A document by David Savitz. Click on the document to view its contents.

Objectives: To examine the association between racial origin and preeclampsia(PE) and gestational hypertension(GH) after adjustment for factors in maternal characteristics and medical history in screening study from the Fetal Medicine Foundation (FMF) in England, and to perform a systematic review and meta-analysis of studies on PE. Methods: In the FMF data regression analysis was performed to examine the association between racial origin and PE or GH. Literature search to December 2021 was carried out to identify peer-reviewed publications on race and PE. Main outcome measure: Relative risk of PE and GH in women of black, South Asian and East Asian racial origin by comparison to white women. Results: In the FMF study there were 168,966 singleton pregnancies without major abnormalities delivering at ≥24 weeks’ gestation. In black women the respective risk of total-PE and preterm-PE was 2-fold and 2.5-fold higher and risk of GH was 25% higher, in South Asian women there was a 1.5-fold higher risk of preterm-PE but not total-PE, and in East Asian women there was no significant difference in risk of hypertensive disorders. The literature search identified 19 studies that provided data on several million of pregnancies, but 17 were at moderate or high-risk of bias and only three provided risks adjusted for some maternal characteristics; consequently, these studies did not provide accurate contribution of different racial groups to the prediction of PE. Conclusion: In women of black and South Asian origin the risk of PE, after adjustment for confounders, is higher than in white women

Sir ,We read with great interest the study by Zhou et al.1, where the authors demonstrated a significant association between preconception paternal smoking and birth defects in the offspring. The study is timely given the increasing recognition of the role that paternal factors play in pregnancy outcomes. The authors must be congratulated on performing a large scale, nationwide study, in which a potential link between preconception paternal smoking and birth defects in offspring was made.A salient point discussed by Zhou and colleagues is the difficulty in estimating the effect of paternal smoking as an independent variable on the risk of birth defects due to a myriad of confounding factors. Although the authors had adequately adjusted for maternal biological, environmental and behavioural factors, as well as paternal alcohol consumption, it may be prudent to note that paternal age could be a potentially significant confounder in this relationship.Advanced paternal age has shown robust links with increases in sperm DNA fragmentation.2 DNA damage is attributed to environmental, hormonal and degenerative changes.2Over time, multiple cycles of mitotic replications generate greater stress on the DNA repair mechanisms.2 The failure to control the DNA repair mechanisms invariably amounts to ejaculated spermatozoa containing a higher proportion of abnormal paternal DNA.2 In the same vein, children born to fathers of advanced age are at a slightly increased risk of birth defects including cardiac, respiratory, gastrointestinal tract and musculoskeletal abnormalities.3 It has been speculated that mutations accumulate over repeated spermatogenesis, subsequently increasing the number of birth defects in the offspring.3 At the opposite end of the age spectrum, young paternal age has also been associated with a slight increased risk of selected birth defects.3At large, prenatal smoke exposure has unfavourable effects on pregnancies. Effects of maternal smoking has been comprehensively studied and is associated with fetal and developmental conditions. Harmful substances in tobacco smoke such as nicotine, carbon monoxide and polycyclic aromatic hydrocarbons are able to cross the placenta and negatively affect the fetal development.4 On the other hand, the extent of paternal smoking has not been well-established. Exposure to cigarette smoke has been found to affect sperm parameters, as well as increase sperm chromatin structural abnormalities and DNA damage.5 Infant low birth weight, increased obesity risk in childhood and high blood pressure have been identified as potential complications of paternal smoking.4 This study provides new evidence that birth defects are also complications of paternal smoking.In conclusion, Zhou et al. have accomplished a tremendous job of investigating the effects of paternal smoking on birth defects. The current study has laid the groundwork for future research to be built upon and to elucidate the true effects of paternal smoking during pregnancy. As exposure to first or second-hand smoke poses a major risk to pregnancies, it might be worthwhile to recommend smoking cessation in both parents during preconception counselling.Jania J. Y. Wu1, Kyla Ng Yin2, Keng Siang Lee3, John J. Y. Zhang11Yong Loo Lin School of Medicine, National University of Singapore, Singapore2Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK3Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, UK

