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Background/Aims: Iron deficiency (ID) and iron deficiency anemia (IDA) are global health concerns associated with adverse perinatal effects. Despite efforts taken at the international level, there is no consensus on unified prevention/treatment strategies, largely stemming from inconsistencies of outcome reporting. Our objective was to comprehensively assess outcome reporting perinatal iron intervention trials as Phase 1 of core outcome set (COS) development to inform future research. Methods: Systematic search in MEDLINE, EMBASE, Cochrane Databases, and CINAHL (January 2000 – April 2016), with inclusion of trials involving pregnant or postpartum women with ID/IDA confirmed before recruitment. Articles were independently screened and selected by 2 reviewers; data were extracted in duplicate. Quality was assessed using published scoring systems. Outcome definitions and measurement methods were tabulated. Results: Of 7,046 citations, 33 randomized controlled trials were included. Sixty-nine reported outcomes were categorized into 8 domains. High methodological quality characterized 25 (76%) studies. Reporting quality was low in 16 (49%), moderate in 13 (39%), and high in 4 (12%) studies. Variation was greatest for outcome definition, timing of assessment and measurement methods. Conclusion: This review identifies a comprehensive long-list of outcomes reported of perinatal iron interventions for ID/IDA. Beyond highlighting existing variation in outcome reporting, it provides a foundation for development of a COS for future trials.

Summary Background Numerous iron preparations are available for the treatment of iron deficiency anaemia in pregnancy. We aimed to provide a summary of the effectiveness and safety of iron preparations used in this setting. Methods We did a systematic review and network meta-analysis of randomised trials. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, trial registers, and grey literature for trials published in any language from Jan 1, 2011, to Feb 28, 2021. We included trials including pregnant women with iron deficiency anaemia and evaluating iron preparations, irrespective of administration route, with at least 60 mg of elemental iron, in comparison with another iron or non-iron preparation. Three authors independently selected studies, extracted data, and did a risk of bias assessment using the Cochrane tool (version 1.0). The primary outcome was the effectiveness of iron preparations, evaluated by changes in haemoglobin concentration at 4 weeks from baseline. The secondary outcomes were change in serum ferritin concentration at 4 weeks from baseline and treatment-related severe and non-severe adverse events. We did random-effects pairwise and network meta-analyses. Side-effects were reported descriptively for each trial. This study is registered with PROSPERO, CRD42018100822. Findings Among 3037 records screened, 128 full-text articles were further assessed for eligibility. Of the 53 eligible trials (reporting on 9145 women), 30 (15 interventions; 3243 women) contributed data to the network meta-analysis for haemoglobin and 15 (nine interventions; 1396 women) for serum ferritin. The risk of bias varied across the trials contributing to network meta-analysis, with 22 of 30 trials in the network meta-analysis for haemoglobin judged to have a high or medium global risk of bias. Compared with oral ferrous sulfate, intravenous iron sucrose improved both haemoglobin (mean difference 7·17 g/L, 95% CI 2·62–11·73; seven trials) and serum ferritin (mean difference 49·66 μg/L, 13·63–85·69; four trials), and intravenous ferric carboxymaltose improved haemoglobin (mean difference 8·52 g/L, 0·51–16·53; one trial). The evidence for other interventions compared with ferrous sulfate was insufficient. The most common side-effects with oral iron preparations were gastrointestinal effects (nausea, vomiting, and altered bowel movements). Side-effects were less common with parenteral iron preparations, although these included local pain, skin irratation, and, on rare occasions, allergic reactions. Interpretation Iron preparations for treatment of iron deficiency anaemia in pregnancy vary in effectiveness, with good evidence of benefit for intravenous iron sucrose and some evidence for intravenous ferric carboxymaltose. Clinicians and policy makers should consider the effectiveness of individual preparations before administration, to ensure effective treatment. Funding None.

