Fetal alcohol spectrum disorder diagnostic clinic capacity in Canadian Provinces and territories.

This study investigated the diagnostic capacity for Fetal Alcohol Spectrum Disorder (FASD) in multidisciplinary clinics across several provincial and one territorial jurisdictions of Canada: Alberta, British Columbia, Manitoba, Ontario and Northwest Territories. The data were collected directly from clinics capable of providing diagnoses of FASD and examined annual capacity for the assessment and diagnosis of FASD per year from 2015 to 2019. In total, 58 FASD diagnostic clinics were identified and 33 clinics participated in this survey. The study identified inadequate FASD diagnostic capacity in all participating jurisdictions. Based on the findings and the current population sizes, it is estimated that 98% of individuals with FASD are undiagnosed or misdiagnosed in Canada. Wait times for FASD diagnosis ranged from 1 month to 4.5 years across participating jurisdictions. The annual FASD diagnostic capacity in the select provinces and territories require at least a 67-fold increase per year.

Fetal alcohol spectrum disorders.

Alcohol readily crosses the placenta and may disrupt fetal development. Harm from prenatal alcohol exposure (PAE) is determined by the dose, pattern, timing and duration of exposure, fetal and maternal genetics, maternal nutrition, concurrent substance use, and epigenetic responses. A safe dose of alcohol use during pregnancy has not been established. PAE can cause fetal alcohol spectrum disorders (FASD), which are characterized by neurodevelopmental impairment with or without facial dysmorphology, congenital anomalies and poor growth. FASD are a leading preventable cause of birth defects and developmental disability. The prevalence of FASD in 76 countries is >1% and is high in individuals living in out-of-home care or engaged in justice and mental health systems. The social and economic effects of FASD are profound, but the diagnosis is often missed or delayed and receives little public recognition. Future research should be informed by people living with FASD and be guided by cultural context, seek consensus on diagnostic criteria and evidence-based treatments, and describe the pathophysiology and lifelong effects of FASD. Imperatives include reducing stigma, equitable access to services, improved quality of life for people with FASD and FASD prevention in future generations.

Screening for Alcohol Use in Pregnancy: a Review of Current Practices and Perspectives.

Global trends of increasing alcohol consumption among women of childbearing age, social acceptability of women's alcohol use, as well as recent changes in alcohol use patterns due to the COVID-19 pandemic may put many pregnancies at higher risk for prenatal alcohol exposure (PAE), which can cause fetal alcohol spectrum disorder (FASD). Therefore, screening of pregnant women for alcohol use has become more important than ever and should be a public health priority. This narrative review presents the state of the science on various existing prenatal alcohol use screening strategies, including the clinical utility of validated alcohol use screening instruments. It also discusses barriers for alcohol use screening in pregnancy, such as practitioner constraints, unplanned pregnancies, delayed access to prenatal care, and stigma associated with substance use in pregnancy, providing recommendations to address these barriers. By implementing consistent alcohol use screening, prenatal care providers have the opportunity to facilitate access to counseling and brief interventions and thus, to prevent new cases of FASD and improve maternal and child health.

Common developmental trajectories and clinical identification of children with fetal alcohol spectrum disorders: A synthesis of the literature.

At an estimated prevalence of up to five percent in the general population, fetal alcohol spectrum disorders (FASD) are the most common neurodevelopmental disorder, at least if not more prevalent than autism (2.3%). Despite this prevalence in the general population, pediatricians and other developmental specialists have thus far failed to diagnose this disability, leaving most children and adults without the supports provided for most other disabilities. This paper will provide a review of clinically relevant literature that describes the developmental challenges of children with fetal alcohol spectrum disorders and addresses similarities to and differences of FASD from other neurodevelopmental disorders such as autism and attention deficit hyperactivity disorder. A subsequent discussion will describe how a diagnosis of an FASD can establish a basis for understanding the developmental and behavioral challenges of children with an FASD, and how specific interventions can help support child development and maximize adult independence.

Screening for fetal alcohol spectrum disorder in infants and young children.

