Impact of previous gestational diabetes management on perinatal outcomes in subsequent pregnancies affected by gestational diabetes mellitus.

OBJECTIVE: To determine the impact of prior gestational diabetes mellitus (GDM) on perinatal outcomes in a subsequent GDM pregnancy. METHODS: This retrospective cohort study included 544 multiparous patients with two consecutive pregnancies between 2012-2019, where the second (index) pregnancy was affected by GDM. The primary exposure was prior GDM diagnosis, categorized into medical and dietary management. The primary outcome was a composite including need for pharmacotherapy, large-for-gestational age, or neonatal hypoglycemia. Adjusted odds ratios (aOR) were calculated using multivariable logistic regression controlling for maternal age, pre-pregnancy body mass index, and gestational age at GDM diagnosis in the index pregnancy. RESULTS: Of the 544 patients, 164 (30.1%) had prior GDM. Prior GDM significantly increased the likelihood of composite outcome compared to no prior GDM (74.4% vs. 57.4%; P < 0.001). After adjusting for confounders, prior GDM remained significantly associated with the composite outcome (aOR 2.03, 95% confidence interval [CI] 1.31-3.15). Stratifying by prior GDM treatment modality, a significant association was found for prior pharmacotherapy-controlled GDM (aOR 3.29, 95% CI 1.64-6.59), but not for prior diet-controlled GDM (aOR = 1.54, 95% CI 0.92-2.60). CONCLUSION: A history of pharmacotherapy-controlled GDM in a previous pregnancy increases odds of adverse perinatal outcomes in a subsequent GDM pregnancy.

A Social-Ecological Model Exploring Gestational Diabetes Mellitus Screening Practices Among Antenatal Health Care Providers.

Gestational diabetes mellitus (GDM) is associated with adverse health outcomes for the pregnant individual and their baby. Screening approaches for GDM have undergone several iterations, introducing variability in practice among healthcare providers. As such, our study aimed to explore the views of antenatal providers regarding their practices of, and counseling experiences on the topic of, GDM screening in Ontario. We conducted a qualitative, grounded theory study. The study population included antenatal providers (midwives, family physicians, and obstetricians) practicing in Hamilton, Ottawa, or Sudbury, Ontario. Semi-structured telephone interviews were conducted and transcribed verbatim. Transcripts were analyzed using inductive coding upon which codes, categories, and themes were developed to generate a theory grounded in the data. Twenty-two participants were interviewed. Using the social-ecological theory, we created a model outlining four contextual levels that shaped the experiences of GDM counseling and screening: Intrapersonal factors included beliefs, knowledge, and skills; interpersonal factors characterized the patient-provider interactions; organizational strengths and challenges shaped collaboration and health services infrastructure; and finally, guidelines and policies were identified as systemic barriers to health care access and delivery. A focus on patient-centered care was a guiding principle for all care providers and permeated all four levels of the model. Patient-centered care and close attention to barriers and facilitators across intrapersonal, interpersonal, organizational, and policy domains can minimize the impact of variations in GDM screening guidelines. Among care providers, there is a desire for additional skill development related to GDM counseling, and for national consensus on optimal screening guidelines.

Maternal Deaths Using Coroner's Data: A Latent Class Analysis.

OBJECTIVE: Knowledge regarding the antecedent clinical and social factors associated with maternal death around the time of pregnancy is limited. This study identified distinct subgroups of maternal deaths using population-based coroner's data, and that may inform ongoing preventative initiatives. METHODS: A detailed review of coroner's death files was performed for all of Ontario, Canada, where there is a single reporting mechanism for maternal deaths. Deaths in pregnancy, or within 365 days thereafter, were identified within the Office of the Chief Coroner for Ontario database, 2004-2020. Variables related to the social and clinical circumstances surrounding the deaths were abstracted in a standardized manner from each death file, including demographics, forensic information, nature and cause of death, and antecedent health and health care factors. These variables were then entered into a latent class analysis (LCA) to identify distinct types of deaths. RESULTS: Among 273 deaths identified in the study period, LCA optimally identified three distinct subgroups, namely, (1) in-hospital deaths arising during birth or soon thereafter (52.7% of the sample); (2) accidents and unforeseen obstetric complications also resulting in infant demise (26.3%); and (3) out-of-hospital suicides occurring postpartum (21.0%). Physical injury (22.0%) was the leading cause of death, followed by hemorrhage (16.8%) and overdose (13.3%). CONCLUSION: Peri-pregnancy maternal deaths can be classified into three distinct sub-types, with somewhat differing causes. These findings may enhance clinical and policy development aimed at reducing pregnancy mortality.

