Severe Maternal Morbidity and Mental Health Hospitalizations or Emergency Department Visits.

Importance: Severe maternal morbidity (SMM) can have long-term health consequences for the affected mother. The association between SMM and future maternal mental health conditions has not been well studied. Objective: To assess the association between SMM in the first recorded birth and the risk of hospitalization or emergency department (ED) visits for a mental health condition over a 13-year period. Design, Setting, and Participants: This population-based retrospective cohort study used data from postpartum individuals aged 18 to 55 years with a first hospital delivery between 2008 and 2021 in 11 provinces and territories in Canada, except Québec. Data were analyzed from January to June 2023. Exposure: SMM, defined as a composite of conditions, such as septic shock, severe preeclampsia or eclampsia, severe hemorrhage with intervention, or other complications, occurring after 20 weeks' gestation and up to 42 days after a first delivery. Main Outcomes and Measures: The main outcome was a hospitalization or ED visit for a mental health condition, including mood and anxiety disorders, substance use, schizophrenia, and other psychotic disorder, or suicidality or self-harm event, arising at least 43 days after the first birth hospitalization. Cox regression models generated hazard ratios with 95% CIs, adjusted for baseline maternal comorbidities, maternal age at delivery, income quintile, type of residence, hospital type, and delivery year. Results: Of 2 026 594 individuals with a first hospital delivery, 1 579 392 individuals (mean [SD] age, 30.0 [5.4] years) had complete ED and hospital records and were included in analyses; among these, 35 825 individuals (2.3%) had SMM. Compared with individuals without SMM, those with SMM were older (mean [SD] age, 29.9 [5.4] years vs 30.7 [6.0] years), were more likely to deliver in a teaching tertiary care hospital (40.8% vs 51.1%), and to have preexisting conditions (eg, ≥2 conditions: 1.2% vs 5.3%), gestational diabetes (8.2% vs 11.7%), stillbirth (0.5% vs 1.6%), preterm birth (7.7% vs 25.0%), or cesarean delivery (31.0% vs 54.3%). After a median (IQR) duration of 2.6 (1.3-6.4) years, 1287 (96.1 per 10 000) individuals with SMM had a mental health hospitalization or ED visit, compared with 41 779 (73.2 per 10 000) individuals without SMM (adjusted hazard ratio, 1.26 [95% CI, 1.19-1.34]). Conclusions and Relevance: In this cohort study of postpartum individuals with and without SMM in pregnancy and delivery, there was an increased risk of mental health hospitalizations or ED visits up to 13 years after a delivery complicated by SMM. Enhanced surveillance and provision of postpartum mental health resources may be especially important after SMM.

Association between maternal hypertension and infant neurodevelopment in extremely preterm infants.

OBJECTIVE: To examine the association between maternal hypertension during pregnancy and neurodevelopmental impairment (NDI) at 24 months post-menstrual age in extremely preterm infants. STUDY DESIGN: Using data from two tertiary neonatal units (2011-2017) for infants born at 23 + 0 to 28 + 6 weeks, we investigated outcomes of NDI related to maternal hypertension and small-for-gestational-age (SGA) status. RESULTS: Of 1019 pre-term infants, 647 had complete data and were included in the analysis. Ninety-six (15%) had maternal hypertension exposure; 25 (4%) were also SGA. Infants with maternal hypertension showed a higher odds of any NDI (aOR: 2.29, 95% CI = 1.36-3.87) and significant NDI (aOR: 2.01, 95% CI = 1.02-3.95). The combination of hypertension and SGA further elevated this risk (aOR for any NDI: 4.88, 95% CI = 1.80-13.22; significant NDI: 6.91, 95% CI = 2.50-19.12). CONCLUSION: Maternal hypertension during pregnancy elevates the risk of NDI in extremely preterm infants, more so when combined with SGA.

