Caesarean Section among Referred and Self-Referred Birthing Women: A Cohort Study from a Tertiary Hospital, Northeastern Tanzania.

The inequity in emergency obstetric care access in Tanzania is unsatisfactory. Despite an existing national obstetric referral system, many birthing women bypass referring facilities and go directly to higher-level care centres. We wanted to compare Caesarean section (CS) rates among women formally referred to a tertiary care centre versus self-referred women, and to assess the effect of referral status on adverse outcomes after CS. We used data from 21,011 deliveries, drawn from the birth registry of a tertiary hospital in northeastern Tanzania, during 2000-07. Referral status was categorized as self-referred if the woman had bypassed or not accessed referral, or formally-referred if referred by a health worker. Because CS indications were insufficiently registered, we applied the Ten-Group Classification System to determine the CS rate by obstetric group and referral status. Associations between referral status and adverse outcomes after CS delivery were analysed using multiple regression models. Outcome measures were CS, maternal death, obstetric haemorrhage ≥ 750 mL, postpartum stay > 9 days, neonatal death, Apgar score < 7 at 5 min and neonatal ward transfer. Referral status contributed substantially to the CS rate, which was 55.0% in formally-referred and 26.9% in self-referred birthing women. In both groups, term nulliparous singleton cephalic pregnancies and women with previous scar(s) constituted two thirds of CS deliveries. Low Apgar score (adjusted OR 1.42, 95% CI 1.09-1.86) and neonatal ward transfer (adjusted OR 1.18, 95% CI 1.04-1.35) were significantly associated with formal referral. Early neonatal death rates after CS were 1.6% in babies of formally-referred versus 1.2% in babies of self-referred birthing women, a non-significant difference after adjusting for confounding factors (adjusted OR 1.37, 95% CI 0.87-2.16). Absolute neonatal death rates were > 2% after CS in breech, multiple gestation and preterm deliveries in both referral groups. Women referred for delivery had higher CS rates and poorer neonatal outcomes, suggesting that the formal referral system successfully identifies high-risk birth, although low volume suggests underutilization. High absolute rates of post-CS adverse outcomes among breech, multiple gestation and preterm deliveries suggest the need to target self-referred birthing women for earlier professional intrapartum care

Prevalence and predictors of alcohol use during pregnancy: findings from international multicentre cohort studies

Objectives To compare the prevalence and predictors of alcohol use in multiple cohorts. Design Cross-cohort comparison of retrospective and prospective studies. Setting Population-based studies in Ireland, the UK, Australia and New Zealand. Participants 17 244 women of predominantly Caucasian origin from two Irish retrospective studies (Growing up in Ireland (GUI) and Pregnancy Risk Assessment Monitoring System Ireland (PRAMS Ireland)), and one multicentre prospective international cohort, Screening for Pregnancy Endpoints (SCOPE) study. Primary and secondary outcome measures Prevalence of alcohol use pre-pregnancy and during pregnancy across cohorts. Sociodemographic factors associated with alcohol consumption in each cohort. Results Alcohol consumption during pregnancy in Ireland ranged from 20% in GUI to 80% in SCOPE, and from 40% to 80% in Australia, New Zealand and the UK. Levels of exposure also varied substantially among drinkers in each cohort ranging from 70% consuming more than 1–2 units/week in the first trimester in SCOPE Ireland, to 46% and 15% in the retrospective studies. Smoking during pregnancy was the most consistent predictor of gestational alcohol use in all three cohorts, and smokers were 17% more likely to drink during pregnancy in SCOPE, relative risk (RR)=1.17 (95% CI 1.12 to 1.22), 50% more likely to drink during pregnancy in GUI, RR=1.50 (95% CI 1.36 to 1.65), and 42% more likely to drink in PRAMS, RR=1.42 (95% CI 1.18 to 1.70). Conclusions Our data suggest that alcohol use during pregnancy is prevalent and socially pervasive in the UK, Ireland, New Zealand and Australia. New policy and interventions are required to reduce alcohol prevalence both prior to and during pregnancy. Further research on biological markers and conventions for measuring alcohol use in pregnancy is required to improve the validity and reliability of prevalence estimates

Maternal Mid-Gestation Cytokine Dysregulation in Mothers of Children with Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a developmental disorder characterised by deficits in social interactions and communication, with stereotypical and repetitive behaviours. Recent evidence suggests that maternal immune dysregulation may predispose offspring to ASD. Independent samples t-tests revealed downregulation of IL-17A concentrations in cases, when compared to controls, at both 15 weeks (p = 0.02), and 20 weeks (p = 0.02), which persisted at 20 weeks following adjustment for confounding variables. This adds to the growing body of evidence that maternal immune regulation may play a role in foetal neurodevelopment

