To systematically review and critically evaluate studies reporting alcohol exposure during pregnancy and miscarriage. We searched PubMed, EMBASE, PsycINFO, and ProQuest Theses for publications from January 1970 to January 2019. We identified studies about alcohol exposure during pregnancy and miscarriage. Information about study population, alcohol exposure assessment, outcome definition, covariates, and measures of association was collected. We assessed study quality using an adapted Newcastle-Ottawa Scale. Data were abstracted by 2 investigators independently. We conducted a random-effects meta-analysis to calculate the association between alcohol exposure and miscarriage risk and performed subgroup analyses to determine robustness of results to study differences. For studies reporting dose-specific effects, a pooled dose-response association was estimated using generalized least squares regression with and without restricted cubic spline terms for number of drinks consumed per week. Of 2,164 articles identified, 24 were eligible for inclusion. Meta-analysis of data from 231,808 pregnant women finds those exposed to alcohol during pregnancy have a greater risk of miscarriage compared to those who abstained (odds ratio [OR] 1.19, 95% confidence intervals [CI] 1.12, 1.28). Estimates did not vary by study design, study country, or method of alcohol ascertainment. For alcohol use of 5 or fewer drinks per week, each additional drink per week was associated with a 6% increase in miscarriage risk (OR 1.06, 95% CI 1.01, 1.10). Common study limitations reflect challenges inherent to this research, including difficulty recruiting participants early enough in pregnancy to observe miscarriage and collecting and quantifying information about alcohol consumption during pregnancy that accurately reflects use. This review provides evidence that alcohol consumption during pregnancy is associated with a dose-mediated increase in miscarriage risk. Future studies evaluating change in alcohol use in pregnancy are needed to provide insight into how alcohol consumption prior to pregnancy recognition impacts risk.

HighlightsWe develop an automated counter-balanced Go/NoGo judgement bias task for rodents.Rats learn Go-for-reward/NoGo-to-avoid-punishment but not the reverse contingency.Mice do exactly the opposite; species may differ in Pavlovian control of decisions.Foraging, predator avoidance, and baseline activity may influence Pavlovian control.Both species show the predicted generalisation of responses in ambiguity tests.

Uterine fibroids affect up to 77% of women by menopause and account for up to $34 billion in healthcare costs each year. Although fibroid risk is heritable, genetic risk for fibroids is not well understood. We conducted a two-stage case-control meta-analysis of genetic variants in European and African ancestry women with and without fibroids classified by a previously published algorithm requiring pelvic imaging or confirmed diagnosis. Women from seven electronic Medical Records and Genomics (eMERGE) network sites (3,704 imaging-confirmed cases and 5,591 imaging-confirmed controls) and women of African and European ancestry from UK Biobank (UKB, 5,772 cases and 61,457 controls) were included in the discovery genome-wide association study (GWAS) meta-analysis. Variants showing evidence of association in Stage I GWAS ( P < 1 × 10 -5 ) were targeted in an independent replication sample of African and European ancestry individuals from the UKB (Stage II) (12,358 cases and 138,477 controls). Logistic regression models were fit with genetic markers imputed to a 1000 Genomes reference and adjusted for principal components for each race- and site-specific dataset, followed by fixed-effects meta-analysis. Final analysis with 21,804 cases and 205,525 controls identified 326 genome-wide significant variants in 11 loci, with three novel loci at chromosome 1q24 (sentinel-SNP rs14361789; P = 4.7 × 10 -8 ), chromosome 16q12.1 (sentinel-SNP rs4785384; P = 1.5 × 10 -9 ) and chromosome 20q13.1 (sentinel-SNP rs6094982; P = 2.6 × 10 -8 ). Our statistically significant findings further support previously reported loci including SNPs near WT1, TNRC6B, SYNE1, BET1L , and CDC42 / WNT4 . We report evidence of ancestry-specific findings for sentinel-SNP rs10917151 in the CDC42 / WNT4 locus ( P = 1.76 × 10 -24 ). Ancestry-specific effect-estimates for rs10917151 were in opposite directions (P-Het-between-groups = 0.04) for predominantly African (OR = 0.84) and predominantly European women (OR = 1.16). Genetically-predicted gene expression of several genes including LUZP1 in vagina ( P = 4.6 × 10 -8 ), OBFC1 in esophageal mucosa ( P = 8.7 × 10 -8 ), NUDT13 in multiple tissues including subcutaneous adipose tissue ( P = 3.3 × 10 -6 ), and HEATR3 in skeletal muscle tissue ( P = 5.8 × 10 -6 ) were associated with fibroids. The finding for HEATR3 was supported by SNP-based summary Mendelian randomization an...

Scientific methods for assessing animal affect, especially affective valence (positivity or negativity), allow us to evaluate animal welfare and the effectiveness of 3Rs Refinements designed to improve wellbeing. Judgement bias tasks measure valence; however, task-training may be lengthy and/or require significant time from researchers. Here we develop an automated and self-initiated judgement bias task for rats which capitalises on their natural investigative behaviour. Rats insert their noses into a food trough to start trials. They then hear a tone and learn either to stay for 2 s to receive a food reward or to withdraw promptly to avoid an air-puff. Which contingency applies is signalled by two different tones. Judgement bias is measured by responses to intermediate ambiguous tones. In two experiments we show that rats learn the task in fewer sessions than other automated variants, generalise responses across ambiguous tones as expected, self-initiate 4–5 trials/min, and can be tested repeatedly. Affect manipulations generate main effect trends in the predicted directions, although not localised to ambiguous tones, so further construct validation is required. We also find that tone-reinforcer pairings and reinforcement or non-reinforcement of ambiguous trials can affect responses to ambiguity. This translatable task should facilitate more widespread uptake of judgement bias testing.

PURPOSE Data about maternal recall accuracy for classifying early pregnancy medication exposure is meager. Nonetheless, studies often rely on recall to evaluate potential impact of pharmaceuticals on the developing fetus. METHODS Right from the Start is a community-based pregnancy cohort that enrolled women from North Carolina, Tennessee, and Texas. A subset of 318 women participated in daily medication diaries initiated prior to conception (2006-2012). We examined nonsteroidal anti-inflammatory drugs (NSAIDs) as an example of a drug type that is difficult to study due to its intermittent and primarily over-the-counter use as well as its incomplete documentation in medical and pharmaceutical records. Selective serotonin reuptake inhibitor (SSRI) were assessed as a prescription medication comparator. Maternal recall of NSAID and SSRI use in early pregnancy was examined by comparing diary data (gold standard) to first trimester interview. RESULTS Sensitivity and specificity for recall of NSAID exposure were 78.6% and 62.3%, respectively (kappa statistic: 0.41), with 72.3% agreement for exposure classification. Sensitivity and specificity for recall of SSRI exposure were 77.8% and 99.0%, respectively (kappa statistic: 0.79), with 97.8% agreement. CONCLUSIONS Our findings suggest the validity of maternal recall varies with medication type and prospective data collection should be prioritized when studying early pregnancy drug exposures.