Prevention of alcohol exposed pregnancies in Europe: the FAR SEAS guidelines.

INTRODUCTION: Drinking during pregnancy is the leading cause of birth defects and child developmental disorders in Europe. The adverse effects of drinking during pregnancy may include physical, behavioural and cognitive problems, known collectively as fetal alcohol spectrum disorders (FASD). Evidence-based comprehensive recommendations at the European level on how to implement preventive and treatment policies to reduce alcohol-exposed pregnancies are needed. FAR SEAS, a tendered service contract (number 20,187,106) awarded by the European Commission, aimed at developing guidelines to respond to this knowledge gap. METHODS: FAR SEAS recommendations were built on (1) a two-phase review of interventions, (2) an international expert consultation, and (3) a pilot study on prevention of FASD conducted in the Mazovia region of Poland. The review of interventions included nineteen electronic open access databases, several repositories of grey literature and a key informant consultation covering most European Union (EU) countries and an additional guidelines search. After triangulating sources, 94 records were collected. Experts contributed in the design of the research questions, addressing the gaps in the literature and reviewing the recommendations formulated. The Polish pilot added nuances from real world practice to the formulated recommendations, resulting in the final set of guidelines for dissemination. RESULTS: The FAR SEAS Guidelines comprise 23 recommendations grouped into different topics areas of policies, communication strategies, screening, brief intervention and referral to treatment, treatment and social services. The recommendations highlight the need to respect women's autonomy and avoid discrimination and stigmatization; using universal screening for women of childbearing age, including detection of other psychosocial risks (such as domestic violence); and individualized, comprehensive and multidisciplinary supportive interventions for those who require it, such as those with alcohol use disorders, including women's partners. Policies to prevent FASD should be multicomponent, and public health communication should combine information about the risks together with self-efficacy messages to promote changes. CONCLUSIONS: The FAR SEAS guidelines are a tool to support policy-makers and service managers in implementing effective programmes to reduce prenatal alcohol exposure among general and at-risk population groups. FASD prevention has to involve comprehensive and multi-level evidence-based policies and practice, with services and activities tailored to the needs of women at differing levels of risk, and with due attention to reducing stigma.

Exercise reduces physical alterations in a rat model of fetal alcohol spectrum disorders.

BACKGROUND: Prenatal alcohol exposure (PAE) has serious physical consequences for children such as behavioral disabilities, growth disorders, neuromuscular problems, impaired motor coordination, and decreased muscle tone. However, it is not known whether loss of muscle strength occurs, and which interventions will effectively mitigate physical PAE impairments. We aimed to investigate whether physical alteration persists during adolescence and whether exercise is an effective intervention. RESULTS: Using paradigms to evaluate different physical qualities, we described that early adolescent PAE animals have significant alterations in agility and strength, without alterations in balance and coordination compared to CTRL animals. We evaluated the effectiveness of 3 different exercise protocols for 4 weeks: Enrichment environment (EE), Endurance exercise (EEX), and Resistance exercise (REX). The enriched environment significantly improved the strength in the PAE group but not in the CTRL group whose strength parameters were maintained even during exercise. Resistance exercise showed the greatest benefits in gaining strength, and endurance exercise did not. CONCLUSION: PAE induced a significant decrease in strength compared to CTRL in PND21. Resistance exercise is the most effective to reverse the effects of PAE on muscular strength. Our data suggests that individualized, scheduled, and supervised training of resistance is more beneficial than endurance or enriched environment exercise for adolescents FASD.

Combining Physician Expertise and Women's Lived Experience to Educate Health Professionals about Preventing Fetal Alcohol Spectrum Disorders.

