BACKGROUND:Worsening neonatal outcomes over time among planned vaginal births following a previous cesarean were reported in Canada; what drove the change remained unclear. OBJECTIVE:We aimed to describe time trends in severe maternal and perinatal-neonatal morbidity associated with a planned vaginal birth vs a repeat cesarean after a previous cesarean delivery and identify risk factors associated with the trends. STUDY DESIGN:This population-based cohort study included all singleton births ≥37 weeks' gestation from Nova Scotia, Canada, April 1, 2003 to March 31, 2021 with 1 previous cesarean and without trial of labor contraindications. Primary outcomes were severe maternal morbidity and severe perinatal-neonatal morbidity. Adjusted risk ratios and 95% confidence intervals were estimated using log-binomial regression, accounting for confounding using inverse probability weighting. RESULTS:Among 12,681 births (4% aged ≥40 years), 5138 (40.5%) had a planned vaginal birth. Among those with a planned vaginal birth vs a repeat cesarean, severe maternal morbidity increased over time, from 5.9 vs 5.0 per 1000 deliveries in 2003-2008 (adjusted risk ratio, 1.13; 95% confidence interval, 0.46-2.8) to 17.3 vs 4.3 per 1000 deliveries in 2015-2021 (adjusted risk ratio, 3.4; 95% confidence interval, 1.38-8.2). In addition, severe perinatal-neonatal morbidity increased over time from 10.6 vs 10.0 per 1000 deliveries in 2003-2008 (adjusted risk ratio, 1.18; 95% confidence interval, 0.60-2.3) to 25.1 vs 17.2 per 1000 deliveries in 2015-2021 (adjusted risk ratio, 1.56, 95% confidence interval, 0.98-2.5). Any oxytocin induction or augmentation of labor increased from 12.1% in 2003-2008 to 37.9% in 2015-2021; its use was strongly associated with severe maternal morbidities in 2015-2021. CONCLUSION:Planned vaginal birth vs a repeat cesarean after a previous cesarean delivery was more strongly associated with severe maternal and perinatal-neonatal morbidity in later years. Oxytocin induction and augmentation increased markedly in this population and could not be ruled out as a factor associated with worsening outcomes.

OBJECTIVE:To compare effectiveness and safety of oral misoprostol (50 μg every four hours as needed), low dose vaginal misoprostol (25 to 50 μg every six hours as needed), and our established dinoprostone vaginal gel (one to two mg every six hours as needed) induction. MATERIALS AND METHODS:Consenting women with a live term single cephalic fetus for indicated labor induction were randomized (3N = 511). Prior uterine surgery or non-reassuring fetal surveillance were exclusions. Concealed computer generated randomization was stratified and blocked. Newborns were assessed by a team unaware of group assignment. The primary outcome was time from induction at randomization to vaginal birth for initial parametric analysis. Sample size was based on mean difference of 240 minutes with α2 = 0.05 and power 95%. Non-parametric analysis was also pre-specified ranking cesareans as longest vaginal births. RESULTS:Enrollment was from April 1999 to December 2000. Demographics were similar across groups. Analysis was by intent to treat, with no loss to follow up. Mean time (±SD) to vaginal birth was 1356 (±1033) minutes for oral misoprostol, 1530 (±3249) minutes for vaginal misoprostol, and 1208 (±613) minutes for vaginal dinoprostone (P = 0.46, ANOVA). Median times to vaginal birth were 1571, 1339, and 1451 minutes respectively (P = 0.46, Kruskal-Wallis). Vaginal births occurred within 24 hours in 44.9, 53.5 and 47.7% respectively (P = 0.27, χ2). There were no significant differences in Kaplan Meier survival analyses, cesareans, adverse effects, or maternal satisfaction. The newborn who met birth asphyxia criteria received vaginal misoprostol, as did. all three other newborns with cord artery pH<7.0 (P = 0.04, Fisher Exact). CONCLUSION:There was no significant difference in effectiveness of the three groups. Profound newborn acidemia, though infrequent, occurred only with low dose vaginal misoprostol.

Obesity does not contraindicate a trial of labour after a previous cesarean section (TOLAC), but it is unclear whether pregnant individuals with obesity experience fewer TOLACs. Our objective is to assess whether pregnant individuals with obesity were less likely to undergo a TOLAC and have a successful vaginal birth after cesarean section (VBAC) than those without obesity.

