Search

Objective To evaluate whether pregnancy outcomes associated with hypertensive disorders of pregnancy in twin pregnancies differ relatively from those in singleton pregnancy. Methods We conducted a retrospective, population-based cohort study of all women with a liveborn singleton or twin hospital birth in Ontario, Canada, between 2012 and 2019. Data were obtained from the Better Outcomes Registry & Network Ontario. Pregnancy outcomes were compared between women with and without hypertensive disorders of pregnancy in twin gestations, and separately in singleton gestations. Adjusted relative risks (aRRs) and 95% CIs were generated using modified Poisson regression and were compared between twins and singletons using relative risk ratios. Results Overall, 932,218 women met the study criteria, of whom 917,542 (98.4%) and 14,676 (1.6%) had singleton and twin gestations, respectively. The incidence of hypertensive disorders of pregnancy was higher in women with twin compared with singleton gestations (14.4% vs 6.4%, aRR 1.85 [1.76-1.94]). Hypertensive disorders of pregnancy were associated with certain adverse outcomes in singleton gestations only and with other adverse outcomes in both the singleton and twin gestations, but the aRR was lower in twins. For example, preterm birth before 37 weeks of gestation (singletons: 15.2% [hypertensive disorders of pregnancy] vs 5.4% [no hypertensive disorders of pregnancy], aRR 2.42; twins: 67.5% [hypertensive disorders of pregnancy] vs 50.4% [no hypertensive disorders of pregnancy], aRR 1.30) and neonatal respiratory morbidity (singletons: 16.3% [hypertensive disorders of pregnancy] vs 8.7% [no hypertensive disorders of pregnancy], aRR 1.50; twins: 39.8% [hypertensive disorders of pregnancy] vs 32.7% [no hypertensive disorders of pregnancy], aRR 1.13). These findings persisted in the subgroups of women with preeclampsia and early-onset preeclampsia. Conclusions Although the absolute risk of adverse maternal and neonatal outcomes is higher in twin compared with singleton pregnancies, the incremental risk of adverse outcomes associated with hypertensive disorders in twin pregnancies is lower than the incremental risk in singleton pregnancies. These findings may be attributed in part to the higher baseline risk of preterm birth and adverse maternal and perinatal outcomes in twin compared with singleton pregnancies.

Objective To determine whether first-trimester visceral adipose tissue (VAT) depth is associated with small-for-gestational-age (SGA; 90th percentile) birthweight, including when taking into consideration ethnicity-specific birthweight curves. Methods We conducted a prospective cohort study involving 452 women with a singleton livebirth. Maternal VAT depth was measured by ultrasound at 11 to 14 weeks gestation. Newborn weight was plotted on population-based and ethnicity-specific birthweight percentile curves. Modelling was performed using linear and logistic regression, adjusting for parity, smoking status, and weight gain. Results Mean maternal age was 32.9 ± 4.7 years, and mean VAT depth was 4.1 ± 1.7 cm. Using a population-based curve, each 1-cm increase in VAT depth was associated with a 1.5 (95% CI 0.03–3.0) higher birthweight percentile. Taking into account ethnicity-specific curves, a 1-cm higher VAT depth was associated with a 1.7 (95% CI 0.02–3.3) greater birthweight percentile. Using a population-based curve, comparing VAT depth Q4 with VAT depth Q1–3, the adjusted odds ratio (aOR) for LGA was 1.9 (95% CI 0.8–4.1); with ethnicity-specific curves, the aOR for LGA was 1.5 (95% CI 0.7–3.2). The aOR for SGA was 0.8 (95% CI 0.4 to 1.7) comparing Q1 with Q2–4 VAT depth. Conclusion Higher first-trimester maternal VAT depth was associated with a somewhat greater newborn weight percentile, which varies by which birthweight curve is used. There were marginally higher odds of giving birth to an LGA infant for women in highest quartile for VAT depth, with no evident association with SGA.

INTRODUCTION Since 2013, various guidelines for hypertension in pregnancy have been refined, no longer requiring proteinuria as a requisite criterion for preeclampsia. We aimed to evaluate the impact of the new definition on preterm birth (PTB) and adverse pregnancy outcomes. MATERIAL AND METHODS Women delivering in Ontario between April 2012 and November 2016 were included. Delivery

Background Hypertension, proteinuria, and hepatic dysfunction have been described as manifestations of coronavirus disease 2019 (COVID-19) and are generally accepted as poor prognostic factors. However, these same findings can also occur in pregnant women with preeclampsia, thus creating a diagnostic challenge. Case We report a case of COVID-19 infection in an otherwise healthy pregnant patient with secondary hypertension, proteinuria, and significant hepatic dysfunction. Maternal placental growth factor (PlGF) testing was used to rule out preeclampsia. The patient received supportive care and improved significantly. She went on to have a spontaneous vaginal term delivery of a healthy male baby. Conclusion COVID-19 infection in pregnancy may present as preeclampsia-like syndrome. PlGF testing can be used to differentiate preeclampsia from COVID-19 and facilitate appropriate management.

OBJECTIVE To develop twin-specific outcome-based oral glucose tolerance test (OGTT) diagnostic thresholds for GDM based on the risk of future maternal type-2 diabetes. DESIGN A population-based retrospective cohort study (2007-2017). SETTING Ontario, Canada. METHODS Nulliparous women with a live singleton (n = 55 361) or twin (n = 1308) birth who underwent testing for gestational diabetes mellitus (GDM) using a 75-g OGTT in Ontario, Canada (2007-2017). We identified the 75-g OGTT thresholds in twin pregnancies that were associated with similar incidence rates of future type-2 diabetes to those associated with the standard OGTT thresholds in singleton pregnancies. RESULTS For any given 75-g OGTT value, the incidence rate of future maternal type-2 diabetes was lower for women with a twin than women with a singleton pregnancy. Using women with a negative OGTT as reference, the risk of future maternal type-2 diabetes in twin pregnancies with a positive OGTT based on the standard OGTT thresholds (9.86 per 1000 person years, adjusted hazard ratio (aHR) 4.79, 95% CI 2.69-8.51) was lower than for singleton pregnancies with a positive OGTT (18.74 per 1000 person years, aHR 8.22, 95% CI 7.38-9.16). The twin-specific OGTT fasting, 1-hour and 2-hour thresholds identified in the current study based on correlation with future maternal type-2 diabetes were 5.8 mmol/l (104 mg/dl), 11.8 mmol/l (213 mg/dl) and 10.4 mmol/l (187 mg/dl), respectively. CONCLUSIONS We identified potential twin-specific OGTT thresholds for GDM that are associated with a similar risk of future type-2 diabetes to that observed in women diagnosed with GDM in singleton pregnancies based on standard OGTT thresholds. TWEETABLE ABSTRACT Potential twin-specific OGTT thresholds for GDM were identified.

OBJECTIVE We aimed to quantify the risk of future maternal type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) based on the type and number of abnormal 75-g oral glucose tolerance test (OGTT) values and the diagnostic criteria used for the diagnosis of GDM. RESEARCH DESIGN AND METHODS We conducted a population-based retrospective cohort study of all nulliparous women with a live singleton birth who underwent testing for GDM using a 75-g OGTT in Ontario, Canada (2007–2017). We estimated the incidence rate (per 1,000 person-years), overall risk (expressed as adjusted hazard ratio [aHR]), and risk at 5 years after the index pregnancy of future maternal T2DM. Estimates were stratified by the type and number of abnormal OGTT values, as well as by the diagnostic criteria for GDM (Diabetes Canada [DC] vs. International Association of the Diabetes and Pregnancy Study Groups [IADPSG] criteria). RESULTS A total of 55,361 women met the study criteria. The median duration of follow-up was 4.4 (interquartile range 2.8–6.3; maximum 10.3) years. Using women without GDM as reference (incidence rate 2.18 per 1,000 person-years), women with GDM were at an increased risk of future T2DM; this risk was greater when using the DC compared with the IADPSG criteria (incidence rate 18.74 [95% CI 17.58–19.90] vs. 14.07 [95% CI 13.24–14.91] per 1,000 person-years, respectively). The risk of future maternal T2DM increased with the number of abnormal OGTT values and was highest for women with three abnormal values (incidence rate 49.93 per 1,000 person-years; aHR 24.57 [95% CI 21.26–28.39]). The risk of future T2DM was also affected by the type of OGTT abnormality: women with an abnormal fasting value had the greatest risk, whereas women with an abnormal 2-h value had the lowest risk (aHR 14.09 [95% CI 12.46–15.93] vs. 9.22 [95% CI 8.19–10.37], respectively). Similar findings to those described above were observed when the risk of T2DM at a fixed time point of 5 years after the index pregnancy was considered as the outcome of interest. CONCLUSIONS In women with GDM, individualized information regarding the future risk of T2DM can be provided based on the type and number of abnormal OGTT values, as well as the diagnostic criteria used for the diagnosis of GDM.