INTRODUCTION: Physician Champions from the American College of Obstetricians and Gynecologists (ACOG) and trained women Speakers from FASD United, who have given birth to a child with a fetal alcohol spectrum disorder (FASD), co-present to healthcare providers (HCPs) in medical residency programs as part of an educational intervention. They present FASDs as a biological and social problem surrounded by stigma that prevent pregnant women from talking openly to their HCPs about their alcohol use or alcohol use disorder (AUD) and getting the medical help they need. METHODS: Semi-structured interviews were conducted with 10 ACOG Champions and nine FASD United Speakers and a thematic analysis assessed how the co-presentations can enhance HCPs' understanding about FASDs and address stigma associated with alcohol use during pregnancy. RESULTS: Interview findings indicated that both Champions and Speakers emphasized the need for HCPs to be nonjudgmental and create a safe space for open dialogue. They reported that residents were moved by mothers' personal stories, wanted to understand AUD better, and asked about the type of help HCPs can offer women. DISCUSSION: Combining physicians' expertise with mothers' personal stories of lived experiences of FASDs directed at residents, who are more reflective and open at this phase of their careers, moved them from a fact-based to an empathy-based approach to learning that is critical to address the stigma surrounding women who may be using alcohol or struggling with an AUD during pregnancy. Collaboration between national organizations allowed this intervention to be widely implemented across the country.

Neural crest cells and fetal alcohol spectrum disorders: Mechanisms and potential targets for prevention.

Fetal alcohol spectrum disorders (FASD) are a group of preventable and nongenetic birth defects caused by prenatal alcohol exposure that can result in a range of cognitive, behavioral, emotional, and functioning deficits, as well as craniofacial dysmorphology and other congenital defects. During embryonic development, neural crest cells (NCCs) play a critical role in giving rise to many cell types in the developing embryos, including those in the peripheral nervous system and craniofacial structures. Ethanol exposure during this critical period can have detrimental effects on NCC induction, migration, differentiation, and survival, leading to a broad range of structural and functional abnormalities observed in individuals with FASD. This review article provides an overview of the current knowledge on the detrimental effects of ethanol on NCC induction, migration, differentiation, and survival. The article also examines the molecular mechanisms involved in ethanol-induced NCC dysfunction, such as oxidative stress, altered gene expression, apoptosis, epigenetic modifications, and other signaling pathways. Furthermore, the review highlights potential therapeutic strategies for preventing or mitigating the detrimental effects of ethanol on NCCs and reducing the risk of FASD. Overall, this article offers a comprehensive overview of the current understanding of the impact of ethanol on NCCs and its role in FASD, shedding light on potential avenues for future research and intervention.

Protecting the future child: Foetal alcohol spectrum disorder, easy rescue and the regulation of maternal behaviour.

This paper argues that social contexts of inequality are crucial to understanding the ethics of gestational harm and responsibility. Recent debates on gestational harm have largely ignored the social context of gestators, including contexts of inequality and injustice. This can reinforce existing social injustices arising from colonialism, socio-economic inequality and racism, for example, through increased regulation of maternal behaviour. To demonstrate this, I focus on the related notions of the 'future child' and an obligation of easy rescue, which have been used to discuss the ethics of gestational harm in the context of alcohol consumption during gestation and foetal alcohol spectrum disorder (FASD). I use a feminist perspective to evaluate these ideas and conclude that anyone concerned with remediation of social injustice has good reason to be suspicious of the notion of the future child in the context of gestational harm.

Neuroprotective Effects of Crocin Against Ethanol Neurotoxicity in the Animal Model of Fetal Alcohol Spectrum Disorders.

Several experimental and clinical findings suggest that ethanol consumption during pregnancy activates an oxidative-inflammatory cascade followed by wide apoptotic neurodegeneration within several brain areas, including the hippocampus. Crocin can protect neurons because of its antioxidant, anti-inflammatory, and antiapoptotic effects. This study evaluated the crocin protective impact on ethanol-related neuroinflammation and neuronal apoptosis in the hippocampus of rat pups exposed to alcohol over postnatal days. Ethanol (5.25 g/kg) was administrated in milk solution (27.8 ml/kg) by intragastric intubation 2-10 days after birth. The animals received crocin (15, 30, and 45 mg/kg) 2-10 days after birth. The hippocampus-dependent memory and spatial learning were evaluated 36 days after birth using the Morris water maze task. Further, the concentrations of TNF-α and antioxidant enzymes were determined using ELISA assay to examine the antioxidant and anti-inflammatory activities. Also, immunohistochemical staining was performed to evaluate the glial fibrillary acidic protein (GFAP), Ionized calcium binding adaptor molecule 1(Iba-1), and caspase-3 expression. The administration of crocin significantly attenuated spatial memory impairment (P < 0.01) after ethanol neurotoxicity. Also, crocin led to a significant enhancement in SOD (P < 0.05) and GSH-PX (P < 0.01), whereas it caused a reduction in the TNF-α and MDA concentrations compared to the ethanol group (P < 0.01). Moreover, the hippocampal level of caspase-3 (P < 0.01) and the number of GFAP and Iba-1-positive cells decreased in the crocin group (P < 0.001). Crocin suppresses apoptotic signaling mediated by the oxidative-inflammatory cascade in rat pups exposed to ethanol after birth.