Gestational diabetes in twin pregnancies-a pathology requiring treatment or a benign physiological adaptation?

There is level-1 evidence that screening for and treating gestational diabetes in singleton pregnancies reduce maternal and neonatal morbidity. However, similar data for gestational diabetes in twin pregnancies are currently lacking. Consequently, the current approach for the diagnosis and management of gestational diabetes in twin pregnancies is based on the same diagnostic criteria and glycemic targets used in singleton pregnancies. However, twin pregnancies have unique physiological characteristics, and many of the typical gestational diabetes-related complications are less relevant for twin pregnancies. These differences raise the question of whether the greater increase in insulin resistance observed in twin pregnancies (which is often diagnosed as diet-treated gestational diabetes) should be considered physiological and potentially beneficial in which case alternative criteria should be used for the diagnosis of gestational diabetes in twin pregnancies. In this review, we summarize the most up-to-date evidence on the epidemiology, pathophysiology, and clinical consequences of gestational diabetes in twin pregnancies and review the available data on twin-specific screening and diagnostic criteria for gestational diabetes. Although twin pregnancies are associated with a higher incidence of diet-treated gestational diabetes, diet-treated gestational diabetes in twin pregnancies is less likely to be associated with adverse outcomes and accelerated fetal growth than in singleton pregnancies and may reduce the risk for intrauterine growth restriction. In addition, there is currently no evidence that treatment of diet-treated gestational diabetes in twin pregnancies improves outcomes, whereas preliminary data suggest that strict glycemic control in such cases might increase the risk for intrauterine growth restriction. Overall, these findings provide support to the hypothesis that the greater transient increase in insulin resistance observed in twin pregnancies is merely a physiological exaggeration of the normal increase in insulin resistance observed in singleton pregnancies (that is meant to support 2 fetuses) rather than a pathology that requires treatment. These data illustrate the need to develop twin-specific screening and diagnostic criteria for gestational diabetes to avoid overdiagnosis of gestational diabetes and to reduce the risks associated with overtreatment of diet-treated gestational diabetes in twin pregnancies. Although data on twin-specific screening and diagnostic criteria are presently scarce, preliminary data suggest that the optimal screening and diagnostic criteria in twin pregnancies are higher than those currently used in singleton pregnancies.

Use of administrative claims data in observational studies of antirheumatic medication effects on pregnancy outcomes: a scoping review protocol.

OBJECTIVE: The primary objective of this review is to examine which disease-modifying antirheumatic drugs (DMARDs) and biologics used to treat pregnant individuals with rheumatic conditions have been reported in observational studies using population-based health administrative data. The secondary objective is to describe which adverse pregnancy outcomes (both maternal and neonatal) have been reported, their definitions, and corresponding diagnostic and/or procedural codes. INTRODUCTION: Pregnant individuals are typically excluded from drug trials due to unknown potential risks to both the pregnant person and fetus, leaving most antirheumatic drugs understudied for use in pregnancy. Despite these substantial knowledge gaps, most pregnant individuals continue to be maintained on antirheumatic medications due to the benefits generally outweighing the risks. In contrast to previous systematic reviews of findings from randomized trials, our scoping review aims to leverage this real-world data to generate real-world evidence of antirheumatic drug safety during pregnancy. INCLUSION CRITERIA: Articles must report on observational studies using population-based health administrative data from pregnant individuals with rheumatic conditions (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and psoriatic arthritis) receiving antirheumatic drug therapy (DMARDs and biologics). Randomized trials, reviews, case studies, opinion pieces, and abstracts will be excluded. METHODS: Electronic databases (MEDLINE [Ovid], Embase [Ovid], CINAHL [EBSCOhost]) and gray literature (OpenGrey, Health Services Research Projects in Progress, World Health Organization Library, and Google Scholar) will be searched for relevant evidence. Search terms will combine 4 concepts: rheumatic diseases, drug therapy, pregnancy, and health care administrative data. Identified articles will be independently screened, selected, and extracted by 2 researchers. Data will be analyzed descriptively and presented in tables. REVIEW REGISTRATION: Open Science Framework https://osf.io/5e6tp.