IntroductionThe incidence of severe postpartum haemorrhage (PPH) that requires blood transfusion is on the increase. Fibrinogen levels have been shown to drop early and significantly during PPH, which is associated with worse outcomes. Early fibrinogen replacement could potentially improve outcomes. No studies have investigated the clinical impact of early cryoprecipitate transfusion in PPH. Prior to performing a full-scale trial, a pilot study is needed to determine feasibility of the intervention and recruitment.MethodsACROBAT is a cluster-randomised pilot study with a qualitative evaluation. Four large London maternity units are randomised to either the intervention or control group. The intervention group will adapt their major obstetric haemorrhage procedures to administer cryoprecipitate early for primary PPH. The control group will retain their standard of care.We include women at >24 weeks gestation who are actively bleeding within 24 hours of delivery and for whom transfusion of red blood cells (RBCs) has been started. We exclude women who decline blood transfusions in advance or have inherited Factor XIII or fibrinogen deficiency. Due to the emergency nature of the intervention, informed consent for administering the intervention is waived.The primary objective is to assess the feasibility of administering cryoprecipitate within 90 min of RBC request, as compared with standard treatment where cryoprecipitate is given later or not at all. Secondary objectives include the feasibility of recruitment and data collection, reasons for and barriers to consent, preliminary maternal clinical outcomes, identification of the optimal infrastructure pathways for study delivery, and acceptability of the intervention and outcomes.Ethics and disseminationThe trial has approvals from the London—Brighton & Sussex Research Ethics Committee (ref. 18/LO/2062), the Confidentiality Advisory Group (ref. 18/CAG/0199) and Health Research Authority (IRAS number 237959). Data analysis and publication of manuscripts will start in Q3 2020.Trial registration numberISRCTN12146519.

IntroductionUp to half of all women diagnosed with gestational diabetes mellitus develop type 2 diabetes within 5 years after delivery. Metformin is effective in preventing type 2 diabetes in high-risk non-pregnant individuals, but its effect when commenced in the postnatal period is not known. We plan to assess the feasibility of evaluating metformin versus placebo in minimising the risk of dysglycaemia including type 2 diabetes after delivery in postnatal women with a history of gestational diabetes through a randomised trial.Methods and analysisOptimising health outcomes with Metformin to prevent diAbetes After pregnancy (OMAhA) is a multicentre placebo-controlled double-blind randomised feasibility trial, where we will randomly allocate 160 postnatal women with gestational diabetes treated with medication to either metformin (intervention) or placebo (control) tablets to be taken until 1 year after delivery. The primary outcomes are rates of recruitment, randomisation, adherence and attrition. The secondary outcomes are maternal dysglycaemia, cost and quality of life outcomes in both arms, and acceptability of the study and intervention, which will be evaluated through a nested qualitative study. Feasibility outcomes will be summarised using descriptive statistics, point estimates and 95% CIs.Ethics and disseminationThe OMAhA study received ethics approval from the London-Brent Research Ethics Committee (18/LO/0505). Trial findings will be published in a peer-reviewed journal, disseminated at conferences, through our Patient and Public Involvement advisory group (Katie’s Team) and through social media platforms.Trial registration numberISRCTN20930880

Introduction Fetal fibronectin (fFN) is a validated test for assessing risk of preterm birth for women presenting with symptoms. Our aim was to evaluate the accuracy of fFN to detect the risk of preterm birth in asymptomatic women. Material and methods Searches were conducted to identify studies where fFN was performed in asymptomatic women beyond 22 weeks' gestation. EMBASE, MEDLINE, CINHAL, AMED and BNI were searched between 2005 and 2017. Studies before 2005 were identified from a published systematic review. Women were grouped as singleton pregnancies, with and without risk factors for preterm birth, and multiple pregnancy. Quality assessment was performed using QUADAS-2. When possible, data were pooled using a hierarchical, bivariate random effects model. Results Fifteen studies met the inclusion criteria: six studies of singleton pregnancies in women without risk factors (1236 women), four in women with risk factors for preterm birth (2628 women) and five studies were of multiple pregnancy (1427 women). The pooled sensitivity and specificity of fFN in "no risk factors singletons" were 0.48 (95% CI 0.20-0.77), and 0.96 (95% CI 0.86-0.99), respectively. The likelihood ratio of a positive test result was 12 (95% CI 4.70-30.68). The pooled sensitivity and specificity of fFN in "risk factors singletons" were 0.34 (95% CI 0.24-0.43), and 0.91 (95% CI 0.88-0.93). The accuracy of fFN in multiple pregnancies was inconclusive. Conclusion Our findings suggest in asymptomatic singleton pregnancies without risk factors, a positive fFN result indicates a large shift from pre- to post-test probability, possibly identifying women at increased risk of preterm birth.