Barriers and facilitators of alcohol abstinence during pregnancy.

Fetal Alcohol Spectrum Disorders (FASD) is a common and under-recognised health burden in South Africa. There is a limited understanding of why pregnant women drink in the South African context, particularly in rural settings, where the prevalence of FASD is highest. A purposive sample included eight women from a rural ante-natal clinic in the Northern Cape province of South Africa. Participants participated in a semi-structured interview. A process of thematic analysis was used to generate themes from the interviews. All participants were aware of the link between alcohol use during pregnancy and adverse fetal outcomes. Furthermore, most participants reduced drinking after pregnancy recognition. Participants described barriers and facilitators of alcohol abstinence. Barriers included social pressure, life stressors, and cravings and habits. Facilitators included the desire to avoid FASD, supportive relationships, availability of alternative activities. Addressing barriers at community and individual levels may aid women in reducing harmful drinking during pregnancy.

Preconception interventions to reduce the risk of alcohol-exposed pregnancies: A systematic review.

BACKGROUND: The preconception period provides a unique opportunity to optimize the health of women and children. High rates of alcohol use and unintended pregnancies are common across many Western societies, and alcohol-exposed pregnancies (AEPs) are a possible unintended outcome. The aim of the current study was to evaluate preconception interventions for the prevention of AEPs. METHODS: A systematic search of four electronic databases (PubMed, Embase, CINAHL, and PsycINFO) was undertaken for relevant peer-reviewed articles published from 1970 onward. Studies were included if they enrolled women and/or their support networks during the preconception period. RESULTS: Nineteen studies met the inclusion criteria. The majority of studies (n = 14) evaluated CHOICES-based interventions, which incorporate motivational interviewing approaches to change alcohol and/or contraceptive behavior. The other five interventions included a range of different approaches and modes of delivery. The majority of interventions were successful in reducing AEP risk. Changes in AEP risk were more often driven by changes in contraceptive behavior, although some approaches led to changes in both alcohol and contraceptive behavior. CONCLUSIONS: The review indicated that many interventions were efficacious at reducing AEP risk during the preconception period through preventing unplanned pregnancy. The effectiveness estimated from these clinical trials may be greater than that seen in interventions when implemented in practice where there is a lack of blinding and greater attrition of participants during follow-up. Further research investigating the real-world effectiveness of these intervention approaches implemented across a wide range of clinical settings would be beneficial.

Glutathione Protects the Developing Heart from Defects and Global DNA Hypomethylation Induced by Prenatal Alcohol Exposure.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is caused by prenatal alcohol exposure (PAE), the intake of ethanol (C2 H5 OH) during pregnancy. Features of FASD cover a range of structural and functional defects including congenital heart defects (CHDs). Folic acid and choline, contributors of methyl groups to one-carbon metabolism (OCM), prevent CHDs in humans. Using our avian model of FASD, we have previously reported that betaine, another methyl donor downstream of choline, prevents CHDs. The CHD preventions are substantial but incomplete. Ethanol causes oxidative stress as well as depleting methyl groups for OCM to support DNA methylation and other epigenetic alterations. To identify more compounds that can safely and effectively prevent CHDs and other effects of PAE, we tested glutathione (GSH), a compound that regulates OCM and is known as a "master antioxidant." METHODS/RESULTS: Quail embryos injected with a single dose of ethanol at gastrulation exhibited congenital defects including CHDs similar to those identified in FASD individuals. GSH injected simultaneously with ethanol not only prevented CHDs, but also improved survival and prevented other PAE-induced defects. Assays of hearts at 8 days (HH stage 34) of quail development, when the heart normally has developed 4-chambers, showed that this single dose of PAE reduced global DNA methylation. GSH supplementation concurrent with PAE normalized global DNA methylation levels. The same assays performed on quail hearts at 3 days (HH stage 19-20) of development, showed no difference in global DNA methylation between controls, ethanol-treated, GSH alone, and GSH plus ethanol-treated cohorts. CONCLUSIONS: GSH supplementation shows promise to inhibit effects of PAE by improving survival, reducing the incidence of morphological defects including CHDs, and preventing global hypomethylation of DNA in heart tissues.

