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Cerebro-placental ratio (CPR) is a doppler tool contributes to clinical decision-making in pregnancies affected by small for gestational age weight (SGA). Pregnancies affected by gestational diabetes mellitus (GDM) tend to have higher newborn weight, but greater risk of adverse perinatal outcomes. We hypothesized that in GDM-complicated-pregnancies CPR will be associated with adverse perinatal outcomes even in the absence of SGA.This prospective single-center cohort study included non-anomalous singleton pregnancies in women with GDM. Those with pre-pregnancy diabetes mellitus, hypertensive disorder or suspected SGA were excluded. Routine fetal sonographic assessment included CPR-defined as middle cerebral artery pulsatilty index/umbilical artery pulsatilty index. Masked CPR measurement closest to birth was used, classified as10th (normal) or ≤10th centile (low). Primary outcome was a composite, consisting of stillbirth, Caesarean birth due to abnormal fetal heart rate pattern, 5-minute Apgar7, cord arterial pH 7.0, hypoxic ischemic encephalopathy, or NICU admission24 hours.Of 281 participants, 24 (8.5%) had low CPR, at a mean gestational age of 36.3 weeks (IQR 34.0-37.4). Birthweight percentile was significantly lower among the low CPR group (35th [IQR 16-31] versus 60th [IQR 31-82]; P = .002). There was no statistically difference in the primary composite outcome between the groups (8.3% versus 7.0%, P = .68). Low CPR was significantly associated with a higher risk of neonatal hypoglycemia (adjusted odds ratio 3.2, 95% CI 1.2-8.3).In pregnancies affected by GDM, CPR ≤10th percentile was not associated with adverse perinatal outcome but was associated with neonatal hypoglycemia.

As an indicator of maternal cardiometabolic health, newborn birthweight may be an important predictor of maternal type 2 diabetes mellitus (diabetes). We evaluated the relation between offspring birthweight and onset of maternal diabetes after pregnancy.This retrospective cohort study used linked population-based health databases from Ontario, Canada. We included women aged 16-50 years without pre-pregnancy diabetes, and who had a live birth between 2006 and 2014. We used Cox proportional hazard regression to evaluate the association between age- and sex-standardized offspring birthweight percentile categories and incident maternal diabetes, while adjusting for maternal age, parity, year, ethnicity, gestational diabetes (GDM) and hypertensive disorders of pregnancy (HDP). Results were further stratified by the presence of GDM in the index pregnancy.Of 893,777 eligible participants, 14,329 (1.6%) women were diagnosed with diabetes over a median (IQR) of 4.4 (1.5-7.4) years of follow-up. There was a continuous positive relation between newborn birthweight above the 75th percentile and maternal diabetes. Relative to a birthweight between the 50th and 74.9th percentiles, women whose newborn had a birthweight between the 97th and 100th percentiles had an adjusted hazards ratio (aHR) of diabetes of 2.30 (95% CI 2.16-2.46), including an aHR of 2.01 (95% CI 1.83-2.21) among those with GDM, and 2.59 (2.36-2.84) in those without GDM.A higher offspring birthweight signals an increased risk of maternal diabetes, offering another potentially useful way to identify women especially predisposed to diabetes.

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.