Background Metformin is increasingly being used during pregnancy, with potentially adverse long-term effects on children. We aimed to examine adiposity in children of women with type 2 diabetes from the Metformin in Women with Type 2 Diabetes in Pregnancy (MiTy) trial, with and without in-utero exposure to metformin, up to 24 months of age.Methods MiTy Kids is a follow-up study that included infants of women who participated in the MiTy randomised controlled trial, receiving either oral 1000 mg metformin twice daily or placebo. Caregivers and researchers remained masked to the type of medication (metformin or placebo) mothers received during their pregnancy. Anthropometric measurements, including weight, height, and skinfold thicknesses, were taken at 3, 6, 12, 18, and 24 months. At 24 months, linear regression was used to compare the BMI Z score and sum of skinfolds in the metformin versus placebo groups, adjusted for confounders. Fractional polynomials were used to assess growth trajectories. This study is registered with ClinicalTrials.gov, NCT01832181.Findings Of the 465 eligible children, 283 (61%) were included from 19 centres in Canada and Australia. At 24 months, there was no difference between groups in mean BMI Z score (0middot84 [SD 1middot52] with metformin vs 0middot91 [1middot38] with placebo; mean difference 0middot07 [95% CI -0middot31 to 0middot45], p=0middot72) or mean sum of skinfolds (23middot0 mm [5middot2] vs 23middot8 mm [5middot4]; mean difference 0middot8 mm [-0middot7 to 2middot3], p=0middot31). Metformin was not a predictor of BMI Z score at 24 months of age (mean difference -0middot01 [95% CI -0middot42 to 0middot37], p=0middot92). There was no overall difference in BMI trajectory but, in males, trajectories were significantly different by treatment (p=0middot048); BMI in the metformin group was higher between 6 and 24 months. Children of women with type 2 diabetes were approximately 1 SD heavier than the WHO reference population.Interpretation Anthropometrics were similar in children exposed and those not exposed to metformin in utero; hence, overall, data are reassuring with regard to the use of metformin during pregnancy in women with type 2 diabetes and the long-term health of their children.Funding Canadian Institute for Health Research.Copyright (c) 2023 Published by Elsevier Ltd. All rights reserved.

Background: In the MiTy trial [pregnant T2D randomized to metformin vs. placebo], infants exposed to metformin in-utero had a lower risk of large-for-gestational-age (LGA) but were at higher risk of small-for-gestational-age (SGA) . To date, there are limited data on the effect of in-utero exposure to metformin on infant/child growth in T2D, according to the intrauterine growth status. The MiTy Kids study followed the offspring of MiTy participants to 24 months of age to examine the effect of metformin exposure in-utero on child growth. Aim: Examine the weight and body mass index (BMI) trajectories of children of women with T2D, according to the intrauterine growth status [appropriate for gestational age (AGA) , LGA, and SGA] and metformin exposure. Methods: The study population included offspring of MiTy trial participants. Height and weight measurements were collected at 3, 6, 12, 18 and 24 months of age. Analysis of data was conducted using a fractional polynomial linear mixed effects approach to compare growth trajectories. Results: Of the 283 children who participated in MiTy Kids (46.3% female) , 194 children were AGA at birth (90 metformin and 1placebo) , 65 were LGA (29 metformin and 36 placebo) , and 24 were SGA (16 metformin and 8 placebo) . In children born AGA, both sexes in the metformin arm had a lower weight gain trajectory than those in the placebo group (p=0.008) . Treatment and sex did not have an effect on the growth trajectories of children born LGA. In SGA children, in both sexes, SGA children in the metformin group had a lower weight gain trajectory (p=<0.001) and BMI trajectory (p=0.042) than children in the placebo group, and achieved a lower weight than the WHO growth standard at 24 months. Conclusion: Metformin exposure in-utero was associated with lower weight gain trajectories and BMI trajectories in children of both sexes born SGA and lower weight gain trajectory in AGA children. Further follow-up will determine subsequent growth in these children. Disclosure J. Sanchez: None. J. Hamilton: Advisory Panel; Novo Nordisk Canada Inc. Research Support; Mead Johnson & Company, LLC. G. Tomlinson: None. E. Asztalos: None. K. Murphy: None. B. Zinman: Advisory Panel; Abbott Diabetes, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Canada Inc., Sanofi K.K. D. Simmons: Research Support; Abbott, Hitachi, Ltd., Novo Nordisk. Speaker's Bureau; Sanofi. Other Relationship; Elsevier. A. Haqq: None. I.G. Fantus: None. A. Armson: None. J.F.R. Barrett: None. L.E. Donovan: Other Relationship; Dexcom, Inc., Inner Analytics, Medtronic, Tandem Diabetes Care, Inc. P. Karanicolas: Research Support; Baxter. Y. Jiang: None. S. Tobin: None. K. Mangoff: None. G. Klein: None. D. Feig: Advisory Panel; Novo Nordisk. Research Support; Apotex. Funding Canadian Institutes of Health Research