Leiomyomata are common benign pelvic masses that occur in up to 77% of reproductive aged women (Flyckt et al Clin Obstet Gynecol 2017;60(2):252-272). Myomectomies are frequently performed for symptomatic leiomyoma unresponsive to non-surgical treatments and can be performed via laparotomy (open) or minimally invasive approaches. Open myomectomies are often performed because of lack of access to or training with minimally invasive approaches, or secondary to concerns surrounding morcellation.Misoprostol is a relatively inexpensive readily accessible uterotonic and vasoconstrictive medication. Based on mechanism of action, misoprostol is often used at the time of myomectomy to decrease blood loss. This led Wali et al. (Wali et al BJOG 2020 xxxx) to perform a systematic review on the effectiveness of preoperative misoprostol specifically at the time of open myomectomy. Eight randomized-controlled trials met inclusion criteria and were included in this systematic review with a total of 385 participants, 192 in the misoprostol group 193 in the control group.These studies provide moderate to high quality evidence on the following six outcomes: 1) estimated blood loss, 2) drop in haemoglobin, 3) need for blood transfusion, 4) operative time, 5) post-operative fever, and 6) length of hospital stay. The specific findings for those six outcomes are as follows. Compared to placebo, misoprostol significantly reduced estimated blood loss by a mean of 170cc with an associated haemoglobin decrease of 0.48 g/dL. Perhaps the most clinically significant finding was that preoperative misoprostol led to a three-fold lower risk of blood transfusion with an odds-ratio of 0.31. The use of preoperative misoprostol also led to a decreased operative time of 11 minutes, which is probably clinically significant based on the relative low expense of misoprostol and relative high cost of time in the operating theater. There was no statistically significant difference in the rates of postoperative fever or length of hospital stay. Patients in the misoprostol group were discharged an average of 3.5 hours earlier than the placebo group which is probably not clinically significant.Based on the overall risk-benefit profile identified in this study, it would seem that preoperative misoprostol should be recommended for most patients prior to open myomectomy. The findings from this systematic review are particularly important for low-resource settings where access to minimally invasive approaches and the availability of blood for possible transfusion are limited. Although there was variability in the timing and the dose of preoperative misoprostol, Wali et al (Wali et al BJOG 2020 xxxx) suggest the evidence supports a single dose of 400μg of misoprostol 30 to 60 minutes prior to surgery, or two doses 3 hours apart. A protocol of one dose of misoprostol 30 minutes prior to taking a patient to the operating theater could be implemented as part of a standard preoperative order set and administered in the pre-anesthesia care unit. This study highlights a simple, low-cost intervention that can significantly improve patient outcomes.Disclosure of interest: None to declare. A completed disclosure of interest form is available to view online as supporting information.

Background: Biologic medications, specifically the TNF-α inhibitors, have become increasingly prevalent in the treatment of chronic inflammatory disease (CID) in pregnancy. Objective: To determine pregnancy outcomes in women with CID exposed to biologics during pregnancy. Search strategy: PubMed and EMBASE databases were searched through January 1998-July 2021. Selection criteria: Peer reviewed, English language cohort, case-control, cross-sectional studies, and case series which contained original data. Data collection and analysis: Two authors independently conducted data extraction and assessed study quality. A meta-analysis of proportions using a random-effects model was used to pool outcomes. Linear regression analysis was used to compare the mean of proportions of outcomes across exposure groups using the ‘treated’ group as the reference category. All studies were evaluated using an appropriate quality assessment tool described by McDonald et al. Main Results: 35 studies, 11172 pregnancies, were eligible for inclusion. Analysis showed pooled proportions for congenital malformations: treated 4%(95% CI 0.03-0.4) vs disease matched 4%(0.03-0.05).Preterm delivery treated 12%(0.10-0.14) vs disease matched 10%(0.09-0.12) Severe neonatal infection: treated 5%(0.03-0.07) vs disease matched 5%(0.02-0.07) Low birth weight: treated 10%(0.07-0.12) vs disease matched 8%(0.07-0.09) The pooled Miscarriage: treated 13%(0.10-0.15) vs disease matched 8%(0.04-0.11) Pre-eclampsia; treated 1%(0.01-0.02) vs disease matched 1%(0.00-0.01). No statistical differences in proportions were observed. Conclusion: We demonstrated comparable pregnancy outcomes in pregnancies exposed to biologics, disease matched controls and CID free pregnancies. Overall, women receiving biologics in pregnancy may be reassured regarding their safety.