Periconceptional Serum Creatinine and Risk of Childhood Autism Spectrum Disorder: A Research Letter.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition that manifests in early childhood, in which the maternal metabolic syndrome may be a risk factor. The kidney is a barometer of maternal metabolic syndrome duration and severity. Objective: The main objective of this study is to determine whether periconceptional kidney function is associated with ASD in early childhood. Design Setting and Participants: This retrospective population-based cohort study was completed in Ontario, Canada. Included were singleton children born in an Ontario hospital between April 2007 and March 2021, who were alive at age 48 months and whose mother had a recorded prepregnancy body mass index (BMI) and a measured serum creatinine (SCr) between 120 days preconception and 28 days postconception. Measurement: The main study outcome was a diagnosis of ASD between ages 24 and 48 months. Methods: Relative risks (RRs) of ASD in association with periconceptional SCr were generated using modified Poisson regression and adjusted for several confounders. Results: The cohort comprised 86 054 women, who had 89 677 liveborn children surviving to at least 48 months of age. There was no significant association between periconceptional SCr and ASD (RR: 0.86; 95 % confidence interval: [0.67, 1.10]). Limitations: Selection bias may have arisen had SCr been ordered on clinical grounds. Conclusions: Further study is warranted to determine whether prepregnancy glomerular hyperfiltration is a marker of ASD and other behavioral conditions in childhood. To do so, a more accurate measure of hyperfiltration is needed than SCr.

Contexte: Des problèmes d'innocuité sont détectés dans environ un tiers des médicaments d'ordonnance au cours des années qui suivent leur approbation par l'organisme de réglementation. Les personnes âgées, en particulier celles qui sont atteintes d'insuffisance rénale chronique, sont particulièrement exposées aux effets indésirables des médicaments d'ordonnance. Ce protocole décrit une nouvelle approche qui, à partir des données administratives du système de santé, pourrait permettre d'identifier plus efficacement les signaux crédibles sur la sécurité des médicaments. Objectif: Utiliser l'informatique à haut débit et l'automatisation pour mener plus de 700 études de cohorte sur l'innocuité des médicaments chez les adultes âgés résidant en Ontario (Canada). Chaque étude comparera 74 résultats aigus (30 jours) chez des patients qui commencent un nouveau médicament sur ordonnance (nouveaux utilisateurs) à ceux d'un groupe de non-utilisateurs avec des caractéristiques de santé initiales similaires. Les risques seront évalués par strates de la fonction rénale initiale. Cadre et type d'étude: Études populationnelles de cohortes de nouveaux utilisateurs de médicaments menées à l'aide des bases de données administratives couplées du système de santé ontarien (Canada). Période étudiée: du 1er janvier 2008 au 1er mars 2020. Population source: les Ontariens de 66 ans ou plus ayant rempli au moins une ordonnance pour patient non hospitalisé par l'entremise du Program de médicaments de l'Ontario (PMO) pendant la période de l'étude (tous les résidents de la province bénéficient d'un système de soins de santé universel; les personnes âgées de 65 ans et plus bénéficient d'une couverture universelle des médicaments d'ordonnance par l'intermédiaire du PMO). Sujets: Nous avons identifié 3,2 millions d'adultes âgés dans la population source au cours de la période d'étude et constitué plus de 700 cohortes de médicaments, chacune contenant des groupes mutuellement exclusifs de nouveaux utilisateurs et de non-utilisateurs. Les non-utilisateurs se sont vu attribuer au hasard des dates d'entrée dans la cohorte qui suivaient les dates de début d'ordonnance des nouveaux utilisateurs. Les critères d'admissibilité étaient d'avoir une mesure initiale du débit de filtration glomérulaire estimé [DFGe] dans les 12 mois précédant la date d'entrée dans la cohorte (dans le groupe des nouveaux utilisateurs, le délai médian était de 71 jours avant l'entrée dans la cohorte), ne pas suivre de dialyze chronique, ne pas avoir eu de greffe rénale et n'avoir jamais eu de prescription d'un médicament de la même sous-classe que le médicament à l'étude. Les nouveaux utilisateurs et les non-utilisateurs seront jumelés selon environ 400 caractéristiques de santé initiales à l'aide de la probabilité inverse de traitement pondérée selon les scores de propension dans les trois strates de mesure du DFGe initial: ≥60 ml/min/1,73 m2; 45 à <60 ml/min/1,73 m2 et <45 ml/min/1,73 m2. Résultats: Nous comparerons les groupes de nouveaux utilisateurs et de non-utilisateurs selon 74 critères de jugement cliniquement pertinents (17 critères composites et 57 critères individuels) pendant les 30 jours suivant l'entrée dans la cohorte. Une approche prédéfinie a permis de déterminer ces 74 résultats. Plan d'analyze statistique: Dans chaque cohorte, nous calculerons les différences de risque (par régression de Poisson) et les rapports de risque (par régression binomiale) pondérés pour chaque strate de DFGe. Les interactions additives et multiplicatives par catégorie de DFGe seront examinées. Les associations médicaments-résultats répondant à des critères prédéfinis (signaux identifiés) seront examinées plus avant dans des analyses supplémentaires (survie, exposition à des témoins négatifs, analyses de la valeur E, etc.) et des visualizations. Résultats: Dans les cohortes initiales de médicaments, les médianes sont de 6 120 nouveaux utilisateurs (intervalle interquartile de 1 469 à 38 839) et de 1 088 301 non-utilisateurs (intervalle interquartile de 751 697 à 1 267 009). Les médicaments comptant le plus grand nombre de nouveaux utilisateurs sont le trihydrate d'amoxicilline (n = 1 000 032), la céfalexine (n = 571 566), l'acétaminophène sur ordonnance (n = 571 563) et la ciprofloxacine (n = 504 374). De 19 à 29 % des nouveaux utilisateurs dans ces cohortes présentaient un DFGe < 60 ml/min/1,73 m2. Limites: Malgré l'utilization de techniques robustes pour équilibrer les indicateurs de base et pour contrôler le risque de confusion par indication, il pourrait subsister des facteurs de confusion résiduels. Seuls les résultats aigus (30 jours) seront examinés. Nos sources de données ne comprennent pas les médicaments sans ordonnance (en vente libre) ni les médicaments prescrits dans les hôpitaux, et n'incluent pas l'utilization de médicaments sur ordonnance en ambulatoire chez les enfants ou les adultes de moins de 65 ans. Conclusion: Cette approche accélérée pour la réalisation d'études d'innocuité des médicaments après leur mise en marché a le potentiel de détecter efficacement les effets indésirables de ces médicaments dans une population vulnérable. Les résultats de ce protocole serviront à améliorer l'innocuité des médicaments.

