The use of network meta-analysis in updating WHO living maternal and perinatal health recommendations.

Drawing on two recent examples of WHO living guidelines in maternal and perinatal health, this paper elucidates a pragmatic, stepwise approach to using network meta-analysis (NMA) in guideline development in the presence of multiple treatment options. NMA has important advantages. These include the ability to compare multiple interventions in a single coherent analysis, provide direct estimates of the relative effects of all available interventions, infer indirect effect estimates for interventions not directly compared and generate rankings of the available treatment options. It can be difficult to harness these advantages in the face of a lack of current guidance on using NMA evidence in guideline development, with several challenges emerging. Challenges include the choice of conceptual approach, the volume and complexity of the evidence, the contribution of treatment rankings, and the fact that the preferable treatment is not always obvious. This paper describes a layered approach to resolving these challenges, which supports systematic guideline decision-making and development of trustworthy clinical guidelines when multiple treatment options are available.

Antenatal corticosteroids in specific groups at risk of preterm birth: a systematic review.

OBJECTIVE: This study aimed to synthesise available evidence on the efficacy of antenatal corticosteroid (ACS) therapy among women at risk of imminent preterm birth with pregestational/gestational diabetes, chorioamnionitis or fetal growth restriction (FGR), or planned caesarean section (CS) in the late preterm period. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, Cochrane Library, Web of Science and Global Index Medicus was conducted for all comparative randomised or non-randomised interventional studies in the four subpopulations on 6 June 2021. Risk of Bias Assessment tool for Non-randomised Studies and the Cochrane Risk of Bias tool were used to assess the risk of bias. Grading of Recommendations Assessment, Development and Evaluations tool assessed the certainty of evidence. RESULTS: Thirty-two studies involving 5018 pregnant women and 10 819 neonates were included. Data on women with diabetes were limited, and evidence on women undergoing planned CS was inconclusive. ACS use was associated with possibly reduced odds of neonatal death (pooled OR: 0.51; 95% CI: 0.31 to 0.85, low certainty), intraventricular haemorrhage (pooled OR: 0.41; 95% CI: 0.23 to 0.72, low certainty) and respiratory distress syndrome (pooled OR: 0.59; 95% CI: 0.45 to 0.77, low certainty) in women with chorioamnionitis. Among women with FGR, the rates of surfactant use (pooled OR: 0.38; 95% CI: 0.23 to 0.62, moderate certainty), mechanical ventilation (pooled OR: 0.42; 95% CI: 0.26 to 0.66, moderate certainty) and oxygen therapy (pooled OR: 0.48; 95% CI: 0.30 to 0.77, moderate certainty) were probably reduced; however, the rate of hypoglycaemia probably increased (pooled OR: 2.06; 95% CI: 1.27 to 3.32, moderate certainty). CONCLUSIONS: There is a paucity of evidence on ACS for women who have diabetes. ACS therapy may have benefits in women with chorioamnionitis and is probably beneficial in FGR. There is limited direct trial evidence on ACS efficacy in women undergoing planned CS in the late preterm period, though the totality of evidence suggests it is probably beneficial. PROSPERO REGISTRATION NUMBER: CRD42021267816.

Tocolytic Therapy Inhibiting Preterm Birth in High-Risk Populations: A Systematic Review and Meta-Analysis.

This systematic review aimed to identify the benefits and possible harms of tocolytic therapy for preterm labour management in the context of pregnant women with extremely preterm birth, multiple gestations, or growth-restricted foetuses. A comprehensive search using MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, CINAHL, and the WHO Global Index Medicus databases was conducted from 10 to 15 July 2021. We included randomized controlled trials and non-randomized studies that assessed the effects of tocolysis compared with placebo or no treatment. We found 744 reports and, finally, nine studies (three randomized controlled trials and six cohort studies) pertaining to women with <28 weeks of gestation were included. No eligible studies were identified among women with a multiple pregnancy or a growth-restricted foetus. A meta-analysis of the trial data showed that there were no clear differences in perinatal death nor for a delay in birth. Non-randomized evidence showed that tocolysis delayed birth by 7 days, though there was no clear difference for preterm birth. In summary, it remains unclear whether tocolytic therapy for inhibiting preterm labour is beneficial for these subgroups of women and their newborns. Further well-designed randomized controlled trials and observational studies are needed to address the lack of evidence regarding tocolytic agents in these populations.