Mini-commentary on BJOG-20-0442.R2: Impact of hysterectomy on analgesic, psychoactive and neuroactive drug use in women with endometriosis: nationwide cohort study

BJOG exchange

Epidemiologic studies performed in the Melbourne Sexual Health Center over several years have explored and emphasized the role of sexual transmission in the pathogenesis of sporadic bacterial vaginosis (BV) as well as recurrent BV (Fethers KA., et al. Infect. Dis. 2008; 47: 1426-1435). Some of the most definitive studies documenting details of heterosexual sexual transmission followed. There can be little doubt as to the causal role of sexual transmission in BV particularly with regard to the initial episode (Cherpes, TL., et al. Sex. Transm. Dis 2008; 35: 78-83). The present study adds solid molecular data to their previous epidemiologic data that recurrent BV is more likely to occur in a heterosexual woman with a single regular male partner (Ratten L., et al BJOG 2020 xxxx): Moreover, the risk is mitigated by use of an oral contraceptive and barrier contraceptives. Specifically, Ratten et al conclude that sex is associated with persistence of non-optimal, BV-associated vaginal dysbiosis following appropriate antimicrobial treatment for BV in a cohort followed prospectively, likely the result of sexual transmission from a regular partner. The key term used in the title of the study is persistence, which implies that the non-optimal vaginal microbiota fails to resolve, as opposed to future reintroduction from the same guilty partner. Persistence in this context, unfortunately, also indirectly suggests that inadequate antimicrobial treatment is currently prescribed to women, perhaps sufficient to relieve symptoms and meet diagnostic criteria of satisfactory response, but insufficient to eradicate BV pathogens. The author emphasizes needed improvement in the, so far, futile male partner therapy to prevent female reinfection, a goal that has repeatedly eluded experts to date.The unanswered question facing patients and clinicians alike is the role of sexual reinfection as opposed to vaginal relapse in the causation and likelihood of BV recurrence. The tone of the article would indicate that reinfection is the more likely causal mechanism of BV recurrence, by emphasizing “persistence” and outweighing the role of unexplained relapse. In dealing with a symptomatic patient suffering from an episode of recurrent BV, it is currently not possible to differentiate relapse from reinfection unless the patient declares herself to be celibate, ergo relapse is the cause of recurrence. The clinical picture is identical as are Amsel or Nugent criteria. Unfortunately, molecular microbiome studies have not revealed significant differences between sequential episodes regardless of causation. We lack a “unique fingerprint” to differentiate cause or nature of the recurrent episode. Even with reinfection, sexual or otherwise, details of pathogenesis are still lacking. We know too that coitus can elicit symptoms of BV (post coital malodor) even with use of a condom. The role of receptive oral-vulvovaginal sex is also undetermined, as is the role of penile – anorectal penetration although the latter was found to be minimal in the latest study by Ratten L., et al. (BJOG 2020 xxxx): Moreover, not all longitudinal studies have revealed that heterosexual sex is a major factor in recurrence (Sobel J.D., et al. Infect. Drug Resist. 2019: 12; 2297-2307).The role of sex and reinfection in causation of RBV will depend significantly upon the population studied, including biologic and behavioral differences. Determination of causation of BV recurrence in different patient populations should be personalized and acknowledged as we admit our current limitations. Will more effective male treatment help reduce BV recurrence? Hopefully but still unknown. Determining all the causes of vaginal microbiota persistence, including the role of biofilm, remains a challenge.No disclosures: A completed disclosure of interest form is available to view online as supporting information.

A document by Becky Liu. Click on the document to view its contents.