Umbilical cord milking improves postnatal adaptation and short-term outcomes of very preterm infants compared to early cord clamping. Little is known about the impact of umbilical cord milking on long-term neurodevelopmental outcomes. The objective of this study is to compare the effects of intact umbilical cord milking (UCM) vs. early cord clamping (ECC) at birth on neurodevelopmental outcomes at 36 months’ corrected age. Preterm infants < 31 weeks’ gestation who were randomized at birth to receive three time milking of their attached cord or ECC (< 10 s) were evaluated at 36 months’ corrected age. Neurodevelopmental outcomes were assessed by blinded examiners using Bayley Scales of Infant and Toddler Development (version III). Analysis was by intention to treat. Out of the 73 infants included in the original trial, 2 died and 65 (92

OBJECTIVE:To identify determinants of cesarean delivery (CD) and examine associations between mode of delivery (MOD) and maternal and perinatal outcomes.METHODS:We conducted a retrospective analysis of a Canadian multicentre birth cohort derived from provincial data collected in 2008/2009. Maternal and perinatal characteristics and outcomes were compared between vaginal and cesarean birth and between the following MOD subgroups: spontaneous vaginal delivery (VD), assisted VD, planned cesarean delivery (CD), and intrapartum CD. Multivariate regression identified determinants of CD and the effects of MOD and previous CD on maternal and perinatal outcomes.RESULTS:The cohort included 264 755 births (72.1% VD and 27.9% CD) from 91 participating institutions. Determinants of CD included maternal age, parity, previous CD, chronic hypertension, diabetes, urinary tract infection or pyelonephritis, gestational hypertension, vaginal bleeding, labour induction, pre-term gestational age, low birth weight, large for gestational age, malpresentation, and male sex. CD was associated with greater risk of maternal and perinatal morbidity and mortality. Subgroup analysis demonstrated higher risk of adverse pregnancy outcomes with assisted VD and intrapartum CD than spontaneous VD. Planned CD reduced the risk of obstetric wound hematoma and perinatal mortality but increased maternal and neonatal morbidity. Previous CD increased the risk of maternal and neonatal morbidity among multiparous women.CONCLUSIONS:The CD rate in Canada is consistent with global trends reflecting demographic and obstetric intervention factors. The risk of adverse pregnancy outcomes with CD warrants evaluation of interventions to safely prevent nonessential cesarean birth.