Where there's a will, there's a way? Strategies to reduce or abstain from alcohol use developed by Northern Plains American Indian women participating in a brief, alcohol-exposed pregnancy preconceptual intervention.

BACKGROUND: Alcohol-exposed pregnancy (AEP) is an ongoing concern, especially within low-resource, high-risk areas such as rural American Indian/Alaska Native (AIAN) communities. Brief, preconceptual AEP-reduction interventions are popular in such areas but have a small impact on alcohol use. Developing a strategic alcohol change plan is a key program component; however, there is little research on strategy selection, especially within contexts that positively or negatively impact selection (e.g., cultural strengths, trauma, collective efficacy within AIAN communities). This study qualitatively analyzed strategies chosen to reduce alcohol use by AIAN women participating in a culturally tailored, brief, preconceptual AEP-reduction intervention. METHODS: One hundred-sixty Northern Plains AIAN women who were participating in a brief AEP-reduction program developed a plan to accomplish an alcohol reduction/abstention goal at the first and last program sessions. The plan included choosing 1 or more strategies to (1) achieve the goal, (2) mitigate barriers, and (3) use cultural strengths. Qualitative analysis of the data involved thematic open and structured coding of all 3 strategies separately. We also examined how many different themes (different individual strategies) participants reported for each strategy component. RESULTS: Most participants reported only 1 strategy (theme) for each of the 3 components. Common goal-achieving and barrier-mitigation strategies included positive social supports and avoiding negative or alcohol-involved social environments. Other strategies involved circular logic (e.g., the strategy to reduce drinking was to drink less). Both traditional and western cultural strengths were reported as important resources, although many participants had no cultural resource strategy. CONCLUSION: Programs aimed at reducing AEPs may need to provide participants more support to develop strong strategies to reduce alcohol use when implemented within areas with high levels of trauma and contextual barriers that can impact strategy selection. Such support could include ways to improve health on both interpersonal and community levels.

Prenatal choline supplementation during mouse pregnancy has differential effects in alcohol-exposed fetal organs.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) are preventable adverse outcomes consequent to prenatal alcohol exposure. Supplemental choline confers neuroprotection to the alcohol-exposed offspring, but its actions outside the brain are unclear. We previously reported that prenatal exposure of mice to 4.5 g/kg of alcohol decreased placental weight in females only, but decreased body weight and liver-to-body weight ratio and increased brain-to-body weight ratio in both sexes. Here we test the hypotheses that a lower alcohol dose will elicit similar outcomes, and that concurrent choline treatment will mitigate these outcomes. METHODS: Pregnant C57BL/6J mice were gavaged with alcohol (3 g/kg; Alc) or maltodextrin (MD) from embryonic day (E) 8.5-17.5. Some also received a subcutaneous injection of 100 mg/kg choline chloride (Alc + Cho, MD + Cho). Outcomes were evaluated on E17.5. RESULTS: Alc dams had lower gestational weight gain than MD; this was normalized by choline. In males, Alc decreased placental weight whereas choline increased placental efficiency, and Alc + Cho (vs. MD) tended to further reduce placental weight and increase efficiency. Despite no significant alcohol effects on these measures, choline increased fetal body weight but not brain weight, thus reducing brain-to-body weight ratio in both sexes. This ratio was also lower in the Alc + Cho (vs. MD) fetuses. Alc reduced liver weight and the liver-to-body weight ratio; choline did not improve these. Placental weight and efficiency correlated with litter size, whereas placental efficiency correlated with fetal morphometric measurements. CONCLUSIONS: Choline prevents an alcohol-induced reduction in gestational weight gain and fetal body weight and corrects fetal brain sparing, consistent with clinical findings of improvements in alcohol-exposed children born to mothers receiving choline supplementation. Importantly, we show that choline enhances placental efficiency in the alcohol-exposed offspring but does not normalize fetal liver growth. Our findings support choline supplementation during pregnancy to mitigate the severity of FASD and emphasize the need to examine choline's actions in different organ systems.

