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Globally, patients living with sickle cell disease are now surviving to reproductive age, with life expectancy approaching 50 years in most countries. Thus, reproductive options are now essential for patients living with the condition. However, it can be associated with maternal, delivery, and fetal complications. Outcomes may vary depending on the level of expertise and resources. In this piece we provide an optional guideline for managing sickle cell disease in pregnancy. The therapeutic option of serial exchange prophylactic transfusion has been offered in the context of a clinical trial (TAPS2).

Introduction and hypothesis Obstetric anal sphincter injuries (OASIS) are a common cause of maternal morbidity with an overall incidence in the UK of 2.9% (range 0–8%). They can cause a range of physical symptoms and psychological distress. This study aims to assess the accuracy of clinical diagnosis of OASIS using endoanal ultrasound (EAUS) and the correlation between confirmed injury and change to anorectal physiology squeeze pressure and the incidence of bowel symptoms. Methods and materials Retrospective study of prospectively collected data from 1135 women who attended the Third- and Fourth-Degree Tears Clinic at our institution, 12 weeks post-delivery, between June 2008 and October 2019. Results OASIS was confirmed in 876 (78.8%) women and 236 (21.3%) had no injury. Of the women who underwent anorectal physiology, 45.6% had a mean maximal resting pressure below the normal range and 68.8% had a mean incremental squeeze pressure below normal. Women with confirmed OASIS had significantly lower pressures (p Conclusion Of the women in this study with a suspected OASIS, 21.2% could be reassured that they did not have an injury. This information is useful for women considering future mode of delivery. Those with confirmed injury are more likely to complain of flatus incontinence and have reduced anal sphincter pressures.

This guideline was compiled according to the British Societyof Haematology (BSH) process at https://b-s-h.org.uk/guidelines/proposing-and-writing-a-new-bsh-guideline/. The Grad-ing of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluatelevels of evidence and to assess the strength of recommenda-tions. The GRADE criteria can be found at http://www.gradeworkinggroup.org

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.

BackgroundIncreasing numbers of UK women have overweight or obese body mass index scores when they become pregnant, or gain excessive weight in pregnancy, increasing their risk of adverse outcomes. Failure to manage postnatal weight is linked to smoking, non-healthy dietary choices, lack of regular exercise and poorer longer-term health. Women living in areas of higher social deprivation are more likely to experience weight management problems postnatally.ObjectivesThe objectives were to assess the feasibility of conducting a definitive randomised controlled trial to determine the clinical effectiveness and cost-effectiveness of lifestyle information and access to a commercial weight management group focusing on self-monitoring, goal-setting and motivation to achieve dietary change commencing 8–16 weeks postnatally to achieve and maintain weight management and positive lifestyle behaviour.DesignThe design was a randomised two-arm feasibility trial with a nested mixed-methods process evaluation.SettingThe setting was a single centre in an inner city setting in the south of England.ParticipantsParticipants were women with body mass index scores of > 25 kg/m2at antenatal ‘booking’ and women with normal body mass index scores (18.0–24.9 kg/m2) at antenatal booking who developed excessive gestational weight gain as assessed at 36 weeks’ gestation.Main outcome measuresRecruitment, retention, acceptability of trial processes and identification of relevant economic data were the feasibility objectives. The proposed primary outcome was difference between groups in weight at 12 months postnatally, expressed as percentage weight change and weight loss from antenatal booking. Other proposed outcomes included assessment of diet, physical activity, smoking, alcohol consumption, body image, maternal esteem, mental health, infant feeding and NHS costs.ResultsMost objectives were achieved. A total of 193 women were recruited, 98 allocated to the intervention arm and 95 to the control arm. High follow-up rates (> 80%) were achieved to 12 months. There was an 8.8% difference in weight loss at 12 months between women allocated to the intervention arm and women allocated to the control arm (13.0% vs. 4.2%, respectively;p = 0.062); 47% of women in the intervention arm attended at least one weight management session, with low risk of contamination between arms. The greatest benefit was among women who attended ≥ 10 sessions. Barriers to attending sessions included capability, opportunity and motivation issues. Data collection tools were appropriate to support economic evaluation in a definitive trial, and economic modelling is feasible to quantify resource impacts and outcomes not directly measurable within a trial.LimitationsThe trial recruited from only one site. It was not possible to recruit women with normal body mass index scores who developed excessive pregnancy weight gain.ConclusionsIt was feasible to recruit and retain women with overweight or obese body mass index scores at antenatal booking to a trial comparing postnatal weight management plus standard care with standard care only and collect relevant data to assess outcomes. Approaches to recruit women with normal body mass index scores who gain excessive gestational weight need to be considered. Commercial weight management groups could support women’s weight management as assessed at 12 months postnatally, with probable greater benefit from attending ≥ 10 sessions. Process evaluation findings highlighted the importance of providing more information about the intervention on trial allocation, extended duration of time to commence sessions following birth and extended number of sessions offered to enhance uptake and retention. Results support the conduct of a future randomised controlled trial.Trial registrationCurrent Controlled Trials ISRCTN39186148.FundingThis project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full inPublic Health Research; Vol. 8, No. 9. See the NIHR Journals Library website for further project information.