Background: Offspring of mothers with T2D are at increased risk of obesity and diabetes. In the MiTy trial [pregnant T2D randomized to metformin vs. placebo], infants exposed to metformin were lighter, had lower fat-mass and risk of large-for-gestational-age, but at higher risk of small-for-gestational-age. There are questions on the long-term effects of in-utero exposure to metformin on offspring of women with T2D. Aim: To examine adiposity in children of women with T2D, with and without exposure to metformin, up to 24 months. Methods: We included infants of women who participated in MiTy. Anthropometric measurements were made at 3, 6, 12, 18 and 24 months of age. At 24 months, t-tests and linear regression were used to estimate differences in BMI z-score and sum of skinfolds by metformin group, adjusted for confounders. Comparisons over time used longitudinal models, with fractional polynomials for growth trajectories. Results: Of the 465 eligible children from MiTy, 283 (60.8%) participated in MiTy Kids. At 24 months, there was no difference in BMI z-score (0·84±1·52 in metformin vs. 0·91±1·38 in placebo (p=0.72)) or sum of skinfolds (23·0±5·2 in metformin vs. 23·8±5·3 in placebo (p=0.31)) between groups. There was no difference in BMI trajectory by treatment overall but in males, treatment had significantly different trajectories (p=0.048) ; the metformin BMI was higher from 8 to 24 months. At 24 months, reduced sleep time (p=0.0125) and increased screen time (p=0.0549) were associated with increased BMI z-score. Offspring of women with T2D were approximately 1 SD heavier than the WHO reference population. Conclusion: Offspring of women with T2D with and without exposure to metformin in-utero had similar anthropometrics overall. In males, metformin led to higher BMI growth trajectory between 8 and 24 months. Future follow-up is needed to see if these findings continue. Disclosure D.Feig: Advisory Panel; Novo Nordisk, Research Support; Apotex. A.Armson: None. J.F.R.Barrett: None. L.E.Donovan: Other Relationship; Dexcom, Inc., Inner Analytics, Medtronic, Tandem Diabetes Care, Inc. P.Karanicolas: Research Support; Baxter. G.Klein: None. S.Tobin: None. K.Mangoff: None. G.Tomlinson: None. J.Hamilton: Advisory Panel; Novo Nordisk Canada Inc., Research Support; Mead Johnson & Company, LLC. J.Sanchez: None. K.Murphy: None. E.Asztalos: None. B.Zinman: Advisory Panel; Abbott Diabetes, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Canada Inc., Sanofi K.K. D.Simmons: Other Relationship; Elsevier, Research Support; Abbott, Hitachi, Ltd., Novo Nordisk, Speaker's Bureau; Sanofi. A.Haqq: None. I.G.Fantus: None. L.Lipscombe: n/a. Funding Canadian Health Institute for Research

ObjectifFournir des recommandations pour que le counseling contraceptif soit adapté à la culture, n'exerce aucune coercition et favorise la prise de décision partagée et l'autonomie de la patiente.Population cibleLes personnes en âge de procréer qui consultent afin d'adopter une méthode contraceptive ou d'obtenir des conseils en planification familiale.OptionsLe counseling contraceptif est offert dans un cadre de planification familiale fondé sur les droits de la personne, dans le respect des croyances, de la culture et des préférences individuelles et de la capacité de la personne à utiliser la méthode choisie.RésultatsPromouvoir l'autonomie de la patiente dans la prise de décisions concernant la planification familiale, y compris le droit d'obtenir et d'utiliser la méthode contraceptive de son choix, de refuser la contraception ou d'utiliser une méthode contraceptive moins efficace et de choisir librement de cesser l'utilisation d'une méthode contraceptive, tout en s'assurant que le fournisseur de soins de santé lui offre un counseling contraceptif impartial et non coercitif ainsi que des renseignements fondés sur des données probantes.Bénéfices, risques et coûtsLa mise en œuvre des recommandations limiterait la prestation de soins contraceptifs coercitifs, réels ou perçus, en particulier chez les populations vulnérables, ce qui se traduirait par une amélioration de l'autonomie et de l'expérience de la patiente dans les milieux de soins.Données probantesBases de données utilisées : Medline, Cochrane, PubMed et CanLII. Termes médicaux utilisés : contraception, family planning services, informed consent, coercion, decision making, sterilization, permanent contraception, counselling. Termes juridiques utilisés : forced sterilization et aboriginal. La recherche initiale a été effectuée en 2020 et mise à jour en 2021.Professionnels concernés :Cette opinion de comité est destinée aux fournisseurs de soins de santé (obstétriciens, gynécologues, médecins de famille, chirurgiens généralistes, infirmières praticiennes, infirmières, sages-femmes, stagiaires en médecine [externat, résidence et monitorat] et autres fournisseurs de soins) qui offrent des services de santé sexuelle et reproductive.

Objective: To provide guidance on culturally competent contraception counselling that is free of coercion and promotes shared decision-making and patient autonomy. Target population: Individuals of reproductive age who seek contraception or counselling for family planning. Options: Contraception counselling is provided within a rights-based family planning framework, where the individual's beliefs, culture, preferences, and ability to use the chosen method are respected. Outcomes: To promote patient autonomy in decision-making surrounding family planning, including the right to access and use their contraceptive method of choice, to decline contraception or use less effective methods of contraception, and to freely choose to discontinue a method of contraception, as well as the right to unbiased, non-coercive contraception counselling and evidence-based information from their health care provider Benefits, Harms, and Costs: Implementation of these recommendations would reduce real or perceived coercive contraceptive care, particularly among vulnerable populations, resulting in improved patient autonomy and a better patient experience in health care settings. Evidence: Databases searched: MEDLINE, Cochrane, PubMed, and CanLII. Medical terms used: contraception, family planning services, informed consent, coercion, decision making, sterilization, permanent contraception, counselling. Legal terms searched: forced sterilization, and aboriginal. Initial search conducted in 2020 and updated in 2021. Intended Audience: This committee opinion is intended for health care providers (obstetricians, gynaecologists, family physicians, general surgeons, nurse practitioners, nurses, midwives, undergraduate/ postgraduate medical trainees, and other health care providers) who provide sexual and reproductive health services.

