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.

Anal endosonographic assessment of the accuracy of clinical diagnosis of obstetric anal sphincter injury.

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 < 0.001) than those without a confirmed sphincter injury. Three hundred ninety-three (34.8%) women reported bowel symptoms, with those with endosonographic evidence of injury more likely to develop flatus incontinence. 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.

Health care professionals' perspectives on screening and management of gestational diabetes mellitus in public hospitals of South India - a qualitative study.

BACKGROUND: Women developing Gestational Diabetes Mellitus (GDM) are subsequently at a higher risk of developing Type 2 Diabetes later in life. Screening and effective management of women with GDM are essential in preventing progression to type 2 diabetes mellitus. We aimed to explore the perspectives of healthcare providers regarding the barriers from the health system context that restrict the timely screening and effective management of GDM. 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 the grounded theory approach by NVivo 12 plus. The findings are put into perspective using the socio-ecological model. RESULTS: Health care providers identified delayed visits to public hospitals and stress on household-level responsibilities as barriers at the individual level for GDM screening. Also, migration of pregnant women to their natal homes during first pregnancy is a cultural barrier in addition to health system barriers such as unmet nurse training needs, long waiting hours, uneven power dynamics, lack of follow-up, resource scarcity, and lack of supportive oversight. The barriers for GDM management included non-reporting women to follow - up visits, irregular self-monitoring of drug and blood sugar, trained staff shortage, ineffective tracking, and lack of standardized protocol. CONCLUSION: There is a pressing need to develop and improve existing GDM Screening and Management services to tackle the growing burden of GDM in public hospitals of India.

Cumulative outcome of pre-implantation genetic diagnosis for sickle cell disease: a 5-year review.

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-müllerian 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.

A novel non-invasive prenatal sickle cell disease test for all at-risk pregnancies.

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 <4% was correctly called as 'unaffected', but with a discordant genotype (Hb AA rather than Hb AS). Six samples gave inconclusive results, of which two had a fetal fraction of <4%. This study demonstrates that NIPD for SCD is approaching clinical utility.

Pulmonary complications for women with sickle cell disease in pregnancy: systematic review and meta-analysis.

BACKGROUND: Sickle 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. METHODS: MEDLINE, 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. FINDINGS: Twenty-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). INTERPRETATION: This 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 NUMBER: CRD42019124708.

Does first-trimester serum pregnancy-associated plasma protein A differ in pregnant women with sickle cell disease?

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.

Adverse maternal and perinatal outcomes in pregnant women with sickle cell disease: systematic review and meta-analysis.

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.

Preferences for prenatal diagnosis of sickle-cell disorder: A discrete choice experiment comparing potential service users and health-care providers.

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.

Dietary patterns in obese pregnant women; influence of a behavioral intervention of diet and physical activity in the UPBEAT randomized controlled trial.

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 <0.0001) and Snacks (-0.24; 95% CI -0.31, -0.17, P <0.0001) pattern scores. In the adjusted model, baseline scores for the African/Caribbean (quartile 4 compared with quartile 1: OR = 2.46; 95% CI 1.41, 4.30) and Processed (quartile 4 compared with quartile 1: OR = 2.05; 95% CI 1.23, 3.41) patterns in the entire cohort were associated with increased risk of gestational diabetes. CONCLUSIONS: In a diverse cohort of obese pregnant women an intensive dietary intervention improved Processed and Snack dietary pattern scores. African/Caribbean and Processed patterns were associated with an increased risk of gestational diabetes, and provide potential targets for future interventions. TRIAL REGISTRATION: Current controlled trials; ISRCTN89971375.

Pregnancy outcome in patients with sickle cell disease in the UK--a national cohort study comparing sickle cell anaemia (HbSS) with HbSC disease.

We describe the findings from a national study of maternal and fetal outcomes of pregnancy in women with sickle cell disease (SCD). Data were collected via the United Kingdom Obstetric Surveillance System between 1 February 2010 and 31 January 2011 from 109 women, of whom 51 (46·8%) had HbSS and 44 (40·4%) had HbSC. Data included antenatal, maternal and fetal outcomes. Comparisons were made between women with HbSS and HbSC. Incidence of complications were acute pain (57%), blood transfusion (26%), urinary tract infection (UTI; 12%) and critical care unit admission (23%) and these were all more common in women with HbSS than HbSC. There was no difference in the incidence of acute chest syndrome, hypertension and venous thromboembolism between HbSS and HbSC. Women with HbSS were more likely to deliver at <37 weeks gestation (P = 0·01) and their babies were more likely to have reduced birth weight. Delivery at <34 weeks was increased in both HbSS and HbSC women (5·9% vs. 4·6%) compared to national data. This study confirms a high rate of maternal and fetal complications in mothers with SCD, even in women with HbSC, which has previously been considered to have a more benign phenotype in pregnancy.

