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

Barriers to the effective treatment and prevention of malaria in Africa: A systematic review of qualitative studies

<p>Abstract</p> <p>Background</p> <p>In Africa, an estimated 300-500 million cases of malaria occur each year resulting in approximately 1 million deaths. More than 90% of these are in children under 5 years of age. To identify commonly held beliefs about malaria that might present barriers to its successful treatment and prevention, we conducted a systematic review of qualitative studies examining beliefs and practices concerning malaria in sub-Saharan African countries.</p> <p>Methods</p> <p>We searched Medline and Scopus (1966-2009) and identified 39 studies that employed qualitative methods (focus groups and interviews) to examine the knowledge, attitudes, and practices of people living in African countries where malaria is endemic. Data were extracted relating to study characteristics, and themes pertaining to barriers to malaria treatment and prevention.</p> <p>Results</p> <p>The majority of studies were conducted in rural areas, and focused mostly or entirely on children. Major barriers to prevention reported included a lack of understanding of the cause and transmission of malaria (29/39), the belief that malaria cannot be prevented (7/39), and the use of ineffective prevention measures (12/39). Thirty-seven of 39 articles identified barriers to malaria treatment, including concerns about the safety and efficacy of conventional medicines (15/39), logistical obstacles, and reliance on traditional remedies. Specific barriers to the treatment of childhood malaria identified included the belief that a child with convulsions could die if given an injection or taken to hospital (10/39).</p> <p>Conclusion</p> <p>These findings suggest that large-scale malaria prevention and treatment programs must account for the social and cultural contexts in which they are deployed. Further quantitative research should be undertaken to more precisely measure the impact of the themes uncovered by this exploratory analysis.</p

Maternal fluoxetine infusion does not alter fetal endocrine and biophysical circadian rhythms in pregnant sheep

ObjectiveDepression during pregnancy is frequently treated with the selective serotonin reuptake inhibitor (SSRI), fluoxetine (FX), commonly known as Prozac (Eli Lilly & Co, Indianapolis, IN). FX potentiates serotoninergic neurotransmission and serotonin has been implicated in the regulation of circadian rhythms. We have therefore investigated the effect of chronic administration of FX on maternal and fetal circadian rhythms in sheep.MethodsFollowing an initial bolus dose of 70 mg FX, an 8-day continuous infusion of FX (n = 11, 98.5 microg/kg x d) was performed. Controls (n = 13) were treated with sterile water vehicle only. Maternal and fetal plasma melatonin and prolactin concentrations were determined every 3 hours for 24 hours and then every 6 hours for 24 hours beginning on the fourth day of infusion.ResultsFX treatment did not alter either the basal or circadian rhythms of either maternal or fetal plasma melatonin and prolactin concentrations. Fetal cardiovascular and behavioral state parameters were measured continuously. While the incidence of low-voltage (LV) electrocortical (ECOG) activity was significantly reduced in fetuses in the FX group, there was no effect of FX on the diurnal rhythms in fetal arterial pressure, heart rate, breathing movements, or behavioral state.ConclusionThese results show that maternal FX treatment does not result in significant alterations in maternal and fetal hormonal and behavioral circadian rhythms.Janna L. Morrison, Dan W. Rurak, Caly Chien, David J. Kennaway, Nancy Gruber, I. Caroline McMillen, and K. Wayne Rigg