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BACKGROUND Data on the association of inappropriate gestational weight gain (GWG) and adverse outcomes in twin pregnancies are limited and inconsistent. OBJECTIVES To perform a systematic review and meta-analysis on the association between GWG and adverse outcomes in twin pregnancies. SEARCH STRATEGY Ovid, Medline, EMBASE and Cochrane Central databases from 1 January 1990 until 23 September 2020. SELECTION CRITERIA Interventional and observational studies evaluating the association between GWG and adverse outcomes in twin pregnancies. DATA COLLECTION AND ANALYSIS Data were extracted by two independent reviewers. Summary odds ratios (OR) were calculated using a random-effects model in a subset of studies that analysed GWG as a categorical variable in relation to the Institute of Medicine (IOM) recommendations. The primary outcome was preterm birth. MAIN RESULTS From 277 citations, 19 studies involving 36 023 women with twin pregnancies were included in the qualitative analysis, of which 14 were included in the meta-analysis. Overall, 56.8% of women experienced inappropriate GWG: 35.4% (95% CI 30.0-41.0%) gained weight below and 21.4% (95% CI 14.2-29.5%) gained weight above IOM recommendations. Compared with GWG within IOM guidelines, GWG below IOM guidelines was associated with preterm birth before 32 weeks of gestation (OR 3.38; 95% CI 2.05-5.58), and a reduction in the risk of pre-eclampsia (OR 0.68; 95% CI 0.48-0.97). GWG above IOM guidelines was associated with an increased risk of pre-eclampsia that was consistent across all body mass index categories. CONCLUSIONS Inappropriate GWG affects over half of twin pregnancies, so is a common and potentially modifiable risk factor for preterm birth and pre-eclampsia.

Pregnancy requires maternal adaptations to support fetal growth: whether these adaptations include temporal shifts in the gut microbiome is still unclear. We investigated the maternal gut microbiome longitudinally over the course of pregnancy and the impact of pre-pregnancy BMI (pBMI) and GWG. We also determined whether parity modulated observed associations. We show that the gut microbiota of participants with higher pBMI changed less over the course of pregnancy in primiparous, but not multiparous participants. This suggests that previous pregnancies may have persistent impacts on maternal adaptations to pregnancy. This ecological memory appears to be passed to the next generation, as parity modulated the impact of maternal GWG on the infant gut microbiome. This work supports a role for the gut microbiome in maternal adaptations to pregnancy and highlights the need for longitudinal sampling and accounting for parity as key considerations for studies of the microbiome in pregnancy and infants.

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

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= 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

Objective To determine the population-level impact of COVID-19 pandemic–related obstetric practice changes on maternal and newborn outcomes. Methods Segmented regression analysis examined changes that occurred 240 weeks pre-pandemic through the first 32 weeks of the pandemic using data from Ontario’s Better Outcomes Registry & Network. Outcomes included birth location, length of stay, labour analgesia, mode of delivery, preterm birth, and stillbirth. Immediate and gradual effects were modelled with terms representing changes in intercepts and slopes, corresponding to the start of the pandemic. Results There were 799 893 eligible pregnant individuals included in the analysis; 705 767 delivered in the pre-pandemic period and 94,126 during the pandemic wave 1 period. Significant immediate decreases were observed for hospital births (relative risk [RR] 0.99; 95% CI 0.98–0.99), length of stay (median change –3.29 h; 95% CI –3.81 to –2.77), use of nitrous oxide (RR 0.11; 95% CI 0.09–0.13) and general anesthesia (RR 0.69; 95% CI 0.58– 0.81), and trial of labour after cesarean (RR 0.89; 95% CI 0.83–0.96). Conversely, there were significant immediate increases in home births (RR 1.35; 95% CI 1.21–1.51), and use of epidural (RR 1.02; 95% CI 1.01–1.04) and regional anesthesia (RR 1.01; 95% CI 1.01–1.02). There were no significant immediate changes for any other outcomes, including preterm birth (RR 0.99; 95% CI 0.93–1.05) and stillbirth (RR 1.11; 95% CI 0.87–1.42). Conclusion Provincial health system changes implemented at the start of the pandemic resulted in immediate clinical practice changes but no significant increases in adverse outcomes.

The mode of delivery in multiple pregnancies has been subject to vigorous debates during the last few decades. Although observational and retrospective data were accumulated, it was not until the publication of the Twin Birth Study that evidence-based recommendations could emerge. However, although some of the most pressing questions were answered by the Twin Birth Study, other questions were left outside the scope of the study. The questions were of great interest and included the following topics: the impact of gestational age, the influence of chorionicity, and the generalizability of the results for women with a previous uterine scar. The current evidence supported a trial of labor in dichorionic-diamniotic or monochorionic-diamniotic twin pregnancies in which the first twin is in cephalic presentation at ≥32 weeks’ gestation. Dichorionic-diamniotic, monochorionic-diamniotic, and monochorionic-monoamniotic twins should be delivered at 37 0/7 to 38 0/7, 36 0/7 to 37 0/7, and 32 0/7 to 34 0/7 weeks’ gestation, respectively. Breech extraction done by a competent healthcare provider seemed to offer a higher chance of successful vaginal delivery of the second twin than the external cephalic version. The current data did not allow for a clear recommendation regarding the mode of delivery in very preterm birth of low birthweight twins, but most studies did not demonstrate a clear benefit of cesarean delivery vs trial of labor. Furthermore, a trial of labor seemed safe in women with a previous cesarean delivery. Cesarean delivery is likely beneficial for twin pregnancies with the first twin in breech presentation, monochorionic-monoamniotic twins, and higher-order multiple pregnancies. In all multiple pregnancies, delivery should be performed by an experienced practitioner competent in multiple pregnancy deliveries.

Maternal and neonatal outcomes of trial of labor after cesarean delivery of twins are similar to those of singleton trials of labor after cesarean delivery. However, previous studies did not stratify outcomes by second-twin presentation on admission to labor.To examine maternal and neonatal outcomes following trial of labor after cesarean delivery in twins with vertex-nonvertex presentation.A retrospective multicenter study was conducted including data on deliveries occurring between the years 2005 and 2020. We included trials of labor after a previous cesarean delivery (at ≥32A total of 236 twin trials of labor after cesarean delivery were included, of which 128 involved nonvertex second twins and 108 a second vertex twin. Uterine rupture rates were comparable between the groups (1/128 [0.9%] vs 1/108 [0.8%]; P=1.000). Successful trial of labor after cesarean delivery of both twins occurred in 76.6% of the exposed group vs 81.5% of the comparison group, whereas cesarean delivery of both twins was performed in 21.9% of the exposed group vs 17.6% of the comparison group (P=.418; odds ratio, 1.32; confidence interval, 0.7-2.5). Two cases of cesarean delivery of the second twin occurred in the exposed group and 1 in the comparison group (1.6% vs 0.9%, respectively, P=1.000). There was no difference between the groups in maternal outcomes, including rates of postpartum hemorrhage, blood transfusion, placental abruption, thromboembolic events, and maternal fever. Neonatal outcomes were also comparable between the groups, including rates of intensive care admission and low (≤7) 5-minute Apgar scores.Our data show that trial of labor after cesarean delivery of noncephalic second twins holds favorable maternal and neonatal outcomes, comparable with those of vertex-vertex trials of labor after cesarean delivery. Second-twin noncephalic presentation should not discourage parturients and caregivers from considering trial of labor after cesarean delivery if desired.