Introduction: With an estimated prevalence of up to five percent in the general population, fetal alcohol spectrum disorders (FASD) are the most common neurodevelopmental disorder and more prevalent than autism. Early identification and subsequent early intervention have the potential to improve developmental trajectory of children with FASD. In addition, new research suggests supplementation with choline may ameliorate the developmental impairments associated with prenatal alcohol exposure. Availability of a screening tool with acceptable epidemiologic performance criteria may be clinical useful in identification of young children at increased risk for FASD. In this paper we describe the Early Fetal Alcohol Spectrum Disorder Screening Test (E-FAST) to identify young children at increased risk for an FASD. Methods: We developed the E-FAST dataset from previously published studies, comprised of 281 children under 5 years of age, 180 (64.1%) were diagnosed with FASD and 101 (35.9%) were non-FASD. Analysis: The analysis identified seven useful variables (prenatal alcohol exposure, ADHD (Attention Deficit Hyperactivity Disorder), foster care or adopted, small OFC (occipital frontal circumference), communication impairments, impaired social skills, and cognitive deficits. All variables were categorized as yes/no for ease of use in a screening tool. Risk ratios for each of the seven indicators were estimated using two-way table analyses. Weights for each variable were estimated based on the relative strength of their odds ratios. Results: The average age was 2.7 years of age (S.D. 1.29) and ranged from infant (6.4%) to 4 years old (35.9%). Maternal alcohol use alone had a sensitivity of 0.97, specificity 0.65, and accuracy 0.86. For the combined seven variables, sensitivity was 0.94, specificity 0.74, and accuracy 0.87. Thus, the seven-item E-FAST screen had acceptable epidemiologic screening characteristics. Discussion: In the United States, up to 547 infants with FASD are born each day which far exceeds the capacity of multidisciplinary diagnostic clinics. During routine clinical management of infants and young children the use of an evidence-based screening tool provides a time efficient means to exclude large numbers of young children from further follow-up for FASD. Conversely, a positive screen identifies a smaller number of children at increased risk for FASD requiring more intensive evaluation and follow-up.

Deficiency in Beclin1 attenuates alcohol-induced cardiac dysfunction via inhibition of ferroptosis.

BACKGROUND: Binge drinking leads to compromised mitochondrial integrity and contractile function in the heart although little effective remedy is readily available. Given the possible derangement of autophagy in ethanol-induced cardiac anomalies, this study was designed to examine involvement of Beclin1 in acute ethanol-induced cardiac contractile dysfunction, in any, and the impact of Beclin1 haploinsufficiency on ethanol cardiotoxicity with a focus on autophagy-related ferroptosis. METHODS: WT and Beclin1 haploinsufficiency (BECN+/-) mice were challenged with ethanol for one week (2 g/kg, i.p. on day 1, 3 and 7) prior to assessment of cardiac injury markers (LDH, CK-MB), cardiac geometry, contractile and mitochondrial integrity, oxidative stress, lipid peroxidation, apoptosis and ferroptosis. RESULTS: Ethanol exposure compromised cardiac geometry and contractile function accompanied with upregulated Beclin1 and autophagy, mitochondrial injury, oxidative stress, lipid peroxidation and apoptosis, and ferroptosis (GPx4, SLC7A11, NCOA4). Although Beclin1 deficiency did not affect cardiac function in the absence of ethanol challenge, it alleviated ethanol-induced changes in cardiac injury biomarkers, cardiomyocyte area, interstitial fibrosis, echocardiographic and cardiomyocyte mechanical properties along with mitochondrial integrity, oxidative stress, lipid peroxidation, apoptosis and ferroptosis. Ethanol challenge evoked pronounced ferroptosis (downregulated GPx4, SLC7A11 and elevated NCOA4, lipid peroxidation), the effect was alleviated by Beclin1 haploinsufficiency. Inhibition of ferroptosis using LIP-1 rescued ethanol-induced cardiac mechanical anomalies. In vitro study noted that ferroptosis induction using erastin abrogated Beclin1 haploinsufficiency-induced response against ethanol. CONCLUSIONS: In sum, our data suggest that Beclin1 haploinsufficiency benefits acute ethanol challenge-induced myocardial remodeling and contractile dysfunction through ferroptosis-mediated manner.