Perspectives of Canadian Health Care Providers on Fetal Alcohol Spectrum Disorder: Has Anything Changed in 15 years? A Brief Report.

Initiatives have been implemented to provide training to health care providers (HCPs) on the adverse health outcomes associated with alcohol use during pregnancy, including the risk of fetal alcohol spectrum disorder (FASD). The purpose of this exploratory study was to compare two cross-sectional data sets of HCP perspectives over 15 years. In 2002 and 2017, two samples of HCPs received a survey on FASD. The findings from these surveys may inform the development of ongoing educational initiatives to help HCPs with screening for alcohol use during pregnancy and early diagnosis and prevention of FASD.

An indigenous framework of the cycle of fetal alcohol spectrum disorder risk and prevention across the generations: historical trauma, harm and healing.

Objective: To build on Evans-Campbell's [2008. "Historical Trauma in American Indian/Native Alaska Communities: A Multilevel Framework for Exploring Impacts on Individuals, Families, and Communities." Journal of Interpersonal Violence 23 (3): 316-338. doi:10.1177/0886260507312290.] multilevel framework of historical trauma and health by focusing on the cycle of fetal alcohol spectrum disorders (FASD) in the socio-cultural, historical, and interpersonal context of trauma shared by American Indian and Alaska Native (AI/AN) peoples.Methods: We analyzed qualitative data from focus groups with seventy four urban AI/ANs who were 15 years of age and older. Community-based participatory research methods were used for data collection and analysis. Our study explored knowledge and attitudes about FASD, perspectives on FASD risk factors, and culturally relevant approaches to FASD prevention and healthcare.Results: According to our study's participants, efforts to address FASD among urban AI/ANs should align with and emerge from community values, promote healing, consider the broader context that influences behaviors, and reflect the community's understanding that FASD risk behaviors are inextricably linked with historical and contemporary trauma.Conclusion: Effective, multiple-level FASD prevention approaches for AI/ANs may include prioritizing Indigenous culture, supporting intergenerational cohesion, focusing on non-stigmatic healing of traumas, and authentically engaging community knowledge. This work draws on community and cultural strengths in an effort to reduce the occurrence of substance-exposed pregnancies, and encourages transformational changes in systems that serve AI/AN peoples to promote a healthy and thriving community and future generations.

Aversive Learning Deficits and Depressive-Like Behaviors Are Accompanied by an Increase in Oxidative Stress in a Rat Model of Fetal Alcohol Spectrum Disorders: The Protective Effect of Rapamycin.

Fetal alcohol spectrum disorders (FASDs) are one of the most common consequences of ethanol exposure during pregnancy. In adulthood, these disorders can be manifested by learning and memory deficits and depressive-like behavior. Ethanol-induced oxidative stress may be one of the factors that induces FASD development. The mammalian target of the Rapamycin (mTOR) signaling pathway that acts via two distinct multiprotein complexes, mTORC1 and mTORC2, can affect oxidative stress. We investigated whether mTOR-dependent or mTOR-independent mechanisms are engaged in this phenomenon. Thus, Rapamycin-a selective inhibitor of mTORC1, Torin-2-a non-selective mTORC1/mTORC2 inhibitor, and FK-506-a drug that impacts oxidative stress in an mTOR-independent manner were used. Behavioral tests were performed in adult (PND60-65) rats using a passive avoidance (PA) task (aversive learning and memory) and forced swimming test (FST) (depressive-like behaviors). In addition, the biochemical parameters of oxidative stress, such as lipid peroxidation (LPO), as well as apurinic/apyrimidinic (AP)-sites were determined in the hippocampus and prefrontal cortex in adult (PND65) rats. The rat FASD model was induced by intragastric ethanol (5 g/kg/day) administration at postnatal day (PND)4-9 (an equivalent to the third trimester of human pregnancy). All substances (3 mg/kg) were given 30 min before ethanol. Our results show that neonatal ethanol exposure leads to deficits in context-dependent fear learning and depressive-like behavior in adult rats that were associated with increased oxidative stress parameters in the hippocampus and prefrontal cortex. Because these effects were completely reversed by Rapamycin, an mTORC1 inhibitor, this outcome suggests its usefulness as a preventive therapy in disorders connected with prenatal ethanol exposure.

