Prophylactic exchange-transfusion in sickle cell disease pregnancy: TAPS2 feasibility randomized controlled trial.

Serial prophylactic exchange blood transfusion (SPEBT) is increasingly used in pregnant women with sickle cell disease (SCD), despite a lack of robust evidence. TAPS2 (Transfusion Antenatally in Pregnant Women with Sickle Cell Disease) study assessed the feasibility and acceptability of conducting a definitive randomized controlled trial of SPEBT (intervention) versus standard care (control) in pregnant women with SCD. Women ≥18 years with SCD, between 6+0 and 18+0 weeks of singleton gestation, were randomized 1:1 to control or intervention every 6-10 weeks throughout pregnancy in seven hospitals in England. The main outcomes evaluated were recruitment rate (primary outcome), acceptability, and retention. Secondary outcomes were safety, maternal and infant clinical outcomes. 194 women were screened over 42 months (extended due to the pandemic), 88 were eligible, and 35 (39.8%) consented to participate. Eighteen participants were randomized to intervention and 17 to control. Follow-up data were collected on all participants. Twelve patients in the intervention group received at least one SPEBT, of these, 11 received  3. The remaining patient was withdrawn from SPEBT due to transfusion reaction. Sixteen control participants required at least one transfusion. There were no statistically significant differences in terms of maternal, infant, or postnatal outcomes. A trend towards a lower incidence of vaso-occlusive crisis, preterm delivery and improved birthweight was observed in the intervention group. Despite the pandemic, this study achieved satisfactory recruitment and retention, confirming its acceptability to participants. TAPS2 demonstrates that it is feasible to perform a definitive international trial of SPEBT in pregnant women with SCD. Trial registration: NIH registry (www.clinicaltrials.gov), registration number NCT03975894 (registered 05/06/19); ISRCTN (www.isrctn.com), registration number ISRCTN52684446 (retrospectively registered 02/08/19). TAPS2 trial Protocol: available at https://rdcu.be/drlwc.

Association between breastfeeding duration and educational attainment in rural Southwest Uganda: a population-based cohort study.

BACKGROUND: Breastfeeding is important for early childhood nutrition and health. The positive effects on educational outcomes may be attributed to socioeconomic factors. Socioeconomic status is not a strong predictor of breastfeeding in sub-Saharan African countries. Yet, few studies have investigated the association between breastfeeding and educational outcomes in these countries. OBJECTIVE: This study investigated the association between breastfeeding duration and children's educational attainment in rural Southwest Uganda. METHODS: We analysed longitudinal data on 3018 children who had information on breastfeeding and were followed for at least 5 years, with at least one primary school grade recorded by 2005. Data on breastfeeding duration were collected from mothers. The highest school grade was recorded repeatedly between ages 6 and 12 years. We calculated age-for-grade based on whether a child was on, over, or under the official age for a grade. Generalised estimating equations and binary logistic regression estimated the effect of breastfeeding duration on being 2 years, 3 or more years, or any years over-age for grade in primary school, adjusting for socioeconomic status and maternal-child characteristics. RESULTS: Most mothers breastfed for more than a year. Just over one-third breastfed for 18-23 months, and 30% breastfed for longer. By age eight, 42% of the children were two years over-age for their grade. Three or more years over-age for grade increased from 19% at age nine to 56% at age 12. Both adjusted and unadjusted estimates were consistent in showing reduced odds for children being 2 years, 3 or more years, or any years over-age for grade among children breastfed for 7-12, 13-17, 18-23, and > 23 months compared to those breastfed for 0-6 months. There was no evidence to support an overall association between breastfeeding duration and being over-age for grade. There was no evidence of association in the sex and age sub-group analyses. CONCLUSION: Although we found no association between breastfeeding duration and educational attainment, breastfeeding remains important for children's health and nutrition, and mothers should be encouraged and supported to breastfeed for the recommended duration.

Main findings: We found no clear evidence of an association between breastfeeding duration and educational attainment in rural Uganda.Added knowledge: The findings of this study contribute to a better understanding of the relationship between breastfeeding and educational outcomes in sub-Saharan African countries, where evidence on this topic is limited.Global health impact for policy and action: Our findings should not discourage breastfeeding, as it is essential for infant health and nutrition.