Impact of Antenatal Care Modifications on Gestational Diabetes Outcomes During the COVID-19 Pandemic.

BACKGROUND: Many of the adverse outcomes of gestational diabetes mellitus (GDM) are linked to excessive fetal growth, which is strongly mediated by the adequacy of maternal glycemic management. The COVID-19 pandemic led to a rapid adoption of virtual care models. We aimed to compare glycemic management, fetal growth, and perinatal outcomes before and during the COVID-19 pandemic. METHODS: A retrospective cohort study was conducted between 2017 and 2020. Singleton pregnancies complicated by GDM were included in the study. The cohort was stratified into "before" and "during" COVID-19 subgroups, using March 11, 2020, as the demarcation time point. Women who began their GDM follow-up starting March 11, 2020, and thereafter were allocated to the COVID-19 era, whereas women who delivered before the demarcation point served as the pre-COVID-19 era. The primary outcome was the rate of large-for-gestational-age (LGA) neonates. Secondary outcomes included select maternal and neonatal adverse outcomes. RESULTS: Seven hundred seventy-five women were included in the analysis, of which 187 (24.13%) were followed during the COVID-19 era and 588 (75.87%) before the COVID-19 era. One hundred seventy-one of the 187 women (91.44%) followed during COVID-19 had at least 1 virtual follow-up visit. No virtual follow-up visits occurred before the COVID-19 era. There was no difference in the rate of LGA neonates between groups on both univariate (5.90% vs 7.30%, p=0.5) and multivariate analyses, controlling for age, ethnicity, parity, body mass index, gestational weight gain, chronic hypertension, smoking, and hypertensive disorders in pregnancy (adjusted odds ratio [aOR] 1.11, 95% confidence interval [CI] 0.49 to 2.51, p=0.80). In the multivariate analysis, there was no difference in composite neonatal outcome between groups (GDM diet: aOR 1.40, 95% CI 0.81 to 2.43, p=0.23; GDM medical treatment: aOR 1.20, 95% CI 0.63 to 2.43, p=0.5). CONCLUSIONS: After adjusting for differences in baseline variables, the combined virtual mode of care was not associated with a higher rate of LGA neonates or other adverse perinatal outcomes in women with GDM. Larger studies are needed to better understand the specific impact of virtual care on less common outcomes in pregnancies with GDM.

Preconception SGLT2 or DPP4 inhibitor use and adverse pregnancy outcomes.

AIMS: To compare preconception use of sodium-glucose cotransporter-2 (SGLT2i) and dipeptidyl peptidase-4 (DPP4i) inhibitors to sulfonylurea agents, and associated peri-conceptional A1c concentration, and risk of pregnancy loss and congenital anomalies. METHODS: This population-based cohort study used administrative datasets for all of Ontario, Canada, and included women eligible for free medication coverage and who achieved a recognized pregnancy from April 2007-November 2021. Exposure was a SGLT2i, DPP4i or sulfonylurea (referent) dispensed at least 90 days preconception. Study outcomes included differences in periconceptional A1c; miscarriage, induced abortion, or stillbirth; and any congenital anomaly - the latter two outcomes assessed using propensity score overlap weighting. RESULTS: The mean (SD) periconceptional A1c was 8.1 % (2.0) among those prescribed any sulfonylurea, compared with 8.3 % (2.0) with a DPP4i and 7.8 % (1.6) with any SGLT2i. The risk of pregnancy loss was lowest among those exclusively prescribed a SGLT2i (relative risk [RR] 0.51, 95 % CI 0.22 to 0.91). Risk of a congenital anomaly at birth did not differ significantly comparing DPP4i or SGLT2i to sulfonylurea agents. CONCLUSIONS: Neither SGLT2i nor DPP4i use before pregnancy was associated with a difference in A1c, or a higher risk of selective adverse outcomes, compared to sulfonylureas. Future larger studies are required, including assessment of medication use after conception, during the critical period of embryogenesis.

Maternal First-Trimester Alpha-Fetoprotein and Placenta-Mediated Pregnancy Complications.