Objective: Observational studies have described associations between obesity and adverse outcomes of pregnancy. Mendelian randomization (MR) takes advantage of the ‘natural’ genetic randomization to risk of an exposure such as body mass index (BMI) to study the effects of the exposure on outcomes. Similar to randomization in a clinical trial, this limits the potential for confounding and bias. Design: A two-sample MR study. Setting: Summary statistics from published genome wide association studies (GWAS) in European ancestry populations. Population or Sample: Instrumental variants for body mass index (BMI) were obtained from a study on 434,794 females. Female-specific genetic association estimates for outcomes were extracted from the sixth round of analysis of the FINNGEN cohort data. Methods: Inverse-variance weighted MR was used to assess the association between BMI and all outcomes. Sensitivity analyses with weighted median and MR-Egger were also performed. Results: A 1-SD increase in BMI was associated with higher risk of pre-eclampsia (OR 1.68, 95%CI 1.46-1.94, p=8.74x10-13), gestational diabetes (OR 1.67, 95%CI 1.46-1.92, p=5.35x10-14), polyhydramnios (OR 1.40, 95%CI 1.00-1.96, p=0.049). There was evidence suggestive of a potential association with higher risk of premature rupture of membranes (OR 1.16, 95%CI 1.00-1.36, p=0.050) and postpartum depression (OR 1.12, 95%CI 0.99-1.27, p=0.062). Conclusions: Higher maternal BMI is associated with marked increase in risk of pre-eclampsia, gestational diabetes and polyhydramnios. The relationship between BMI and premature rupture of membranes and postpartum depression should be assessed in further studies. Our study supports efforts to target BMI as a cardinal risk factor for maternal morbidity.

Objective: To study the impact of absolute uterine factor infertility (AUFI) and uterus transplantation (UTx) on women, and UTx recipients’ perceptions of Utx and reproductive autonomy Design: Convergent mixed-methods study. Setting: UTx program in a large academic medical centre in the United States. Population/Sample: 20 Utx recipients Methods: A medical chart review was conducted to collect patient demographic information, and clinical outcomes. Semi-structured interviews collected information regarding participants’ experience. Main Outcome Measure(s): The outcomes of interest were participants’ experience of infertility, experience with UTx, and general perceptions of UTx. Results: 7 participants were pregnant (one with a second child), 6 had experienced early graft failure and removal, 5 had delivered a healthy baby, and 4 had a viable graft and were awaiting embryo transfer. The primary themes identified were: the negative impact of AUFI diagnosis on psychological wellbeing, relationships, and female identity; the positive impact of UTx on healing the emotional scars of AUFI, female identity, and value of research trial participation; and the perception of UTx as an expansion of reproductive autonomy. All participants reported Utx was worthwhile, regardless of individual outcome. On bivariate analysis, disease aetiology, having a child after uterus transplantation, experiencing graft failure and current pregnancy were not significantly associated with the impact of AUFI or of UTx on participants’ identities. Conclusion: AUFI has a negative impact on women from a young age, affects multiple relationships, and challenges female identity. UTx helps reverse this impact, transforming women’s life narrative of infertility and enhancing female identity.

Dear editor, we have read with interest the study by Deo et al.published in BJOG: An International Journal of Obstetrics and Gynaecology 1. We have noted that although the control and VR group were ‘comparable’ regarding previous hysteroscopies, differences in baseline pain expectation scores between patients with a previous hysteroscopy and those without were not given. Each patient has an individual pain experience during hysteroscopy, some may not experience any pain at all, whereas others feel pain during cervical manipulation, distension of the uterus, during pipelle biopsy or delayed pain due to the release of prostaglandins2. Therefore, it could be possible the VR group has patients who do not experience any pain at all. It would be beneficial to know if there was any difference in pain expectation scores between those with prior experience of hysteroscopy and those without. A further study with a group known to have painful hysteroscopies could be of immense clinical value, as this group of patients may experience the greatest benefit.Furthermore, it is mentioned that ‘patients were instructed to self administer analgesics prior to the procedure (either paracetamol or non steroidal anti-inflammatory drugs)’ . It would be useful to ask the patients which specific analgesic they took, the dosage and how long before the procedure they took the medication. As use of analgesia prior to the procedure could potentially affect the pain perceived and therefore the pain scores in both groups; potentially being a confounding factor. Having more information about analgesia used prior to the procedure could allow clinicians to identify significant differences between cohorts with regards to analgesia use and signify a possible correlation to pain scores.Finally, it is mentioned that one patient in the VR group had a previous history of claustrophobia and decided to remove the headset when the procedure started as she felt claustrophobic. Therefore, the patient would not have experienced VR throughout the procedure, rather only for a small period of time, potentially effecting the reported pain score for that patient and the larger results as study populations were only 20 patients per cohort. To avoid this, the patient could have perhaps not been included in the results.Disclosure of Interests: No conflicts to declare.Contribution to Authorship: All authors were involved in the conception, analysis, drafting of intellectual content and final approval of this correspondence letter. All authors are also in agreement to be accountable for all aspects of work in this correspondence letter.Details of Ethics Approval: No ethics approval required.Funding : No funding.