BackgroundSickle cell disease (SCD) is a multisystem disease characterised by vaso-occlusive crisis, chronic anaemia and a shorter lifespan. More patients with SCD are living till reproductive age and contemplating pregnancy. Pulmonary complications in pregnancy are significant causes of maternal morbidity and mortality but yet this has not been systematically quantified. A systematic review and meta-analysis were conducted to quantify the association between SCD and pulmonary complications in pregnancy.MethodsMEDLINE, EMBASE, Web of Science, Cochrane and Maternity and Infant Care databases were searched for publications between January 1998 and April 2019. Observational studies involving at least 30 participants were included. Random-effects models were used for statistical meta-analysis.FindingsTwenty-two studies were included in the systematic review and 18 in the quantitative analysis. The meta-analysis included 3964 pregnancies with SCD and 336 559 controls. Compared with women without SCD, pregnancies complicated by SCD were at increased risk of pulmonary thromboembolism (relative risk (RR) 7.74; 95% CI 4.65 to 12.89). The estimated prevalence of acute chest syndrome and pneumonia was 6.46% (95% CI 4.66% to 8.25%), with no significant difference between the HbSS and HbSC genotypes (RR 1.42; 95% CI 0.90 to 2.23).InterpretationThis meta-analysis highlighted a strong association between SCD and maternal pulmonary complications. Understanding the risks of and the factors associated with pulmonary complications would aid preconceptual counselling and optimal management of the condition in pregnancy, thereby reducing associated maternal morbidity and mortality.PROSPERO registration numberCRD42019124708.

Objectives(1) To report maternal and newborn outcomes of pregnant women in areas of social deprivation in inner city London. (2) To compare the effect of caseload midwifery with standard care on maternal and newborn outcomes in this cohort of women.DesignRetrospective observational cohort study.SettingFour council wards (electoral districts) in inner city London, where over 90% of residents are in the two most deprived quintiles of the English Index of Multiple Deprivation (IMD) (2019) and the population is ethnically diverse.ParticipantsAll women booked for antenatal care under Guys and St Thomas’ National Health Service Foundation Trust after 11 July 2018 (when the Lambeth Early Action Partnership (LEAP*) caseload midwifery team was implemented) until data collection 18 June 2020. This included 523 pregnancies in the LEAP area, of which 230 were allocated to caseload midwifery, and 8430 pregnancies from other areas.Main outcome measuresTo explore if targeted caseload midwifery (known to reduce preterm birth) will improve important measurable outcomes (preterm birth, mode of birth and newborn outcomes).ResultsThere was a significant reduction in preterm birth rate in women allocated to caseload midwifery, when compared with those who received traditional midwifery care (5.1% vs 11.2%; risk ratio: 0.41; p=0.02; 95% CI 0.18 to 0.86; number needed to treat: 11.9). Caesarean section births were significantly reduced in women allocated to caseload midwifery care, when compared with traditional midwifery care (24.3% vs 38.0%; risk ratio: 0.64: p=0.01; 95% CI 0.47 to 0.90; number needed to treat: 7.4) including emergency caesarean deliveries (15.2% vs 22.5%; risk ratio: 0.59; p=0.03; 95% CI 0.38 to 0.94; number needed to treat: 10) without increase in neonatal unit admission or stillbirth.ConclusionThis study shows that a model of caseload midwifery care implemented in an inner city deprived community improves outcome by significantly reducing preterm birth and birth by caesarean section when compared with traditional care. This data trend suggests that when applied to targeted groups (women in higher IMD quintile and women of diverse ethnicity) that the impact of intervention is greater.

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.

Sickle cell disease (SCD) patients are commonly affected by pulmonary complications such as acute chest syndrome (ACS), pulmonary embolism (PE) and pneumonia that contribute to significant mortality risks. With a greater susceptibility to infection, they are deemed to be vulnerable patients during the current COVID‐19 pandemic. In emerging small case studies of SCD patients with COVID‐19 and further complicated by pneumonia, ACS, and/or PE, the clinical benefits of early exchange transfusion and Tocilizumab are evident. However, further clinical trials and larger cohort studies are essential to evaluate effective diagnostic and management options for this high‐risk group.

OBJECTIVE: To assess whether levels of first-trimester pregnancy-associated plasma protein A (PAPP-A) differ between women with and without sickle cell disease (SCD). METHODS: Retrospective study of 101 singleton pregnancies in women with SCD (including 55 with genotype HbSS, 37 with genotype HbSC, and nine with other genotypes). Measured levels of PAPP-A were converted to multiple of the median (MoM) values corrected for gestational age and maternal characteristics. Median PAPP-A MoM in the SCD group was compared with that of 1010 controls. RESULTS: In the SCD group median, PAPP-A MoM was lower than in the non-SCD group (0.72, interquartile range [IQR] = 0.54-1.14 versus 1.09, IQR = 0.74-1.49; P < .001). Within the SCD group median PAPP-A MoM was lower for those with genotype HbSS than HbSC (0.62, IQR = 0.44-1.14 versus 0.94, IQR = 0.72-1.25; .006). In 7.3% (4/55) of the HbSS group, there was stillbirth, and in these cases, PAPP-A was less than or equal to 0.5 MoM; in the control group, the incidence of stillbirth was lower (1%; P < .001). In HbSS disease, the incidence of small for gestational age (SGA) neonates was increased. CONCLUSION: Pregnancies with HbSS have lower PAPP-A MoM values and higher incidence of stillbirth and birth of SGA neonates than in non-SCD controls.