Increased thromboembolic events have been seen in patients hospitalised with COVID-19 pneumonia, especially those with acute respiratory distress syndrome requiring intensive care support. The coronavirus pandemic has had varied effects on pregnant women globally. Concerns about the potential for thromboembolic events in the prothrombotic period of pregnancy and puerperium when combined with COVID-19 infection, and the impact this may have on maternal and infant morbidity and mortality has led to the development of expert-led guidance providing increased use of thromboprophylaxis in this group. We discuss the impact of SARS-CoV-2 on national and international guidance to prevent thromboembolic events in pregnant women.

Purpose of review Anaemia affects up to 50% of pregnancies worldwide, and is associated with maternal and neonatal morbidity and mortality. Prevention and management of anaemia remains a priority. Despite this, there is ongoing debate on the optimal approach to identifying anaemia in pregnant women and the best strategies for prevention and management. The objective of this review is to describe the current landscape of haemoglobin testing in pregnancy in low and high-income countries. Recent findings Current definitions of anaemia in pregnancy comprise a laboratory threshold of haemoglobin below which treatment is offered. Haemoglobin measurement is not sensitive in detecting iron deficiency - the most common cause of maternal anaemia. Furthermore, these historical thresholds were derived from heterogeneous populations comprising men and women. Women with anaemia in pregnancy are offered iron therapy, without testing for the underlying cause. This may be appropriate in high-income settings, where iron deficiency is the likely cause, but may not address the complex causes of anaemia in other geographical areas. Summary Current thresholds of haemoglobin defining anaemia in pregnancy are under review. Further research and policy should focus on optimal strategies to identify women at risk of anaemia from all causes.

Katie’s Team is funded by a grant from the Centre for Public Engagement Queen Mary University of London.

IntroductionGestational diabetes increases maternal and offspring complications in pregnancy and cardiovascular complications in the long term. The nutritional supplementmyo-inositol may prevent gestational diabetes; however, further evaluation is required, especially in multiethnic high-risk mothers. Our pilot trial onmyo-inositol to prevent gestational diabetes will evaluate trial processes, assess acceptability to mothers and obtain preliminary estimates of effect and cost data prior to a large full-scale trial.Methods and analysisEMmY is a multicentre, placebo-controlled, double-blind, pilot, randomised trial, with qualitative evaluation. We will recruit pregnant women at 12–15+6weeks’ gestation, with gestational diabetes risk factors, from five maternity units in England between 2018 and 2019. We will randomise 200 women to take either 2 g ofmyo-inositol powder (intervention) or placebo, twice daily until delivery. We will assess rates of recruitment, randomisation, adherence to intervention and follow-up. Gestational diabetes will be diagnosed at 24–28 weeks as per the National Institute for Health and Care Excellence (NICE) criteria (fasting plasma glucose: ≥5.6 mmol/L and 2-hour plasma glucose: ≥7.8 mmol/L). We will assess the effects ofmyo-inositol on glycaemic indices at 28 weeks and on other maternal, fetal and neonatal outcomes at postnatal discharge. Qualitative evaluation will explore the acceptability of the trial and the intervention among women and healthcare professionals. Cost data and health-related quality of life measures will be captured. We will summarise feasibility outcomes using standard methods for proportions and other descriptive statistics, and where appropriate, report point estimates of effect sizes (eg, mean differences and relative risks) and associated 95% CIs.Ethics and disseminationEthical approval was obtained through the London Queen Square Research Ethics Committee (17/LO/1741). Study findings will be submitted for publication in peer-reviewed journals. Newsletters will be made available to participants, healthcare professionals and members of Katie’s Team (a patient and public advisory group) to disseminate.Trial registration numberISRCTN48872100.Protocol version and dateVersion 4.0, 15 January 2018.