Covariate analysis query: Hospital surgical volume-outcome relationship in caesarean hysterectomy for placenta accreta spectrumOguljemal Redjepovaa, Jack Lowe-Zinolab, Christopher Griffinc

Mini-commentary on BJOG-20-0142.R1: Acupuncture for recurrent urinary tract infection in women: A systematic review and meta-analysis

BJOG perspectives

Time to move on from the hCG hypothesis regarding nausea and vomiting of pregnancy and hyperemesis gravidarumMarlena S. Fejzo, PhDKeck School of Medicine, University of Southern California, Department of Maternal-FetalMedicine, Los Angeles, CA 90033, United StatesThank you for your letter1 highlighting our study that implicates GDF15 and does not support a direct causal role for hCG in Hyperemesis Gravidarum (HG).2 Both GDF15 and hCG are expressed in blastocysts and increase in the 1st trimester,2 so any association between the two hormones in early pregnancy is not surprising and does not imply one controls expression of the other. While it is possible hCG plays a secondary role contributing to GDF15 levels, it is unlikely to be important for HG for the following reasons:From Deruelle and Tranchant‘s letter,1 “nausea and vomiting are not common side-effects of hCG,” but are for GDF15.Circulating hCG reaches its peak at 9-10 weeks,3 while GDF15 levels and HG symptoms do not.4While the Petry et al. study mentioned by Deruelle and Tranchant shows GDF15 and hCG concentrations correlate, they failed to mention Petry also found that only GDF15 levels, and not hCG levels correlated with maternal antiemetic use and second trimester vomiting. Similarly, our study comparing GDF15 and hCG levels in pregnant patients hospitalized with HG compared to healthy pregnant controls also found an association with GDF15 levels, but not hCG.4At least 14 studies, one including 4,372 pregnancies found no association between hCG and HG.4 While other studies find an association, continuing to spend limited resources attempting to prove an association, or a secondary relationship, while interesting, is unlikely to provide any clinically relevant finding regarding hCG and HG.We recently presented a multi-ancestry meta-analysis of 7,197 HG cases and 178,953 controls that confirmed GDF15 as the greatest genetic risk factor, but also replicated associations with placental genes insulin-like growth factor-binding protein 7 (IGFBP7 ) and progesterone receptor (PGR ).5 Therefore, resources would be better spent determining whether IGFBP7 and PGR alter GDF15 levels, and if not, elucidating their etiological role.Both GDF15 and hCG are present in pregnancy directly because of the placental genes that code for them, and yet while the GDF15gene was the most significant locus in 4 individual GWASes,5 none identified any association with genes encoding hCG. If hCG plays a secondary role in HG through upregulating GDF15, genetic variation causing higher levels or overactive hCG should show up in larger GWASes -so far it has not. The theory that hCG causes NVP and HG was a good one, and the lack of a genetic association was surprising. But the fascinating association with the nausea and vomiting hormone GDF15, a hormone highly expressed by the placenta, and the discovery of a mutation in GDF15resulting in > 10-fold increased risk for HG, strongly implicates GDF15 as a causal factor.2 This discovery leads to a potentially clinically relevant pathway for treatment of HG. Drugs that disrupt this pathway are currently in clinical trials to treat nausea and vomiting associated with cancer, and if safe in pregnancy, may be a game changer for HG. It is time to move on from hCG and focus on GDF15.Deruelle and Tranchant‘s letter, in press.Fejzo, M. S., MacGibbon, K. W., First, O., Quan, C., & Mullin, P. M. (2022). Whole-exome sequencing uncovers new variants in GDF15 associated with hyperemesis gravidarum. BJOG : an international journal of obstetrics and gynaecology , 129 (11), 1845–1852. https://doi.org/10.1111/1471-0528.17129Rull, K., & Laan, M. (2005). Expression of beta-subunit of HCG genes during normal and failed pregnancy. Human reproduction (Oxford, England) , 20 (12), 3360–3368. https://doi.org/10.1093/humrep/dei261Fejzo, M. S., Trovik, J., Grooten, I. J., Sridharan, K., Roseboom, T. J., Vikanes, Å., Painter, R. C., & Mullin, P. M. (2019). Nausea and vomiting of pregnancy and hyperemesis gravidarum. Nature reviews. Disease primers , 5 (1), 62. https://doi.org/10.1038/s41572-019-0110-3Fejzo M., Mulin P., Pujol Gualdo N., Laisk T., E. Biobank Research Team, MacGibbon K.W., Wang X., Mancuso N. (2022). Large-scale genome-wide association study meta-analysis of Hyperemesis Gravidarum confirms the nausea and vomiting hormonegene GDF15 is the greatest genetic risk factor and identifies additional risk loci. ASHG, Los Angeles, CA.