Objective To compare the effect of umbilical cord milking (UCM) vs. early cord clamping (ECC) on cerebral blood flow (CBF). Method Preterm infants <31 weeks’ gestation were randomized to receive UCM or ECC at birth. Blood flow velocities and resistive & pulsatility indices of middle and anterior cerebral arteries were measured at 4–6 and 10–12 h after birth as an estimate of CBF. Results Randomization allocated 37 infants to UCM and 36 to ECC. Maternal and antenatal variables were similar. There were no significant differences between groups in middle or anterior CBF velocities and resistive indices at either study time point. CBF variables were not correlated with mean blood pressure, systemic blood flow, or intraventricular hemorrhage. Conclusions In very preterm infants, UCM compared with ECC was not shown to change CBF indices during the first 12 h of age or correlate with other hemodynamic measures or with intraventricular hemorrhage. Trial registration ClinicalTrials.gov: NCT01487187.

Centres providing maternity care and offering a trial of labour after cesarean must develop and use maternal educational and consent processes that emphasize choice and autonomy related to options for and decisions surrounding vaginal birth after cesarean and elective repeat cesarean delivery. These centres should have administrative systems and processes that take into account local resources for cesarean delivery services, including team-based complex maternity risk support and an urgency consensus on the fetal, maternal, and maternal-fetal indications for a surgical delivery to ensure an appropriate decision-to-delivery interval.

Sepsis is one of the leading causes of maternal morbidity and mortality. Analyses have determined that delays in early recognition and prompt initiation of appropriate management are key contributing factors in maternal sepsis deaths. Recent cases of sepsis-related maternal morbidity and mortality across Canada have highlighted the urgent need for a national standardized approach to the detection and treatment of maternal sepsis. The SOGC has established a national multidisciplinary maternal sepsis task force to address this priority. The adoption of a national modified obstetric early warning system (MEOWS) is recommended as a key first step. This early warning scoring (EWS) system will facilitate early detection of maternal clinical deterioration and mandate timely escalation of care appropriate for the severity of illness. There is currently limited use of EWSs in Canada. Introducing a national EWS and a standardized maternal sepsis management guideline provides a tremendous opportunity to improve maternal care. A standardized approach will facilitate future evidence-based evaluation and refinement of the tool, and enable the reduction of preventable maternal morbidity and mortality from sepsis, as well as all causes duplicated.

ObjectiveThe purpose of this study was to assess compliance with fetal fibronectin (fFN) testing recommendations at a single tertiary care perinatal centre. The secondary objective was to identify factors associated with compliance with these recommendations.MethodsA retrospective cohort study was conducted from January 1, 2016 to December 31, 2016 of all patients who presented to the IWK Health Centre with suspected preterm labour. Inclusion criteria included symptoms of preterm labour prior to 370 weeks gestation, singleton or multiple pregnancy, and established fetal wellbeing. Exclusion criteria included severe fetal anomaly, contraindications to tocolysis, transfer from community hospital, or inadequate documentation. Provider compliance was evaluated to determine: 1) whether the test was performed for appropriate indications according to provincial fFN guidelines; 2) whether fFN results were appropriately being used to inform patient care. Logistic regression was used to determine factors associated with compliance.ResultsA total of 528 patients presented with symptoms of preterm labour. The overall compliance with testing recommendations was 76.1%. Compliance for patients who met criteria for fFN testing was 73%, and compliance for those not meeting criteria was 76.4%. Of patients with a negative fFN result, 85.3% were appropriately discharged home without intervention. Gestational age, time of day, and non-obstetrician provider type were found to be associated with compliance.ConclusionDespite regional and national guidelines, this study demonstrates a compliance rate of 76% in our centre, indicating a gap in provider knowledge regarding proper use and interpretation of fFN. Non-obstetrician provider type was associated with decreased compliance.