Objective: The aim of the current study was to identify the optimal cutoff that should define discordance in dichorionic twin gestations through correlation with abnormal placental pathology as a specific measure of fetal growth restriction of the smaller twin. Methods: We performed a retrospective cohort study of all women with dichorionic twin pregnancies who gave birth in a single center between 2002 and 2015. We investigated the association between the level of growth discordance and maternal vascular malperfusion (MVM) pathology in the placenta of the smaller twin, with and without adjustment for whether the smaller twin is small for gestational age (SGA). Results: A total of 1,198 women with dichorionic twin gestation met the study criteria. The rate of MVM pathology in the placenta of the smaller twin increased with the level of discordance and was most obvious for discordance ≥25% (rate of MVM 12.0% compared with 2.8% in cases with discordance Conclusion: Our findings suggest that discordant growth in dichorionic twins should raise the concern of fetal growth restriction of the smaller twin, irrespective of whether the smaller twin is SGA, only when the discordance s ≥25%. The association of lower levels of discordance with abnormal placental pathology is mainly driven by the confounding effect of SGA of the smaller twin.

Objectives In women with gestational diabetes mellitus (GDM), glycemic control is typically assessed by capillary blood glucose (BG) self-monitoring. Currently, the standard method of monitoring is by 4-times-daily self-measurements. The goal of our study was to determine whether twice-daily capillary BG testing is comparable with 4-times-daily testing in women with GDM. Methods Thirty-two women with GDM completed initial dietary counselling and recorded consecutive fasting and 2-h postprandial BG over a 14-day period. We randomly selected 2 of 4 BG measurements on each given day and compared mean (95% confidence interval [CI]) twice-daily vs 4-times-daily BG measurements using paired t tests and Bland-Altman plots. The proportion of 14-day BG measurements above glycemic targets was also compared between twice-daily vs 4-times-daily testing for fasting and postprandial readings. Results Comparing twice-daily vs 4-times-daily mean BG, there was a small difference for fasting BG (0.09 mmol/L; 95% CI, 0.03 to 0.14), but not for 2-h postbreakfast (−0.05 mmol/L; 95% CI, −0.17 to 0.06), 2-h postlunch (−0.03 mmol/L; 95% CI, −0.13 to 0.08) or 2-h postdinner (0.05 mmol/L; 95% CI, −0.09 to 0.19) BG. Bland-Altman plots showed general agreement and minimal bias between twice-daily vs 4-times-daily BG, whether fasting or postprandial. There was no significant difference in the proportion of 14-day BG measurements above glycemic targets comparing twice-daily vs 4-times-daily testing in the fasting or postprandial states. Conclusions Twice-daily BG testing appears to generate 14-day average values similar to 4-times-daily BG testing. In women with GDM, whose BG is in target range, twice-daily BG monitoring may reduce inconvenience and cost.

Background Aberrancies in fetal DNA methylation programming may modify disease susceptibility of the offspring. Maternal folate status has potential to alter fetal DNA methylation. Objectives We examined the association of maternal and cord blood concentrations of folate and unmetabolized folic acid (UMFA), vitamin B-12, vitamin B-6, and choline with fetal DNA methylation and hydroxymethylation and assessed potential modifying effects of 38 fetal genetic variants in 22 genes. Methods Nutrient blood concentrations were measured in 368 pregnant women in early pregnancy (12-16 wk of gestation) and at delivery (37-42 wk of gestation) and in cord blood. DNA methylation and hydroxymethylation in cord blood mononuclear cells were quantified by LC-MS/MS. Pearson partial correlations were used to determine the association between individual nutrients and DNA methylation and hydroxymethylation. Results Serum and RBC folate and plasma UMFA concentrations (primary outcomes) in early pregnancy, at delivery, and in cord blood were not significantly associated with fetal DNA methylation. In contrast, maternal RBC folate in early pregnancy (r = -0.16, P = 0.04) and cord plasma UMFA (r = -0.23, P = 0.004) were inversely correlated with fetal DNA hydroxymethylation. Neither maternal and cord blood concentrations of other nutrients nor fetal genotypes (secondary outcomes) were significantly associated with fetal DNA methylation or hydroxymethylation. Infants born to mothers with RBC folate concentrations in the highest quartile and serum vitamin B-12 concentrations in the lowest quartile in early pregnancy had significantly lower fetal DNA methylation and higher birth weight compared with those born to mothers with lower RBC folate and higher serum vitamin B-12 concentrations (P = 0.01). Conclusions Maternal and cord blood folate concentrations are associated with fetal DNA hydroxymethylation, but not DNA methylation, in a cohort of pregnant Canadian women. The observation that high folate and low vitamin B-12 maternal status in early pregnancy may be associated with decreased fetal DNA methylation and higher birth weight warrants further investigation. This trial was registered at clinicaltrials.gov as NCT02244684.

The screening accuracy of the 50 g-glucose challenge test (50 g-GCT) for gestational diabetes (GDM) has been described in singleton pregnancies. Given the physiologic differences and greater increase in insulin resistance in twin compared with singleton pregnancies, the performance of the 50 g-GCT in twin pregnancies may differ.To perform a systematic review on the screening performance of the 50 g-GCT for gestational diabetes in twin pregnancies.Ovid Medline, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL).We included randomized controlled trials or cohort studies that evaluated the screening accuracy of the 50 g-GCT for GDM in twin pregnancies using the two-step approach. The primary outcome was the positive predictive value of the 50 g-GCT for GDM using the 140 mg/dL (7.8 mmol/L) threshold.Methodological quality of included studies was assessed using the QUADAS-2 tool. The positive predictive value (PPV) was pooled for studies that used similar test characteristics.From 2044 citations, 7 retrospective cohort studies with a total of 55,597 participants were included (6.5% twins and 93.5% singletons). The majority of studies evaluated a 50-g GCT cutoff point of 140 mg/dL. The pooled PPV for a threshold of 140 mg/dL (7.8 mmol/L) for twins was 22.58% (95% CI: 0.1912-0.2647,The PPV of 50 g-GCT for GDM in twin pregnancies when using a threshold of 140 mg/dL (7.8 mmol/L) is approximately 23%. There is currently no data on the sensitivity and specificity of the 50 g-GCT in twins.

Background The primary aim of this study was to examine weight gain during pregnancy and associated adverse outcomes across different types of antenatal health care providers. Our research question examined whether type of antenatal health care provider (family physician, obstetrician, midwife, or family physician plus obstetrician) was associated with differing rates of excess or inadequate weight gain and associated adverse outcomes including being large for gestational age, being small for gestational age, cesarean delivery and preterm birth. Methods This retrospective cohort study used data from the Better Outcomes Registry & Network Information System, 2014-2016, for singleton hospital births at 20-42 weeks' gestation in Ontario. We calculated descriptive statistics to summarize patient characteristics and outcomes by antenatal health care provider. We calculated crude and adjusted relative risks with 95% confidence intervals (CIs) for the exposure (weight gain during pregnancy) relative to each secondary outcome by health care provider. We calculated population attributable fractions with 95% CIs to assess the proportion of secondary outcomes that could be prevented if inadequate or excess weight gain (according to the 2009 Institute of Medicine guidelines) were removed by health care provider. Results The final cohort consisted of 231 697 pregnancies, of which 26 043 (11.2%), 136 994 (59.1%), 32 262 (13.9%) and 36 298 (15.7%) were managed by a family physician, obstetrician, midwife, and family physician plus obstetrician, respectively. Rates of weight gain below, within or above recommended levels were 31 742 (13.7%), 71 826 (31.0%) and 128 128 (55.3%), respectively, and did not differ across health care provider groups. No difference was observed in rates of secondary outcomes according to weight gain across health care providers. Excess weight gain was associated with a significant risk of being large for gestational age and cesarean delivery, and inadequate weight gain was associated with an increased risk of being small for gestational age and preterm birth. The population attributable fractions indicated a pronounced contribution of excess weight gain to being large for gestational age across all health care provider groups. Interpretation Weight gain during pregnancy and rates of associated secondary outcomes did not differ according to antenatal health care provider. This suggests a need for further research exploring counselling techniques and strategies for all types of antenatal health care providers to use in order to promote optimal weight gain during pregnancy.

Background: People whose singleton pregnancy is affected by hypertensive disorders of pregnancy (HDP) are at risk of future cardiovascular disease. It is unclear, however, whether this association can be extrapolated to twin pregnancies. We aimed to compare the association between HDP and future cardiovascular disease after twin and singleton pregnancies. Methods: We conducted a population-based retrospective cohort study that included nulliparous people in Ontario, Canada, 1992–2017. We compared the future risk of cardiovascular disease among pregnant people from the following 4 groups: those who delivered a singleton without HDP (referent) and with HDP, and those who delivered twins either with or without HDP. Results: The populations of the 4 groups were as follows: 1 431 651 pregnant people in the singleton birth without HDP group; 98 631 singleton birth with HDP; 21 046 twin birth without HDP; and 4283 twin birth with HDP. The median duration of follow-up was 13 (interquartile range 7–20) years. The incidence rate of cardiovascular disease was lowest among those with a singleton or twin birth without HDP (0.72 and 0.74 per 1000 person-years, respectively). Compared with people with a singleton birth without HDP, the risk of cardiovascular disease was highest among those with a singleton birth and HDP (1.47 per 1000 person-years; adjusted hazard ratio [HR] 1.81 [95% confidence interval (CI) 1.72–1.90]), followed by people with a twin pregnancy and HDP (1.07 per 1000 person-years; adjusted HR 1.36 [95% CI 1.04–1.77]). The risk of the primary outcome after a twin pregnancy with HDP was lower than that after a singleton pregnancy with HDP (adjusted HR 0.74 [95% CI 0.57–0.97]), when compared directly. Interpretation: In a twin pregnancy, HDP are weaker risk factors for postpartum cardiovascular disease than in a singleton pregnancy.

