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To determine the impact of pre-pregnancy diabetes mellitus (D), obesity (O) and chronic hypertension (H) on preterm birth (PTB). Retrospective population-based cohort study in Ontario, Canada between 2012-2016. Women who had a singleton livebirth or stillbirth at > 20 weeks gestation were included in the cohort. Exposures of interest were D, O and H, individually, and in various combinations. The primary outcome was PTB at 241/7 to 366/7 weeks. PTB was further analyzed by spontaneous or provider-initiated, early (< 34 weeks) or late (34-37 weeks), and the co-presence of preeclampsia, large for gestational age (LGA), and small for gestational age (SGA). Multivariable Poisson regression models with robust error variance were used to generate relative risks (RR), further adjusted for maternal age and parity (aRR). Population attributable fractions (PAF) were calculated for each of the outcomes by exposure state. 506,483 women were eligible for analysis. 30,139 pregnancies (6.0%) were complicated by PTB < 37 weeks, of which 7375 (24.5%) had D or O or H. Relative to women without D or O or H, the aRR for PTB < 37 weeks was higher for D (3.51; 95% CI 3.26-3.78) and H (3.81; 95% CI 3.55-4.10) than O (1.14; 95% CI 1.10-1.17). The combined state of DH was associated with a significantly higher aRR of PTB < 37 weeks (6.34; 95% CI 5.14-7.80) and < 34 weeks (aRR 10.33, 95% CI 6.96-15.33) than D alone. The risk of provider initiated PTB was generally higher than that for spontaneous PTB. Pre-pregnancy hypertension was associated with the highest risk for PTB with preeclampsia (aRR 45.42, 95% CI 39.69-51.99) and PTB with SGA (aRR 9.78, 95% CI 7.81-12.26) while pre-pregnancy diabetes was associated with increased risk for PTB with LGA (aRR 28.85, 95% CI 24.65-33.76). Combinations of DOH significantly magnify the risk of PTB, especially provider initiated PTB, and PTB with altered fetal growth or preeclampsia.

Despite increasing rheumatic disease prevalence among female individuals in Ontario, Canada, research is limited on whether this has translated to an increased proportion of pregnancies with rheumatic diseases. This study aimed to assess rheumatic disease rates among pregnant individuals in Ontario, Canada. Using healthcare administrative claims databases from ICES, the proportion of pregnancies with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) from April 2011 to March 2021 were examined. The Mann-Kendall rank correlation test was used to test for trends in overall and individual rheumatic disease rates across the study period. In total, 1,408,100 pregnancies were recorded from fiscal years 2011-2020 in Ontario. Of these, 4,392 involved patients with rheumatic diseases. The overall rheumatic disease rate among pregnant individuals increased by 24% from 28.3 to 35.2 pregnancies per 10,000 over the study period (p = 0.0157). RA rates increased 22% from 11.1 to 13.5 per 10,000 (p = 0.0056), while PsA rates increased 111% from 0.9 to 1.9 per 10,000 (p = 0.0157). SLE, AS, and multiple rheumatic disease rates did not increase significantly. The proportion of individuals with rheumatic diseases pursuing pregnancy in Ontario has increased, perhaps aided by advancements in disease diagnostics and treatment strategies. Further research is needed to link antirheumatic drug safety to pregnancy outcomes and explore other factors that may influence pregnancy rates among this patient population.

The safety of antirheumatic drugs in pregnancy and their impact on maternal and neonatal outcomes are understudied. Despite pregnant individuals being excluded from clinical trials, their continued use of medications raises the importance of addressing knowledge gaps regarding safety and impact on outcomes. A scoping review was conducted following JBI methodology and PRISMA reporting guidelines to describe how antirheumatic drugs and associated adverse pregnancy outcomes have been investigated in observational studies using claims data. Electronic databases (MEDLINE (Ovid), Embase (Ovid), and CINAHL (EBSCO)) and grey literature were searched for observational studies using claims data to evaluate antirheumatic drug effects on pregnancy outcomes in individuals with rheumatic diseases. Of 4,325 articles identified, 38 eligible articles were included. The effects of conventional synthetic disease-modifying antirheumatic drugs (n =  37, 97.4%) and tumor necrosis factor inhibitor biological agents (n =  23, 60.5%) were extensively reported. Preterm birth (n =  25, 65.8%), preeclampsia (n =  17, 44.7%), stillbirth (n =  17, 44.7%), caesarean delivery (n =  16, 42.1%), and congenital anomalies (n =  14, 36.8%) were the most reported adverse pregnancy outcomes. Of 14 studies reporting congenital anomalies, 12 (85.7%) specified ICD codes and 4 (28.6%) specified validated definitions for identification in claims data, the most of any reported adverse pregnancy outcome. We found considerable ambiguity and heterogeneity in adverse pregnancy outcome definitions in claims data. There is a need for greater transparency and consistency in outcome reporting in observational studies using claims data. Protocol registration details: OSF, https://osf.io/5e6tp