BACKGROUND: Maternal serum markers used for trisomy 21 screening are associated with placenta-mediated complications. Recently, there has been a transition from the traditional first-trimester screening (FTS) that included PAPP-A (pregnancy-associated plasma protein-A) and beta-hCG (human chorionic gonadotropin), to the enhanced FTS test, which added first-trimester AFP (alpha-fetoprotein) and PlGF (placental growth factor). However, whether elevated first-trimester AFP has a similar association with placenta-mediated complications to that observed for elevated second-trimester AFP remains unclear. Our objective was to estimate the association of first-trimester AFP with placenta-mediated complications and compare it with the corresponding associations of second-trimester AFP and other first-trimester serum markers. METHODS: Retrospective population-based cohort study of women who underwent trisomy 21 screening in Ontario, Canada (2013-2019). The association of first-trimester AFP with placenta-mediated complications was estimated and compared with that of the traditional serum markers. The primary outcome was a composite of stillbirth or preterm placental complications (preeclampsia, birthweight less than third centile, or placental abruption). RESULTS: A total of 244 990 and 96 167 women underwent FTS and enhanced FTS test screening, respectively. All markers were associated with the primary outcome, but the association for elevated first-trimester AFP (adjusted relative risk [aRR], 1.57 [95% CI, 1.37-1.81]) was weaker than that observed for low PAPP-A (aRR, 2.48 [95% CI, 2.2-2.8]), low PlGF (aRR, 2.28 [95% CI, 1.97-2.64]), and elevated second-trimester AFP (aRR, 1.97 [95% CI, 1.81-2.15]). When the models were adjusted for all 4 enhanced FTS test markers, elevated first-trimester AFP was no longer associated with the primary outcome (aRR, 0.77 [95% CI, 0.58-1.02]). CONCLUSIONS: Unlike second-trimester AFP, elevated first-trimester AFP is not an independent risk factor for placenta-mediated complications.

Glycemic control and neonatal outcomes in twin pregnancies with gestational diabetes mellitus.

BACKGROUND: Preliminary data suggest that strict glycemic control in twin pregnancies with gestational diabetes mellitus may not improve outcomes but might increase the risk of fetal growth restriction. OBJECTIVE: This study aimed to investigate the association of maternal glycemic control with the risk of gestational diabetes mellitus-related complications and small for gestational age in twin pregnancies complicated by gestational diabetes mellitus. STUDY DESIGN: This was a retrospective cohort study of all patients with a twin pregnancy complicated by gestational diabetes mellitus in a single tertiary center between 2011 and 2020, and a matched control group of patients with a twin pregnancy without gestational diabetes mellitus in a 1:3 ratio. The exposure was the level of glycemic control, described as the proportion of fasting, postprandial, and overall glucose values within target. Good glycemic control was defined as a proportion of values within target above the 50th percentile. The first coprimary outcome was a composite variable of neonatal morbidity, defined as at least 1 of the following: birthweight >90th centile for gestational age, hypoglycemia requiring treatment, jaundice requiring phototherapy, birth trauma, or admission to the neonatal intensive care unit at term. A second coprimary outcome was small for gestational age, defined as birthweight <10th centile or <3rd centile for gestational age. Associations between the level of glycemic control and the study outcomes were estimated using logistic regression analysis and were expressed as adjusted odds ratio with 95% confidence interval. RESULTS: A total of 105 patients with gestational diabetes mellitus in a twin pregnancy met the study criteria. The overall rate of the primary outcome was 32.4% (34/105), and the overall proportion of pregnancies with a small for gestational age newborn at birth was 43.8% (46/105). Good glycemic control was not associated with a reduction in the risk of composite neonatal morbidity when compared with suboptimal glycemic control (32.1% vs 32.7%; adjusted odds ratio, 2.06 [95% confidence interval, 0.77-5.49]). However, good glycemic control was associated with higher odds of small for gestational age compared with nongestational diabetes mellitus pregnancies, especially in the subgroup of diet-treated gestational diabetes mellitus (65.5% vs 34.0%, respectively; adjusted odds ratio, 4.17 [95% confidence interval, 1.74-10.01] for small for gestational age <10th centile; and 24.1% vs 7.0%, respectively; adjusted odds ratio, 3.97 [95% confidence interval, 1.42-11.10] for small for gestational age <3rd centile). In contrast, the rate of small for gestational age in gestational diabetes mellitus pregnancies with suboptimal control was not considerably different when compared with non-gestational diabetes mellitus pregnancies. In addition, in cases of diet-treated gestational diabetes mellitus, good glycemic control was associated with a left-shift of the distribution of birthweight centiles, whereas the distribution of birthweight centiles among gestational diabetes mellitus pregnancies with suboptimal control was similar to that of nongestational diabetes mellitus pregnancies. CONCLUSION: In patients with gestational diabetes mellitus in a twin pregnancy, good glycemic control is not associated with a reduction in the risk of gestational diabetes mellitus-related complications but may increase the risk of a small for gestational age newborn in the subgroup of patients with mild (diet-treated) gestational diabetes mellitus. These findings further question whether the gestational diabetes mellitus glycemic targets used in singleton pregnancies also apply to twin pregnancies and support the concern that applying the same diagnostic criteria and glycemic targets in twin pregnancies may result in overdiagnosis and overtreatment of gestational diabetes mellitus and potential neonatal harm.

