Objectives: To assess fetal circulating free fetal haemoglobin (fHbF) levels and heme defences, correlated to fetal circulatory biometry and fetal sex in severe early-onset fetal growth restriction. Design, Setting & Population: A prospective study severe early-onset fetal growth restriction pregnancies with close clinical management (EFW<3 rd centile and <600g at 20-26+6 weeks; N=20). Method & Main Outcome Measures: Temporal fetal vascular obstetric biometry was recorded. Cord blood fHbF and key heme-scavenger defences were measured and compared with normal term births (N=26) and births with late-onset FGR (N=12). Results: fHbF was elevated in early-onset FGR compared with normal pregnancy: 0.437(0.337/0.753) mg/mL; P<0.0001; 0.098(0.045/0.264) mg/mL; P<0.0001), respectively; whilst hemopexin was downregulated in early- and late-onset FGR compared to normal pregnancy: 36(14/81) μg/mL, P<0.001; 25(19/40) μg/mL, P<0.0001; 155(132/219) μg/mL, respectively; median(interquartile ranges). Early-onset FGR male fetuses had higher fetal haemoglobin compared with the normal males: 0.710(0.433/0.857) mg/mL; P<0.001; 0.099(0.043/0.246) mg/mL, respectively; median(interquartile ranges). In early-onset FGR, ratios of mid-cerebral artery and umbilical artery pulsatility indices correlated positively with heme-scavenger levels (hemopexin and a heme-handling composite measure: P<0.05 and P<0.01, respectively), indicating lower levels are associated with cerebral vascular redistribution. These heme handling measures also positively correlated with gestational age at delivery (P<0.01, both) and birthweight (P<0.001 and P<0.05, respectively). Conclusion: Free fetal haemoglobin overproduction may be one route to placental vascular compromise in early-onset FGR, implicated in reduced placental and fetal blood flow.

Background Antenatal corticosteroids (ACS) are recommended in threatened preterm labour to improve short term neonatal outcome. Preclinical animal studies suggest detrimental effects of ACS exposure on offspring cardiac development; their effects in humans are unknown. Objectives To systematically review the human clinical literature to determine the effects of ACS on offspring cardiovascular function. Main results Twenty-six studies including 1921 patients were included, of which most were cohort studies of mixed quality. The type of ACS exposure, gestational age at exposure, dose and number of administrations varied widely. Offspring cardiovascular outcomes were assessed from one day to 36 years postnatally. The most commonly assessed parameter was arterial blood pressure (18 studies), followed by echocardiography (8 studies), heart rate (5 studies), electrocardiogram (ECG, 3 studies) and cardiac magnetic resonance imaging (MRI, 1 study). There were no clinically significant effects of ACS exposure on offspring blood pressure. However, there were insufficient studies assessing cardiac structure and function using echocardiography or cardiac MRI to be able to determine an effect. Conclusions Administration of ACS is not associated with long-term effects on blood pressure in exposed human offspring. The effects on cardiac structure and other measures of cardiac function were unclear due to the small number of studies, study heterogeneity and mixed quality. Given the emerging preclinical evidence of harm following ACS exposure, there is a need for further research to assess central cardiac function in human offspring exposed to ACS. Keywords: Antenatal corticosteroids, ACS, cardiovascular, offspring, blood pressure

Background: Methodological and reporting assessment tools have been developed which allow us to investigate the core outcome set development process Objective: To characterise core outcome sets relevant to women’s and newborn health and assess methodological and reporting quality. Search Strategy: Systematic search using the Core Outcome Measures in Effectiveness Trials (COMET) and the Core Outcomes in Women’s and Newborn Health (CROWN) Initiative databases from inception to March 2020. Selection Criteria: Registered, progressing, and completed core outcome sets. Data Collection and analysis: Descriptive summaries of characteristics and results. Published protocols were assessed using the Core Outcome Set-STAndardised Protocol Items (COS-STAP). Completed core outcome sets were evaluated using COS-STAD (standards for development) and COS-STAR (standards for reporting). Main Results: Eighty studies were identified. Twenty-four studies had published a protocol; four (17%) met all COS-STAP criteria. This was primarily due to poorly defined steering groups and lack of discussion around the potential impact of attrition. Thirty-nine systematic reviews characterized inconsistency in outcome reporting. Twenty studies published a core outcome set development process with four (20%) and three (15%) meeting COS-STAD and COS-STAR recommendations respectively, largely due to variation in patient involvement, outcome selection and the Delphi process Conclusions: Future core outcome set developers should actively engage with the methodological and reporting criteria to enhance the quality of their studies. Clarity is also required within the assessment guidelines as to how these issues should be adequately addressed. We have identified 5 key areas for improvement for future core outcome set developers and wider stakeholders