Alcohol's Impact on the Fetus.

BACKGROUND: Alcohol is a teratogen and prenatal exposure may adversely impact the developing fetus, increasing risk for negative outcomes, including Fetal Alcohol Spectrum Disorder (FASD). Global trends of increasing alcohol use among women of childbearing age due to economic development, changing gender roles, increased availability of alcohol, peer pressure and social acceptability of women's alcohol use may put an increasing number of pregnancies at risk for prenatal alcohol exposure (PAE). This risk has been exacerbated by the ongoing COVID-19 pandemic in some countries. METHOD: This literature review presents an overview on the epidemiology of alcohol use among childbearing age and pregnant women and FASD by World Health Organization regions; impact of PAE on fetal health, including FASD; associated comorbidities; and social outcomes. RESULTS/CONCLUSION: The impact of alcohol on fetal health and social outcomes later in life is enormous, placing a huge economic burden on countries. Prevention of prenatal alcohol exposure and early identification of affected individuals should be a global public health priority.

Effects of Prenatal Exposure to Alcohol and Smoking on Fetal Heart Rate and Movement Regulation.

Negative associations of prenatal tobacco and alcohol exposure (PTE and PAE) on birth outcomes and childhood development have been well documented, but less is known about underlying mechanisms. A possible pathway for the adverse fetal outcomes associated with PTE and PAE is the alteration of fetal autonomic nervous system development. This study assessed PTE and PAE effects on measures of fetal autonomic regulation, as quantified by heart rate (HR), heart rate variability (SD-HR), movement, and HR-movement coupling in a population of fetuses at ≥ 34 weeks gestational age. Participants are a subset of the Safe Passage Study, a prospective cohort study that enrolled pregnant women from clinical sites in Cape Town, South Africa, and the Northern Plains region, United States. PAE was defined by six levels: no alcohol, low quit early, high quit early, low continuous, moderate continuous, and high continuous; while PTE by 4 levels: no smoking, quit early, low continuous, and moderate/high continuous. Linear regression analyses of autonomic measures were employed controlling for fetal sex, gestational age at assessment, site, maternal education, household crowding, and depression. Analyses were also stratified by sleep state (1F and 2F) and site (South Africa, N = 4025, Northern Plains, N = 2466). The final sample included 6491 maternal-fetal-dyad assessed in the third trimester [35.21 ± 1.26 (mean ± SD) weeks gestation]. PTE was associated with a decrease in mean HR in state 2F, in a dose dependent fashion, only for fetuses of mothers who continued smoking after the first trimester. In state 1F, there was a significant increase in mean HR in fetuses whose mother quit during the first trimester. This effect was driven by the Norther Plains cohort. PTE was also associated with a significant reduction in fetal movement in the most highly exposed group. In South Africa a significant increase in mean HR both for the high quit early and the high continuous group was observed. In conclusion, this investigation addresses a critical knowledge gap regarding the relationship between PTE and PAE and fetal autonomic regulation. We believe these results can contribute to elucidating mechanisms underlying risk for adverse outcomes.

Association of Prenatal Exposure to Maternal Drinking and Smoking With the Risk of Stillbirth.