Statistical analysis plan and protocol updates for Gestational diabetes in Uganda and India: Design and Evaluation of Educational Films for Improving Screening and Self-management (GUIDES) trial.

BACKGROUND: Timely detection and management of gestational diabetes mellitus (GDM) have been identified as a high priority for policymakers in low- and middle-income countries (LMICs). The GUIDES trial will evaluate a package of three interconnected film-based interventions aimed at improving the timely detection and management of GDM. The protocol for this trial has previously been published; this publication outlines the statistical analysis plan for the trial. METHODS AND DESIGN: The GUIDES study is a multi-country cluster-randomised controlled trial consisting of one trial conducted in Uganda and one in India (30 clusters in each country). Mixed effects models will be used to compare the primary study outcomes of the proportion of women who are tested for GDM between 24 and 32 weeks of pregnancy and the mean fasting blood sugar of women with GDM at 34-week follow-up while accounting for clustering. Secondary analyses will compare the proportion of women with self-reported GDM diagnosis at 32 weeks of pregnancy and the proportion of women with adverse perinatal outcomes related to GDM up to 4 weeks after birth in each trial arm. TRIAL STATUS AND DISCUSSION: Follow-up is expected to end in March 2023 in Uganda and in May 2023 in India. Analyses will be carried out following this statistical analysis plan in the month following trial completion. TRIAL REGISTRATION: ClinicalTrials.gov NCT03937050. Registered on 3 May 2019. Clinical Trials Registry India CTRI/2020/02/023605. Registered on 26 February 2020.

Effects of exclusive breastfeeding on educational attainment and longitudinal trajectories of grade progression among children in a 13-year follow-up study in Malawi.

The benefits of exclusive breastfeeding (EBF) for infant health and survival are well documented. However, its impact on educational outcomes has been contested and poorly researched in Africa. It has been hypothesised that positive associations reported in high-income countries can be attributed to residual confounding by socioeconomic status (SES). Our study investigated whether EBF duration in infancy is associated with educational attainment and age-for-grade attainment trajectories at school-age in rural Malawi. Longitudinal data on 1021 children at the Karonga demographic surveillance site in Malawi were analysed. Breastfeeding data were collected 3 months after birth and again at age one. The school grade of each child was recorded each year from age 6 until age 13. We calculated age-for-grade based on whether a child was at, over, or under the official expected age for a grade. Generalised estimating equations estimated the average effect of breastfeeding on age-for-grade. Latent class growth analysis identified age-for-grade trajectories, and multinomial logistic regression examined their associations with EBF. Maternal-child characteristics, SES, and HIV status were controlled. Overall, 35.9% of the children were exclusively breastfed for 6 months. Over-age for grade steadily increased from 9.6% at age 8 to 41.9% at age 13. There was some evidence that EBF for 6 months was associated with lower odds of being over-age for grade than EBF for less than 3 months (aOR = 0.82, 95%CI = 0.64-1.06). In subgroup analyses, children exclusively breastfed for 6 months in infancy were less likely to be over-age for grades between ages 6-9 (aOR = 0.64, 95%CI = 0.43-0.94). Latent class growth analysis also provided some evidence that EBF reduced the odds of falling behind in the early school grades (aOR = 0.66, 95%CI = 0.41-1.08) but not later. Our study adds to the growing evidence that EBF for 6 months has benefits beyond infant health and survival, supporting the WHO's recommendation on EBF.

Contraceptive use and pregnancy planning in Britain during the first year of the COVID-19 pandemic: findings from a large, quasi-representative survey (Natsal-COVID).