Prediction of birthweight and risk of macrosomia in pregnancies complicated by diabetes.

BACKGROUND: Antenatal detection of accelerated fetal growth and macrosomia in pregnancies complicated by diabetes mellitus is important for patient counseling and management. Sonographic fetal weight estimation is the most commonly used tool to predict birthweight and macrosomia. However, the predictive accuracy of sonographic fetal weight estimation for these outcomes is limited. In addition, an up-to-date sonographic fetal weight estimation is often unavailable before birth. This may result in a failure to identify macrosomia, especially in pregnancies complicated by diabetes mellitus where care providers might underestimate fetal growth rate. Therefore, there is a need for better tools to detect and alert care providers to the potential risk of accelerated fetal growth and macrosomia. OBJECTIVE: This study aimed to develop and validate prediction models for birthweight and macrosomia in pregnancies complicated by diabetes mellitus. STUDY DESIGN: This was a completed retrospective cohort study of all patients with a singleton live birth at ≥36 weeks of gestation complicated by preexisting or gestational diabetes mellitus observed at a single tertiary center between January 2011 and May 2022. Candidate predictors included maternal age, parity, type of diabetes mellitus, information from the most recent sonographic fetal weight estimation (including estimated fetal weight, abdominal circumference z score, head circumference-to-abdomen circumference z score ratio, and amniotic fluid), fetal sex, and the interval between ultrasound examination and birth. The study outcomes were macrosomia (defined as birthweights >4000 and >4500 g), large for gestational age (defined as a birthweight >90th percentile for gestational age), and birthweight (in grams). Multivariable logistic regression models were used to estimate the probability of dichotomous outcomes, and multivariable linear regression models were used to estimate birthweight. Model discrimination and predictive accuracy were calculated. Internal validation was performed using the bootstrap resampling technique. RESULTS: A total of 2465 patients met the study criteria. Most patients had gestational diabetes mellitus (90%), 6% of patients had type 2 diabetes mellitus, and 4% of patients had type 1 diabetes mellitus. The overall proportions of infants with birthweights >4000 g, >4500 g, and >90th percentile for gestational age were 8%, 1%, and 12%, respectively. The most contributory predictor variables were estimated fetal weight, abdominal circumference z score, ultrasound examination to birth interval, and type of diabetes mellitus. The models for the 3 dichotomous outcomes had high discriminative accuracy (area under the curve receiver operating characteristic curve, 0.929-0.979), which was higher than that achieved with estimated fetal weight alone (area under the curve receiver operating characteristic curve, 0.880-0.931). The predictive accuracy of the models had high sensitivity (87%-100%), specificity (84%-92%), and negative predictive values (84%-92%). The predictive accuracy of the model for birthweight had low systematic and random errors (0.6% and 7.5%, respectively), which were considerably smaller than the corresponding errors achieved with estimated fetal weight alone (-5.9% and 10.8%, respectively). The proportions of estimates within 5%, 10%, and 15% of the actual birthweight were high (52.3%, 82.9%, and 94.9%, respectively). CONCLUSION: The prediction models developed in the current study were associated with greater predictive accuracy for macrosomia, large for gestational age, and birthweight than the current standard of care that includes estimated fetal weight alone. These models may assist care providers in counseling patients regarding the optimal timing and mode of delivery.

The association between immigration status and the development of type 2 diabetes in women with a prior diagnosis of gestational diabetes: A population-based study.