Importance: Prenatal smoking is a known modifiable risk factor for stillbirth; however, the contribution of prenatal drinking or the combination of smoking and drinking is uncertain. Objective: To examine whether prenatal exposure to alcohol and tobacco cigarettes is associated with the risk of stillbirth. Design, Setting, and Participants: The Safe Passage Study was a longitudinal, prospective cohort study with data collection conducted between August 1, 2007, and January 31, 2015. Pregnant women from Cape Town, South Africa, and the Northern Plains region of the US were recruited and followed up throughout pregnancy. Data analysis was performed from November 1, 2018, to November 20, 2020. Exposure: Maternal consumption of alcohol and tobacco cigarettes in the prenatal period. Main Outcomes and Measures: The main outcomes were stillbirth, defined as fetal death at 20 or more weeks' gestation, and late stillbirth, defined as fetal death at 28 or more weeks' gestation. Self-reported alcohol and tobacco cigarette consumption was captured at the recruitment interview and up to 3 scheduled visits during pregnancy. Participants were followed up during pregnancy to obtain delivery outcome. Results: Of 11663 pregnancies (mean [SD] gestational age at enrollment, 18.6 [6.6] weeks) in 8506 women for whom the pregnancy outcome was known by 20 weeks' gestation or later and who did not terminate their pregnancies, there were 145 stillbirths (12.4 per 1000 pregnancies) and 82 late stillbirths (7.1 per 1000 pregnancies). A total of 59% of pregnancies were in women from South Africa, 59% were in multiracial women, 23% were in White women, 17% were in American Indian women, and 0.9% were in women of other races. A total of 8% were older than 35 years. In 51% of pregnancies, women reported no alcohol or tobacco cigarette exposure (risk of stillbirth, 4 per 1000 pregnancies). After the first trimester, 18% drank and smoked (risk of stillbirth, 15 per 1000 births), 9% drank only (risk of stillbirth, 10 per 1000 pregnancies), and 22% smoked only (risk of stillbirth, 8 per 1000 pregnancies). Compared with the reference group (pregnancies not prenatally exposed or without any exposure after the first trimester), the adjusted relative risk of late stillbirth was 2.78 (98.3% CI, 1.12-6.67) for pregnancies prenatally exposed to drinking and smoking, 2.22 (98.3% CI, 0.78-6.18) for pregnancies prenatally exposed to drinking only after the first trimester, and 1.60 (98.3% CI, 0.64-3.98) for pregnancies prenatally exposed to smoking only after the first trimester. The adjusted relative risk for all stillbirths was 1.75 (98.3% CI, 0.96-3.18) for dual exposure, 1.26 (98.3% CI, 0.58-2.74) for drinking only, and 1.27 (98.3% CI, 0.69-2.35) for smoking only compared with the reference group. Conclusions and Relevance: These results suggest that combined drinking and smoking after the first trimester of pregnancy, compared with no exposure or quitting before the end of the first trimester, may be associated with a significantly increased risk of late stillbirth.

Urine Methotrexate Concentration at 46-48 Hours Post-Treatment Reflects Methotrexate-Induced Acute Kidney Injury.

Early identification of methotrexate-induced acute kidney injury (AKI) and delayed elimination of methotrexate are critical to limiting toxicity of the drug. The current monitoring strategy consists of serial serum methotrexate concentrations at 24, 36, 42, and 48 hours. Appropriate serum concentration monitoring and intervention does not always prevent AKI. Therefore, ongoing study of biomarkers and improved methods of screening for methotrexate-induced AKI is critical to reduce toxicity. This case series reports urine methotrexate values of 4 patients undergoing treatment with high-dose methotrexate. Urine methotrexate concentration was measured 46 to 48 hours after methotrexate infusion. Urine methotrexate concentration was compared with the duration of drug clearance from the serum. Only 1 patient (case 3) developed AKI. Serum concentration of methotrexate were < 0.3 µmol/L at 42, 48, and 48 hours in patients 1, 2, and 4, respectively, and at 168 hours in patient 3 (p < 0.01). Urine methotrexate concentrations were 2.77, 6.45, and 7.8 (µmol/L), in patients 1, 2, and 4, respectively, and 113.69 (µmol/L) in patient 3 (p < 0.001). This case series provides preliminary data that urine methotrexate concentration at hours 46 to 48 may reflect AKI. Future studies should investigate the ability of serial urine methotrexate concentrations to predict delayed drug clearance and the development of AKI.

A Validation Study of the Alcohol Related Neurodevelopmental Disorders Behavioral Checklist.