Background Although metformin is increasingly being used in women with type 2 diabetes during pregnancy, little data exist on the benefits and harms of metformin use on pregnancy outcomes in these women. We aimed to investigate the effects of the addition of metformin to a standard regimen of insulin on neonatal morbidity and mortality in pregnant women with type 2 diabetes. Methods In this prospective, multicentre, international, randomised, parallel, double-masked, placebo-controlled trial, women with type 2 diabetes during pregnancy were randomly assigned from 25 centres in Canada and four in Australia to receive either metformin 1000 mg twice daily or placebo, added to insulin. Randomisation was done via a web-based computerised randomisation service and stratified by centre and pre-pregnancy BMI (<30 kg/m(2) or >= 30 kg/m(2)) in a ratio of 1:1 using random block sizes of 4 and 6. Women were eligible if they had type 2 diabetes, were on insulin, had a singleton viable pregnancy, and were between 6 and 22 weeks plus 6 days' gestation. Participants were asked to check their fasting blood glucose level before the first meal of the day, before the last meal of the day, and 2 h after each meal. Insulin doses were adjusted aiming for identical glucose targets (fasting glucose <5.3 mmol/L [95 mg/dL], 2-h postprandial glucose <6.7 mmol/L [120 mg/dL]). Study visits were done monthly and patients were seen every 1-4 weeks as was needed for standard clinical care. At study visits blood pressure and bodyweight were measured; patients were asked about tolerance to their pills, any hospitalisations, insulin doses, and severe hypoglycaemia events; and glucometer readings were downloaded to the central coordinating centre. Participants, caregivers, and outcome assessors were masked to the intervention. The primary outcome was a composite of fetal and neonatal outcomes, for which we calculated the relative risk and 95% CI between groups, stratifying by site and BMI using a log-binomial regression model with an intention-to-treat analysis. Secondary outcomes included several relevant maternal and neonatal outcomes. The trial was registered with ClinicalTrials.gov, NCT01353391. Findings Between May 25, 2011, and Oct 11, 2018, we randomly assigned 502 women, 253 (50%) to metformin and 249 (50%) to placebo. Complete data were available for 233 (92%) participants in the metformin group and 240 (96%) in the placebo group for the primary outcome. We found no significant difference in the primary composite neonatal outcome between the two groups (40% vs 40%; p=0.86; relative risk [RR] 1.02 [0.83 to 1.26]). Compared with women in the placebo group, metformin-treated women achieved better glycaemic control (HbA 1c at 34 weeks' gestation 41.0 mmol/mol [SD 8.5] vs 43.2 mmol/mol [-10]; 5.90% vs 6.10%; p=0.015; mean glucose 6.05 [0.93] vs 6.27 [0.90]; difference -0.2 [-0.4 to 0.0]), required less insulin (1.1 units per kg per day vs 1.5 units per kg per day; difference -0.4 [95% CI -0.5 to -0.2]; p<0.0001), gained less weight (7.2 kg vs 9.0 kg; difference -1.8 [-2.7 to -0.9]; p<0.0001) and had fewer caesarean births (125 [53%] of 234 in the metformin group vs 148 [63%] of 236 in the placebo group; relative risk [RR] 0.85 [95% CI 0.73 to 0.99]; p=0.031). We found no significant difference between the groups in hypertensive disorders (55 [23%] in the metformin group vs 56 [23%] in the placebo group; p=0.93; RR 0.99 [0.72 to 1.35]). Compared with those in the placebo group, metformin-exposed infants weighed less (mean birthweight 3156 g [SD 742] vs 3375 g [742]; difference -218 [-353 to -82]; p=0.002), fewer were above the 97th centile for birthweight (20 [9%] in the metformin group vs 34 [15%] in the placebo group; RR 0.58 [0.34 to 0.97]; p=0.041), fewer weighed 4000 g or more at birth (28 [12%] in the metformin group vs 44 [19%] in the placebo group; RR 0.65 [0.43 to 0.99]; p=0.046), and metformin-exposed infants had reduced adiposity measures (mean sum of skinfolds 16.0 mm [SD 5.0] vs 17.4 [6.2] mm; difference -1.41 [-2.6 to -0.2]; p=0.024; mean neonatal fat mass 13.2 [SD 6.2] vs 14.6 [5.0]; p=0.017). 30 (13%) infants in the metformin group and 15 (7%) in the placebo group were small for gestational age (RR 1.96 [1.10 to 3.64]; p=0.026). We found no significant difference in the cord c-peptide between groups (673 pmol/L [435] in the metformin group vs 758 pmol/L [595] in the placebo group; p=0.10; ratio of means 0.88 [0.72 to 1.02]). The most common adverse event reported was gastrointestinal (38 events in the metformin group and 38 events in the placebo group). Interpretation We found several maternal glycaemic and neonatal adiposity benefits in the metformin group. Along with reduced maternal weight gain and insulin dosage and improved glycaemic control, the lower adiposity and infant size measurements resulted in fewer large infants but a higher proportion of small-for-gestational-age infants. Understanding the implications of these effects on infants will be important to properly advise patients who are contemplating the use of metformin during pregnancy.