PAP Treatment of Obstructive Sleep Apnea-Hypopnea in Hypertensive Disorders of Pregnancy: A Pilot Randomized Proof-of-the-Concept Study.

RATIONALE: Maternal obstructive sleep apnea-hypopnea (OSAH) is associated with hypertensive disorders of pregnancy (HDP). OSAH treatment with positive airway pressure (PAP) in the general population lowers blood pressure (BP). However, there is limited data on the effects of PAP therapy in maternal OSAH. OBJECTIVE: Our primary objective was to assess the feasibility of recruitment to a pilot randomized trial and adherence to PAP therapy for OSAH in women with HDP. Secondary objectives included assessment of PAP effects on 24-h BP, arterial stiffness, and maternal and fetal outcomes. METHODS: Women with a singleton pregnancy ≥ 12 weeks' gestation and hypertension underwent home level II PSG; those with mild-moderate OSAH (AHI ≥ 5 events/h; severe OSAH with AHI >30 and ODI > 30 excluded) were randomized to either PAP or nasal dilator strip (NDS; control) therapy. Following PAP education, adherence was monitored online with episodic phone or in-person support by research personnel. 24-h BP and arterial stiffness were assessed at baseline and pre-delivery. Maternal and fetal outcomes were also recorded. RESULTS: Of 105 potentially eligible participants, 67 agreed to undergo screening for OSAH over 38 months; 48 women meeting OSAH inclusion criteria were randomized to PAP (n=27) or NDS (n=21). Of these, 14 PAP (52%) and 13 NDS (62%) participants completed all predelivery measurements, with lack of completion due to urgent delivery (PAP 19%, NDS 14%), PAP intolerance at initiation (19%) or other factors. Mean PAP use was 3.1±2.5 h/night, with use ≥ 4 h/night on 38.4 ± 33.7% of nights during 9.6 ± 4.0 weeks of treatment. BP was controlled within target range in most participants. There were no differences in mean change in 24-h BP or arterial stiffness measurements or in adverse maternal & fetal outcomes, between PAP and NDS groups in either intention-to-treat or per-protocol analyses. CONCLUSION: CPAP adherence was sub-optimal in this HDP cohort despite education and trouble-shooting. Further work is required to identify optimal OSAH treatment strategies during pregnancy. CLINICAL TRIAL REGISTRATION: NCT03309826.