Background Women developing Gestational Diabetes Mellitus are subsequently at a higher risk of developing Type 2 Diabetes later in life. Screening and effective management of women with GDM is essential in preventing progression to type 2 diabetes mellitus. Although the burden of Gestational Diabetes Mellitus is high in India, Gestational Diabetes Mellitus screening and management is suboptimal in public hospitals. We aimed to explore the perspectives of healthcare providers regarding the barriers and facilitators from the health system context that restrict the timely screening and effective management of Gestational Diabetes Mellitus. Methods We conducted six in-depth interviews of health care providers- four with nurses and two with obstetricians in the public hospitals in India's major city (Bengaluru). The interviews were conducted in the preferred language of the participants ( Kannada for nurses, English for the obstetricians) and audio-recorded. All Kannada interviews were transcribed and translated into English for analysis. The primary data were analyzed using grounded theory approach by NVivo 12 plus Results Health care providers recognized and supported the need for design and implementation of Gestational Diabetes Mellitus screening and management services. While obstetricians were aware of the national guidelines regarding screening and management; nurses mentioned that they had unmet training needs in health promotion. Barriers identified to timely screening and management of Gestational Diabetes Mellitus included unmet training needs of nurses regarding Gestational Diabetes Mellitus, delay in screening of pregnant women accessing antenatal care at private clinics initially and subsequently reporting at public hospital in late gestation, migration of pregnant women due to delivery of first born at natal home, lack of follow up system of deferred cases for gestational diabetes screening, resource deficit, and long waiting hours. Conclusion Provided the fact that there is effectiveness of Gestational Diabetes Mellitus screening and management services, there is a pressing need to develop and improve existing Gestational Diabetes Mellitus Screening and Management services to tackle the growing burden of Gestational Diabetes Mellitus in India. With the urgent need for these services, it needs to be extended to public hospitals.

To review the cumulative outcome of pre-implantation genetic diagnosis (PGD) cycles performed for prevention of sickle cell disease (SCD). Couples referred for PGD for SCD between April 2012 and October 2017 were included. Ovarian stimulation was performed using a short gonadotrophin-releasing hormone (GnRH) antagonist protocol and follicle-stimulating hormone injections. The GnRH agonist was used to trigger oocyte maturation. Oocytes were fertilised using intracytoplasmic sperm injection. Trophectoderm biopsy was performed on day 5 or 6 followed by vitrification. Genetic testing was done using pre-implantation genetic haplotyping. A total of 60 couples started 70 fresh PGD cycles (mean 1·2 cycles/couple) and underwent a total of 74 frozen-embryo-transfer (FET) cycles (mean 1·3 FET/couple). The mean (SD) female age was 33 (4·4) years and the mean (SD) anti-mullerian hormone level was 22·9 (2·8) pmol/l. The cumulative live-birth rate was 54%/PGD cycle started and 63%/couple embarking on PGD. The rate of multiple births was 8%. The cumulative outcome of PGD treatment for prevention of SCD transmission is high and PGD treatment should be offered to all at-risk couples.

Maternal sickle cell disease (SCD) and multiple gestations are well known separately as causes of high-risk pregnancies, however, there is sparse information available on maternal and perinatal outcome when both conditions occur together. This case series describes the outcomes of women with maternal SCD and twin pregnancy in the largest single-center case series to date.Retrospective identification of all twin pregnancies in maternal SCD patients between 2006 and 2016 at Guy's and St. Thomas' Hospital, United Kingdom Results: Eight women were included: seven with HbSS and one with HbSC. Our cohort experienced common SCD-related and pregnancy-related complications such as painful vaso-occlusive crises (VOC), acute chest syndrome (ACS), and pre-eclampsia and less common complications such as peri-partum cardiomyopathy and delayed hemolytic transfusion reaction. Only two out of eight women had relatively uncomplicated pregnancies. Seven out of eight women required transfusion antenatally and there was no maternal or perinatal mortality. A review of the available literature highlighted the lack of available information on this uncommon cohort. It was evident that outcomes have improved over the years, where historical studies demonstrate higher rates of maternal and perinatal mortality.The antenatal and postnatal complications described in our study and literature review highlights the significant morbidity and mortality associated with these high-risk pregnancies.Our case series highlights the advantage of closer monitoring and comprehensive multidisciplinary care in delivering improved clinical outcomes.