Background: Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality. Interventions aimed at preventing PTB can be classified as primary, secondary, or tertiary prevention. Objective: To conduct a review of systematic reviews on the effectiveness and safety of primary and secondary preterm birth prevention interventions. Search strategy: A systematic literature search of the Cochrane, PubMed/Medline, EMBASE and CINAHL databases was conducted on 2 September 2015, and updated on 21 November 2016. Selection criteria: We included any published systematic review of randomized controlled trials (RCTs) or individual patient data (IPD) of RCTs related to primary or secondary prevention of PTB, published between 2005-2016 where gestational age at birth (of any interval) was a pre-specified outcome. Individual trials and non-systematic reviews were not eligible. Data collection and analysis: The population of interest was all pregnant women, regardless of PTB risk. The primary outcome was PTB <37 weeks. Main Results: In total, 112 reviews were included in this study. Overall there were 49 Cochrane and 63 non-Cochrane reviews. Eight were individual participant data (IPD) reviews. Sixty reviews assessed the effect of primary prevention interventions on risk of PTB. Positive effects were reported for lifestyle and behavioural changes (including diet and exercise); nutritional supplements (including calcium and zinc supplementation); nutritional education; screening for lower genital tract infections. Eighty-three systematic reviews were identified relating to secondary PTB prevention interventions. Positive effects were found for low dose aspirin among women at risk of preeclampsia; clindamycin for treatment of bacterial vaginosis; treatment of vaginal candidiasis; progesterone in women with prior spontaneous PTB and in those with short midtrimester cervical length; L-arginine in women at risk for preeclampsia; levothyroxine among women with tyroid disease; calcium supplementation in women at risk of hypertensive disorders; smoking cessation; cervical length screening in women with history of PTB with placement of cerclage in those with short cervix; cervical pessary in singleton gestations with short cervix; and treatment of periodontal disease. Conclusion: The overview serves as a guide to current evidence relevant to PTB prevention. Only a few interventions have been demononstrated to be effective, including cerclage, progesterone, low dose aspirin, and lifestyle and behavioural changes. For several of the interventions evaluated, there was insufficient evidence to assess whether they were effective or not. (C) 2019 Elsevier B.V. All rights reserved.

Objective: To identify research priorities of interventions for the primary prevention of preterm birth (PTB), by conducting an international stakeholder survey. Study design: A prospective cross-sectional online survey was conducted in November 2016. Fifteen interventions to prevent spontaneous PTB were identified and ranked by stakeholders (n = 159) in the field of maternal and perinatal health research, using nine equally weighted criteria. Medians and interquartile ranges (IQRs) were calculated and the interventions ranked accordingly. Results: Respondents to the survey were from 46 different countries, mostly from low and middle-income countries (62%, 99/159) and were mainly clinicians (80%, 127/159). Of the fifteen interventions ranked, the following five were identified as research priorities in the primary prevention of PTB: dietary counselling and nutritional education, risk scoring, vitamin D supplementation, exercise and antioxidant supplementation. Conclusion: We have identified research priorities of interventions to prevent spontaneous PTB through a global stakeholder survey. The interventions prioritized in this exercise can be used by researchers, grant funding bodies and research-policy decision makers to inform calls on future clinical trials or individual patient data meta-analyses on the primary prevention of PTB. (C) 2019 Elsevier B.V. All rights reserved.