Fexofenadine is a well-identified in vivo probe substrate of P-glycoprotein (P-gp) and/or organic anion transporting polypeptide (OATP). This work aimed to investigate the transplacental pharmacokinetics of fexofenadine enantiomers with and without the selective P-gp inhibitor fluoxetine. The chiral transplacental pharmacokinetics of fexofenadine-fluoxetine interaction was determined using the ex vivo human placenta perfusion model (n = 4). In the Control period, racemic fexofenadine (75 ng of each enantiomer/ml) was added in the maternal circuit. In the Interaction period, racemic fluoxetine (50 ng of each enantiomer/mL) and racemic fexofenadine (75 ng of each enantiomer/mL) were added to the maternal circulation. In both periods, maternal and fetal perfusate samples were taken over 90 min. The (S)-(−)- and (R)-(+)-fexofenadine fetal-to-maternal ratio values in Control and Interaction periods were similar (~0.18). The placental transfer rates were similar between (S)-(−)- and (R)-(+)-fexofenadine in both Control (0.0024 vs 0.0019 min−1) and Interaction (0.0019 vs 0.0021 min−1) periods. In both Control and Interaction periods, the enantiomeric fexofenadine ratios [R-(+)/S-(−)] were approximately 1. Our study showed a low extent, slow rate of non-enantioselective placental transfer of fexofenadine enantiomers, indicating a limited fetal fexofenadine exposure mediated by placental P-gp and/or OATP2B1. The fluoxetine interaction did not affect the non-enantioselective transplacental transfer of fexofenadine. The ex vivo placental perfusion model accurately predicts in vivo placental transfer of fexofenadine enantiomers with remarkably similar values (~0.17), and thus estimates the limited fetal exposure.

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.

Context The optimal 50 g-glucose challenge test (GCT) cutoff for the diagnosis of gestational diabetes mellitus (GDM) in twin pregnancies is unknown. Objective This work aimed to explore the screening accuracy of the 50 g-GCT and its correlation with the risk of large for gestational age (LGA) newborn in twin compared to singleton pregnancies. A population-based retrospective cohort study (2007-2017) was conducted in Ontario, Canada. Participants included patients with a singleton (n = 546 892 [98.4%]) or twin (n = 8832 [1.6%]) birth who underwent screening for GDM using the 50 g-GCT. Methods We compared the screening accuracy, risk of GDM, and risk of LGA between twin and singleton pregnancies using various 50 g-GCT cutoffs. Results For any given 50 g-GCT result, the probability of GDM was higher (P = .0.007), whereas the probability of LGA was considerably lower in the twin compared with the singleton group, even when a twin-specific growth chart was used to diagnose LGA in the twin group (P Conclusion The screening performance of the 50 g-GCT for GDM and its correlation with LGA differ between twin and singleton pregnancies.

Background: Ondansetron is a highly effective antiemetic for the treatment of nausea and vomiting. However, this medication has also been associated with QT prolongation. Pharmacogenomic information on therapeutic response to ondansetron exists, but no investigation has been performed on genetic factors that influence the cardiac safety of this medication. Methods: Three patient groups receiving ondansetron were recruited and followed prospectively (pediatric post-surgical patients n = 101; pediatric oncology patients n = 98; pregnant women n = 62). Electrocardiograms were conducted at baseline, and 5- and 30-min post-ondansetron administration, to determine the effect of ondansetron treatment on QT interval. Pharmacogenomic associations were assessed via analyses of comprehensive CYP2D6 genotyping and genome-wide association study data. Results: In the entire cohort, 62 patients (24.1%) met the criteria for prolonged QT, with 1.2% of the cohort exhibiting unsafe QT prolongation. The most significant shift from baseline occurred at five minutes post-ondansetron administration (P = 9.8 × 10−4). CYP2D6 activity score was not associated with prolonged QT. Genome-wide analyses identified novel associations with a missense variant in TLR3 (rs3775291; P = 2.00 × 10−7) and a variant linked to the expression of SLC36A1 (rs34124313; P = 1.97 × 10−7). Conclusions: This study has provided insight into the genomic basis of ondansetron-induced cardiac changes and has emphasized the importance of genes that have been implicated in serotonin-related traits. These biologically-relevant findings represent the first step towards understanding this adverse event with the overall goal to improve the safety of this commonly used antiemetic medication.

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.

Cohort study of singleton pregnancies with risk factors for placental insufficiency, managed at St. Michael's Hospital in Toronto, Canada. Patients undergone UA Doppler assessment at 18-22 weeks' gestation and 6 weeks postpartum. 15 pregnancies complicated by preeclampsia or intrauterine growth restriction (IUGR) (cases) were compared to 17 unaffected pregnancies (controls). Cases with preeclampsia and/or IUGR had higher UA PI at 18-22 weeks than controls. By 6 weeks' postpartum, the corresponding mean values were 2.60 and 2.14 (p = 0.20). This preliminary study suggests a potential different trajectory for physiologic recovery of UA flow after a pregnancy affected by placental insufficiency.