AIMS: The aim of this study was to examine the influence of immigration status and region of origin on the risk of type 2 diabetes in women with prior gestational diabetes (GDM). METHODS: This retrospective population-based cohort study included women with gestational diabetes (GDM) aged 16 to 50 years in Ontario, Canada, who gave birth between 2006 and 2014. We compared the incidence of type 2 diabetes after delivery between long-term residents and immigrants-overall, by time since immigration and by region of-using Cox regression adjusted for age, year, neighbourhood income, rurality, infant birth weight and presence of hypertensive disorders of pregnancy (HDP). RESULTS: Among 38,515 women with prior GDM (42% immigrants), immigrants had a significantly higher risk of type 2 diabetes compared with long-term residents (adjusted hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.13-1.26), with no meaningful difference based on time since immigration. The highest adjusted relative risks of type 2 diabetes compared with long-term residents were found for immigrants from Sub-Saharan Africa (HR 1.63, 95% CI 1.40-1.90), Latin America/Caribbean (HR 1.44, 95% CI 1.28-1.62) and South Asia (HR 1.34, 95% CI 1.25-1.44). CONCLUSIONS: Immigration is associated with a significantly higher risk of type 2 diabetes after GDM, particularly for women from certain low- and middle-income countries. Diabetes prevention strategies will need to consider the unique needs of immigrants from these regions.

Maternal age and pregnancy outcomes in twin compared with singleton gestations.

OBJECTIVE: To estimate the association of advanced maternal age with pregnancy complications in twin pregnancies and compare it with that observed in singleton pregnancies. METHODS: A population-based retrospective cohort study of all patients with a singleton or twin hospital birth in Ontario, Canada, between 2012 and 2019. The primary outcome was preterm birth (PTB) less than 34 weeks. Pregnancy outcomes were stratified by maternal age groups in twin pregnancies and, separately, in singleton pregnancies. RESULTS: A total of 935 378 patients met the study criteria: 920503 (98.4%) had a singleton pregnancy and 14 875 (1.6%) had twins. In singletons, the rate of PTB less than 34 weeks increased progressively with increasing maternal age and was highest for patients aged 45 years or more (3.4%; adjusted risk ratio [aRR] 1.56, 95% confidence interval [CI] 1.05-2.33). By contrast, in twins, although the rate of PTB less than 34 was highest patients under 20 years of age (25.3%) and was lowest among patients aged 35-39 years (11.7%), the associations between maternal age group and the risk of PTB were not statistically significant in the adjusted analysis. CONCLUSION: Although the absolute rates of pregnancy complications are higher in twin pregnancies, there are considerable differences in the relationship between maternal age and the risk of certain complications between twin and singleton pregnancies.

Exploring patients' perspectives of gestational diabetes mellitus screening and counselling in Ontario: A grounded theory study.

INTRODUCTION: Gestational diabetes mellitus (GDM) is associated with adverse perinatal outcomes. Approaches to screening for GDM continue to evolve, introducing potential variability of care. This study explored the impact of these variations on GDM counselling and screening from the perspectives of pregnant individuals. METHODS: Following a Corbin and Strauss approach to qualitative, grounded theory we recruited 28 individuals from three cities in Ontario, Canada who had a singleton pregnancy under the care of either a midwife, family physician or obstetrician. Convenience and purposive sampling techniques were used. Semi-structured telephone interviews were conducted and transcribed verbatim between March and December 2020. Transcripts were analysed inductively resulting in codes, categories and themes. RESULTS: Three themes were derived from the data about GDM screening and counselling: 'informing oneself', 'deciding' and 'screening'. All participants, regardless of geographical region, or antenatal care provider, moved through these three steps during the GDM counselling and screening process. Differences in counselling approaches between pregnancy care providers were noted throughout the 'informing' and 'deciding' stages of care. Factors influencing these differences included communication, healthcare autonomy and patient motivation to engage with health services. No differences were noted within care provider groups across the three geographic regions. Participant experiences of GDM screening were influenced by logistical challenges and personal preferences towards testing. CONCLUSION: Informing oneself about GDM may be a crucial step for facilitating decision-making and screening uptake, with an emphasis on information provision to facilitate patient autonomy and motivation. PATIENT OR PUBLIC CONTRIBUTION: Participants of our study included patients and service users. Participants were actively involved in the study design due to the qualitative, patient-centred nature of the research methods employed. Analysis of results was structured according to the emergent themes of the data which were grounded in patient perspectives and experiences.

Pre-phototherapy total serum bilirubin levels in extremely preterm infants.

