal alcohol consumption during pregnancy and child's cognitive performance at 6-8 years of age in rural Burkina Faso: an observational study.

BACKGROUND: In Burkina Faso, it is not uncommon for mothers to drink alcohol, even during pregnancy. We aimed to study the association between maternal alcohol consumption during pregnancy and the child's cognitive performance using the Kaufman Assessment Battery for Children, 2nd edition (KABC-II) and the Children's Category Test Level 1 (CCT-1) in rural Burkina Faso. METHODS: We conducted a follow-up study of a community cluster-randomised Exclusive breastfeeding trial, and re-enrolled the children in rural Burkina Faso. A total of 518 children (268 boys and 250 girls) aged 6-8 years were assessed using the KABC-II and the CCT-1. We examined the effect size difference using Cohen's d and conducted a linear regression analysis to examine the association. RESULTS: Self-reported alcohol consumption during pregnancy was 18.5% (96/518). Children whose mothers reported alcohol consumption during pregnancy performed significantly poorly for memory and spatial abilities tests from small effect size difference for 'Atlantis' (0.27) and 'Triangle' (0.29) to moderate effect size difference for 'Number recall' (0.72) compared to children whose mothers did not consume alcohol during pregnancy; the exposed children scored significantly higher errors with a small effect size (0.37) at problem solving (CCT-1) test compared to unexposed children. At unstandardized and standardized multivariable analysis, children whose mothers reported alcohol consumption during pregnancy performed significantly poorer for memory-'Atlantis' (p = 0.03) and 'Number recall' (p = 0.0001), and spatial ability tests-'Triangle' (p = 0.03); they scored significantly higher errors at problem solving CCT-1 test (p = 0.002); all the results were adjusted for age, sex, schooling, stunting, father's education, mother's employment and the promotion of exclusive breastfeeding. No statistical association was found for visual abilities-'Conceptual Thinking', 'Face recognition', 'Story completion', and reasoning tests-'Rover', 'Block counting', and 'Pattern Reasoning'. CONCLUSION: Maternal alcohol consumption during pregnancy is associated with poorer cognitive performance for memory, spatial ability, and problem solving tests in the offspring in rural Burkina Faso. Futures studies needs to assess in more detail the maternal alcohol consumption patterns in Burkina Faso and possible preventive strategies.

Maternal alcohol exposure during mid-pregnancy dilates fetal cerebral arteries via endocannabinoid receptors.

Prenatal alcohol exposure often results in fetal alcohol syndrome and fetal alcohol spectrum disorders. Mechanisms of fetal brain damage by alcohol remain unclear. We used baboons (Papio spp.) to study alcohol-driven changes in the fetal cerebral artery endocannabinoid system. Pregnant baboons were subjected to binge alcohol exposure via gastric infusion three times during a period equivalent to the second trimester of human pregnancy. A control group was infused with orange-flavored drink that was isocaloric to the alcohol-containing solution. Cesarean sections were performed at a time equivalent to the end of the second trimester of human pregnancy. Fetal cerebral arteries were harvested and subjected to in vitro pressurization followed by pharmacological profiling. During each alcohol-infusion episode, maternal blood alcohol concentrations (BAC) reached 80 mg/dL, that is, equivalent to the BAC considered legal intoxication in humans. Circulating anandamide (AEA) and 2-arachidonoylglycerol (2-AG) remained unchanged. Ultrasound studies on pregnant mothers revealed that fetal alcohol exposure decreased peak systolic blood velocity in middle cerebral arteries when compared to pre-alcohol levels. Moreover, ethanol-induced dilation was observed in fetal cerebral arteries pressurized in vitro. This dilation was abolished by the mixture of AM251 and AM630, which block cannabinoid receptors 1 and 2, respectively. In the presence of AM251, the cannabinoid receptor agonist AEA evoked a higher, concentration-dependent dilation of cerebral arteries from alcohol-exposed fetuses. The difference in AEA-induced cerebral artery dilation vanished in the presence of AM630. CB1 and CB2 receptor mRNA and protein levels were similar in cerebral arteries from alcohol-exposed and control-exposed fetuses. In summary, alcohol exposure dilates fetal cerebral arteries via endocannabinoid receptors and results in an increased function of CB2.

Alcohol Use During Pregnancy is Associated with Specific Alterations in MicroRNA Levels in Maternal Serum.

BACKGROUND: Given the challenges of confirming prenatal alcohol exposure (PAE) during pregnancy using currently established biomarkers of alcohol consumption, we examined whether serum microRNAs (miRNAs) may serve as stable biomarkers for PAE. Alterations in the levels of specific circulating miRNAs have been associated with various disease states and in animal models of fetal alcohol spectrum disorder. METHODS: Pregnant women in this prospective study were recruited from substance abuse and general maternity clinics affiliated with the University of New Mexico. Serum was collected at the time of admission for delivery from 14 subjects who reported ≥1 binge-drinking episode or ≥3 drinks/wk during pregnancy and 16 subjects who reported abstinence during pregnancy and tested negative for 5 ethanol biomarkers. Total RNA was isolated from serum and used for microarray analysis. RESULTS: False discovery rate-corrected analyses of covariance revealed that 55 miRNAs were significantly altered between the 2 groups. Hierarchical clustering using only the significantly altered miRNAs grouped samples into alcohol-consuming and non-alcohol-consuming individuals. Discriminant analysis then identified miRs-122*, -126, -216b, -221*, -3119, -3942-5p, -4704-3p, -4743, -514-5p, and -602 as the top 10 discriminators between the 2 groups. Ingenuity Pathway Analysis of putative miRNA targets illustrated that miRNAs identified in this study are involved in biological pathways that mediate the effects of alcohol, such as brain-derived neurotrophic factor, ERK1/2, and PI3K/AKT signaling. CONCLUSIONS: This is the first report of alterations in serum miRNA expression that are associated with alcohol use during human pregnancy. These results suggest that serum miRNAs could be useful as biomarkers of alcohol exposure.

Reduction of Nfia gene expression and subsequent target genes by binge alcohol in the fetal brain.

The objective of the present study was to investigate the changes in gene expression in the fetal brain (forebrain and hippocampus) caused by maternal binge alcohol consumption. Pregnant C57BL/6J mice were treated intragastrically with distilled phosphate-buffered saline (PBS) or ethanol (2.9 g/kg) from embryonic day (ED) 8-12. Microarray analysis revealed that a significant number of genes were altered at ED 18 in the developing brain. Specifically, in hippocampus, nuclear factor one alpha (Nfia) and three N-methyl-D-aspartate (Nmda) receptors (Nmdar1, Nmdar2b, and Nmdar2d) were down-regulated. The transcription factor Nfia controls gliogenesis, cell proliferation and Nmda-induced neuronal survival by regulating the expression of target genes. Some of the Nfia-target gene (Aldh1a, Folh1, Gjb6, Fgf1, Neurod1, Sept4, and Ntsr2) expressions were also altered as expected. These results suggest that the altered expression of Nfia and Nmda receptors may be associated with the etiology of fetal alcohol syndrome (FAS). The data presented in this report will contribute to the understanding of the molecular mechanisms associated with the effects of alcohol in FASD individuals.