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.

A complex intervention to improve pregnancy outcome in obese women; the UPBEAT randomised controlled trial.

BACKGROUND: Despite the widespread recognition that obesity in pregnant women is associated with adverse outcomes for mother and child, there is no intervention proven to reduce the risk of these complications. The primary aim of this randomised controlled trial is to assess in obese pregnant women, whether a complex behavioural intervention, based on changing diet (to foods with a lower glycemic index) and physical activity, will reduce the risk of gestational diabetes (GDM) and delivery of a large for gestational age (LGA) infant. A secondary aim is to determine whether the intervention lowers the long term risk of obesity in the offspring. METHODS/DESIGN: Multicentre randomised controlled trial comparing a behavioural intervention designed to improve glycemic control with standard antenatal care in obese pregnant women.Inclusion criteria; women with a BMI ≥30 kg/m2 and a singleton pregnancy between 15+0 weeks and 18+6 weeks' gestation. Exclusion criteria; pre-defined, pre-existing diseases and multiple pregnancy. Randomisation is on-line by a computer generated programme and is minimised by BMI category, maternal age, ethnicity, parity and centre. Intervention; this is delivered by a health trainer over 8 sessions. Based on control theory, with elements of social cognitive theory, the intervention is designed to improve maternal glycemic control. Women randomised to the control arm receive standard antenatal care until delivery according to local guidelines. All women have a 75 g oral glucose tolerance test at 27+0- 28+6 weeks' gestation.Primary outcome; Maternal: diagnosis of GDM, according to the International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria. Neonatal; infant LGA defined as >90th customised birth weight centile.Sample size; 1546 women to provide 80% power to detect a 25% reduction in the incidence of GDM and a 30% reduction in infants large for gestational age. DISCUSSION: All aspects of this protocol have been evaluated in a pilot randomised controlled trial, with subsequent optimisation of the intervention. The findings of this trial will inform whether lifestyle mediated improvement of glycemic control in obese pregnant women can minimise the risk of pregnancy complications. TRIAL REGISTRATION: Current controlled trials; ISRCTN89971375.

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.

Developing a complex intervention for diet and activity behaviour change in obese pregnant women (the UPBEAT trial); assessment of behavioural change and process evaluation in a pilot randomised controlled trial.

BACKGROUND: Complex interventions in obese pregnant women should be theoretically based, feasible and shown to demonstrate anticipated behavioural change prior to inception of large randomised controlled trials (RCTs). The aim was to determine if a) a complex intervention in obese pregnant women leads to anticipated changes in diet and physical activity behaviours, and b) to refine the intervention protocol through process evaluation of intervention fidelity. METHODS: We undertook a pilot RCT of a complex intervention in obese pregnant women, comparing routine antenatal care with an intervention to reduce dietary glycaemic load and saturated fat intake, and increase physical activity. Subjects included 183 obese pregnant women (mean BMI 36.3 kg/m2). RESULTS: Compared to women in the control arm, women in the intervention arm had a significant reduction in dietary glycaemic load (33 points, 95% CI -47 to -20), (p < 0.001) and saturated fat intake (-1.6% energy, 95% CI -2.8 to -0. 3) at 28 weeks' gestation. Objectively measured physical activity did not change. Physical discomfort and sustained barriers to physical activity were common at 28 weeks' gestation. Process evaluation identified barriers to recruitment, group attendance and compliance, leading to modification of intervention delivery. CONCLUSIONS: This pilot trial of a complex intervention in obese pregnant women suggests greater potential for change in dietary intake than for change in physical activity, and through process evaluation illustrates the considerable advantage of performing an exploratory trial of a complex intervention in obese pregnant women before undertaking a large RCT. TRIAL REGISTRATION NUMBER: ISRCTN89971375.

Development and validation of a measure of health literacy in the UK: the newest vital sign.