BACKGROUND: The initial confirmatory factor analysis of the Alcohol Related Neurodevelopmental Disorder Behavioral Checklist (ABC) utilized a population of 203 children. The analysis identified 10 independent measures (executive functioning, attention and concentration, cognition, memory, confabulation, gullibility, communication skills, academic skills, living/social skills, and juvenile justice). The 10 measures differentiated children with FASD from non-FASD controls. In this study, we present a validity study of the ABC using a different population of children with FASD and non-FASD controls. METHODS: A chart review identified 224 children with ABC checklist scores who had been evaluated for FASD. From this sample, we implemented a case-control study of 76 children diagnosed with FASD and 76 non-FASD controls who were matched by gender and closest age in years (mean age was 8.5 years). RESULTS: The averages of the total score and individual domain scores were compared between the 2 data sets and then between children with FASD and non-FASD controls. Children with FASD had significantly higher scores on all 10 measures than the non-FASD controls. There were very high sensitivity and specificity scores for the total score cutoff and for all 10 of the individual measures. CONCLUSIONS: In an independent sample, we found minimal differences between the previous data and the current validation study on measures of average total score cutoffs, scores for the 10 measures and correlations. Combining the 2 samples yielded robust differences in scores between children with FASD and non-FASD controls. The sensitivity, specificity and accuracy estimates were also very high. The ABC Screen appears to have acceptable epidemiologic performance data to support its use as a screening tool and as an initial step in differentiating children with FASD from those who do not have FASD.

Protective factors against tobacco and alcohol use among pregnant women from a tribal nation in the Central United States.

Identifying social determinants of tobacco and alcohol use during pregnancy is critical to improving health outcomes for the next generation. This is especially important on a rural Tribal Nation where influences such as isolation, cultural barriers, and historical trauma have made it uniquely challenging to prevent substance use during pregnancy. The purpose of this study is to identify population-specific factors that are protective against smoking and drinking during pregnancy. We used data from 421 pregnancies collected as a part of the Safe Passages study from a rural Tribal Nation in the central United States. Pregnant women were classified as women who did not smoke (n = 84), women who quit during pregnancy (n = 23), women who smoked during pregnancy (n = 314), and women who both smoked and drank alcohol during pregnancy (n = 149). Demographic data revealed that 28.8% of the mothers were currently employed, and 91.8% of mothers reported a household income of less than $3,000 per year. Substance use rates were higher than national averages: 74.6% smoked during pregnancy and 35.4% of the women both smoked and drank alcohol during pregnancy. Five factors were identified as being protective against substance use during pregnancy: 1) living with someone (81% less likely to smoke and 92% less likely to smoke and drink), 2) having at least 12 years of education (128% less likely to smoke, and 126% less likely to smoke and drink), 3) having over 12 years of education (235% less likely to smoke, and 206% less likely to smoke and drink), 4) being employed (158% less likely to smoke, and 111% less likely to smoke and drink), and 5) not being depressed (214% less likely to smoke, and 229% less likely to smoke and drink). These social determinants should be considered for intervention research to decrease rates of substance use during pregnancy.

Profile of Mothers of Children with Fetal Alcohol Spectrum Disorder: A Population-Based Study in Canada.

OBJECTIVE: To compare the characteristics of mothers of children with Fetal Alcohol Spectrum Disorder (FASD) with mothers of typically developing control children. METHODS: The study utilized a cross-sectional, observational design, using active case ascertainment. Biological mothers were interviewed using a standardized retrospective questionnaire to collect data on demographics, living environment, pregnancy history, nutrition, alcohol and other drug use prior to and following pregnancy recognition. RESULTS: A total of 173 mothers were interviewed. Of these, 19 had a child who was diagnosed with FASD, five had a child who had received a deferred FASD diagnosis, and 37 had children who were selected into the control group as typically developing children. The remaining 112 mothers had children who did not meet diagnostic criteria for FASD. The mothers of children with FASD did not differ significantly from mothers of the control group children with respect to age, ethnicity, marital status, and employment status at the time of pregnancy. However, mothers of children with FASD had lower levels of education (p < 0.01) and were more likely to have received financial support (p < 0.05) at the time of pregnancy, to have smoked tobacco (p < 0.001), and to have used marijuana or hashish (p < 0.01) prior to pregnancy recognition, compared with mothers of control children. All mothers of children with FASD reported alcohol consumption prior to pregnancy recognition; however, only 10.5% reported alcohol consumption following pregnancy recognition. None of the mothers interviewed reported any drug use following pregnancy recognition. CONCLUSIONS: Population-based preventive interventions, including repeated screening, monitoring, and education regarding the effects of alcohol use, as well as other substances, before and during pregnancy, are needed to eliminate risk for FASD and other negative consequences on child and maternal health.