Different corticosteroids and regimens for accelerating fetal lung maturation for babies at risk of preterm birth.

BACKGROUND: Despite the widespread use of antenatal corticosteroids to prevent respiratory distress syndrome (RDS) in preterm infants, there is currently no consensus as to the type of corticosteroid to use, dose, frequency, timing of use or the route of administration.  OBJECTIVES: To assess the effects on fetal and neonatal morbidity and mortality, on maternal morbidity and mortality, and on the child and adult in later life, of administering different types of corticosteroids (dexamethasone or betamethasone), or different corticosteroid dose regimens, including timing, frequency and mode of administration. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (9 May 2022) and reference lists of retrieved studies. SELECTION CRITERIA: We included all identified published and unpublished randomised controlled trials or quasi-randomised controlled trials comparing any two corticosteroids (dexamethasone or betamethasone or any other corticosteroid that can cross the placenta), comparing different dose regimens (including frequency and timing of administration) in women at risk of preterm birth. We planned to exclude cross-over trials and cluster-randomised trials. We planned to include studies published as abstracts only along with studies published as full-text manuscripts. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. Data were checked for accuracy. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 11 trials (2494 women and 2762 infants) in this update, all of which recruited women who were at increased risk of preterm birth or had a medical indication for preterm birth. All trials were conducted in high-income countries. Dexamethasone versus betamethasone Nine trials (2096 women and 2319 infants) compared dexamethasone versus betamethasone. All trials administered both drugs intramuscularly, and the total dose in the course was consistent (22.8 mg or 24 mg), but the regimen varied. We assessed one new study to have no serious risk of bias concerns for most outcomes, but other studies were at moderate (six trials) or high (two trials) risk of bias due to selection, detection and attrition bias. Our GRADE assessments ranged between high- and low-certainty, with downgrades due to risk of bias and imprecision.  Maternal outcomes The only maternal primary outcome reported was chorioamnionitis (death and puerperal sepsis were not reported). Although the rate of chorioamnionitis was lower with dexamethasone, we did not find conclusive evidence of a difference between the two drugs (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.48 to 1.06; 1 trial, 1346 women; moderate-certainty evidence). The proportion of women experiencing maternal adverse effects of therapy was lower with dexamethasone; however, there was not conclusive evidence of a difference between interventions (RR 0.63, 95% CI 0.35 to 1.13; 2 trials, 1705 women; moderate-certainty evidence). Infant outcomes We are unsure whether the choice of drug makes a difference to the risk of any known death after randomisation, because the 95% CI was compatible with both appreciable benefit and harm with dexamethasone (RR 1.03, 95% CI 0.66 to 1.63; 5 trials, 2105 infants; moderate-certainty evidence). The choice of drug may make little or no difference to the risk of RDS (RR 1.06, 95% CI 0.91 to 1.22; 5 trials, 2105 infants; high-certainty evidence). While there may be little or no difference in the risk of intraventricular haemorrhage (IVH), there was substantial unexplained statistical heterogeneity in this result (average (a) RR 0.71, 95% CI 0.28 to 1.81; 4 trials, 1902 infants; I² = 62%; low-certainty evidence). We found no evidence of a difference between the two drugs for chronic lung disease (RR 0.92, 95% CI 0.64 to 1.34; 1 trial, 1509 infants; moderate-certainty evidence), and we are unsure of the effects on necrotising enterocolitis, because there were few events in the studies reporting this outcome (RR 5.08, 95% CI 0.25 to 105.15; 2 studies, 441 infants; low-certainty evidence). Longer-term child outcomes Only one trial consistently followed up children longer term, reporting  at two years' adjusted age. There is probably little or no difference between dexamethasone and betamethasone in the risk of neurodevelopmental disability at follow-up (RR 1.02, 95% CI 0.85 to 1.22; 2 trials, 1151 infants; moderate-certainty evidence). It is unclear whether the choice of drug makes a difference to the risk of visual impairment (RR 0.33, 95% CI 0.01 to 8.15; 1 trial, 1227 children; low-certainty evidence). There may be little or no difference between the drugs for hearing impairment (RR 1.16, 95% CI 0.63 to 2.16; 1 trial, 1227 children; moderate-certainty evidence), motor developmental delay (RR 0.89, 95% CI 0.66 to 1.20; 1 trial, 1166 children; moderate-certainty evidence) or intellectual impairment (RR 0.97, 95% CI 0.79 to 1.20; 1 trial, 1161 children; moderate-certainty evidence). However, the effect estimate for cerebral palsy is compatible with both an important increase in risk with dexamethasone, and no difference between interventions (RR 2.50, 95% CI 0.97 to 6.39; 1 trial, 1223 children; low-certainty evidence). No trials followed the children beyond early childhood. Comparisons of different preparations and regimens of corticosteroids We found three studies that included a comparison of a different regimen or preparation of either dexamethasone or betamethasone (oral dexamethasone 32 mg versus intramuscular dexamethasone 24 mg; betamethasone acetate plus phosphate versus betamethasone phosphate; 12-hourly betamethasone versus 24-hourly betamethasone). The certainty of the evidence for the main outcomes from all three studies was very low, due to  small sample size and  risk of bias. Therefore, we were limited in our ability to draw conclusions from any of these studies. AUTHORS' CONCLUSIONS: Overall, it remains unclear whether there are important differences between dexamethasone and betamethasone, or between one regimen and another.  Most trials compared dexamethasone versus betamethasone. While for most infant and early childhood outcomes there may be no difference between these drugs, for several important outcomes for the mother, infant and child the evidence was inconclusive and did not rule out significant benefits or harms. The evidence on different antenatal corticosteroid regimens was sparse, and does not support the use of one particular corticosteroid regimen over another.