Mini-commentary on BJOG-19-1802.R1 & BJOG-19-1803.R1Title: To be decodedZarko Alfirevic,Department of Women’s and Children’s Health, University of LiverpoolSimon GatesCancer Research UK Clinical Trials Unit, University of BirminghamEmail contact: Zarko Alfirevic, Zarko@liverpool.ac.ukRandomised trials remain gold standard for evaluation of effectiveness of medical interventions. However, they are expensive, time consuming and demand huge efforts from participants, researchers and clinical services that facilitate them. Even when trials are successfully completed, peer reviewers often find them wanting. One of the most common criticisms is a ‘lack of power’ to tackle clinically important outcomes. Why is this happening time and again?When an important clinical question creates an equipoise, trialists are faced with difficult choices. If they design a trial to tackle the most important (often rare) outcomes aiming to detect modest, but plausible, risk reductions from a proposed intervention, such studies are rarely feasible and very expensive forcing most funders to simply walk away. Common ‘remedies’ are to change the outcome to something more common and less important (often composite), or to propose an unrealistic risk reduction, sometimes in excess of 50%. Trials of magnesium sulphate for neuroprotection included in the seminal Cochrane review (Doyle LW et al. DOI: 10.1002/14651858.CD004661.pub3) that triggered changes in numerous guidelines world-wide were not an exception (Table 1).Cerebral palsy is a rare, but devastating complication of prematurity and even a very modest reduction would, surely, be worth detecting. The problem is that even in the most ‘at risk’ groups, the incidence of cerebral palsy will not exceed 10%. A conventional sample size calculation estimates that to detect a ‘massive’ 25% risk reduction in cerebral palsy, in excess of 5,000 women would have to be randomised.Interestingly, such a priori sample size calculations are not a feature of most published meta-analyses. Step forward Trial Sequential Analysis (TSA). The TSA is a deceptively simple concept; meta-analysis sample size needs to be increased to allow not only for the heterogeneity of included studies, but also for repeated testing when meta-analyses are being updated and therefore subjected to repeated significance testing. Interested readers can find out more from the Copenhagen Trial Unit’s website - vocal proponents of this methodology (www.ctu.dk/tsa).In their two sister papers, Wolf et al have, quite ingeniously, used TSA to determine the size of their randomised trial and, by doing so, avoided the risk of their randomised trial and updated meta analysis being criticised as ‘underpowered’ (Wolf H et al. BJOG 2020 xxxx (RCT); Wolf H et al. (BJOG 2020 xxxx (SR & MA). Could this concept be a methodological ‘game changer’ in perinatal trials?The concept of TSA has been widely criticised, and a Cochrane Collaboration expert panel recommended against its use (https://methods.cochrane.org/sites/default/files/public/uploads/tsa_expert_panel_guidance_and_recommendation_final.pdf). Key criticisms are, first, that decision-makers require a summary of the currently available evidence and this should not depend on past and future updates. Second, TSA focuses only on statistical significance. Interpretation of meta-analysis should be based on the estimates of the treatment effect and its uncertainty, rather than whether an arbitrary significance threshold is passed. Third, the ways that evidence accumulates in systematic reviews and individual trials are fundamentally different. Review updates are not equivalent to trial interim analyses; updates are not pre-planned and their number cannot be determined in advance. Furthermore, reviews address multiple clinically-relevant effects on several outcomes or subgroup analyses, which need to be integrated into an overall conclusion. The Cochrane expert panel concluded: “Any sequential adjustment procedure is necessarily based on a particular instance of the evolution of evidence that applies to a limited context and cannot satisfy the requirements of all decision makers.”Table 1. Key features of randomised trials of MgSO4given to pregnant women for prevention of cerebral palsy in infants born preterm

BJOG commentary for BJOG-21-0466 A core outcome set for the treatment of pregnant women with pregestational diabetes: an international consensus study