BACKGROUND: Health literacy (HL) is an important public health issue. Current measures have drawbacks in length and/or acceptability. The US-developed Newest Vital Sign (NVS) health literacy instrument measures both reading comprehension and numeracy skills using a nutrition label, takes 3 minutes to administer, and has proven to be acceptable to research subjects. This study aimed to amend and validate it for the UK population. METHODS: We used a three-stage process; (1) a Delphi study with academic and clinical experts to amend the NVS label to reflect UK nutrition labeling (2) community-based cognitive testing to assess and improve ease of understanding and acceptability of the test (3) validation of the NVS-UK against an accepted standard test of health literacy, the Test of Functional Health Literacy in Adults (TOFHLA) (Pearson's r and the area under the Receiver Operating Characteristic (ROC) curve) and participant educational level. A sample size calculation indicated that 250 participants would be required. Inclusion criteria were age 18-75 years and ability to converse in English. We excluded people working in the health field and those with impaired vision or inability to undertake the interview due to cognitive impairment or inability to converse in English. RESULTS: In the Delphi study, 28 experts reached consensus (3 cycles). Cognitive testing (80 participants) yielded an instrument that needed no further refinement. Validation testing (337 participants) showed high internal consistency (Cronbach's Alpha = 0.74). Validation against the TOFHLA demonstrated a Pearson's r of 0.49 and an area under the ROC curve of 0.81. CONCLUSIONS: The NVS-UK is a valid measure of HL. Its acceptability and ease of application makes it an ideal tool for use in the UK. It has potential uses in public health research including epidemiological surveys and randomized controlled trials, and in enabling practitioners to tailor care to patient need.

Expecting more: the case for incorporating fertility services into comprehensive sickle cell disease care.

Assisted reproductive technologies (ART) are not yet systematically available to people with sickle cell disease or their parents. Fertility care for these groups requires addressing sickle cell disease-associated infertility risks, fertility preservation options, pregnancy possibilities and outcomes, and, when needed, infertility treatment. People with a chance of having a child with sickle cell disease can use in-vitro fertilisation with preimplantation genetic testing to conceive a child unaffected by sickle cell disease. Also, parents of children with sickle cell disease can use this technology to identify embryos to become potential future matched sibling donors for stem cell transplant. In the USA, disparities in fertility care for the sickle cell disease community are especially stark. Universal screening of newborn babies' identifies sickle cell disease and sickle cell trait, guidelines direct preconception genetic carrier screening, and standard-of-care fertility preserving options exist. However, potentially transformative treatments and cures for patients with sickle cell disease are not used due to iatrogenic infertility concerns. In diversely resourced care settings, obstacles to providing fertility care to people affected by sickle cell disease persist. In this Viewpoint, we contend that fertility care should be incorporated into the comprehensive care model for sickle cell disease, supporting alignment of treatment goals with reproductive life plans and delivering on the promise of individualised high-quality care for people with sickle cell disease and their families. We consider the obligation to provide fertility care in light of medical evidence, with acknowledgment of formidable obstacles to optimising care, and powerful historical and ethical considerations.

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).

Lifestyle interventions for overweight and obese pregnant women to improve pregnancy outcome: systematic review and meta-analysis.

BACKGROUND: Overweight and obesity pose a big challenge to pregnancy as they are associated with adverse maternal and perinatal outcome. Evidence of lifestyle intervention resulting in improved pregnancy outcome is conflicting. Hence the objective of this study is to determine the efficacy of antenatal dietary, activity, behaviour or lifestyle interventions in overweight and obese pregnant women to improve maternal and perinatal outcomes. METHODS: A systematic review and meta-analyses of randomised and non-randomised clinical trials following prior registration (CRD420111122 http://www.crd.york.ac.uk/PROSPERO) and PRISMA guidelines was employed. A search of the Cochrane Library, EMBASE, MEDLINE, CINAHL, Maternity and Infant care and eight other databases for studies published prior to January 2012 was undertaken. Electronic literature searches, study selection, methodology and quality appraisal were performed independently by two authors. Methodological quality of the studies was assessed according to Cochrane risk of bias tool. All appropriate randomised and non-randomised clinical trials were included while exclusions consisted of interventions in pregnant women who were not overweight or obese, had pre-existing diabetes or polycystic ovarian syndrome, and systematic reviews. Maternal outcome measures, including maternal gestational weight gain, gestational diabetes and Caesarean section, were documented. Fetal outcomes, including large for gestational age and macrosomia (birth weight > 4 kg), were also documented. RESULTS: Thirteen randomised and six non-randomised clinical trials were identified and included in the meta-analysis. The evidence suggests antenatal dietary and lifestyle intervention in obese pregnant women reduces maternal pregnancy weight gain (10 randomised clinical trials; n = 1228; -2.21 kg (95% confidence interval -2.86 kg to -1.59 kg)) and a trend towards a reduction in the prevalence of gestational diabetes (six randomised clinical trials; n = 1,011; odds ratio 0.80 (95% confidence interval 0.58 to 1.10)). There were no clear differences reported for other outcomes such as Caesarean delivery, large for gestational age, birth weight or macrosomia. All available studies were assessed to be of low to medium quality. CONCLUSION: Antenatal lifestyle intervention is associated with restricted gestational weight gain and a trend towards a reduced prevalence of gestational diabetes in the overweight and obese population. These findings need to be interpreted with caution as the available studies were of poor to medium quality.