BACKGROUND: Contraceptive services were significantly disrupted during the COVID-19 pandemic in Britain. We investigated contraception-related health inequalities in the first year of the pandemic. METHODS: Natsal-COVID Wave 2 surveyed 6658 adults aged 18-59 years between March and April 2021, using quotas and weighting to achieve quasi-representativeness. Our analysis included sexually active participants aged 18-44 years, described as female at birth. We analysed contraception use, contraceptive switching due to the pandemic, contraceptive service access, and pregnancy plannedness. RESULTS: Of 1488 participants, 1619 were at risk of unplanned pregnancy, of whom 54.1% (51.0%-57.1%) reported routinely using effective contraception in the past year. Among all participants, 14.3% (12.5%-16.3%) reported switching or stopping contraception due to the pandemic. 3.2% (2.0%-5.1%) of those using effective methods pre-pandemic switched to less effective methods, while 3.8% (2.5%-5.9%) stopped. 29.3% (26.9%-31.8%) of at-risk participants reported seeking contraceptive services, of whom 16.4% (13.0%-20.4%) reported difficulty accessing services. Clinic closures and cancelled appointments were commonly reported pandemic-related reasons for difficulty accessing services. This unmet need was associated with younger age, diverse sexual identities and anxiety symptoms. Of 199 pregnancies, 6.6% (3.9%-11.1%) scored as 'unplanned'; less planning was associated with younger age, lower social grade and unemployment. CONCLUSIONS: Just under a third of participants sought contraceptive services during the pandemic and most were successful, indicating resilience and adaptability of service delivery. However, one in six reported an unmet need due to the pandemic. COVID-induced inequalities in service access potentially exacerbated existing reproductive health inequalities. These should be addressed in the post-pandemic period and beyond.

Serial prophylactic exchange blood transfusion in pregnant women with sickle cell disease (TAPS-2): statistical and qualitative analysis plan for a randomised controlled feasibility trial.

BACKGROUND: There are significant knowledge gaps regarding the effectiveness of serial prophylactic exchange blood transfusion (SPEBT) for pregnant women with sickle cell disease (SCD). The protocol for the randomised feasibility trial assessing SPEBT versus usual care in women with SCD (TAPS2 trial) has previously been published. This publication outlines the statistical and qualitative analysis plan for the study. METHODS AND DESIGN: TAPS2 is a randomised two-arm phase 2 feasibility trial with a nested qualitative study and health economic evaluation. Up to 50 pregnant women with SCD and a singleton pregnancy will be recruited and individually randomised to either SPEBT approximately every 6-10 weeks until delivery (intervention arm) or to usual care (control arm). Information will be collected on a range of feasibility and clinical outcomes. RESULTS: Due to the impact of COVID-19 on study recruitment, the initial study period of 24 months was extended to 48 months. Other protocol updates designed to mitigate the impact of COVID-19-related disruption included allowing for remote consent and conducting all qualitative interviews by telephone. The primary outcome for the trial is the overall recruitment rate. The number of women screened, eligible, consented, randomised and withdrawn will be summarised as a CONSORT flow diagram. Differences in clinical outcomes will additionally be presented as an initial assessment of efficacy and to inform sample size calculations for a future definitive trial. Qualitative interviews with trial participants and clinicians will be analysed using reflexive thematic analysis; data from interviews with participants who declined to participate in the trial will be extracted and incorporated into summary tables to report key findings. The health economic analysis plan is not covered by this update. CONCLUSION: The publication of this analysis plan is designed to aid transparency and to reduce the potential for reporting bias. TRIAL REGISTRATION: NIH registry ( www. CLINICALTRIALS: gov ), registration number NCT03975894 (registered 05/06/19); ISRCTN ( www.isrctn.com ), registration number ISRCTN52684446 (retrospectively registered 02/08/19).

Fetal death after the introduction of COVID-19 mitigation measures in Sweden, Denmark and Norway: a registry-based study.

It remains unclear whether the rate of fetal death has changed during the COVID-19 pandemic. We assessed the impact of COVID-19 mitigation measures on fetal death in Sweden (449,347 births), Denmark (290,857 pregnancies) and Norway (261,057 pregnancies) using robust population-based registry data. We used Cox regression to assess the impact of the implementation of pandemic mitigation measures on March 12th, 2020, on miscarriage (fetal loss before gestational week 22) and stillbirth (fetal loss after gestational week 22). A total of 11% of 551,914 pregnancies in Denmark and Norway ended in miscarriage, while the proportion of stillbirths among 937,174 births across the three countries was 0.3%. There was no difference in the risk of fetal death during the year following pandemic mitigation measures. For miscarriage, the combined hazard ratio (HR) for Norway and Denmark was 1.01 (95% CI 0.98, 1.03), and for stillbirth, the combined HR for all three countries was 0.99 (95% CI 0.89, 1.09). We observed a slightly decreased risk of miscarriage during the first 4 months, with an HR of 0.94 (95% CI 0.90, 0.99) after lockdown. In conclusion, the risk of fetal death did not change after the implementation of COVID-19 pandemic mitigation measures in the three Scandinavian countries.