[Fetal alcohol spectrum disorders-diagnosis, prognosis, and prevention]. / Fetale Alkoholspektrumstörungen ­ Diagnose, Prognose und Prävention.

Fetal alcohol spectrum disorder is one of the most common chronic diseases at birth. It is very often not or falsely diagnosed. This leads to inadequate, ineffective care and treatment of the affected children as well as to insufficient support of their families. The result is not only a high rate of secondary disorders, but it also leads to fewer opportunities for secondary and tertiary prevention for each child and family. With the right diagnosis these opportunities are guaranteed. The primary prevention in the field of alcohol consumption during pregnancy and fetal alcohol spectrum disorder should be planned and performed by the medical and political partners in a structured interdisciplinary and scientifically based way. Besides health promotion and education of the general population, the knowledge transfer to doctors and other medical, psychological, and pedagogical professionals is of particular relevance.

A brief overview of fetal alcohol syndrome for health professionals.

Fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders (FASDs) are caused by prenatal alcohol exposure (PAE). They cause epigenetic changes, permanent neurodevelopmental deficits, and anomalies in growth and facial structure. This article enforces the need for health and social care professionals to have a greater understanding and awareness of how FAS and FASD may impact on the individual, the family and the community, to enable them to provide the most effective preventive and supportive care possible.

Prevention of Alcohol-Exposed Pregnancies and Fetal Alcohol Spectrum Disorder Among Pregnant and Postpartum Women: A Systematic Review.

BACKGROUND: Prenatal alcohol exposure can result in a wide range of adverse health outcomes, including in some cases fetal alcohol spectrum disorder (FASD), a lifelong neurodevelopmental disorder. Thus, there is pressing need for effective interventions to prevent alcohol-exposed pregnancies (AEPs). METHODS: A systematic review was undertaken to provide an up-to-date analysis of the current prevention literature. PubMed, Embase, CINAHL, and PsycINFO were searched for relevant English-language articles published from 1970 onward. Studies were eligible for the current systematic review if the interventions included pregnant and postpartum women and/or their support networks to prevent AEPs and FASD. Outcomes of interest included alcohol consumption, knowledge, contraceptive use, neonatal outcomes, family well-being or functioning, economics, and healthcare utilization outcomes. RESULTS: Thirty-four peer-reviewed studies met the inclusion criteria. Fifteen studies employed brief intervention (BI) methods, 6 used long-term/intensive strategies, and 5 were educational interventions. A further 3 studies assessed counseling approaches, 2 evaluated multicomponent interventions, and 3 assessed nutritional supplementation interventions. CONCLUSIONS: The current review identified variable results from available interventions to prevent alcohol use among pregnant and postpartum women. Preliminary evidence demonstrated that BIs may be effective among subgroups of pregnant women with higher initial alcohol consumption, those with partner involvement, and those who used alcohol and other substances concurrently. Some preliminary evidence relating to long-term interventions with pregnant women with polysubstance use emerged, specifically case management that not only focused on reduction in substance use, but also on addressing the complex interplay between health and social well-being of families. Overall, additional research is required to improve the effectiveness of preventative approaches during pregnancy and the postpartum period.

Hippocampus-dependent memory and allele-specific gene expression in adult offspring of alcohol-consuming dams after neonatal treatment with thyroxin or metformin.