Introduction: Sickle cell disease (SCD) is a genetically inherited, recessive mutation of the haemoglobin I²S-gene. Each year, over 300,000 babies are born with SCD, which will have a significant impact on their quality of life and average life expectancy. Currently, for SCD to be tested prenatally, foetal DNA is extracted by amniocentesis, chorionic villus sampling or cordocentesis, and then analysed by polymerase chain reaction (PCR), for instance. These procedures increase the risk of foetal miscarriage by less than 0.5%. SCD may, however, be tested non-invasively using cell-free foetal DNA (cffDNA), which is extracted from maternal blood plasma. In this study, the current accuracy of using cffDNA testing for non-invasive prenatal diagnosis (NIPD) of SCD will be shown.Methods: Using databases such as PubMed, Web of Science and Scopus, this study systematically reviewed existing studies pertaining to the use of cffDNA maternal blood samples for non-invasive prenatal testing (NIPT) or diagnosis (NIPD) for SCD in patients who were at risk of having a baby with SCD. The data collected from the systematic review of the studies was statistically analysed in the form of a meta-analysis, describing the proportion of correct diagnosis results for this method of prenatal testing.Results: Of over 3,600 papers identified from the database searches, only five studies contained data pertaining to the use of cffDNA for prenatal testing of SCD and conformed to the inclusion criteria set out by this study. Collectively, these data showed an average of 81.30% accuracy of diagnosis when using cffDNA to test for SCD, with 18.70% of foetuses incorrectly diagnosed. These data were compiled as a Forest Plot meta-analysis.Conclusion: CffDNA for non-invasive prenatal SCD diagnosis appears to have the potential to be an accurate technique for the testing of this genetic disease, despite not currently indicating a proportion of correct diagnosis results which would encourage the technique for clinical implementation. Whilst there are currently very limited data on the use of this technique for the specific testing of SCD, there is great opportunity for further research into the standardisation and clinical application of this procedure.

Background Non-invasive prenatal diagnosis (NIPD) for sickle-cell disorder (SCD) is moving closer to implementation and studies considering stakeholder preferences are required to underpin strategies for offering NIPD in clinical practice. Objective Determine service user and provider preferences for key attributes of prenatal diagnostic tests for SCD and examine views on NIPD. Method A questionnaire that includes a discrete choice experiment was used to determine the preferences of service users and providers for prenatal tests that varied across three attributes: accuracy, time of test and risk of miscarriage. Results Adults who were carriers of SCD or affected with the condition (N=67) were recruited from haemoglobinopathy clinics at two maternity units. Health professionals, predominately midwives, who offer antenatal care (N=62) were recruited from one maternity unit. No miscarriage risk was a key driver of decision making for both service users and providers. Service providers placed greater emphasis on accuracy than service users. Current uptake of invasive tests was 63%, whilst predicted uptake of NIPD was 93.8%. Many service users (55.4%) and providers (52.5%) think pressure to have prenatal testing will increase when NIPD for SCD becomes available. Conclusions There are clear differences between service users and health professionals’ preferences for prenatal tests for sickle-cell disorder. The safety of NIPD is welcomed by parents and uptake is likely to be high. To promote informed choice, pretest counselling should be balanced and not exclusively focused on test safety. Counselling strategies that are sensitive to feelings of pressure to test will be essential.

Background\ud Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage.\ud \ud Methods\ud In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283.\ud \ud Findings\ud Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group.\ud \ud Interpretation\ud Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset.\ud \ud Funding\ud London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation.

Objectives:Randomised controlled trials are required to address causality in the reported associations between maternal influences and offspring adiposity. The aim of this study was to determine whether an antenatal lifestyle intervention, associated with improvements in maternal diet and reduced gestational weight gain (GWG) in obese pregnant women leads to a reduction in infant adiposity and sustained improvements in maternal lifestyle behaviours at 6 months postpartum.Subjects and methods:We conducted a planned postnatal follow-up of a randomised controlled trial (UK Pregnancies Better Eating and Activity Trial (UPBEAT)) of a complex behavioural intervention targeting maternal diet (glycaemic load (GL) and saturated fat intake) and physical activity in 1555 obese pregnant women. The main outcome measure was infant adiposity, assessed by subscapular and triceps skinfold thicknesses. Maternal diet and physical activity, indices of the familial lifestyle environment, were assessed by questionnaire.Results:A total of 698 (45.9%) infants (342 intervention and 356 standard antenatal care) were followed up at a mean age of 5.92 months. There was no difference in triceps skinfold thickness z-scores between the intervention vs standard care arms (difference −0.14 s.d., 95% confidence interval −0.38 to 0.10, P=0.246), but subscapular skinfold thickness z-score was 0.26 s.d. (−0.49 to −0.02; P=0.03) lower in the intervention arm. Maternal dietary GL (−35.34; −48.0 to −22.67; P

Objectives To assess feasibility of a future randomised controlled trial (RCT) of clinical and cost‐effectiveness of lifestyle information and commercial weight management groups to support postnatal weight management to 12 months post‐birth. Design Two‐arm feasibility trial, with nested mixed‐methods process evaluation. Setting Inner‐city unit, south England. Population Women with body mass indices (BMIs) ≥25 kg/m2 at pregnancy booking or normal BMIs (18.5–24.9 kg/m2) identified with excessive gestational weight gain at 36 weeks of gestation. Methods Randomised to standard care plus commercial weight management sessions commencing 8–16 weeks postnatally or standard care only. Main outcomes Feasibility outcomes included assessment of recruitment, retention, acceptability and economic data collation. Primary and secondary end points included difference between groups in weight 12 months postnatally compared with booking (proposed primary outcome for a future trial), diet, physical activity, smoking, alcohol, mental health, infant feeding, NHS resource use. Results In all, 193 women were randomised: 98 intervention and 95 control; only four women had excessive gestational weight gain. A slightly greater weight change was found among intervention women at 12 months, with greatest benefit. Among women attending ten or more weight management sessions. There was >80% follow up to 12 months, low risk of contamination and no group differences in trial completion. Conclusion It was feasible to recruit and retain women with BMIs ≥25 kg/m2 to an intervention to support postnatal weight management; identification of excessive gestational weight gain requires consideration. Economic modelling could inform out‐of‐trial costs and benefits in a future trial. A definitive trial is an important next step. Tweetable abstract A feasibility RCT of postnatal weight support showed women with BMIs ≥25 kg/m2 can be recruited and followed to 12 months postnatally.