Objective: To evaluate which immigrant groups to Canada are at increased risk of diabetes (DM) after gestational diabetes (GDM), including the influence of time since migration. Research Design and Methods: This retrospective cohort study used administrative data within a universal healthcare system. Included were women with GDM who had given birth in Ontario, Canada, 2006-2014. Women from each World region were compared to native-born/long-term residents of Canada for risk of DM using Cox regression. Results were further evaluated by time since immigration (0-5, 5-10, 10-20 years vs. native-born/long-term residents [referent]), adjusting for age at index pregnancy, income, BMI, parity and any hypertensive disorder of pregnancy. Results: A total of 8630 women with GDM were followed for a median of 4.9 years. Relative to native-born/long-term residents (incidence rate 29.2 person-years), the age-adjusted hazard ratios (aHR) for DM were higher among women from South Asia (1.28, 95% confidence interval, CI 1.20-1.36), Latin America/the Caribbean (1.42, 95% CI 1.28-1.57), and Sub-Saharan Africa (1.59, 95% CI 1.39-1.83). Relative to native-born/long-term residents, the aHR for DM were 1.42 (95% CI 1.20-1.67) for those residing 0-5 years, 1.19 (95% CI 1.00-1.42) 5-10 years, and 1.41 (95% 1.20-1.65) 10-20 years since immigration. Conclusions: Certain broadly-defined immigrant groups are at a significantly higher future risk of developing diabetes after having GDM, especially those who are recent immigrants. Disclosure J. S. S. Ho: None. L. Lipscombe: None. S. H. Read: Employee; Self; Certara. L. Rosella: None. H. Berger: None. D. Feig: Advisory Panel; Self; Novo Nordisk. K. Fleming: None. J. G. Ray: None. B. R. Shah: None. S. Sarma: None.

Data on the optimal gestational weight gain in twin pregnancies are limited. As a result, the Institute of Medicine currently provides only provisional recommendations on gestational weight gain in this population.This study aimed to identify the optimal range of gestational weight gain in twin pregnancies and to estimate the association between inappropriate gestational weight gain and adverse pregnancy outcomes.This was a retrospective cohort study of all women with twin pregnancies that were followed up in a single, tertiary center between 2000 and 2014. We used 2 approaches to identify the optimal range of gestational weight gain: a statistical approach (the interquartile range of gestational weight gain in low-risk pregnancies with normal outcomes) and an outcome-based approach (by identifying thresholds of gestational weight gain below or above which the rate of adverse outcomes increases). The primary outcome was preterm birth. Associations of gestational weight gain below or above the normal range with the study outcomes were estimated using logistic regression analysis and were expressed as adjusted odds ratio with 95% confidence intervals. These associations were stratified by prepregnancy body mass index group.A total of 1274 women with twin pregnancies met the study criteria: 43 were classified as underweight, 777 were normal weight, 278 were overweight, and 176 were obese. Our estimates of the optimal gestational weight gain range were similar to those recommended by the Institute of Medicine except for the obese category, in which our optimal gestational weight gain range at 37 weeks (9.3-16.3 kg) was lower than in the provisional Institute of Medicine recommendations (11.3-19.1 kg). Nearly half of our cohort experienced inappropriate gestational weight gain: 30% (n=381) gained weight below and 17% (n=216) gained weight above current Institute of Medicine recommendations. In the normal weight group, gestational weight gain below recommendations was associated with an increased risk of preterm birth and birthweight at the10th centile and with a reduction in the risk of hypertensive disorders, whereas gestational weight gain above recommendations was associated with an increased risk of hypertensive disorders and a reduction in the risk of birthweight at the10th centile. Associations were less consistent in the overweight and obese groups.These findings identify gestational weight gain as a potentially modifiable risk factor for preterm birth and other pregnancy complications in twin gestations. Further prospective studies are needed to determine whether interventions aimed at optimizing gestational weight gain can improve the outcomes of these high-risk pregnancies.

BackgroundPregnancy offers a unique opportunity to identify women at higher future risk of type 2 diabetes mellitus (DM). In pregnancy, a woman has greater engagement with the healthcare system, and certain conditions are more apt to manifest, such as gestational DM (GDM) that are important markers for future DM risk. This study protocol describes the development and validation of a risk prediction model (RPM) for estimating a woman’s 5-year risk of developing type 2 DM after pregnancy.MethodsData will be obtained from existing Ontario population-based administrative datasets. The derivation cohort will consist of all women who gave birth in Ontario, Canada between April 2006 and March 2014. Pre-specified predictors will include socio-demographic factors (age at delivery, ethnicity), maternal clinical factors (e.g., body mass index), pregnancy-related events (gestational DM, hypertensive disorders of pregnancy), and newborn factors (birthweight percentile). Incident type 2 DM will be identified by linkage to the Ontario Diabetes Database. Weibull accelerated failure time models will be developed to predict 5-year risk of type 2 DM. Measures of predictive accuracy (Nagelkerke’sR2), discrimination (C-statistics), and calibration plots will be generated. Internal validation will be conducted using a bootstrapping approach in 500 samples with replacement, and an optimism-corrected C-statistic will be calculated. External validation of the RPM will be conducted by applying the model in a large population-based pregnancy cohort in Alberta, and estimating the above measures of model performance. The model will be re-calibrated by adjusting baseline hazards and coefficients where appropriate.DiscussionThe derived RPM may help identify women at high risk of developing DM in a 5-year period after pregnancy, thus facilitate lifestyle changes for women at higher risk, as well as more frequent screening for type 2 DM after pregnancy.

IntroductionThe ‘Developmental Origins of Health and Disease’ hypothesis suggests that a healthy trajectory of growth and development in pregnancy and early childhood is necessary for optimal health, development and lifetime well-being. The purpose of this paper is to present the protocol for a randomised controlled trial evaluating a preconception-early childhood telephone-based intervention with tailored e-health resources for women and their partners to optimise growth and development among children in Canada: a Healthy Life Trajectory Initiative (HeLTI Canada). The primary objective of HeLTI Canada is to determine whether a 4-phase ‘preconception to early childhood’ lifecourse intervention can reduce the rate of child overweight and obesity. Secondary objectives include improved child: (1) growth trajectories; (2) cardiometabolic risk factors; (3) health behaviours, including nutrition, physical activity, sedentary behaviour and sleep; and (4) development and school readiness at age 5 years.Method and analysisA randomised controlled multicentre trial will be conducted in two of Canada’s highly populous provinces—Alberta and Ontario—with 786 nulliparous (15%) and 4444 primiparous (85%) women, their partners and, when possible, the first ‘sibling child.’ The intervention is telephone-based collaborative care delivered by experienced public health nurses trained in healthy conversation skills that includes detailed risk assessments, individualised structured management plans, scheduled follow-up calls, and access to a web-based app with individualised, evidence-based resources. An ‘index child’ conceived after randomisation will be followed until age 5 years and assessed for the primary and secondary outcomes. Pregnancy, infancy (age 2 years) and parental outcomes across time will also be assessed.Ethics and disseminationThe study has received approval from Clinical Trials Ontario (CTO 1776). The findings will be published in peer-reviewed journals and disseminated to policymakers at local, national and international agencies. Findings will also be shared with study participants and their communities.Trial registration numberISRCTN13308752; Pre-results.