Objective: This study sought to determine the optimal timing of ultrasound in the third trimester to predict birth weight accurately in diabetic women with a singleton pregnancy. Methods: A retrospective cohort study of all diabetic women with a singleton pregnancy treated in Halifax, Nova Scotia, was performed. Estimated fetal weight was derived from ultrasound measures using the Hadlock2 equation. The Mongelli equation was used to predict birth weight. The association between gestational age at ultrasound and accuracy of predicted birth weight was assessed, with accuracy as a continuous variable representing the difference between predicted and actual birth weight and as a categorical variable (with four gestational age categories) representing whether predicted birth weight was within, over, or under 250 g of actual birth weight Results: The cohort of 943 women comprised 121 (12.8%) with type 1 diabetes, 111 (11.7%) with type 2 diabetes, and 711 (75.4%) with gestational diabetes. Ultrasound scans performed at term were the most accurate in predicting birth weight. At this gestational age, the mean difference between predicted and actual birth weight was -30 g (95% confidence interval -109 to -48). After adjusting for maternal body mass index, age, smoking, type of diabetes, and interval between ultrasound examination and delivery, accuracy improved as gestational age at ultrasound increased (P = 0.005). The odds of underpredicting or overpredicting birth weight were not significantly affected by the timing of the ultrasound examination. Conclusion: Because the predictive accuracy of ultrasound prediction of birth weight improves with gestational age, fetal growth assessment at term is recommended to aid with delivery planning in women with diabetes.

Umbilical cord milking at birth has been reported to have short-term benefits to preterm infants. Long-term neurodevelopmental outcomes need more exploration. To compare the effects of cord milking (CM) vs. early cord clamping (ECC) at birth on neurodevelopmental outcomes at 36 months corrected age. Preterm infants <31 weeks’ gestation who were randomized to receive CM or ECC at birth, were evaluated at 36 months corrected age. Neuro-developmental outcomes were assessed by blinded examiners using Bayley Scales of Infant and Toddler Development (version III). Intention-to-treat was used for primary analyses. Out of the 74 infants included in the original trial, 2 died and 65 (90%) infants were evaluated at 36 months corrected age. Patients’ characteristics were similar in both study groups except for higher hemoglobin concentration on NICU admission (p=0.02) and longer duration of phototherapy (p=0.02) in the CM group (Table 1). The median cognitive, motor or language scores were higher in the CM group but the difference didn’t reach statistical significance (Table 2). Similarly, there were no significant differences in the rates of cerebral palsy, developmental impairment, deafness or blindness though cerebral palsy was higher in the CM group. In this randomised controlled trial, no significant differences in neuro-developmental outcomes at 36 months corrected age, were found between preterm infants who received CM and those who received ECC at birth. The absence of difference may be attributed to the small sample size. Larger trials are needed to evaluate the neuro-developmental outcomes of CM.

ObjectiveTo investigate whether umbilical cord milking (UCM) at birth improves systemic blood flow and short-term outcomes, as compared with immediate cord clamping (ICC).DesignRandomised clinical trial.SettingSingle tertiary care centre.PatientsInfants born to eligible women presenting in preterm labour between 24 and 31 weeks’ gestation.InterventionsUCM three times at birth or ICC.Outcome measuresPrimary outcome included systemic blood flow as represented by echo-derived superior vena cava(SVC) flow at 4–6 hours after birth. The echocardiographer and interpreter were blinded to the randomisation. Secondary outcomes included cardiac output, neonatal morbidities and mortality. Analysis was by intention to treat.ResultsA total of 73 infants were randomised (37 to UCM and 36 to ICC). Mean (SD) gestational age was 27 (2) weeks and mean (SD) birth weight was 1040 (283) g. Haemoglobin on admission was higher in the UCM than in the ICC group (16.1 vs 15.0 g/L), p=0.049 (mean difference 1.1, 95% CI 0.003 to 2.2). No statistically significant differences were found between groups in SVC flow at 4–6 hours (88.9±37.8 and 107.3±60.1 mL/kg/min), p=0.13 (mean difference −18.4, 95% CI −41.7 to 5.0 mL/kg/min) or at 10–12 hours of age (102.5±41.8 and 90.6±28.4 mL/kg/min), p=0.17 (mean difference 12.0, 95% CI −4.7 to 28.7 mL/kg/min), cardiac output or neonatal morbidities.ConclusionsCord milking was not shown to improve functional cardiac outcomes, neonatal morbidity or mortality. More research is needed before routine cord milking can be recommended for very preterm infants.Trial registrationNCT01487187.