The association of breastfeeding with cognitive development and educational achievement in sub-Saharan Africa: A systematic review.

Background: Systematic reviews and meta-analyses of studies mainly from high-income countries suggest that breastfeeding improves cognitive function and educational achievement. However, these associations may be a manifestation of who breastfeeds in these settings rather than an actual effect of breastfeeding. We investigated the association of breastfeeding with cognitive development and educational achievements in sub-Saharan Africa, where breastfeeding is the norm, and socioeconomic status is not strongly correlated with ever breastfeeding. Methods: We searched Medline, Embase, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), and Africa-Wide Information in January 2021 for studies that assessed the cognitive and educational benefits of breastfeeding in children and adolescents in sub-Saharan Africa. Two reviewers independently screened, extracted, and critically appraised the included studies. Results: After reviewing 5552 abstracts and 151 full-text articles, seventeen studies on cognitive development and two on educational achievements met our predefined inclusion criteria. The included studies were from ten sub-Saharan African countries and published between 2013 and 2021, with sample sizes ranging from 54 to 6573. Most of the studies (n = 14) were prospective cohort studies, but only nine collected data on breastfeeding prospectively. The studies differed in analytic approaches and cognitive and educational achievements measurements. Of the 17 studies on cognitive development, only four adjusted sufficiently for key confounders. None of these four studies found an overall association between breastfeeding and cognitive development in children or adolescents in sub-Saharan Africa. The two studies on education measured achievements based on the highest grade of school attained, 12 or more years of education, or grade repetition at age 7-11 years. Both studies adjusted for a range of sociodemographic factors and found no evidence that children exclusively breastfed or breastfed for a longer duration have a better educational outcome than sub-optimally breastfed children. Conclusions: The current evidence from sub-Saharan Africa is limited but does not corroborate previous findings that breastfeeding is associated with improved cognitive development and educational achievement. Registration: This study is registered with PROSPERO, CRD42021236009.

Time trends in the prevalence and determinants of age-appropriate breast feeding among children aged 0-23 months in Ghana: a pooled analysis of population-based surveys, 2003-2017.

OBJECTIVE: We assessed the sociodemographic and maternal-child characteristics associated with age-appropriate breast feeding among children aged 0-23 months in Ghana. METHODS: We pooled data on 12 743 children aged 0-23 months from three Demographic and Health Surveys (2003, 2008 and 2014) and three Multiple Indicator Cluster Surveys (2006, 2011 and 2017-2018). The outcome was age-appropriate breast feeding from birth to 23 months, with age-appropriate breast feeding defined as exclusive breast feeding at 0-5 months (ie, at less than 6 months) and breastfeeding alongside appropriate complementary feeding at 6-23 months. Potential determinants were maternal-child sociodemographic, obstetric and healthcare factors. Logistic regression was used to determine the factors associated with age-appropriate breast feeding. We accounted for the complex sampling design of the cross-sectional surveys in the analysis. RESULTS: Most children aged 0-3 months were exclusively breastfed. Among children aged 4-5 months, the most common feeding pattern was breastfeeding alongside water and/or solid foods. Exclusive breastfeeding prevalence in children less than 6 months peaked in 2008 at 62.8% and declined to 42.9% in 2017. For 6-11 month olds, the percentage experiencing age-appropriate breast feeding has been stable over the last four surveys, ranging from 79.3% in 2008 to 81.1% in 2017. Age-appropriate breast feeding in 12-23 month olds declined from 77.8% in 2003 to 61.2% in 2017. Rural residence, younger age, non-facility births and multiple births were associated with decreased odds of exclusively breast feeding. For 6-11 month olds, age-appropriate breast feeding was less likely if the woman did not receive postnatal care. Younger age, being unmarried, high income, wanting a child later and earlier birth order were associated with decreased odds of age-appropriate breast feeding in 12-23 month olds. CONCLUSION: Ghanaian children are now less likely to be exclusively breastfed than they were a decade ago. To succeed, breastfeeding promotion programmes should adopt approaches that address the predictors of suboptimal breast feeding at each age, as identified in this study.

Childhood seizures after prenatal exposure to maternal influenza infection: a population-based cohort study from Norway, Australia and Canada.