Association Between Prenatal Exposure to Alcohol and Tobacco and Neonatal Brain Activity: Results From the Safe Passage Study.

Importance: Research to date has not determined a safe level of alcohol or tobacco use during pregnancy. Electroencephalography (EEG) is a noninvasive measure of cortical function that has previously been used to examine effects of in utero exposures and associations with neurodevelopment. Objective: To examine the association of prenatal exposure to alcohol (PAE) and tobacco smoking (PTE) with brain activity in newborns. Design, Setting, and Participants: This prospective cohort study enrolled mother-newborn dyads from December 2011 through August 2015, with data analyzed from June 2018 through June 2019. Pregnant women were recruited from clinical sites in Cape Town, South Africa, and the Northern Plains region of the US. Participants were a subset of newborns enrolled in the Safe Passage Study. Exclusions included birth at less than 37 or more than 41 weeks' gestation, multiple birth, or maternal use of psychiatric medication during pregnancy. Exposures: PAE and PTE groups were determined by cluster analysis. Main Outcomes and Measures: Analyses of covariance were run on EEG spectral power at 12 scalp locations across the frequency spectrum from 1 to 45 Hz in 3-Hz bins by sleep state. Results: The final sample consisted of 1739 newborns (median [interquartile range] gestational age at birth, 39.29 [1.57] weeks; 886 [50.9%] were female; median [interquartile range] newborn age at assessment, 48.53 [44.96] hours). Newborns whose mothers were in the low continuous (95% CI, -0.379 to -0.031; P < .05; 95% CI, -0.379 to -0.045; P < .05), quit (95% CI, -0.419 to -0.127; P < .001; 95% CI, -0.398 to -0.106; P < .005), and moderate or high continuous (95% CI, -0.430 to -0.124; P < .001; 95% CI, -0.420 to -0.119; P < .005) PAE clusters had increased 4- to 6-Hz and 7- to 9-Hz left-temporal EEG power. Newborns with moderate or high continuous PTE had decreased 19- to 21-Hz (95% CI, 0.034 to 0.327; P < .05) and 22- to 24-Hz (95% CI, 0.022 to 0.316; P < .05) right-central EEG compared with newborns with no PTE. Newborns with moderate or high continuous PTE had significantly decreased 22- to 36-Hz right-central EEG power compared with the quit smoking group (22-24 Hz, 95% CI, 0.001 to 0.579; P < .05; 25-27 Hz, 95% CI, 0.008 to 0.586; P < .05; 28-30 Hz, 95% CI, 0.028 to 0.607; P < .05; 31-33 Hz, 95% CI, 0.038 to 0.617; P < .05; 34-36 Hz, 95% CI, 0.057 to 0.636; P < .05). Conclusions and Relevance: These findings suggest that even low levels of PAE or PTE are associated with changes in offspring brain development.

High prevalence of prenatal alcohol exposure detected by breathalyzer in the Republic of the Congo, Africa.

OBJECTIVE: Assess the prevalence of prenatal alcohol exposure in the Republic of the Congo by measuring breath alcohol concentration (BrAC) levels using a breathalyzer device. METHODS: Pregnant women were assessed for alcohol use with a breathalyzer reading during two prenatal visits and during labor and delivery. RESULTS: Among 662 pregnant women consented and screened with a breathalyzer, 192 (29.0%) had a positive BrAC during 1st trimester. During the second assessment, approximately 69% (132) of the 192 pregnant women had a second positive BrAC. A third assessment during labor and delivery identified 60 women (31%) with a third positive BrAC. About 19% (36) of the 192 pregnant women had positive BrACs at all three times. Among women who were positive on the first and second assessments, 30% had a BrAC that was above 0.07, which is almost equivalent of binge drinking (four or more standard drinks in about 2 h). The mean BrAC reading decreased as the pregnancy progressed. CONCLUSIONS: The results of this study utilizing a unique exposure detection methodology suggest that the use of BrAC may be a useful objective option to detect and quantify alcohol consumption during pregnancy. The prevalence of alcohol use identified during pregnancy in the Republic of the Congo was increased over 20% when compared to maternal reports from a previous study. Nearly one of every five women identified at the first prenatal visit continued drinking throughout pregnancy. Urgent measures are needed to reduce alcohol consumption among this population of pregnant women.