Introduction: Transcutaneous bilirubin (TcB) measurement offers a noninvasive approach for bilirubin screening; however, its accuracy in preterm infants is unclear. This study determined the agreement between TcB and total serum bilirubin (TSB) among preterm infants. Methods: A multisite prospective cohort study was conducted at 3 NICUs in Ontario, Canada, September 2016 to June 2018. Among 296 preterm infants born at 240/7 to 356/7 weeks, 856 TcB levels were taken at the forehead, sternum, and before and after the initiation of phototherapy with TSB measurements. Bland-Altman plots and 95% limits of agreement (LOA) expressed agreement between TcB and TSB. Results: The overall mean TcB-TSB difference was −24.5 μmol/L (95% LOA −103.3 to 54.3), 1.6 μmol/L (95% LOA −73.4 to 76.5) before phototherapy, and −31.1 μmol/L (95% LOA −105.5 to 43.4) after the initiation of phototherapy. The overall mean TcB-TSB difference was −15.2 μmol/L (95% LOA −86.8 to 56.3) at the forehead and −24.4 μmol/L (95% LOA −112.9 to 64.0) at the sternum. The mean TcB-TSB difference was −31.4 μmol/L (95% LOA −95.3 to 32.4) among infants born 24–28 weeks, −25.5 μmol/L (95% LOA −102.7 to 51.8) at 29–32 weeks, and −15.9 μmol/L (95% LOA −107.4 to 75.6) at 33–35 weeks. Measures did not differ by maternal ethnicity. Conclusion: Among preterm infants, TcB may offer a noninvasive, immediate approach to screening for hyperbilirubinemia with more careful use in preterm infants born at

Key Points Question Among women with prepregnancy diabetes, is improved glycemic control, from preconception to early pregnancy to midpregnancy, associated with reduced risk of adverse perinatal and maternal outcomes? Findings In this population-based cohort study of 3459 births among women with prepregnancy diabetes, a reduced risk was found for congenital anomalies, preterm birth, perinatal mortality, and severe maternal morbidity per 0.5% net absolute decline in serum glycated hemoglobin A1c from preconception up to early pregnancy to midpregnancy. Meaning These findings suggest that women with prepregnancy diabetes who achieve a reduction in glycated hemoglobin A1c from preconception up to early pregnancy to midpregnancy may have improved perinatal and maternal outcomes., This cohort study examines whether there is an association between a reduction in hemoglobin A1c during the first half of pregnancy and both perinatal and maternal outcomes among women with prepregnacy diabetes in Ontario, Canada., Importance Prepregnancy diabetes is associated with higher perinatal and maternal morbidity, especially if periconception glycemic control is suboptimal. It is not known whether improved glycemic control from preconception to early pregnancy and midpregnancy periods can reduce the risk of adverse perinatal and maternal outcomes. Objective To determine whether a net decline in glycated hemoglobin A1c (HbA1c) from preconception to the first half of pregnancy is associated with a lower risk of adverse outcomes for mother and child. Design, Setting, and Participants This population-based cohort study was completed in all of Ontario, Canada, from 2007 to 2018. Included were births among women with prepregnancy diabetes whose HbA1c was measured within 90 days preconception and again from conception through 21 weeks completed gestation (early pregnancy to midpregnancy). Statistical analysis was performed from July to September 2020. Exposures Net decrease in HbA1c from preconception to early pregnancy and midpregnancy. Main Outcomes and Measures The main outcome was a congenital anomaly from birth to age 1 year. Other outcomes included preterm birth or perinatal mortality among offspring as well as severe maternal morbidity (SMM) or death among mothers. Adjusted relative risks (aRRs) were calculated per 0.5% absolute net decline in HbA1c from preconception up to early pregnancy and midpregnancy, adjusting for maternal age at conception, preconception HbA1c and hemoglobin concentration, and gestational age at HbA1c measurement. Results A total of 3459 births were included, with a mean (SD) maternal age of 32.6 (5.0) years at conception. Overall, the mean (SD) HbA1c decreased from 7.2% (1.6%) preconception to 6.4% (1.1%) in early pregnancy to midpregnancy. There were 497 pregnancies (14.4%) with a congenital anomaly, with an aRR of 0.94 (95% CI, 0.89-0.98) per 0.5% net decrease in HbA1c, including for cardiac anomalies (237 infants; aRR, 0.89; 95% CI, 0.84-0.95). The risk was also reduced for preterm birth (847 events; aRR, 0.89; 95% CI, 0.86-0.91). SMM or death occurred among 191 women (5.5%), with an aRR of 0.90 (95% CI, 0.84-0.96) per 0.5% net decrease in HbA1c. Conclusions and Relevance These findings suggest that women with prepregnancy diabetes who achieve a reduction in HbA1c may have improved perinatal and maternal outcomes. Further study is recommended to determine the best combination of factors, such as lifestyle changes and/or glucose-lowering medications, that can influence periconception HbA1c reduction.

Summary 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 ( 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 (HbA1c 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 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. Funding Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, University of Toronto.

Gestational diabetes (GDM) prevalence increases with increasing body mass index (BMI), and evidence suggests that the association may vary by ethnicity. Using a cross-sectional study, we examined the association between BMI and GDM by ethnicity. Data were obtained from administrative health datasets for all of Ontario, Canada. Using a validated algorithm, we identified Chinese and South Asian maternal ethnicity; all others were categorized as the general population. GDM was ascertained through hospital and claims records. The study population consisted of women without pre-existing diabetes who had a livebirth between April 2012 and March 2014. The relation between pre-pregnancy BMI and GDM was modeled using adjusted logistic regression, stratified by ethnicity. The study population consisted of 231,618 women, of whom 10,895 (4.7%) developed GDM. The prevalence of GDM was 9.9% among South Asians, 8.2% among Chinese and 4.3% of the general population of women. Compared to a normal BMI, having an overweight BMI (25-30 kg/m2) was associated with a higher aOR of GDM among Chinese (1.96, 95% CI: 1.50-2.56), South Asian (1.87, 1.47-2.36) and the general population of women (1.84, 1.69-2.01) (Figure). GDM prevalence is considerably higher across all levels of BMI in South Asian and Chinese women compared with the general population, suggesting the need for an ethnicity-specific screening approach for GDM. Disclosure S. Read: None. H. Berger: None. D. Feig: Advisory Panel; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Medtronic. K. Fleming: None. J.G. Ray: None. B.R. Shah: None. L. Lipscombe: None. Funding Diabetes Action Canada (PSI19-23)

Background: In Canada, the 2-step approach for the diagnosis of gestational diabetes (GDM) continues to be used, due to uncertain treatment benefit at the lower diagnostic thresholds recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). GDM diagnosed by 2 step criteria is associated with an elevated risk of subsequent diabetes; however, the impact of GDM based on IADPSG criteria on future diabetes risk is unknown. Aim: To evaluate the risk of future diabetes associated with a GDM diagnosis using the 2 step and IADPSG criteria. Methods: Using Ontario population-based databases, we evaluated the incidence of diabetes in women with a live birth recorded between April 2011 and March 2014 and available prenatal glucose tolerance test records. Women were categorized according to their prenatal glucose tolerance results as no GDM, GDM based on 2-step criteria, and GDM based on IADPSG criteria (positive by IADPSG, negative by 2 step criteria). They were followed until April 2018 for a diagnosis of diabetes. Risk of diabetes associated with GDM based on each definition was compared to no GDM using a multivariable Cox proportional hazards model. Results: Of the 104,942 women included in the study, 5,371 (5.1%) had GDM by 2 step criteria and 2,436 (2.3%) had GDM based on IADPSG criteria. There were 821 (0.78%) diabetes cases over 329 771 person-years of follow-up. After adjusting for age, body-mass index, history of GDM, gestational weight gain, birth weight, income, and ethnicity, diabetes risk was significantly higher for both GDM women by 2 step criteria (HR 14.1; 95% CI 11.7-16.9) and for GDM based on IADPSG criteria alone (HR 3.1; 95% CI:2.0-4.7) compared to no GDM. Conclusion: While the relative risk of diabetes compared to normal glucose tolerance is higher for women diagnosed with GDM using the conventional 2 step criteria, GDM based on IADPSG criteria also confers a significant 3-fold increase in diabetes risk. Disclosure B. Balaji: None. S. Read: None. H. Berger: None. D. Feig: Advisory Panel; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Medtronic. B.R. Shah: None. L. Lipscombe: None.

Background The relation between prepregnancy average glucose concentration and a woman’s risk of severe maternal morbidity (SMM) is unknown. The current study evaluated whether an elevated preconception hemoglobin A1c (A1c) is associated with SMM or maternal death among women with and without known prepregnancy diabetes mellitus (DM). Methods and findings A population-based cohort study was completed in Ontario, Canada, where there is universal healthcare. The main cohort included 31,225 women aged 16–50 years with a hospital live birth or stillbirth from 2007 to 2015, and who had an A1c measured within 90 days before conception, including 28,075 women (90%) without known prepregnancy DM. The main outcome was SMM or maternal mortality from 23 weeks’ gestation up to 42 days postpartum. Relative risks (RRs) were generated using modified Poisson regression, adjusting for the main covariates of maternal age, multifetal pregnancy, world region of origin, and tobacco/drug dependence. The mean maternal age was 31.1 years. Overall, SMM or death arose among 682 births (2.2%). The RR of SMM or death was 1.16 (95% CI 1.14–1.19; p < 0.001) per 0.5% increase in A1c and 1.16 (95% CI 1.13–1.18; p < 0.001) after adjusting for the main covariates. The adjusted relative risk (aRR) was increased among those with (1.11, 95% CI 1.07–1.14; p < 0.001) and without (1.15, 95% CI 1.02–1.29; p < 0.001) known prepregnancy diabetes, and upon further adjusting for body mass index (BMI) (1.15, 95% CI 1.11–1.20; p < 0.001), or chronic hypertension and prepregnancy serum creatinine (1.11, 95% CI 1.04–1.18; p = 0.002). The aRR of SMM or death was 1.31 (95% CI 1.06–1.62; p = 0.01) in those with a preconception A1c of 5.8%–6.4%, and 2.84 (95% CI 2.31–3.49; p < 0.001) at an A1c > 6.4%, each relative to an A1c < 5.8%. Among those without previously recognized prepregnancy diabetes and whose A1c was >6.4%, the aRR of SMM or death was 3.25 (95% CI 1.76–6.00; p < 0.001). Study limitations include that selection bias may have incorporated less healthy women tested for A1c, and BMI was unknown for many women. Conclusions Our findings indicate that women with an elevated A1c preconception may be at higher risk of SMM or death in pregnancy or postpartum, including those without known prepregnancy DM., Joel Ray and colleagues investigate the potential risks to pregnant women with hyperglycemia., Author summary Why was this study done? Diabetes mellitus (DM) and obesity are highly prevalent, and each are associated with adverse pregnancy outcomes. Hemoglobin A1c (A1c) offers a convenient and representative measure of average blood glucose concentration. However, its relation to severe maternal morbidity (SMM) or death is unknown. What did the researchers do and find? This population-based cohort study used data from across the province of Ontario, Canada, 2007–2015. Included were 31,225 women with a live birth or stillbirth, and who had an A1c measured within 90 days before conception. We investigated the risk of SMM or death from 23 weeks’ gestation up to 42 days postpartum, per 0.5% absolute increase in preconception A1c. SMM or death arose among 682 births (2.2%). The relative risk (RR) of SMM or death was 1.16 (95% CI 1.13–1.18; p < 0.001) per 0.5% increase in A1c, after adjusting for maternal age, multifetal pregnancy, world region of origin, and tobacco/drug dependence. Among those without previously recognized prepregnancy diabetes and whose A1c was >6.4%, the adjusted relative risk (aRR) of SMM or death was 3.25 (95% CI 1.76–6.00; p < 0.001). What do these findings mean? An elevated preconception A1c is associated with a higher risk of SMM or death among women without known diabetes, and below thresholds commonly used to diagnose DM. These findings underscore the importance of a healthy diet and lifestyle before pregnancy, and call attention to the value of identifying women with varying degrees of hyperglycemia before pregnancy.