Sickle cell disease (SCD) is the most common genetic haematological disorder. The availability of non-invasive prenatal diagnosis (NIPD) is predicted to increase uptake of prenatal diagnosis for SCD, as it has no perceived procedure-related miscarriage risk. We report the development of a targeted massively parallel sequencing (MPS) assay for the NIPD of fetal SCD using fetal cell-free (cf)DNA from maternal plasma, with no requirement for paternal or proband samples. In all, 64 plasma samples from pregnant women were analysed: 42 from SCD carriers, 15 from women with homozygous (Hb SS) SCD and seven from women with compound heterozygous (Hb SC) SCD. Our assay incorporated a relative mutation dosage assay for maternal carriers and a wild type allele detection assay for affected women (Hb SS/Hb SC). Selective analysis of only smaller cfDNA fragments and modifications to DNA fragment hybridisation capture improved diagnostic accuracy. Clinical sensitivity was 100% and clinical specificity was 100%. One sample with a fetal fraction of

IntroductionA high BMI during and after pregnancy is linked to poor pregnancy outcomes and contributes to long-term maternal obesity, hypertension, and diabetes. Evidence of feasible, effective postnatal interventions is lacking. This randomised controlled trial will assess the feasibility of conducting a future definitive trial to determine effectiveness and cost-effectiveness of lifestyle information and access to Slimming World® (Alfreton, UK) groups for 12 weeks commencing from 8 to 16 weeks postnatally, in relation to supporting longer-term postnatal weight management in women in an ethnically diverse inner city population.Methods/analysisWomen will be recruited from one maternity unit in London. To be eligible, women will be overweight (BMI 25–29.9 kg/m2) or obese (BMI ≥ 30 kg/m2) as identified at their first antenatal contact, or have a normal BMI (18.5–24.9 kg/m2) at booking but gain excessive gestational weight as assessed at 36 weeks gestation. Women will be aged 18 and over, can speak and read English, expecting a single baby, and will not have accessed weight management groups in this pregnancy. Women will be randomly allocated to standard care plus lifestyle information and access to Slimming World® (Alfreton, UK) groups or standard care only. A sample of 130 women is required.Feasibility trial objectives reflect those considered most important inform a decision about undertaking a definitive future trial. These include estimation of impact of lifestyle information and postnatal access to Slimming World® (Alfreton, UK) on maternal weight change between antenatal booking weight and weight at 12 months postbirth, recruitment rate and time to recruitment, retention rate, influence of lifestyle information and Slimming World® (Alfreton, UK) groups on weight management, diet, physical activity, breastfeeding, smoking cessation, alcohol intake, physical and mental health, infant health, and health-related quality of life 6 and 12 months postnatally. An embedded process evaluation will assess acceptability of study processes and procedures to women.Ethics/disseminationLondon–Camberwell St Giles Research Ethics Committee, reference: 16/LO/1422. Outcomes will be disseminated in peer-reviewed journals and presentations at national and international conferences.Trial registrationTrial registration number:ISRCTN 39186148. Protocol version number: v7, 13 August 17. Trial sponsor: King’s College London.

Pulmonary hypertension is associated with 36% mortality in pregnancy, and 6–10% of patients with sickle cell disease have pulmonary hypertension. Tricuspid regurgitant velocity ≥2.5 m/s on echocardiography is a well validated means of screening for pulmonary hypertension in the non-pregnant population. This is a pilot study to determine if this is a useful non-invasive screening test for pulmonary hypertension in pregnancy, and whether raised tricuspid regurgitant velocity ≥2.5 m/s was associated with poor outcomes. This is a cross-sectional study over a five-year period in a tertiary referral centre with a specialised multidisciplinary clinic for pregnant women with sickle cell disease. Women with sickle cell disease, no prior pulmonary hypertension and singleton pregnancies who had echocardiography with a measurable tricuspid regurgitant velocity in pregnancy were included. There were 34 pregnancies, of which eight had tricuspid regurgitant velocity ≥2.5 m/s. There were no significant differences in their characteristics, sickle cell-related complications or medical co-morbidities. The women with tricuspid regurgitant velocity ≥2.5 m/s had similar obstetric and perinatal outcomes as those with a tricuspid regurgitant velocity