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Explaining the Atypical Reaction Profiles of Heme Enzymes with a Novel Mechanistic Hypothesis and Kinetic Treatment

Many heme enzymes show remarkable versatility and atypical kinetics. The fungal extracellular enzyme chloroperoxidase (CPO) characterizes a variety of one and two electron redox reactions in the presence of hydroperoxides. A structural counterpart, found in mammalian microsomal cytochrome P450 (CYP), uses molecular oxygen plus NADPH for the oxidative metabolism (predominantly hydroxylation) of substrate in conjunction with a redox partner enzyme, cytochrome P450 reductase. In this study, we employ the two above-mentioned heme-thiolate proteins to probe the reaction kinetics and mechanism of heme enzymes. Hitherto, a substrate inhibition model based upon non-productive binding of substrate (two-site model) was used to account for the inhibition of reaction at higher substrate concentrations for the CYP reaction systems. Herein, the observation of substrate inhibition is shown for both peroxide and final substrate in CPO catalyzed peroxidations. Further, analogy is drawn in the “steady state kinetics” of CPO and CYP reaction systems. New experimental observations and analyses indicate that a scheme of competing reactions (involving primary product with enzyme or other reaction components/intermediates) is relevant in such complex reaction mixtures. The presence of non-selective reactive intermediate(s) affords alternate reaction routes at various substrate/product concentrations, thereby leading to a lowered detectable concentration of “the product of interest” in the reaction milieu. Occam's razor favors the new hypothesis. With the new hypothesis as foundation, a new biphasic treatment to analyze the kinetics is put forth. We also introduce a key concept of “substrate concentration at maximum observed rate”. The new treatment affords a more acceptable fit for observable experimental kinetic data of heme redox enzymes

Prevalence of positive depression screen among post miscarriage women- A cross sectional study

Background: Miscarriages are a common pregnancy complication affecting about 10–15% of pregnancies. Miscarriages may be associated with a myriad of psychiatric morbidity at various timelines after the event. Depression has been shown to affect about 10–20% of all women following a miscarriage. However, no data exists in the local setting informing on the prevalence of post-miscarriage depression. We set out to determine the prevalence of positive depression screen among women who have experienced a miscarriage at the Aga Khan University hospital, Nairobi. Methods: The study was cross-sectional in design. Patients who had a miscarriage were recruited at the post-miscarriage clinic review at the gynecology clinics at Aga Khan University Hospital, Nairobi. The Edinburgh postpartum depression scale was used to screen for depression in the patients. Prevalence was calculated from the percentage of patients achieving the cut –off score of 13 over the total number of patients. Results: A total of 182 patients were recruited for the study. The prevalence of positive depression screen was 34.1% since 62 of the 182 patients had a positive depression screen. Moreover, of the patients who had a positive depression screen, 21(33.1%) had thoughts of self-harm. Conclusion: A positive depression screen is present in 34.1% of women in our population two weeks after a miscarriage. Thoughts of self-harm are present in about a third of these women (33.1%) hence pointing out the importance of screening these women using the EPDS after a miscarriage

Exploring the views of young women and their healthcare professionals on dietary habits and supplementation practices in adolescent pregnancy: a qualitative study

Background: Nutrition is a modifiable factor affecting foetal growth and pregnancy outcomes. Inadequate nutrition is of particular concern in adolescent pregnancies with poor quality diet and competing demands for nutrients. The aim of this study was to explore knowledge and understanding of nutrition advice during adolescent pregnancy,and identify barriers and facilitators to dietary change and supplementation use in this vulnerable population. Methods: Semi-structured interviews were conducted with young women and key antenatal healthcare providers: midwives, family nurses and obstetricians. Doncaster, Manchester and London were chosen as sites offering different models of midwifery care alongside referral to the Family Nurse Partnership programme. Results: A total of 34 young women (adolescents aged 16–19 years) and 20 health professionals were interviewed. Young women made small changes to their dietary intake despite limited knowledge and social constraints. Supplementation use varied; the tablet format was identified by few participants as a barrier but forgetting to take them was the main reason for poor adherence. Health professionals provided nutrition information but often lack the time and resources to tailor this appropriately. Young women’s prime motivator was a desire to have a healthy baby; they wanted to understand the benefits of supplementation and dietary change in those terms. Conclusion: Pregnancy is a window of opportunity for improving nutrition but often constrained by social circumstances. Health professionals should be supported in their role to access education, training and resources which build their self-efficacy to facilitate change in this vulnerable population group beyond the routine care they provide