OBJECTIVE: To assess whether clinical and/or laboratory-confirmed diagnosis of maternal influenza during pregnancy increases the risk of seizures in early childhood. DESIGN: Analysis of prospectively collected registry data for children born between 2009 and 2013 in three high-income countries. We used Cox regression to estimate country-level adjusted HRs (aHRs); fixed-effects meta-analyses were used to pool adjusted estimates. SETTING: Population-based. PARTICIPANTS: 1 360 629 children born between 1 January 2009 and 31 December 2013 in Norway, Australia (New South Wales) and Canada (Ontario). EXPOSURE: Clinical and/or laboratory-confirmed diagnosis of maternal influenza infection during pregnancy. MAIN OUTCOME MEASURES: We extracted data on recorded seizure diagnosis in secondary/specialist healthcare between birth and up to 7 years of age; additional analyses were performed for the specific seizure outcomes 'epilepsy' and 'febrile seizures'. RESULTS: Among 1 360 629 children in the study population, 14 280 (1.0%) were exposed to maternal influenza in utero. Exposed children were at increased risk of seizures (aHR 1.17, 95% CI 1.07 to 1.28), and also febrile seizures (aHR 1.20, 95% CI 1.07 to 1.34). There was no strong evidence of an increased risk of epilepsy (aHR 1.07, 95% CI 0.81 to 1.41). Risk estimates for seizures were higher after influenza infection during the second and third trimester than for first trimester. CONCLUSIONS: In this large international study, prenatal exposure to influenza infection was associated with increased risk of childhood seizures.

Preterm birth after the introduction of COVID-19 mitigation measures in Norway, Sweden, and Denmark: a registry-based difference-in-differences study.

BACKGROUND: Although some studies have reported a decrease in preterm birth following the start of the COVID-19 pandemic, the findings are inconsistent. OBJECTIVE: This study aimed to compare the incidences of preterm birth before and after the introduction of COVID-19 mitigation measures in Scandinavian countries using robust population-based registry data. STUDY DESIGN: This was a registry-based difference-in-differences study using births from January 2014 through December 2020 in Norway, Sweden, and Denmark. The changes in the preterm birth (<37 weeks) rates before and after the introduction of COVID-19 mitigation measures (set to March 12, 2020) were compared with the changes in preterm birth before and after March 12 from 2014 to 2019. The differences per 1000 births were calculated for 2-, 4-, 8-, 12-, and 16-week intervals before and after March 12. The secondary analyses included medically indicated preterm birth, spontaneous preterm birth, and very preterm (<32 weeks) birth. RESULTS: A total of 1,519,521 births were included in this study. During the study period, 5.6% of the births were preterm in Norway and Sweden, and 5.7% were preterm in Denmark. There was a seasonal variation in the incidence of preterm birth, with the highest incidence during winter. In all the 3 countries, there was a slight overall decline in preterm births from 2014 to 2020. There was no consistent evidence of a change in the preterm birth rates following the introduction of COVID-19 mitigation measures, with difference-in-differences estimates ranging from 3.7 per 1000 births (95% confidence interval, -3.8 to 11.1) for the first 2 weeks after March 12, 2020, to -1.8 per 1000 births (95% confidence interval, -4.6 to 1.1) in the 16 weeks after March 12, 2020. Similarly, there was no evidence of an impact on medically indicated preterm birth, spontaneous preterm birth, or very preterm birth. CONCLUSION: Using high-quality national data on births in 3 Scandinavian countries, each of which implemented different approaches to address the pandemic, there was no evidence of a decline in preterm births following the introduction of COVID-19 mitigation measures.

Perinatal outcomes in women with sickle cell disease: a matched cohort study from London, UK.