OBJECTIVE Data regarding low maternal haemoglobin concentration and severe maternal morbidity (SMM) are limited and potentially biased. This study evaluated the relation between early maternal haemoglobin concentration and SMM or maternal mortality. DESIGN Population-based cohort study. SETTING Ontario, Canada, in a public healthcare system. POPULATION 737 393 births with a routine outpatient haemoglobin measured at a calculated gestational age of 2-16 weeks. METHODS The relation between early-pregnancy outpatient blood haemoglobin concentration and each study outcome was expressed as adjusted relative risks (aRR) and absolute risk differences (aRD), with 95% confidence intervals (CI), generated by modified Poisson regression. MAIN OUTCOME MEASURES The primary outcome was SMM or maternal mortality, from 23 weeks' gestation to 42 days postpartum. RESULTS The mean (SD) haemoglobin concentration was 126.9 (9.3) g/l. Overall, SMM or death occurred in 13 514 pregnancies (1.8%). Relative to a haemoglobin level of 125-129 g/l, the aRR was 1.07 (95% CI 1.02-1.13) and aRD (0.09%, 95% CI 0.01-0.18) at 120-124 g/l; aRR 1.31 (95% CI 1.17-1.46) and aRD 0.47% (95% CI 0.24-0.69) at 105-109 g/l; and aRR 4.53 (95% CI 3.59-5.72) and aRD 5.94% (95% CI 4.12-7.76) at

Background Inappropriate gestational weight gain in pregnancy may negatively impact health outcomes for mothers and babies. While optimal gestational weight gain is often not acheived, effective counselling by antenatal health care providers is recommended. It is not known if gestational weight gain counselling practices differ by type of antenatal health care provider, namely, family physicians, midwives and obstetricians, and what barriers impede the delivery of such counselling. The objective of this study was to understand the counselling of family physicians, midwives and obstetricians in Ontario and what factors act as barriers and enablers to the provision of counselling about GWG. Methods Semi-structured interviews were conducted with seven family physicians, six midwives and five obstetricians in Ontario, Canada, where pregnancy care is universally covered. Convenience and purposive sampling techniques were employed. A grounded theory approach was used for data analysis. Codes, categories and themes were generated using NVIVO software. Results Providers reported that they offered gestational weight gain counselling to all patients early in pregnancy. Counselling topics included gestational weight gain targets, nutrition & exercise, gestational diabetes prevention, while dispelling misconceptions about gestational weight gain. Most do not routinely address the adverse outcomes linked to gestational weight gain, or daily caloric intake goals for pregnancy. The health care providers all faced similar barriers to counselling including patient attitudes, social and cultural issues, and accessibility of resources. Patient enthusiasm and access to a dietician motivated health care providers to provide more in-depth gestational weight gain counselling. Conclusion Reported gestational weight gain counselling practices were similar between midwives, obstetricians and family physicians. Antenatal knowledge translation tools for patients and health care providers are needed, and would seem to be suitable for use across all three types of health care provider specialties.

Background: Preterm birth (PTB) is a major cause of infant death globally. The rising rates of pre-pregnancy diabetes mellitus (D), obesity (O) and chronic hypertension (H) will place a significant burden on maternal-fetal health but their combined influence on PTB is unknown. Methods: Population-based cohort study, Ontario, Canada, April 1, 2012 to March 31 2016. Participants were 506,483 women with a singleton livebirth or stillbirth at > 20 weeks' gestation. The exposures of interest were D, O and H, individually, and in various combinations. The primary outcome was PTB at 241/7 to 366/7 weeks. PTB was further analyzed by spontaneous or provider-initiated, early (< 34 weeks) or late (34-37 weeks), and the co-presence of preeclampsia, large for gestational age (LGA), and small for gestational age (SGA) birthweight. Multivariable Poisson regression models with robust error variance were used to generate relative risks (RR), further adjusted for maternal age and parity (aRR). Population attributable fractions were then calculated for each of the outcomes by exposure state. Findings: Relative to women without D or O or H, the aRR for PTB were (3.09, 95% CI 2.80-3.40) with D + O, 6.34 (95% CI 5.15-7.81) with D + H, 2.96 (95% CI 2.70-3.24) with O + H, and 5.55 (95% CI 4.76-6.47) with D + O + H. In women with D + H, aRR was more pronounced for provider-initiated PTB (10.99, 95% CI 8.40-14.38) than for spontaneous PTB (3.05, 95% CI 1.92-4.85). Those with D + O + H had an aRR of 9.21 (95% CI 4.97-17.04) for PTB with an SGA newborn relative to those without D or O or H. Interpretation: Combinations of D, O and H significantly magnify the risk of PTB, especially provider-initiated PTB, and PTB with altered fetal growth or preeclampsia. These data may inform health policy and clinical decision-making both at the population and patient level. Funding: CIHR. Declaration of Interest: All authors report no conflict of interest Ethical Approval: Ethics approval was obtained from the St. Michael’s Hospital Research Ethics Board (REB # 16-345).

Background The rate of cesarean delivery is continuously increasing with the leading indication being a previous cesarean delivery. For women with 1 previous cesarean delivery, it is generally agreed that the optimal timing of delivery by elective cesarean delivery is during the 39th week of gestation, whereas for women with ≥2 previous cesarean deliveries, the optimal delivery time remains debatable. Objective To assess the maternal and neonatal risks associated with elective delivery at different gestational ages ranging from 37 0/7 to 39 6/7 weeks’ gestation and to compare it with expectant management among women with at least 2 previous cesarean deliveries. Study Design This was a retrospective, population-based cohort study of all women with at least 2 previous cesarean deliveries who delivered after 36 6/7 weeks of gestation in Ontario, Canada, between April 2012 and March 2019. Women with multifetal pregnancies or major fetal anomalies were excluded. For each completed gestational week, outcomes of women who had an elective repeat cesarean delivery at that week solely because of 2 previous cesarean deliveries were compared with the outcomes of those who were managed expectantly and delivered at a later gestational age. The primary outcome was a composite of maternal outcomes including mortality and severe maternal morbidity. Secondary outcomes were adverse neonatal outcomes. Results A total of 26,522 women met the inclusion criteria. The maternal risk was similar for elective delivery at 37 0/7 to 38 6/7 weeks of gestation compared with expectant management. However, elective delivery at 39 0/7 to 39 6/7 weeks’ gestation was associated with a decreased risk for adverse outcomes when compared with expectant management (adjusted risk ratio, 0.51; 95% confidence interval, 0.29–0.91). For the neonate, elective delivery during the 37th week of gestation significantly increased the incidence of the composite adverse outcome than in an ongoing pregnancy (adjusted risk ratio, 1.68; 95% confidence interval, 1.39–2.01), but was comparable for elective delivery at 38 0/7 to 39 6/7 weeks’ gestation and expectant management. The risk for an unplanned cesarean delivery increased from 6.5% before 38 weeks’ gestation to 21.7% before 39 weeks’ gestation and to 32.6% before 40 weeks’ gestation. Conclusion For women with ≥2 cesarean deliveries, elective delivery at 38 0/7 to 38 6/7 weeks’ gestation likely represents the optimal balance between neonatal and maternal risk while decreasing the likelihood of an unplanned cesarean delivery.