OBJECTIVES: To evaluate the effect of interpregnancy body mass index (BMI) change on pregnancy outcomes, including large-for-gestational-age babies (LGA), small-for-gestational-age babies (SGA), macrosomia, gestational diabetes mellitus (GDM) and caesarean section (CS). DESIGN: Systematic review and meta-analysis of observational cohort studies. DATA SOURCES: Literature searches were performed across Cochrane, MEDLINE, EMBASE, CINAHL, Global Health and MIDIRS databases. STUDY SELECTION: Observational cohort studies with participants parity from 0 to 1. MAIN OUTCOME MEASURES: Adjusted ORs (aORs) with 95% CIs were used to evaluate the association between interpregnancy BMI change on five outcomes. RESULTS: 925 065 women with singleton births from parity 0 to 1 were included in the meta-analysis of 11 studies selected from 924 identified studies. A substantial increase in interpregnancy BMI (>3 BMI units) was associated with an increased risk of LGA (aOR 1.85, 95% CI 1.71 to 2.00, p

BACKGROUND: Behavioural interventions might improve clinical outcomes in pregnant women who are obese. We aimed to investigate whether a complex intervention addressing diet and physical activity could reduce the incidence of gestational diabetes and large-for-gestational-age infants.METHODS: The UK Pregnancies Better Eating and Activity Trial (UPBEAT) is a randomised controlled trial done at antenatal clinics in eight hospitals in multi-ethnic, inner-city locations in the UK. We recruited pregnant women (15-18 weeks plus 6 days of gestation) older than 16 years who were obese (BMI ≥30 kg/m(2)). We randomly assigned participants to either a behavioural intervention or standard antenatal care with an internet-based, computer-generated, randomisation procedure, minimising by age, ethnic origin, centre, BMI, and parity. The intervention was delivered once a week through eight health trainer-led sessions. Primary outcomes were gestational diabetes (diagnosed with an oral glucose tolerance test and by criteria from the International Association of Diabetes in Pregnancy Study Groups) and large-for-gestational-age infants (≥90th customised birthweight centile). Analysis was by intention to treat. This trial is registered with Current Controlled Trials, ISCRTN89971375. Recruitment and pregnancy outcomes are complete but childhood follow-up is ongoing.FINDINGS: Between March 31, 2009, and June 2, 2014, we assessed 8820 women for eligibility and recruited 1555, with a mean BMI of 36·3 kg/m(2) (SD 4·8). 772 were randomly assigned to standard antenatal care and 783 were allocated the behavioural intervention, of which 651 and 629 women, respectively, completed an oral glucose tolerance test. Gestational diabetes was reported in 172 (26%) women in the standard care group compared with 160 (25%) in the intervention group (risk ratio 0·96, 95% CI 0·79-1·16; p=0·68). 61 (8%) of 751 babies in the standard care group were large for gestational age compared with 71 (9%) of 761 in the intervention group (1·15, 0·83-1·59; p=0·40). Thus, the primary outcomes did not differ between groups, despite improvements in some maternal secondary outcomes in the intervention group, including reduced dietary glycaemic load, gestational weight gain, and maternal sum-of-skinfold thicknesses, and increased physical activity. Adverse events included neonatal death (two in the standard care group and three in the intervention group) and fetal death in utero (ten in the standard care group and six in the intervention group). No maternal deaths were reported. Incidence of miscarriage (2% in the standard care group vs 2% in the intervention group), major obstetric haemorrhage (1% vs 3%), and small-for-gestational-age infants (≤5th customised birthweight centile; 6% vs 5%) did not differ between groups.INTERPRETATION: A behavioural intervention addressing diet and physical activity in women with obesity during pregnancy is not adequate to prevent gestational diabetes, or to reduce the incidence of large-for-gestational-age infants.FUNDING: National Institute for Health Research, Guys and St Thomas' Charity, Chief Scientist Office Scotland, Tommy's Charity.

A systematic review and meta-analysis of observational studies were conducted to quantify the association between sickle cell disease in pregnancy and adverse maternal and perinatal outcomes. Data sources (Medline, Embase, Maternity and Infant care, Cochrane, Web of Science, Popline) were searched for publications to June 2014. Eligibility criteria included observational studies reporting maternal and perinatal health outcomes in pregnant women with sickle cell disease against a comparative group of pregnant women without sickle cell disease. Twenty-one studies (including 26,349 women with sickle cell disease; 26,151,746 women without sickle cell disease) were eligible for inclusion. Pregnancies in women with HbSS genotype, compared with women without sickle cell disease, were at increased risk of maternal mortality (relative risk [RR], 5.98; 95% confidence interval [CI], 1.94-18.44), preeclampsia (RR, 2.43; 95% CI, 1.75-3.39), stillbirth (RR, 3.94; 95% CI, 2.60-5.96), preterm delivery (RR, 2.21; 95% CI, 1.47-3.31), and small for gestational age infants (RR, 3.72; 95% CI, 2.32-5.98). Meta-regression demonstrated that genotype (HbSS vs HbSC), low gross national income, and high study quality were associated with increased RRs. Despite advances in the management of sickle cell disease, obstetrics, and neonatal medicine, pregnancies complicated by the disease remain associated with increased risk of adverse maternal and perinatal outcomes.