There are limited data on contemporary outcomes for women with sickle cell disease (SCD) in pregnancy. We conducted a single-site matched cohort study, comparing 131 pregnancies to women with SCD between 2007 and 2017 to a comparison group of 1310 pregnancies unaffected by SCD. Restricting our analysis to singleton pregnancies that reached 24 weeks of gestation, we used conditional Poisson regression to estimate adjusted risk ratios (aRRs) for perinatal outcomes. Infants born to mothers with SCD were more likely to be small for gestational age [aRR 1·69, 95% confidence interval (CI) 1·13-2·48], preterm (aRR 2·62, 95% CI 1·82-3·78) and require Neonatal Unit (NNU) admission (aRR 3·59, 95% CI 2·18-5·90). Pregnant women with SCD were at higher risk of pre-eclampsia/eclampsia (aRR 3·53, 95% CI 2·00-6·24), more likely to receive induction of labour (aRR 2·50, 95% CI 1·82-1·76) and caesarean birth (aRR 1·44, 95% CI 1·18-1·76). In analysis stratified by genotype, the risk of adverse outcomes was highest in haemoglobin SS (HbSS) pregnancies (n = 80). There was no strong evidence that haemoglobin SC (HbSC) pregnancies (n = 46) were at higher risk of preterm birth, caesarean delivery, or NNU admission. Pre-eclampsia/eclampsia was more frequently observed in HbSC pregnancies. Despite improvements in the care of pregnant women with SCD, the increased risk of adverse perinatal outcomes remains.

Educational films for improving screening and self-management of gestational diabetes in India and Uganda (GUIDES): study protocol for a cluster-randomised controlled trial.

BACKGROUND: The prevalence of gestational diabetes mellitus (GDM) is rising rapidly in many low- and middle-income countries (LMICs). Most women with GDM in LMICs are undiagnosed and/or inadequately managed due to a lack of knowledge and skills about GDM on the part of both providers and patients. Following contextual analysis, we developed an educational/behavioural intervention for GDM delivered through a package of culturally tailored films. This trial aims to evaluate whether the intervention can improve the timely detection and management of GDM in two LMIC settings. METHODS: Two independent cluster randomised controlled trials, one each to be conducted in Uganda and India. Thirty maternity facilities in each country have been recruited to the study and randomised in a 1:1 ratio to the intervention and control arms. The intervention comprises of three interconnected sets of films with the following aims: to improve knowledge of GDM guidelines and skills of health providers, to raise awareness of GDM screening among pregnant women and their families, and to improve confidence and skills in self-management among those diagnosed with GDM. In facilities randomised to the intervention arm, a GDM awareness-raising film will be shown in antenatal care waiting rooms, and four films for pregnant women with GDM will be shown in group settings and made available for viewing on mobile devices. Short films for doctors and nurses will be presented at professional development meetings. Data will be collected on approximately 10,000 pregnant women receiving care at participating facilities, with follow-up at 32 weeks gestational age and 6 weeks postnatally. Women who self-report a GDM diagnosis will be invited for a clinic visit at 34 weeks. Primary outcomes are (a) the proportion of women who report a GDM diagnosis by 32 weeks of pregnancy and (b) glycaemic control (fasting glucose and HbA1C) in women with GDM at ~34 weeks of pregnancy. The secondary outcome is a composite measure of GDM-related adverse perinatal-neonatal outcome. DISCUSSION: Screening and management of GDM are suboptimal in most LMICs. We hypothesise that a scalable film-based intervention has the potential to improve the timely detection and management of GDM in varied LMIC settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT03937050 , registered on 3 May 2019. Clinical Trials Registry India CTRI/2020/02/023605 , registered on 26 February 2020.

Serial prophylactic exchange blood transfusion in pregnant women with sickle cell disease (TAPS-2): study protocol for a randomised controlled feasibility trial.