Background The symptoms of anemia and depression are very similar suggesting that there may be an association between the two entities. The aim of this study is to assess whether postpartum anemia (PPA) is an independent risk factor for de novo postpartum depression (PPD)in women undergoing elective cesarean section. Methods Women after an uncomplicated term cesarean section were recruited and their hemoglobin and iron status were measured on day 3–5 post section and again at 6 weeks. Postpartum depression was screened using the Edinburgh Postnatal Depression Scale (EPDS) and functional capacity was assessed with the RAND 12-item Health survey. Results One hundred and three women completed the study. The incidence of probable postpartum depression (PPD) as defined by EPDS score ≥ 10 was 17% at 6 weeks. There was no difference in hemoglobin or iron status in women who had PPD compared to those without (OR-0.69; 95% CI-0.15-2.49). Similarly, there was no significant association between low hemoglobin and maternal functional status (OR -1.03; 95% CI-0.34 - 2.94). Conclusions Neither anemia or low iron stores were found to be an independent risk factors for postpartum depression or decreased postpartum functional capacity in women who undergo an elective cesarean section.

To assess whether routine induction of labor at 38 or 39 weeks in women with chronic hypertension is associated with the risk of superimposed preeclampsia or cesarean delivery.We conducted a retrospective population-based study of women with chronic hypertension who had a singleton hospital birth at 38 0/7 weeks of gestation of gestation in Ontario, Canada, between 2012 and 2016. Women who underwent induction of labor at 38 0/7 to 38 6/7 weeks of gestation for chronic hypertension (n=281) were compared with those who were managed expectantly during that week and remained undelivered at 39 0/7 weeks of gestation (n=1,606). Separately, women who underwent induction of labor at 39 0/7 to 39 6/7 weeks of gestation for chronic hypertension (n=259) were compared with women who remained undelivered at 40 0/7 weeks of gestation (n=801).Of 534,529 women gave birth during the study period, 6,054 (1.1%) had chronic hypertension and 2,420 met the inclusion criteria. Women managed expectantly at 38 or 39 weeks of gestation were at risk of new-onset superimposed preeclampsia (19.2% [308/1,606] and 19.0% [152/801], respectively) and eclampsia (0.6% [10/1,606] and 0.7% [6/801], respectively), and more than half underwent induction of labor later in gestation (56.8% and 57.8%, respectively). The risk of cesarean delivery in the induction groups was lower (38 weeks of gestation) or similar (39 weeks of gestation) to that observed in women managed expectantly at the corresponding weeks (38 weeks of gestation: 17.1% vs 24.0%, adjusted relative risk 0.74 [95% CI 0.57-0.95]; 39 weeks of gestation: 20.1% vs 26.0%, adjusted relative risk 0.90 [95% CI 0.69-1.17]).Our findings suggest that in women with isolated chronic hypertension, induction of labor at 38 or 39 weeks of gestation may prevent severe hypertensive complications without increasing the risk of cesarean delivery.

OBJECTIVE To measure the difference between first-trimester and postpartum visceral adipose tissue (VAT), the agreement of this difference with change in body mass index, and whether a difference in VAT is associated with insulin resistance or glucose mishandling. METHODS Prospective study of 93 women with singleton pregnancies without a history of diabetes. Visceral adipose tissue depth was sonographically assessed at 11 to 14 weeks and at 6 to 12 weeks postpartum. Metabolic measures, sampled at 24 to 28 weeks and 6 to 12 weeks postpartum, included homeostatic model assessment of insulin resistance, insulin sensitivity index composite, and area under the 75-g oral glucose tolerance test curve. RESULTS First-trimester VAT depth explained only 37% (95% confidence interval [CI], 22-52) of the variation in postpartum VAT depth. There was limited agreement between the net change in postpartum minus first-trimester VAT depth and that same net change for body mass index (Cohen's kappa, 0.26; 95% CI, 0.05-0.47). Those with a net gain in VAT depth demonstrated poorer insulin sensitivity index postpartum than women with a net regression in VAT depth-a difference of -2.0 (95% CI, -3.3 to -0.69). CONCLUSION Sonographic assessment of postpartum VAT is feasible and may provide insight to metabolic changes between pregnancy and postpartum, beyond body mass index.

To compare the incidence and risk factors for gestational diabetes mellitus (GDM) between women with twin and singleton pregnancies. Retrospective study of all women who had a twin or singleton birth in Ontario (2012–2016). Risk ratios (RR) and 95% CIs for GDM (stratified by type of treatment) were adjusted for relevant confounding variables. Multivariable Poisson regression analysis was used to identify risk factors for GDM in twin and singleton gestations. Of 270,843 women who met inclusion criteria, 266,942 (98.6%) and 3901 (1.4%) had a singleton and a twin pregnancy, respectively. Women with twins had a significantly higher risk for overall GDM (aRR = 1.13, 95% CI 1.01–1.28) and diet-treated GDM (aRR = 1.20, 95% CI 1.01–1.42) while the association with insulin-treated GDM was not significant (aRR = 1.07, 95% CI 0.89–1.28). Maternal age ≥ 35 years, non-Caucasian ethnicity and BMI > 30 kg/m2 were independent risk factors for GDM among women with twins and singletons, and the magnitude of the association of these factors with GDM was similar. Women with twins are at increased risk of GDM, mainly due to a higher rate of diet-treated GDM. Despite higher baseline risk of GDM in women with twins, the effect of known risk factors for GDM is similar to that observed in singletons.

Both insufficiency and excess of one-carbon nutrients (folate, choline, vitamins B6 and B12) during pregnancy have been associated with gestational diabetes mellitus (GDM). However, the precise nature of this association has not been clearly established. We hypothesized that GDM may affect one-carbon nutrients concentrations in the fetus, thus possibly participating in epigenetic programing of the offspring. Maternal blood was collected at recruitment (12-16 weeks). At delivery (28-42 weeks), both maternal and cord blood were collected. Blood concentrations of one-carbon nutrients and their metabolites were compared between the two groups. A total of 368 women were included in the study, of whom 19 (5.6%) were later diagnosed with GDM. No significant differences were found in maternal blood concentrations of one-carbon nutrients and their metabolites between the GDM and control groups at recruitment or at delivery. In cord blood, however, serum folate (87.7 [IQR 70.4-103.9] vs 66.6 [IQR 45.5-80.3] nmol/L, P = .025) and plasma TMAO (2.82 [IQR 1.3-3.2] vs 1.35 [IQR 1.0-2.0] μmol/L, P = .017) concentrations were higher, while plasma betaine concentrations were lower (17.5 [IQR 16.3-19.4] vs 21.1 [IQR 18.0-24.1] μmol/L, P = .019) in infants born to mothers with GDM compared with control. Our data suggest that while maternal blood concentrations of one-carbon nutrients and their metabolites may not affect the risk of GDM, GDM may alter concentrations of serum folate, plasma betaine and TMAO in cord blood. These alterations in one-carbon nutrient concentrations in fetal circulation may impact epigenetic programing, thereby contributing to physiologic changes and disease susceptibility in adulthood associated with GDM offspring.

Gestational diabetes mellitus is associated with accelerated fetal growth in singleton pregnancies but may affect twin pregnancies differently because of the slower growth of twin fetuses during the third trimester of pregnancy and their greater predisposition to fetal growth restriction.This study aimed to evaluate the association of gestational diabetes mellitus with longitudinal fetal growth in twin pregnancies and to compare this association with that observed in singleton pregnancies.This was a retrospective cohort study of all women with a singleton or twin pregnancy who were followed up at a single tertiary referral center between January 2011 and April 2020. Data on estimated fetal weight and individual fetal biometric indices were extracted from ultrasound examinations of eligible women. Generalized linear models were used to model and compare the change in fetal weight and individual biometric indices as a function of gestational age between women with and without gestational diabetes mellitus in twin pregnancies and between women with and without gestational diabetes mellitus in singleton pregnancies. The primary outcome was estimated fetal weight as a function of gestational age. The secondary outcomes were longitudinal growth of individual fetal biometric indices and the rate of small for gestational age and large for gestational age at birth.A total of 26,651 women (94,437 ultrasound examinations) were included in the analysis: 1881 with a twin pregnancy and 24,770 with a singleton pregnancy. The rate of gestational diabetes mellitus in the twin and singleton groups was 9.6% (n=180) and 7.6% (n=1893), respectively. The estimated fetal weight in singleton pregnancies with gestational diabetes mellitus was significantly higher than that in pregnancies without gestational diabetes mellitus (P.001) starting at approximately 30 weeks of gestation. The differences remained similar after adjusting for maternal age, chronic hypertension, nulliparity, and neonatal sex (P.001). In twin pregnancies, fetal growth was similar between pregnancies with and without gestational diabetes mellitus (P=.105 and P=.483 for unadjusted and adjusted models, respectively). The findings were similar to the association of gestational diabetes mellitus with the risk of large for gestational fetuses and the growth of each biometric index. When stratified by type of gestational diabetes mellitus treatment, twin pregnancies with gestational diabetes mellitus was associated with accelerated fetal growth only in the subgroup of women with medically treated gestational diabetes mellitus (P.001), which represented 12% (n=21) of the twin pregnancy group with gestational diabetes mellitus.In contrast to singleton pregnancies, twin pregnancies with gestational diabetes mellitus is less likely to be associated with accelerated fetal growth. This finding has raised the question of whether the diagnostic criteria for gestational diabetes mellitus and the blood glucose targets in women diagnosed with gestational diabetes mellitus should be individualized for twin pregnancies.

