Influence of a small fraction of individuals with enhanced mutations on a population genetic pool

Computer simulations of the Penna ageing model suggest that already a small fraction of births with enhanced number of new mutations can negatively influence the whole population.Comment: 10 pages including 6 figures; draf

Impact of sample collection participation on the validity of estimated measures of association in the National Birth Defects Prevention Study when assessing gene-environment interactions

To better understand the impact that nonresponse for specimen collection has on the validity of estimates of association, we examined associations between self-reported maternal periconceptional smoking, folic acid use, or pregestational diabetes mellitus and six birth defects among families who did and did not submit buccal cell samples for DNA following a telephone interview as part of the National Birth Defects Prevention Study (NBDPS). Analyses included control families with live born infants who had no birth defects (N = 9,465), families of infants with anorectal atresia or stenosis (N = 873), limb reduction defects (N = 1,037), gastroschisis (N = 1,090), neural tube defects (N = 1,764), orofacial clefts (N = 3,836), or septal heart defects (N = 4,157). Estimated dates of delivery were between 1997 and 2009. For each exposure and birth defect, odds ratios and 95% confidence intervals were calculated using logistic regression stratified by race-ethnicity and sample collection status. Tests for interaction were applied to identify potential differences between estimated measures of association based on sample collection status. Significant differences in estimated measures of association were observed in only four of 48 analyses with sufficient sample sizes. Despite lower than desired participation rates in buccal cell sample collection, this validation provides some reassurance that the estimates obtained for sample collectors and noncollectors are comparable. These findings support the validity of observed associations in gene-environment interaction studies for the selected exposures and birth defects among NBDPS participants who submitted DNA samples

Birth defect and risk factor surveillance in the northern and southwestern Netherlands

Objective: To survey the associations between several risk factors and birth defects, in order to detect potential new teratogens.Methods: Data of the two Dutch European Registration of Congenital Anomalies (EUROCAT) registries collected before January 1, 1998 were used to perform X2 tests for a large number of risk factors and birth defects. Defects caused by chromosomal or monogenic disorders were analyzed separately.Results: Cross- tabulations of 80 groups of birth defects with 303 risk factors were studied. Of these, 126 combinations had a p value under 0.05, and 34 had a p value under 0.001. Of these 34 associations, some are known in the literature, some were found before in the same databases and some were new associations.Conclusions: This is a good method for generating new hypotheses for associations between risk factors and birth defects. It can be a start for new, more in-depth studies of potential teratogens. Copyright (C) 2000 S. Karger AG, Basel.</p

Variation and ethnic inequalities in treatment of common mental disorders before, during and after pregnancy : combined analysis of routine and research data in the Born in Bradford cohort

BACKGROUND: Common mental disorders (CMD) such as anxiety and depression during the maternal period can cause significant morbidity to the mother in addition to disrupting biological, attachment and parenting processes that affect child development. Pharmacological treatment is a first-line option for moderate to severe episodes. Many women prescribed pharmacological treatments cease them during pregnancy but it is unclear to what extent non-pharmacological options are offered as replacement. There are also concerns that treatments offered may not be proportionate to need in minority ethnic groups, but few data exist on treatment disparities in the maternal period. We examined these questions in a multi-ethnic cohort of women with CMD living in Bradford, England before, during and up to one year after pregnancy. METHODS: We searched the primary care records of women enrolled in the Born in Bradford cohort for diagnoses, symptoms, signs ('identification'), referrals for treatment, non-pharmacological and pharmacological treatment and monitoring ('treatment') related to CMD. Records were linked with maternity data to classify women identified with a CMD as treated prior to, and one year after, delivery. We examined rates and types of treatment during pregnancy, and analysed potential ethnic group differences using adjusted Poisson and multinomial logistic regression models. RESULTS: We analysed data on 2,234 women with indicators of CMD. Most women were discontinued from pharmacological treatment early in pregnancy, but this was accompanied by recorded access to non-drug treatments in only 15 % at the time of delivery. Fewer minority ethnic women accessed treatments compared to White British women despite minority ethnic women being 55-70 % more likely than White British women to have been identified with anxiety in their medical record. CONCLUSIONS: Very few women who discontinued pharmacological treatment early in their pregnancy were offered other non-pharmacological treatments as replacement, and most appeared to complete their pregnancy untreated. Further investigation is warranted to replicate the finding that minority ethnic women are more likely to be identified as being anxious or having anxiety and understand what causes the variation in access to treatments

Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in Pregnancy and Congenital Anomalies: Analysis of Linked Databases in Wales, Norway and Funen, Denmark

Background: Hypothesised associations between in utero exposure to selective serotonin reuptake inhibitors (SSRIs) and congenital anomalies, particularly congenital heart defects (CHD), remain controversial. We investigated the putative teratogenicity of SSRI prescription in the 91 days either side of first day of last menstrual period (LMP). Methods and Findings: Three population-based EUROCAT congenital anomaly registries- Norway (2004–2010), Wales (2000–2010) and Funen, Denmark (2000–2010)—were linked to the electronic healthcare databases holding prospectively collected prescription information for all pregnancies in the timeframes available. We included 519,117 deliveries, including foetuses terminated for congenital anomalies, with data covering pregnancy and the preceding quarter, including 462,641 with data covering pregnancy and one year either side. For SSRI exposures 91 days either side of LMP, separately and together, odds ratios with 95% confidence intervals (ORs, 95%CI) for all major anomalies were estimated. We also explored: pausing or discontinuing SSRIs preconception, confounding, high dose regimens, and, in Wales, diagnosis of depression. Results were combined in meta-analyses. SSRI prescription 91 days either side of LMP was associated with increased prevalence of severe congenital heart defects (CHD) (as defined by EUROCAT guide 1.3, 2005) (34/12,962 [0.26%] vs. 865/506,155 [0.17%] OR 1.50, 1.06–2.11), and the composite adverse outcome of 'anomaly or stillbirth' (473/12962, 3.65% vs. 15829/506,155, 3.13%, OR 1.13, 1.03–1.24). The increased prevalence of all major anomalies combined did not reach statistical significance (3.09% [400/12,962] vs. 2.67% [13,536/506,155] OR 1.09, 0.99–1.21). Adjusting for socio-economic status left ORs largely unchanged. The prevalence of anomalies and severe CHD was reduced when SSRI prescriptions were stopped or paused preconception, and increased when >1 prescription was recorded, but differences were not statistically significant. The dose-response relationship between severe CHD and SSRI dose (meta-regression OR 1.49, 1.12–1.97) was consistent with SSRI-exposure related risk. Analyses in Wales suggested no associations between anomalies and diagnosed depression. Conclusion: The additional absolute risk of teratogenesis associated with SSRIs, if causal, is small. However, the high prevalence of SSRI use augments its public health importance, justifying modifications to preconception care