BACKGROUND: Pregnancies in women with sickle cell disease (SCD) are associated with a higher risk of sickle and pregnancy complications. Limited options exist for treating SCD during pregnancy. Serial prophylactic exchange blood transfusion (SPEBT) has been shown to be effective in treating SCD outside pregnancy, but evidence is lacking regarding its use during pregnancy. The aim of this study is to assess the feasibility and acceptability of conducting a future phase 3 randomised controlled trial (RCT) to establish the clinical and cost effectiveness of SPEBT in pregnant women with SCD. METHODS: The study is an individually randomised, two-arm, feasibility trial with embedded qualitative and health economic studies. Fifty women, 18 years of age and older, with SCD and a singleton pregnancy at ≤ 18 weeks' gestation will be recruited from six hospitals in England. Randomisation will be conducted using a secure online database and minimised by centre, SCD genotype and maternal age. Women allocated to the intervention arm will receive SPEBT commencing at ≤ 18 weeks' gestation, performed using automated erythrocytapheresis every 6-10 weeks until the end of pregnancy, aiming to maintain HbS% or combined HbS/HbC% below 30%. Women in the standard care arm will only receive transfusion when clinically indicated. The primary outcome will be the recruitment rate. Additional endpoints include reasons for refusal to participate, attrition rate, protocol adherence, and maternal and neonatal outcomes. Women will be monitored throughout pregnancy to assess maternal, sickle, and foetal complications. Detailed information about adverse events (including hospital admission) and birth outcomes will be extracted from medical records and via interview at 6 weeks postpartum. An embedded qualitative study will consist of interviews with (a) 15-25 trial participants to assess experiences and acceptability, (b) 5-15 women who decline to participate to identify barriers to recruitment and (c) 15-20 clinical staff to explore fidelity and acceptability. A health economic study will inform a future cost effectiveness and cost-utility analysis. DISCUSSION: This feasibility study aims to rigorously evaluate SPEBT as a treatment for SCD in pregnancy and its impact on maternal and infant outcomes. TRIAL REGISTRATION: NIH registry (www.clinicaltrials.gov), registration number NCT03975894 (registered 05/06/19); ISRCTN (www.isrctn.com), registration number ISRCTN52684446 (retrospectively registered 02/08/19).

Breastfeeding in England: time trends 2005-2006 to 2012-2013 and inequalities by area profile.

Breastfeeding rates in England have risen steadily since the 1970s, but rates remain low and little is known about area-based trends. We report an ecological analysis of time trends in area breastfeeding rates in England using annual data on breastfeeding initiation (2005-2006 to 2012-2013) and any breastfeeding at 6-8 weeks (2008-2009 to 2012-2013) for 151 primary care trusts (PCTs). Overall, breastfeeding initiation rose from 65.5% in 2005-2006 to 72.4% in 2012-2013 (average annual absolute increase 0.9%). There was a statistically significantly higher (interaction P < 0.001) annual increase in initiation in PCTs in the most deprived (1.2%) compared with the least deprived tertile (0.7%), and in PCTs with low baseline breastfeeding initiation (2005-2006; 1.4%) compared with high baseline initiation (0.6%). Similar trends were observed when PCTs were stratified by the proportion of teenage mothers and maternal smoking, but not when stratified by ethnicity. Although breastfeeding prevalence at 6-8 weeks also increased significantly over the observed time period (41.2% in 2008-2009, 43.7% in 2012-2013; annual increase 0.7%), there was no difference in the average increase by deprivation profile, ethnicity, teenage mothers and maternal smoking. However, PCTs with low baseline prevalence in 2008-2009 saw a significantly larger annual increase (0.8%) compared with PCTs with high baseline prevalence (0.07%). In conclusion, breastfeeding initiation and prevalence have seen higher increases in areas with low initial breastfeeding, and for initiation, more disadvantaged areas. Although these results suggest that inequalities in breastfeeding have narrowed, rates have plateaued since 2010-2011. Sustained efforts are needed to address breastfeeding inequalities.

Ethnic variation in stillbirth risk and the role of maternal obesity: analysis of routine data from a London maternity unit.

BACKGROUND: Approximately 5 in 1,000 deliveries in England and Wales result in stillbirth, with little improvement in figures over the last few decades. The aim of this study was to investigate the association between clinical and socio-demographic factors and stillbirth, with a particular focus on ethnicity and obesity. METHODS: Analysis of routine maternity data on 53,293 singleton births occurring in a large London teaching hospital between 2004 and 2012. Logistic regression was used to investigate risk factors for stillbirth and to explore potential effect modification. RESULTS: 53,293 deliveries occurred during the time period, of which 329 resulted in a stillbirth (6.2 per 1,000 births). Compared to White women, non-White ethnicity was associated with a doubling of the odds of stillbirth (aOR for Black women 2.15, 95% CI 1.56-2.97; aOR for South Asian women 2.33, 95% CI 1.42-3.83). Obese women had a trend towards higher odds of stillbirth compared to women of recommended BMI (aOR 1.38, 95% CI 0.98-1.96), though this was not significant (p 0.07). Both higher parity (≥2 compared to para 1) and hypertension were associated with a higher odds of stillbirth (parity ≥2 aOR 1.65, 95% CI 1.13-2.39; hypertension aOR 1.84, 95% CI 1.22-2.78) but there was no evidence that area deprivation or maternal age were independently associated with stillbirth in this population. There was some evidence of effect modification between ethnicity and obesity (p value for interaction 0.06), with obesity a particularly strong risk factor for stillbirth in South Asian women (aOR 4.64, 95% CI 1.84-11.70). CONCLUSIONS: There was a high prevalence of stillbirth in this multi-ethnic urban population. The increased risk of stillbirth observed in non-White women remains after adjusting for other factors. Our finding of possible effect modification between ethnicity and obesity suggests that further research should be conducted in order to improve understanding of the interplay between ethnicity, obesity and stillbirth.