An outstanding issue is how to efficiently identify women at high risk of preeclampsia. This retrospective cohort study included 8672 pregnancies at a single centre in Toronto. We tested our simple method - presence vs. absence of≥1 major (pre-pregnancy BMI>30kg/m2, chronic hypertension, pre-pregnancy diabetes mellitus and assisted reproductive therapy) or≥2 minor (prior stillbirth, age>40years, nulliparity, multifetal pregnancy, chronic kidney disease, and SLE) risk factors for PE. The RR of PE was 8.4 (95% CI 5.3-13.2) and the model C-statistic 0.74 (95% CI 0.69-0.79). Further testing of this method elsewhere is warranted.

The current systematic review and meta-analysis evaluate the perinatal outcomes in twin pregnancies following multifetal pregnancy reduction (MPR) compared with non-reduced triplet pregnancies. All studies comparing perinatal outcome of twin pregnancies following MPR to non-reduced triplet pregnancies were considered. MEDLINE, non-indexed MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science were searched for relevant published articles up to August 2016. The search yielded 653 publications of which 92 were assessed for eligibility. A total of 24 studies met the inclusion criteria. Overall, the outcomes of pregnancies following MPR were better compared with expectantly managed triplets. The MPR group delivered at a later gestational age and was less likely to be delivered before 32 or 28 weeks' gestation. Newborns in the MPR group had significantly higher birthweight at delivery (mean difference 500 g [95% CI 439.95, 560.04]). Rates of pregnancy loss before 24 weeks' gestation and overall infant survival were comparable between the groups. This meta-analysis suggests that MPR of triplet pregnancies to twins is associated with improved perinatal outcome compared with non-reduced triplets. Should primary prevention of high order multiple pregnancy fail, MPR is an appropriate alternative to minimize the perinatal morbidity and mortality of triplet pregnancies.

Objective Traditionally, physiological variation in fetal weight is believed to emerge during the latter half of pregnancy. Although recent evidence suggests that crown-rump length (CRL) and nuchal translucency (NT) measured at 11–14 weeks correlate with abnormal fetal growth, findings have been limited by dating accuracy in spontaneous gestations. Therefore, we sought to determine whether CRL or NT measurements correlated with term birth weight (BW) or BW ratio in a cohort of IVF pregnancies, in which the date of conception is precisely known. Methods This retrospective cohort study included 227 term, singleton IVF pregnancies. Subjects were included if they had an early first-trimester ultrasound examination and subsequent nuchal translucency (NT) screening. The difference between the measured and the expected CRL and the biparietal diameter (BPD) and NT measurement were calculated and correlated with the actual term BW or BW ratio. The BW ratio was calculated using the actual BW and the expected BW for GA. Results The difference between measured and expected mid–first-trimester CRL, and the BPD at NT assessment, correlated with BW ratio at delivery ( r Spearman = 0.15, P = 0.023 and r Spearman = 0.27, P r Spearman = 0.18, r = 0.14, and P = 0.005 and 0.038, respectively). Conclusion In this well-dated IVF population, we report a significant correlation between BW ratio and first-trimester CRL, BPD, and NT measurements. These findings support the hypothesis that physiological variation in BW can be reflected by variation in first-trimester fetal measurements.

BACKGROUND Chronic placental inflammation is associated with preterm birth (PTB) and perinatal mortality. Ferritin is often elevated in chronic inflammatory conditions, but prior studies of its relation to PTB were restricted to ferritin measurement within pregnancy, were underpowered to detect rarer outcomes, and did not account for pre-existing maternal inflammatory conditions, such as inflammatory bowel or rheumatological disease. OBJECTIVES To evaluate whether an elevated ferritin level prior to pregnancy is associated with major adverse pregnancy outcomes. METHODS A population-based cohort study was completed using Ontario, Canada. Included were all Ontarian women with a hospital livebirth or stillbirth at ≥20 weeks' gestation, 2007-2018, and serum haemoglobin and ferritin measured as an outpatient within 120 days before conception. Excluded were women with a diagnosed iron overload disorder or a ferritin concentration

Objectif La presente Directive passe en revue les donnees probantes liees au diagnostic et a la prise en charge obstetricale du diabete durant la grossesse. Issues Les issues evaluees etaient les issues maternelles a court et a long terme, dont la preeclampsie, la cesarienne, le diabete eventuel et d'autres complications cardiovasculaires et les issues fœtales, dont les anomalies congenitales, la mortinaissance, la macrosomie, le traumatisme de la naissance, l'hypoglycemie et les effets a long terme. ReSULTATS: La litterature publiee a ete recuperee par l'intermediaire de recherches menees dans PubMed et The Cochrane Library au moyen d'un vocabulaire controle (termes MeSH « diabete » et « grossesse ») approprie. Le cas echeant, les resultats ont ete restreints aux analyses systematiques, aux essais comparatifs randomises / essais cliniques comparatifs et aux etudes observationnelles. Aucune limite n'a ete imposee en matiere de date, mais les resultats ont ete limites aux articles publies en anglais ou en francais. Valeurs La qualite des resultats a ete evaluee au moyen des criteres decrits dans le rapport du Groupe d'etude canadien sur les soins de sante preventifs. DECLARATIONS SOMMAIRES: RECOMMANDATIONS.

Objectives This guideline reviews the evidence relating to the diagnosis and obstetrical management of diabetes in pregnancy. Outcomes The outcomes evaluated were short and long-term maternal outcomes including pre-eclampsia, Caesarean section, future diabetes and other cardiovascular complications; and fetal outcomes including congenital anomalies, stillbirth, macrosomia, birth trauma, hypoglycemia and long-term effects. Evidence Published literature was retrieved through searches of PubMed and The Cochrane Library using appropriate controlled vocabulary (MeSH terms "diabetes" and "pregnancy"). Where appropriate, results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date limits but results were limited to English or French language materials. Values The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Summary Statements 1The adverse outcomes associated with diabetes in pregnancy are substantially associated with hyperglycemia as well as the co-existing metabolic environment. Women with pre-existing diabetes should receive preconception care to optimize blood sugar control and other co-morbidities. Outcomes for the fetus/neonate and the mother in both pre-gestational diabetes mellitus and gestational diabetes mellitus pregnancies are improved by multidisciplinary management whose goal is achieving optimal blood sugar control and appropriate fetal surveillance (II-2). 2Retrospective studies indicate that women with pre-gestational diabetes mellitus have an increased risk of stillbirth before 40 weeks of gestation when compared with the general obstetrical population. Similarly, large recent cohort and simulation studies of women with gestational diabetes mellitus pregnancies also indicate a higher risk of stillbirth between 36-39 weeks gestation (II-2). 3Women with gestational diabetes mellitus have a higher risk of pre-eclampsia, shoulder dystocia, Caesarean section and large for gestational age infants (II-2). 4Treatment of women with gestational diabetes mellitus and optimization of glycemic control reduces the risk of pre-eclampsia, shoulder dystocia, and large for gestational age infants (I). 5The occurrence of gestational diabetes mellitus increases the risk of developing type 2 diabetes in the future for the mother (II-2). Recommendations 1The "preferred screening and diagnostic 2-step" approach for gestational diabetes mellitus of the Canadian Diabetes Association 2013 guidelines is endorsed. All pregnant women should be offered screening between 24-28 weeks using a standardized non-fasting 50-g glucose challenge screening test (GCT) with plasma glucose (PG) measured 1 hour later (III-B). 1.1If the value is 1.2If the value of the GCT is 7.8–11.0, a 2-hour 75-g oral glucose tolerance test with fasting PG (FPG), 1-hour PG, 2-hour PG should be performed.Gestational diabetes mellitus is diagnosed if 1 value is met or exceeded: iFPG ≥5.3 mmol/L ii1-h PG ≥10.6 mmol/L iii2-h PG ≥9.0 mmol/L 1.3If the value of the GCT is ≥11.1 mmol/L, gestational diabetes mellitus is diagnosed 2The "alternative 1-step diagnostic" approach of the Canadian Diabetes Association 2013 guidelines is acceptable. In this strategy pregnant women should be offered testing between 24-28 weeks using a standardized 2-hour 75-g oral glucose tolerance test with fasting plasma glucose (FPG), 1-hour plasma glucose (PG), 2-hour PG (III-B).Gestational diabetes mellitus is diagnosed if 1 value is met or exceeded: iFPG ≥5.1 mmol/L ii1-h PG ≥10.0 mmol/L iii2-h PG ≥8.5 mmol/L It is recognized that the use of different diagnostic thresholds for the "preferred" and "alternate" strategies could cause confusion in certain settings. Despite this the committee has identified the importance of remaining aligned with the current CDA 2013 guidelines as being a priority. It is thus recommended that each care centre strategically align with one of the two strategies and implement protocols to ensure consistent and uniform reporting of test results. 3If there is a high risk of gestational diabetes mellitus based on multiple risk factors, screening or testing should be offered during the first half of the pregnancy and repeated at 24-28 weeks gestation if initially normal. If for any reason it was missed or if there is a clinical suspicion of later onset gestational diabetes, a screening or diagnostic test should be performed (II-2B). 4Women with pre-existing or gestational diabetes mellitus should be provided with care by a multidisciplinary team aimed at attaining and then maintaining euglycemia (II-2B). 5For patients with pre-gestational diabetes mellitus or gestational diabetes mellitus, starting at 28 weeks as a baseline, with subsequent serial assessment of fetal growth every 3-4 weeks is suggested to assess the effect of maternal glycemic control on fetal growth rate and amniotic fluid volume (II-2B). 6Initiation of weekly assessment of fetal well-being at 36 weeks is recommended in pre-gestational diabetes mellitus and in gestational diabetes mellitus. It is also reasonable to consider weekly fetal assessment for women with diet controlled gestational diabetes mellitus beginning at 36 weeks. Acceptable methods of assessment of fetal well-being near term can include the non-stress test, non-stress test + amniotic fluid index, biophysical profile or a combination of the above (III-A). 7If co-morbid factors are present such as obesity, evidence of suboptimal glycemic control, large for gestational age (>90%), previous stillbirth, hypertension or small for gestational age ( 8Pregnant women with gestational diabetes mellitus or with pre-gestational diabetes mellitus should be offered induction between 38-40 weeks of gestation depending on their glycemic control and other co-morbidity factors (II2-B). 9Antenatal corticosteroid therapy should be administered to women with insulin-treated gestational diabetes mellitus and pregestational diabetic women at the same dosage, according to the same indications, and in the same gestational age range as that recommended for non-diabetic women (Skoll A, et al. No. 364-Antenatal Corticosteroid Therapy for Improving Neonatal Outcomes. J Obstet Gynaecol Can 2018;40:1219-39). When administered to women with preexisting or poorly controlled diabetes, close maternal glycemic surveillance is recommended (III-B). Following the first dose of betamethasone, the following insulin adjustments are recommended as per CDA guidelines (Diabetes Canada Clinical Practice Guidelines Expert C, et al. Diabetes and Pregnancy. Can J Diabetes 2018;42 Suppl 1:S255-S82): •Day 1: Increase the night insulin dose by 25% •Days 2 and 3: Increase all insulin doses by 40% •Day 4: Increase all insulin doses by 20% •Day 5: Increase all insulin doses by 10% to 20% •Days 6 and 7: Gradually taper insulin doses to pre-betamethasone doses 10If not previously done, in women with threatened preterm labour requiring betamethasone, a screening and diagnostic test for gestational diabetes mellitus should be performed either before or at least 7 days after the administration of betamethasone (III-B). 11Women with GDM should be offered testing with a 75-g oral glucose tolerance test between 6 weeks and 6 months postpartum to detect prediabetes and diabetes (Thompson D, et al. Diabetes and pregnancy. Can J Diabetes 2013;37 Suppl 1:S168–83) (II-2A). 11.1 Normal iFasting plasma glucose (FPG) ii2h iiiHbA1C 11.2 Pre-diabetic iFPG 6.1-6.9 mmol/L or ii2h plasma glucose (PG) 7.8-11.0 mmol/L or iiiHbA1C 6.0-6.4% 11.3 Type 2 Diabetes mellitus iFPG ≥ 7.0 mmol/L iiRandom PG or 2h PG ≥11.1 mmol/L iiiHbA1C ≥6.5% 12Breastfeeding is strongly recommended after delivery for all women with pre-gestational diabetes mellitus or gestational diabetes mellitus (II-2A).