Concurrent prenatal drinking and smoking increases risk for SIDS: Safe Passage Study report.

BACKGROUND: Sudden infant death syndrome (SIDS) is the leading cause of postneonatal mortality. Although the rate has plateaued, any unexpected death of an infant is a family tragedy thus finding causes and contributors to risk remains a major public health concern. The primary objective of this investigation was to determine patterns of drinking and smoking during pregnancy that increase risk of SIDS. METHODS: The Safe Passage Study was a prospective, multi-center, observational study with 10,088 women, 11,892 pregnancies, and 12,029 fetuses, followed to 1-year post delivery. Subjects were from two sites in Cape Town, South Africa and five United States sites, including two American Indian Reservations. Group-based trajectory modeling was utilized to categorize patterns of drinking and smoking exposure during pregnancy. FINDINGS: One-year outcome was ascertained in 94·2% infants, with 28 SIDS (2·43/1000) and 38 known causes of death (3·30/1000). The increase in relative risk for SIDS, adjusted for key demographic and clinical characteristics, was 11·79 (98·3% CI: 2·59-53·7, p < 0·001) in infants whose mothers reported both prenatal drinking and smoking beyond the first trimester, 3.95 (98·3% CI: 0·44-35·83, p = 0·14), for drinking only beyond the first trimester and 4·86 (95% CI: 0·97-24·27, p = 0·02) for smoking only beyond the first trimester as compared to those unexposed or reported quitting early in pregnancy. INTERPRETATION: Infants prenatally exposed to both alcohol and cigarettes continuing beyond the first trimester have a substantially higher risk for SIDS compared to those unexposed, exposed to alcohol or cigarettes alone, or when mother reported quitting early in pregnancy. Given that prenatal drinking and smoking are modifiable risk factors, these results address a major global public health problem. FUNDING: National Institute on Alcohol Abuse and Alcoholism, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute on Deafness and Other Communication Disorders.

Prenatal Drinking in the Northern Plains: Differences Between American Indian and Caucasian Mothers.

INTRODUCTION: Prenatal alcohol exposure is associated with adverse pregnancy outcomes such as fetal alcohol spectrum disorders. The study characterizes the pattern and risk factors of alcohol use during pregnancy for American Indian and Caucasian mothers in the Northern Plains. METHODS: A general population of pregnant women was recruited from 5 sites, including 2,753 Caucasians and 2,124 American Indians (2006-2017). Alcohol consumption was based on self-report using a modified Timeline Followback interview, administered 3-4 times during pregnancy and 1 month postpartum. Risk for prenatal drinking was calculated using logistic regression models after controlling for demographics, reproductive history, prenatal care, mental health, and SES. The analysis was conducted in 2019. RESULTS: More Caucasian mothers consumed alcoholic beverages during pregnancy than American Indians (63% vs 52%), whereas more American Indian mothers were binge drinkers than Caucasians (41% vs 28%). American Indian mothers had a lower risk of drinking in the second and third trimesters and postpartum, but a higher risk of binge drinking in the first trimester compared with Caucasians. Frequent relocation increased the risk of prenatal alcohol use among American Indian mothers, whereas age, marriage, income, parity, and fertility treatment affected the risk of prenatal drinking among Caucasian mothers. CONCLUSIONS: Alcohol use was more prevalent among Caucasian mothers. Among those who consumed alcohol during pregnancy, American Indian mothers consumed larger quantities. Change of residence was found to be the sole risk factor for prenatal drinking among American Indian mothers, whereas different and multiple risk factors were found for Caucasian mothers.