The relation between prepregnancy average glucose concentration and a woman's risk of severe maternal morbidity (SMM) is unknown. The current study evaluated whether an elevated preconception hemoglobin A1c (A1c) is associated with SMM or maternal death among women with and without known prepregnancy diabetes mellitus (DM). A population-based cohort study was completed in Ontario, Canada, where there is universal healthcare. The main cohort included 31,225 women aged 16-50 years with a hospital live birth or stillbirth from 2007 to 2015, and who had an A1c measured within 90 days before conception, including 28,075 women (90%) without known prepregnancy DM. The main outcome was SMM or maternal mortality from 23 weeks' gestation up to 42 days postpartum. Relative risks (RRs) were generated using modified Poisson regression, adjusting for the main covariates of maternal age, multifetal pregnancy, world region of origin, and tobacco/drug dependence. The mean maternal age was 31.1 years. Overall, SMM or death arose among 682 births (2.2%). The RR of SMM or death was 1.16 (95% CI 1.14-1.19; p < 0.001) per 0.5% increase in A1c and 1.16 (95% CI 1.13-1.18; p < 0.001) after adjusting for the main covariates. The adjusted relative risk (aRR) was increased among those with (1.11, 95% CI 1.07-1.14; p < 0.001) and without (1.15, 95% CI 1.02-1.29; p < 0.001) known prepregnancy diabetes, and upon further adjusting for body mass index (BMI) (1.15, 95% CI 1.11-1.20; p < 0.001), or chronic hypertension and prepregnancy serum creatinine (1.11, 95% CI 1.04-1.18; p = 0.002). The aRR of SMM or death was 1.31 (95% CI 1.06-1.62; p = 0.01) in those with a preconception A1c of 5.8%-6.4%, and 2.84 (95% CI 2.31-3.49; p < 0.001) at an A1c > 6.4%, each relative to an A1c < 5.8%. Among those without previously recognized prepregnancy diabetes and whose A1c was >6.4%, the aRR of SMM or death was 3.25 (95% CI 1.76-6.00; p < 0.001). Study limitations include that selection bias may have incorporated less healthy women tested for A1c, and BMI was unknown for many women. Our findings indicate that women with an elevated A1c preconception may be at higher risk of SMM or death in pregnancy or postpartum, including those without known prepregnancy DM.

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

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. 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. 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. In a twin pregnancy, HDP are weaker risk factors for postpartum cardiovascular disease than in a singleton pregnancy.

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

Background Uterine rupture in the non-laboring uterus is a rare occurrence, which can lead to significant morbidity and mortality for the mother and fetus. Management of this presentation is complex at pre-viable gestations. Case presentation A 35 year old primigravid woman with multiple previous myomectomies presented with spontaneous complete thickness uterine rupture at 21 weeks gestation. A 10 cm myometrial defect and iatrogenic amniotomy were surgically corrected with fetal preservation. This led to pregnancy continuation to 32 weeks gestation when elective cesarean delivery resulted in excellent neonatal outcome. Conclusions Early surgical diagnosis, multidisciplinary team approach, iatrogenic amniotomy and continuous two-layer myometrial closure were factors that contributed to pregnancy prolongation in this large myometrial rupture.

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

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 < 0.01). Combination treatment decreased the mRNA expression of BCRP and OAT4 but increased that of OCT3 (p < 0.01). Decreased accumulation of the OATP substrate, cascade blue, was seen in IL-23-treated choriocarcinoma JAr cells (p < 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.