Objective: To investigate the ethnicity-specific association between body mass index (BMI) and diabetes in pregnancy, with a focus on the appropriateness of using BMI cut-offs to identify pregnant women at risk of diabetes. Study design: Analysis of routinely-collected data from a maternity unit in London, UK. Data were available on 53 264 women delivering between 2004 and 2012. Logistic regression was used to explore the association between diabetes in pregnancy and BMI among women of different ethnicities, and adjusted probability estimates were used to derive risk equivalent cut-offs. ROC curve analysis was used to assess the performance of BMI as a predictor of diabetes in pregnancy. Results: The prevalence of diabetes in pregnancy was 2.3% overall; highest in South and East Asian women (4.6% and 3.7%). In adjusted analysis, BMI category was strongly associated with diabetes in all ethnic groups. Modelled as a continuous variable with a quadratic term, BMI was an acceptable predictor of diabetes according to ROC curve analysis. Applying a BMI cut-off of 30 kg/m2 would identify just over half of Black women with diabetes in pregnancy, a third of White (32%) and South Asian (35%) women, but only 13% of East Asian women. The ‘risk equivalent’ (comparable to 30 kg/m2 in White women) threshold for South Asian and East Asian women was approximately 21 kg/m2, and 27.5 kg/m2 for Black women. Conclusions: This study suggests that current BMI thresholds are likely to be ineffective for diabetes screening in South and East Asian women, as many cases of diabetes will occur at low BMI levels. Our results suggest that East Asian women appear to face a similarly high risk of diabetes to South Asian women. Current UK guidelines recommend diabetes screening should be offered to all pregnant South Asian women; extending this recommendation to include women of East Asian ethnicity may be appropriate.

BackgroundObesity in pregnancy is associated with insulin resistance, which underpins many common complications including gestational diabetes mellitus (GDM) and fetal macrosomia.ObjectivesTo assess the effect of a complex behavioural intervention based on diet and physical activity (PA) on the risk of GDM and delivery of a large-for-gestational age (LGA) infant.DesignThree phases: (1) the development phase, (2) the pilot study and (3) a multicentre randomised controlled trial (RCT) comparing a behavioural intervention to improve glycaemic control with standard antenatal care in obese pregnant women. A cost–utility analysis was undertaken to estimate the cost-effectiveness of the health training (intervention) over and above standard care (control).SettingPilot study: antenatal clinics in four inner-city UK hospitals. RCT: eight antenatal clinics in eight UK inner-city hospitals.ParticipantsWomen were eligible for inclusion if they had a body mass index of ≥ 30 kg/m2, were pregnant with a single fetus and at 15+0to 18+6weeks’ gestation, were able to give written informed consent and were without predefined disorders.InterventionThe intervention comprised an initial session with a health trainer, followed by eight weekly sessions. Dietary advice recommended foods with a low dietary glycaemic index, avoidance of sugar-sweetened beverages and reduced saturated fats. Women were encouraged to increase daily PA.Main outcome measuresDevelopment phase: intervention development, acceptability and optimal approach for delivery. Pilot study: change in dietary and PA behaviours at 28 weeks’ gestation. RCT: the primary outcome of the RCT was, for the mother, GDM [as measured by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)’s diagnostic criteria] and, for the infant, LGA delivery (i.e. customised birthweight ≥ 90th centile for gestational age).ResultsDevelopment phase: following a literature meta-analysis, a study of dietary intention questionnaires and semistructured interviews, an intervention based on behavioural science was developed that incorporated optimal and acceptable methods for delivery. Pilot study: the pilot study demonstrated improvement in dietary behaviours in the intervention compared with the standard care arm but no increase in objectively measured PA. Process evaluation demonstrated feasibility and general acceptability. RCT: the RCT showed no effect of the intervention on GDM in obese pregnant women or the number of deliveries of LGA infants. There was a reduction in dietary glycaemic load (GL) and reduced saturated fat intake, an increase in PA and a modest reduction in gestational weight gain, all secondary outcomes. Lower than expected was the number of LGA infant deliveries in all women, which suggested that universal screening for GDM with IADPSG’s diagnostic criteria, and subsequent treatment, may reduce the number of deliveries of LGA infants. According to the cost–utility analysis, the estimated probability that the UK Pregnancies Better Eating and Activity Trial (UPBEAT) behavioural intervention is cost-effective at the £30,000/quality-adjusted life-year willingness-to-pay threshold was 1%.LimitationsIncluded the high refusal rate for participation and self-reported assessment of diet and PA.ConclusionsThe UPBEAT intervention, an intense theoretically based intervention in obese pregnant women, did not reduce the risk of GDM in women or the number of LGA infant deliveries, despite successfully reducing the dietary GL. Based on total cost to the NHS provider and health gains, the UPBEAT intervention provided no supporting evidence to suggest that the intervention represents value for money based on the National Institute for Health and Care Excellence benchmarks for cost-effectiveness.Future workAlternative strategies for reducing the risk of GDM in obese pregnant women and the number of LGA infant deliveries should be considered, including development of clinically effective interventions to prevent obesity in women of reproductive age, of clinically effective interventions to reduce weight retention following pregnancy and of risk stratification tools in early pregnancy.Trial registrationCurrent Controlled Trials ISRCTN89971375 and UK Clinical Research Network Portfolio 5035.FundingThis project was funded by the NIHR Programme Grant for Applied Research programme and will be published in full inProgramme Grants for Applied Research, Vol. 5, No. 10. See the NIHR journals library website for further project information. Contributions to funding were also provided by the Chief Scientist Office CZB/4/680, Scottish Government Health Directorates, Edinburgh; Guys and St Thomas’ Charity, Tommy’s Charity (Lucilla Poston, Annette L Briley, Paul T Seed) and the NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, UK and the Academy of Finland, Finland. Keith M Godfrey was supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Centre. Lucilla Poston and Keith M Godfrey were supported by the European Union’s Seventh Framework Programme (FP7/2007-2013), project EarlyNutrition under grant agreement number 289346.