BACKGROUND: Extremely preterm infants are prone to hyperbilirubinemia and its sequelae. Currently recommended thresholds for initiating phototherapy in these newborns are consensus-based (CB). METHODS: A multi-site retrospective cohort study of 642 infants born at 240/7 to 286/7 weeks' gestation, between January 2013 and June 2017, was conducted at three NICUs in Canada. Pre-phototherapy TSB percentile levels at 24 h of age were generated and contrasted with published CB thresholds. RESULTS: Among infants born 240/7 to 256/7 weeks' gestation, the differences between our TSB percentiles vs. the CB threshold of 85.0 µmol/L were 10.0 µmol/L (95% CI, 6.0-16.0) at the 75th percentile and 35.3 µmol/L (95% CI, 26.1-42.8) at the 95th percentile. Respectively, among infants born at 260/7 to 276/7 weeks, differences were 19.4 µmol/L (95% CI, 16.8-23.4) and 43.3 µmol/L (95% CI, 34.7-46.9). Born at 280/7 to 286/7 weeks' gestation, differences between our 75th and 95th TSB percentiles and the CB threshold of 103 µmol/L were 6.9 µmol/L (95% CI, 3.2-12.0) and 36.0 µmol/L (95% CI, 31.0-44.3), respectively. CONCLUSIONS: We provide statistically derived pre-phototherapy TSB levels that may clarify patterns of pre-phototherapy TSB levels in extremely preterm infants. IMPACT: 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 association between offspring birthweight and future risk of maternal diabetes: A population-based study.

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: A higher offspring birthweight signals an increased risk of maternal diabetes, offering another potentially useful way to identify women especially predisposed to diabetes.

A framework for understanding how midwives perceive and provide care management for pregnancies complicated by gestational diabetes or hypertensive disorders of pregnancy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Screening Accuracy of the 50 g-Glucose Challenge Test in Twin Compared With Singleton Pregnancies.

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 < .001). The estimated false-positive rate (FPR) for GDM was higher in twin compared with singleton pregnancies irrespective of the 50 g-GCT cutoff used. The cutoff of 8.2 mmol/L (148 mg/dL) in twin pregnancies was associated with an estimated FPR (10.7%-11.1%) that was similar to the FPR associated with the cutoff of 7.8 mmol/L (140 mg/dL) in singleton pregnancies (10.8%). CONCLUSION: The screening performance of the 50 g-GCT for GDM and its correlation with LGA differ between twin and singleton pregnancies.

The prognostic value of the oral glucose tolerance test for future type-2 diabetes in nulliparous pregnant women testing negative for gestational diabetes.

AIM: To determine the prognostic value of the antepartum 75g-oral glucose tolerance test (OGTT) for future type 2 diabetes mellitus (T2DM) in nulliparous pregnant women who tested negative for GDM. METHODS: A population-based retrospective cohort study of nulliparous pregnant women who underwent testing for GDM using a 75g-OGTT in Ontario, Canada (2007-2017). The overwhelming majority of women in Ontario undergo screening using the preferred 2-step approach where the 75g-OGTT is performed following an abnormal non-fasting 1 h 50g-glucose challenge test. The relationship between the 75g-OGTT results in women who tested negative for GDM (defined as normal glucose at fasting, 1 and 2 h post 75g-glucose load) and future T2DM (as recorded in the Ontario Diabetes Database by the end date of follow up period) was explored. FINDINGS: Of the 162,622 women who underwent 75g-OGTT during the study period, there were 41,507 (75.0%) who met the study criteria. In women without GDM, the adjusted hazard ratios (aHR) for T2DM were-At fasting 2.82 (95%-CI 2.18-3.64), at 1 h 1.26 (1.15-1.37), at 2 h 1.14 (1.04-1.25) for a 1 mmol/L increase in glucose. A model that combined all 3 OGTT values and clinical characteristics could detect 43% (42.6%-43.4%) of those who developed T2DM at 5-years post the index pregnancy for a false-positive rate of 20%. INTERPRETATION: The results of the antepartum OGTT can be used to refine the future risk of T2DM even in nulliparous pregnant women who tested negative for GDM.

Persistence of abnormal uterine artery flow postpartum: Case-control study.

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.

A pharmacogenomic investigation of the cardiac safety profile of ondansetron in children and pregnant women.

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.