Extremely preterm infants are prone to hyperbilirubinemia and its sequelae. Currently recommended thresholds for initiating phototherapy in these newborns are consensus-based (CB).A multi-site retrospective cohort study of 642 infants born at 24Among infants born 24We provide statistically derived pre-phototherapy TSB levels that may clarify patterns of pre-phototherapy TSB levels in extremely preterm infants.We present statistically derived pre-phototherapy total serum bilirubin levels in a cohort of extremely preterm infants. Most of these preterm infants received phototherapy-some at below currently published thresholds. There are notable differences between our statistically derived pre-phototherapy TSB levels and currently published lower limit TSB thresholds for phototherapy. Our study results assist in the understanding of pre-phototherapy TSB levels in extremely preterm infants.

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.

Activated T helper 17 (Th-17) cytokines play a role in the pathophysiology of autoimmune and infectious diseases. While these diseases affect many women of childbearing age, little is known about the effect of these cytokines on placental transporters. As several pro-inflammatory cytokines impact the expression of ABC and SLC placental transporters, we hypothesized that these transporters may be similarly altered by elevated levels of circulating Th-17 cytokines. Cultured term human villous explants were treated with IL-17A, IL-22, or IL-23, alone or in combination. Samples were analyzed using qRT-PCR and Western blotting. The mRNA expression of OATP2B1 was significantly downregulated in explants by all individual cytokines and combination treatments, while decreased protein expression was seen with IL-23 and combination (p &lt, 0.01). Combination treatment decreased the mRNA expression of BCRP and OAT4 but increased that of OCT3 (p &lt, 0.01). Decreased accumulation of the OATP substrate, cascade blue, was seen in IL-23-treated choriocarcinoma JAr cells (p &lt, 0.01). Elevated Th-17 cytokines, which are seen in infectious and autoimmune diseases, affect the expression and activity of OATP2B1, as well as mRNA expression of placental BCRP, OAT4, and OCT3. This dysregulation could impact the fetal exposure to endogenous and exogenous substrates.

Both gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) are common, and each are associated with adverse maternal and perinatal outcomes. Midwives may be the first point of care when these conditions arise. This study evaluated the experiences of midwives when providing care to women and people with pregnancies complicated by GDM or HDP.A mixed methods study was completed in Ontario, Canada, using a sequential, explanatory approach. A total of 144 online surveys were completed by midwives, followed by 20 semi-structured interviews that were audio recorded and transcribed verbatim. Survey data were analysed using descriptive statistics. Thematic analysis was used to generate codes from the interview data, which were mapped to the Theoretical Domains Framework (TDF), to elucidate factors that might influence management.Most of the midwives' clinical behaviours relating to GDM or HDP were in keeping with guidelines and regulatory standards set by existing provincial standards. Six theoretical domains from the TDF appeared to influence midwives'care pathway: "Internal influences" included knowledge, skills and beliefs about capabilities; while "external influences" included social/professional role and identity, environmental context, and social influences. Interprofessional collaboration emerged as a significant factor on both the internal and external levels of influence.We identified barriers and facilitators that may improve the experiences of midwives and clients when GDM or HDP newly arises in a pregnancy, necessitating further consultation or management by another health care provider.

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.