OBJECTIVE To perform a systematic review of success rates of trial of labor after cesarean (TOLAC) and maternal and neonatal outcomes in twin pregnancy versus elective repeat cesarean delivery (ERCD). METHODS We searched MEDLINE, EMBASE, and Web of Science from data inception to May 2018 with no language or regional restrictions, to identify all studies that compared twin TOLAC and ERCD for maternal and/or neonatal outcomes. The Newcastle-Ottawa Scale was used to assess the methodological quality of the included studies. We assessed the pooled relative risk and mean difference using a random-effects model. The pooled event rates for successful VBAC, cesarean delivery for twin B after vaginal delivery of twin A, and uterine rupture were determined. RESULTS Of the 841 citations identified, 10 were eligible for analysis (2336 TOLAC cases and 5763 ERCD cases). The pooled event rates for successful VBAC and uterine rupture during TOLAC were 72.2% (95% CI 59.7%-83.2%) and 0.87% (95% CI 0.51%-1.31%), respectively. TOLAC was associated with a significantly higher risk of neonatal death (RR 3.02 [95% CI 1.07-8.54]) with no significant differences in mean gestational age at birth, NICU admission rates, or 5-minute Apgar

Objective To examine the effect of antenatal corticosteroid administration (ACS) on fetal thymus growth in women who received ACS compared with gestational-age-matched controls. Study design Fetal thymus size and growth were measured in women at risk for preterm delivery who received ACS and compared with a matched cohort of women who were at low risk for preterm delivery and did not receive ACS. Fetal thymus perimeter and diameter were measured by 2-D ultrasound at baseline and every 2 weeks until delivery. Results After adjusting for confounders, ACS exposure was associated with a significant reduction in thymus perimeter size (-0.70; 95% CI: -1.33, -0.07; P = 0.03). For every additional week of exposure, thymus growth trajectory was significantly decreased in ACS-exposed fetuses (P = 0.04). Conclusion The association between ACS and reduced fetal thymus growth should be further examined to establish the impact of ACS on childhood thymus development and immune programming.

Controversy surrounds the impact of the fetal head station on labor duration and mode of delivery. Although an extensive body of evidence has been published evaluating fetal head station in early labor, there is a paucity of data on the impact of fetal head descent during the second stage.This study aimed to explore the association between fetal head station at the diagnosis of the second stage of labor and the second stage duration and the risk of operative delivery.This is a retrospective cohort study of all singleton vertex deliveries in a single tertiary center (2011-2016). Women were grouped according to fetal head station upon the diagnosis of the second stage of labor as follows: above (S0), at the level (S=0), and below (S0) the level of the ischial spine. The duration of the second stage and the risk of operative delivery were compared between the groups and stratified by parity.Overall, 34,334 women met the inclusion criteria. Of these, 18,743 (54.6%) were nulliparous and 15,591 (45.4%) were multiparous. Of the nulliparous women, 8.1%, 35.8%, and 56.1% were diagnosed as having fetal head above, at the level, and below the ischial spine upon second stage diagnosis. Of the multiparous women, 19.7%, 35.6%, and 44.7% were diagnosed as having fetal head above, at the level, and below the ischial spine. Fetal head station upon second stage diagnosis was independently and significantly associated with second stage duration (P.001); however, its contribution was 4.5-fold among nulliparous women compared with multiparous women. In multivariable analysis, after controlling for maternal age, gestational age at delivery, prepregnancy body mass index, epidural anesthesia, and birthweight, the risk of operative delivery was substantially increased in a dose-dependent pattern for both nulliparous and multiparous women.The fetal head station at the first diagnosis of the second stage is significantly and independently associated with the duration of the second stage and correlated with the risk of operative delivery in both nulliparous and multiparous women (P.001).

To determine the perceptions and attitudes of Canadian women to Noninvasive Prenatal Testing of fetal DNA.A designed questionnaire was administered to women attending the outpatient antenatal clinic at a tertiary urban hospital. Attitudes to current and new prenatal screening modalities were assessed using a five-point Likert scale. Bowker's test of symmetry was used to compare individual responses regarding the two screening modalities. Changes in women's responses pre- and post-delivery were also compared.One hundred and twenty-nine women were enrolled in this study. 88% of women state that they would perform prenatal screening via fetal DNA in the maternal plasma if available. When compared to conventional screening, significantly less women believe that the NIPT should be available upon request for non-medical traits (36.4% versus 60.4%, p 0.001). When compared to their answer before delivery, more women agreed that screening with fetal DNA in maternal plasma could be used in a negative way to select for desired non-medical traits such as gender.The use of fetal DNA in the maternal plasma is widely accepted in our Canadian population as a future method of noninvasive prenatal screening despite recognition of certain ethical concerns. This information can be used when implementing new genetic screening programs.

Background Uterine anomalies causing fetal complications are very rarely encountered in obstetric practice and thus pose a diagnostic dilemma. Case A multigravid patient attended the clinic for an ultrasound examination in the third trimester following a recent hospital admission for abdominal pain. Ultrasound imaging revealed a large uterine diverticulum in the right cornu of the uterus with evidence of fetal leg entrapment. Because of concerns of increased soft tissue edema in the entrapped leg, the patient was delivered at 35 weeks' gestation by elective CS. The CS was complicated by uterine rupture at the diverticular portion. The neonatal course was complicated by compartment syndrome of the leg, and the infant underwent surgery on post-delivery day one with good outcome. Conclusion Uterine diverticula are rare anomalies, and once they are diagnosed, the possibility of entrapment of fetal parts or placenta in pregnancy should be considered.