The role of support and other factors in early breastfeeding cessation: an analysis of data from a maternity survey in England.

BACKGROUND: Although the majority of women in England initiate breastfeeding, approximately one third cease breastfeeding by six weeks and many of these women report they would like to have breastfed for longer. METHODS: Data from a survey of women ≥16 years who gave birth to singleton term infants in 2009 in England; questionnaires were completed approximately three months postnatally. Logistic regression was used to investigate the association between postnatal support and other factors, and breastfeeding cessation at 10 days and six weeks. Population attributable fractions (PAFs) were calculated to estimate the relative contribution of breastfeeding support factors to overall breastfeeding cessation at these two time points. RESULTS: Of the 3840 women who initiated breastfeeding and reported timing of breastfeeding cessation, 13% had stopped by 10 days; and of the 3354 women who were breastfeeding at 10 days, 17% had stopped by six weeks. Socio-demographic factors (maternal age, ethnicity, country of birth, deprivation, education) and antenatal feeding intention were all independently associated with breastfeeding cessation at 10 days and six weeks. Women who did not receive feeding advice or support from a parent or peer support group, voluntary organisation, or breastfeeding clinic were more likely to stop breastfeeding by 10 days. Perceived active support and encouragement from midwives was associated with a lower odds of breastfeeding cessation at both 10 days and six weeks. Estimated PAFs suggest that 34-59% of breastfeeding cessations by 10 days could be avoided if more women in the study population received breastfeeding support. CONCLUSION: Although multiple factors influence a mother's likelihood of continuing breastfeeding, it is clear that socio-demographic factors are strongly associated with breastfeeding continuation. However, there is evidence that breastfeeding support, including that delivered by peer or lay support workers, may have an important role in preventing cessations in the first few weeks.

Factors associated with breastfeeding in England: an analysis by primary care trust.

OBJECTIVES: To identify the sociodemographic factors associated with variation in area-based breastfeeding in England; to calculate the predicted breastfeeding rates adjusted for sociodemographic variations. DESIGN: Ecological analysis of routine data using random effects logistic regression. SETTING: All 151 primary care trusts (PCTs) in England 2010-2011. OUTCOME MEASURES: PCT level data on breastfeeding: initiation, any and exclusive breastfeeding at 6-8 weeks. RESULTS: There was considerable variation in breastfeeding across PCTs (breastfeeding initiation mean 72%, range 39-93%; any breastfeeding at 6-8 weeks mean 45%, range 19-83%; exclusive breastfeeding at 6-8 weeks mean 32%, range 14-58%), with London PCTs reporting markedly higher rates. Maternal age was strongly associated with area-based breastfeeding, with a 4-6% increase in odds of breastfeeding associated with a unit increase in the percentage of older mothers. Outside London, the proportion of the local population from a Black and Minority Ethnic (BME) background, compared with those from a White British background, was associated with higher breastfeeding (1-3% increase in odds per unit increase in the proportion from a BME background). Area-based deprivation was associated with reduced odds of breastfeeding (21-32% reduced odds comparing most deprived quintile to least deprived quintile). Weaker associations were observed between sociodemographic factors and breastfeeding in London PCTs. Very few PCTs reported breastfeeding figures substantially above or below the national average, having adjusted for variations in sociodemographic factors. CONCLUSIONS: Our results show striking associations between sociodemographic factors and breastfeeding at the area level, with much of the variation in breastfeeding rates explained by the sociodemographic profile. The sociodemographic context of breastfeeding is clearly important at the area level as well as the individual level. Our findings can be used to inform decision-making relating to local priorities and service provision.