Commentary on: Boafor TK, Olayemi E, Galadanci N, et al. Pregnancy outcomes in women with sickle-cell disease in low and high income countries: a systematic review and meta-analysis. BJOG 2016;123:691–8.[OpenUrl][1] Sickle cell disease (SCD) is among the most common genetic conditions globally.1 SCD has a significant worldwide public … [1]: {openurl}?query=rft.jtitle%253DBJOG%26rft.volume%253D123%26rft.spage%253D691%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx

Sickle cell disease (SCD) is the most common genetic haematological disorder worldwide. Around 300.000 affected infants are born every year, including at least 1000 in the United States. Prenatal diagnosis is currently carried out using amniotic fluid or chorionic villus sampling. These invasive procedures are perceived to have a small risk of miscarriage. The availability of non-invasive prenatal diagnosis (NIPD) is predicted to increase uptake of prenatal diagnosis for SCD, as it has no perceived miscarriage risk. NIPD may also be more readily implemented than invasive prenatal diagnosis in the low-resource countries in which SCD is the most prevalent. However, accurate NIPD of autosomal recessive disorders such as sickle cell disease has proven challenging as this requires detection of fetal inheritance of a maternal allele from a mixed maternal-fetal pool of cell-free DNA. We report the development of a targeted massively parallel sequencing assay for the NIPD of fetal SCD using cell-free fetal DNA from maternal plasma. No paternal or previous offspring samples were required. 44 clinical samples were analysed, including 37 plasma samples from pregnant SCD carriers and 7 plasma samples from women with SCD due to Hb SC. We used a relative mutation dosage based approach for the 37 samples from maternal SCD carriers (Hb AS or Hb AC), integrating Unique Molecular Identifiers (UMIs) into the analysis to improve the accuracy of wildtype and mutant allele counts. We used a separate wildtype allele detection approach for the 7 samples from women with compound heterozygous SCD, in whom the detection of wildtype cell-free DNA indicates the presence of a carrier fetus. The success of the assay was evaluated by comparing results with the established fetal sickle status as determined through either invasive prenatal diagnosis or newborn screening. During development, two key factors improved the accuracy of the results: i) Selective analysis of only smaller cell-free DNA fragments enhanced the fetal fraction for all samples, with greater effects observed in samples from earlier gestations. This approach improved diagnostic accuracy: for 3 out of 44 samples, the genotype was inconclusive or incorrect before size selection, but correct after size selection. ii) Modifications to DNA fragment hybridisation capture optimised the diversity of Unique Molecular Identifier-tagged molecules analysed. This led to improvements in the results obtained for 5 samples, with 3 previously inconclusive samples correctly called and 2 previously discrepant results moved into the inconclusive range. In total, 37 results were concordant with the established fetal sickle status; this included 30/37 samples from carrier women and 7/7 samples from women with sickle cell disease due to Hb SC. The remaining 7 carrier samples gave an inconclusive result, which for 3 samples was attributed to a low fetal fraction. Samples from as early as 8 weeks gestation were successfully genotyped. There were no false positive or false negative results. This study is the largest to use NGS-based NIPD on clinical plasma samples from pregnancies at risk of SCD. Efforts to validate the assay on a larger sample cohort and to reduce the inconclusive rate are warranted. This study shows that NIPD for SCD is approaching clinical utility and has the potential to provide increased choice to women with pregnancies at risk of sickle cell disease. Disclosures Silcock: Nonacus Ltd.: Employment.

A 37-year-old Indian woman in her first pregnancy was referred to the preterm surveillance clinic as she was carrying dichorionic diamniotic twins from assisted conception. She had no other risk fa...

Background Understanding dietary patterns in obese pregnant women will inform future intervention strategies to improve pregnancy outcomes and the health of the child. The aim of this study was to investigate the effect of a behavioral intervention of diet and physical activity advice on dietary patterns in obese pregnant woman participating in the UPBEAT study, and to explore associations of dietary patterns with pregnancy outcomes. Methods In the UPBEAT randomized controlled trial, pregnant obese women from eight UK multi-ethnic, inner-city populations were randomly assigned to receive a diet/physical activity intervention or standard antenatal care. The dietary intervention aimed to reduce glycemic load and saturated fat intake. Diet was assessed using a food frequency questionnaire (FFQ) at baseline (15+0-18+6 weeks’ gestation), post intervention (27+0-28+6 weeks) and in late pregnancy (34+0-36+0 weeks). Dietary patterns were characterized using factor analysis of the baseline FFQ data, and changes compared in the control and intervention arms. Patterns were related to pregnancy outcomes in the combined control/intervention cohort (n = 1023). Results Four distinct baseline dietary patterns were defined; Fruit and vegetables, African/Caribbean, Processed, and Snacks, which were differently associated with social and demographic factors. The UPBEAT intervention significantly reduced the Processed (−0.14; 95% CI −0.19, −0.08, P