Fetal alcohol spectrum disorder (FASD), the result of fetal alcohol exposure (FAE), affects 2-11% of children worldwide, with no effective treatments. Hippocampus-based learning and memory deficits are key symptoms of FASD. Our previous studies show hypothyroxinemia and hyperglycemia of the alcohol-consuming pregnant rat, which likely affects fetal neurodevelopment. We administered vehicle, thyroxine (T4) or metformin to neonatal rats post FAE and rats were tested in the hippocampus-dependent contextual fear-conditioning paradigm in adulthood. Both T4 and metformin alleviated contextual fear memory deficit induced by FAE, and reversed the hippocampal expression changes in the thyroid hormone-inactivating enzyme, deiodinase-III (Dio3) and insulin-like growth factor 2 (Igf2), genes that are known to modulate memory processes. Neonatal T4 restored maternal allelic expressions of the imprinted Dio3 and Igf2 in the adult male hippocampus, while metformin restored FAE-caused changes in Igf2 expression only. The decreased hippocampal expression of DNA methyltransferase 1 (Dnmt1) that maintains the imprinting of Dio3 and Igf2 during development was normalized by both treatments. Administering Dnmt1 inhibitor to control neonates resulted in FAE-like deficits in fear memory and hippocampal allele-specific expression of Igf2, which were reversed by metformin. We propose that neonatal administration of T4 and metformin post FAE affect memory via elevating Dnmt1 and consequently normalizing hippocampal Dio3 and Igf2 expressions in the adult offspring. The present results indicate that T4 and metformin, administered during the neonatal period that is equivalent to the third trimester of human pregnancy, are potential treatments for FASD and conceivably for other neurodevelopmental disorders with cognitive deficits.

Persistent Changes in Stress-Regulatory Genes in Pregnant Women or Children Exposed Prenatally to Alcohol.

BACKGROUND: We have recently shown that binge or heavy levels of alcohol drinking increase deoxyribonucleic acid (DNA) methylation and reduce gene expression of proopiomelanocortin (POMC) and period 2 (PER2) in adult human subjects (Gangisetty et al., Alcohol Clin Exp Res, 43, 2019, 212). One hypothesis would be that methylation of these 2 genes is consistently associated with alcohol exposure and could be used as biomarkers to predict risk of prenatal alcohol exposure (PAE). Results of the present study provided some support for this hypothesis. METHODS: We conducted a series of studies to determine DNA methylation changes in stress regulatory genes proopiomelanocortin (POMC) and period 2 (PER2) using biological samples from 3 separate cohorts of patients: (i) pregnant women who consumed moderate-to-high levels of alcohol or low/unexposed controls, (ii) children with PAE and non-alcohol-exposed controls, and (iii) children with PAE treated with or without choline. RESULTS: We found pregnant women who consumed moderate-to-high levels of alcohol and gave birth to PAE children had higher DNA methylation of POMC and PER2. PAE children also had increased methylation of POMC and PER2. The differences in the gene methylation of PER2 and POMC between PAE and controls did not differ by maternal smoking status. PAE children had increased levels of stress hormone cortisol and adrenocorticotropic hormone. Choline supplementation reduced DNA hypermethylation and increased expression of POMC and PER2 in children with PAE. CONCLUSIONS: These data suggest that PAE significantly elevates DNA methylation of POMC and PER2 and increases levels of stress hormones. Furthermore, these results suggest the possibility that measuring DNA methylation levels of PER2 and POMC in biological samples from pregnant women or from children may be useful for identification of a woman or a child with PAE.

The conversation matters: a qualitative study exploring the implementation of alcohol screening and brief interventions in antenatal care in Scotland.

BACKGROUND: Alcohol screening and brief intervention (SBI) in antenatal care is internationally recommended to prevent harm caused by alcohol exposure during pregnancy. There is, however, limited understanding of how SBI is implemented within antenatal care; particularly the approach taken by midwives. This study aimed to explore the implementation of a national antenatal SBI programme in Scotland. METHODS: Qualitative interviews were conducted with antenatal SBI implementation leaders (N = 8) in eight Scottish health boards. Interviews were analysed thematically and using the 'practical, robust implementation and sustainability model' (PRISM) to understand differences in implementation across health boards and perceived setting-specific barriers and challenges. RESULTS: In several health boards, where reported maternal alcohol use was lower than expected, implementation leaders sought to optimize enquires about women's alcohol use to facilitate honest disclosure. Strategies focused on having positive conversations, exploring pre-pregnancy drinking habits, and building a trusting relationship between pregnant women and midwives. Women's responses were encouraging and disclosure rates appeared improved, though with some unexpected variation over time. Adapting the intervention to the local context was also considered important. CONCLUSIONS: This is the first study to explore implementation leaders' experiences of antenatal SBI delivery and identify possible changes in disclosure rates arising from the approach taken. In contrast with current antenatal alcohol screening recommendations, a conversational approach was advocated to enhance the accuracy and honesty of reporting. This may enable provision of support to more women to prevent Fetal Alcohol Spectrum Disorders (FASD) and will therefore be of international interest.