Updated clinical practice guidelines on pregnancy care.

INTRODUCTION: The clinical practice guidelines on pregnancy care have been developed to provide reliable and standardised guidance for health professionals providing antenatal care in Australia. They were originally released as the Clinical Practice Guidelines: Antenatal Care in two separate editions (modules 1 and 2) in 2012 and 2014. These modules have now been combined and updated to form a single set of consolidated guidelines that were publicly released in February 2018 as the Clinical Practice Guidelines: Pregnancy Care. Eleven topics have been updated and new guidance on substance use in pregnancy has been added. Main recommendations: The updated guidelines include the following key changes to practice: recommend routine testing for hepatitis C at the first antenatal visit; recommend against routine testing for vitamin D status in the absence of a specific indication; recommend discussing weight change, diet and physical activity with all pregnant women; and recommend offering pregnant women the opportunity to be weighed at every antenatal visit and encouraging women to self-monitor weight gain. Changes in management as a result of the guidelines: The guidelines will enable pregnant women diagnosed with hepatitis C to be identified and thus avoid invasive procedures that increase the risk of mother-to-baby transmission. Women can be treated postpartum, reducing the risk of liver disease and removing the risk of perinatal infection for subsequent pregnancies. Routine testing of all pregnant women for vitamin D status and subsequent vitamin D supplementation is not supported by evidence and should cease as the benefits and harms of vitamin D supplementation remain unclear. The recommendation for health professionals to provide advice to pregnant women about weight, diet and physical activity, and the opportunity to be weighed will help women to make changes leading to better health outcomes for themselves and their babies.