SUMMARYBackground The prevalence of anaemia in pregnancy in Europe is 25% and that resulting from iron deficiency is estimated at 40%. The maternal and fetal morbidity of non-anaemic iron deficiency (NAID) in pregnancy is likely to be significant. Objectives To determine the views and opinions of health service users and clinicians concerning NAID in pregnancy in order to inform future research. Methods Two semi-structured focus groups were carried out to determine health service users' views on anaemia and NAID in pregnancy. A questionnaire was administered to obstetricians, haematologists, midwives and anaesthetists to elucidate their views on NAID in pregnancy. Results The study indicated that health service users and clinicians were interested in implementing testing for NAID in pregnancy with serum ferritin, if proven to be effective at reducing the effects of anaemia and improving maternal and neonatal outcomes. Clinicians had reservations in the use of intravenous iron supplementation for NAID in pregnancy. Conclusion NAID is now accepted as a target condition for research by health service users and clinicians. The focus of future research should be on screening for NAID and its treatment.

Summary Background Anaemia affects as many as half of all pregnant women in low-income and middle-income countries, but the burden of disease and associated maternal mortality are not robustly quantified. We aimed to assess the association between severe anaemia and maternal death with data from the WHO Multicountry Survey on maternal and newborn health. Methods We used multilevel and propensity score regression analyses to establish the relation between severe anaemia and maternal death in 359 health facilities in 29 countries across Latin America, Africa, the Western Pacific, eastern Mediterranean, and southeast Asia. Severe anaemia was defined as antenatal or postnatal haemoglobin concentrations of less than 70 g/L in a blood sample obtained before death. Maternal death was defined as death any time after admission until the seventh day post partum or discharge. In regression analyses, we adjusted for post-partum haemorrhage, general anaesthesia, admission to intensive care, sepsis, pre-eclampsia or eclampsia, thrombocytopenia, shock, massive transfusion, severe oliguria, failure to form clots, and severe acidosis as confounding variables. These variables were used to develop the propensity score. Findings 312 281 women admitted in labour or with ectopic pregnancies were included in the adjusted multilevel logistic analysis, and 12 470 were included in the propensity score regression analysis. The adjusted odds ratio for maternal death in women with severe anaemia compared with those without severe anaemia was 2·36 (95% CI 1·60–3·48). In the propensity score analysis, severe anaemia was also associated with maternal death (adjusted odds ratio 1·86 [95% CI 1·39–2·49]). Interpretation Prevention and treatment of anaemia during pregnancy and post partum should remain a global public health and research priority. Funding Barts and the London Charity.

Determination of iron status in pregnancy and in young children is essential for both clinical and public health practice. Clinical diagnosis of iron deficiency (ID) through sampling of bone marrow to identify the absence of body iron stores is impractical in most cases. Serum ferritin (SF) concentrations are the most commonly deployed indicator for determining ID, and low SF concentrations reflect a state of iron depletion. However, there is considerable variation in SF cutoffs recommended by different expert groups to diagnose ID. Moreover, the cutoffs used in different clinical laboratories are heterogeneous. There are few studies of diagnostic test accuracy to establish the sensitivity and specificity of SF compared with key gold standards (such as absent bone marrow iron stores, increased intestinal iron absorption, and hemoglobin response to SF) among noninflamed, outpatient populations. The limited data available suggest the commonly recommended SF cutoff of 30 y ago, do not reflect ethnic or geographic diversity, and were performed in an era for which laboratory methods no longer reflect present practice. Future studies to define the appropriate SF cutoffs are urgently needed and would also provide an opportunity to compare this indicator with other established and emerging iron indexes. In addition, future work would benefit from a focus on elucidating cutoffs and indexes relevant to iron adequacy.