Fexofenadine is a well-identified in vivo probe substrate of P-glycoprotein (P-gp) and/or organic anion transporting polypeptide (OATP). This work aimed to investigate the transplacental pharmacokinetics of fexofenadine enantiomers with and without the selective P-gp inhibitor fluoxetine.The chiral transplacental pharmacokinetics of fexofenadine-fluoxetine interaction was determined using the ex vivo human placenta perfusion model (n = 4). In the Control period, racemic fexofenadine (75 ng of each enantiomer/ml) was added in the maternal circuit. In the Interaction period, racemic fluoxetine (50 ng of each enantiomer/mL) and racemic fexofenadine (75 ng of each enantiomer/mL) were added to the maternal circulation. In both periods, maternal and fetal perfusate samples were taken over 90 min.The (S)-(-)- and (R)-(+)-fexofenadine fetal-to-maternal ratio values in Control and Interaction periods were similar (~0.18). The placental transfer rates were similar between (S)-(-)- and (R)-(+)-fexofenadine in both Control (0.0024 vs 0.0019 minOur study showed a low extent, slow rate of non-enantioselective placental transfer of fexofenadine enantiomers, indicating a limited fetal fexofenadine exposure mediated by placental P-gp and/or OATP2B1. The fluoxetine interaction did not affect the non-enantioselective transplacental transfer of fexofenadine. The ex vivo placental perfusion model accurately predicts in vivo placental transfer of fexofenadine enantiomers with remarkably similar values (~0.17), and thus estimates the limited fetal exposure.

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.

The growing prevalence of obesity is a concern for midwives. In Canada, the absence of regulatory standards, varying protocols and consultant preferences shape clinical decision making for the midwife and may lead to inconsistent practice. Our aim was to understand the barriers, enablers, and knowledge gaps that influenced experiences of midwives in Ontario, Canada when providing care to clients impacted by obesity.Mixed methods design using a sequential, explanatory approach. Surveys conducted with midwives were administered using an online platform, followed by semi-structured interviews to understand the perspectives elicited in the survey in greater detail. Interviews were audio recorded and transcribed verbatim. Survey data were analyzed using descriptive statistics, and thematic analysis was used for generating codes, categories and themes from the interview data.144 midwives completed the survey and 20 participated in an interview. The participants described their clinical management when caring for those with obesity which included considerations regarding additional tests/investigations, consultation and transfer of care, and place of birth. Up to 93% of surveyed midwives believed that clients with obesity were appropriate for midwifery-led care however there was less certainty about suitability as BMI increased to higher ranges such as45). The care management was influenced by beliefs and attitudes, knowledge, and system-level factors. Midwives experienced barriers such as inconsistent practices and role confusion, and felt ill equipped to care for pregnancies affected by obesity due to unclear guidelines.Overall, midwives believe clients with obesity are suitable for midwifery-led care due to its individualized, non-judgmental approach to care. Additional training for midwives and other obstetric care providers would be beneficial to help overcome barriers in providing effective care to pregnancies affected by obesity.

The aim of this study was to examine how BMI influences the association between Asian ethnicity and risk of gestational diabetes (GDM).This population-based cohort study included pregnant women without pre-existing diabetes mellitus in Ontario, Canada between 2012 and 2014. Women of Chinese and South Asian ethnicity were identified using a validated surname algorithm. GDM was ascertained using hospitalisation codes. The relationship between ethnicity and GDM was modelled using modified Poisson regression, adjusted for maternal age, pre-pregnancy BMI, parity, previous GDM, long-term residency status, income quintile and smoking status. An interaction term between ethnicity and pre-pregnancy BMI was tested.Of 231,618 pregnant women, 9289 (4.0%) were of South Asian ethnicity and 12,240 (5.3%) were of Chinese ethnicity. Relative to women from the general population, in whom prevalence of GDM was 4.3%, the adjusted RR of GDM was higher among those of South Asian ethnicity (1.81 [95% CI 1.64, 1.99]) and Chinese ethnicity (1.66 [95% CI 1.53, 1.80]). The association between GDM and Asian ethnicity remained significant across BMI categories but differed according to BMI. The prevalence of GDM exceeded 5% at an estimated BMI of 21.5 kg/mThe risk of GDM is significantly higher in South Asian and Chinese women, whose BMI is lower than that of women in the general population. Accordingly, targeted GDM prevention strategies may need to consider lower BMI cut-points for Asian populations.

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.