Infertility and Risk of Autism Spectrum Disorder in Children.

Importance: Previous studies on the risk of childhood autism spectrum disorder (ASD) following fertility treatment did not account for the infertility itself or the mediating effect of obstetrical and neonatal factors. Objective: To assess the association between infertility and its treatments on the risk of ASD and the mediating effect of selected adverse pregnancy outcomes on that association. Design, Setting, and Participants: This was a population-based cohort study in Ontario, Canada. Participants were all singleton and multifetal live births at 24 or more weeks' gestation from 2006 to 2018. Data were analyzed from October 2022 to October 2023. Exposures: The exposure was mode of conception, namely, (1) unassisted conception, (2) infertility without fertility treatment (ie, subfertility), (3) ovulation induction (OI) or intrauterine insemination (IUI), or (4) in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Main Outcome and Measures: The study outcome was a diagnosis of ASD at age 18 months or older. Cox regression models generated hazard ratios (HR) adjusted for maternal and infant characteristics. Mediation analysis further accounted for the separate effect of (1) preeclampsia, (2) cesarean birth, (3) multifetal pregnancy, (4) preterm birth at less than 37 weeks, and (5) severe neonatal morbidity. Results: A total of 1 370 152 children (703 407 male [51.3%]) were included: 1 185 024 (86.5%) with unassisted conception, 141 180 (10.3%) with parental subfertility, 20 429 (1.5%) following OI or IUI, and 23 519 (1.7%) following IVF or ICSI. Individuals with subfertility or fertility treatment were older and resided in higher-income areas; the mean (SD) age of each group was as follows: 30.1 (5.2) years in the unassisted conception group, 33.3 (4.7) years in the subfertility group, 33.1 (4.4) years in the OI or IUI group, and 35.8 (4.9) years in the IVF or ICSI group. The incidence rate of ASD was 1.93 per 1000 person-years among children in the unassisted conception group. Relative to the latter, the adjusted HR for ASD was 1.20 (95% CI, 1.15-1.25) in the subfertility group, 1.21 (95% CI, 1.09-1.34) following OI or IUI, and 1.16 (95% CI, 1.04-1.28) after IVF or ICSI. Obstetrical and neonatal factors appeared to mediate a sizeable proportion of the aforementioned association between mode of conception and ASD risk. For example, following IVF or ICSI, the proportion mediated by cesarean birth was 29%, multifetal pregnancy was 78%, preterm birth was 50%, and severe neonatal morbidity was 25%. Conclusions and Relevance: In this cohort study, a slightly higher risk of ASD was observed in children born to individuals with infertility, which appears partly mediated by certain obstetrical and neonatal factors. To optimize child neurodevelopment, strategies should further explore these other factors in individuals with infertility, even among those not receiving fertility treatment.

Impact of Covid-19 on risk of severe maternal morbidity.

BACKGROUND: We examined the risk of severe life-threatening morbidity in pregnant patients with Covid-19 infection. METHODS: We conducted a population-based study of 162,576 pregnancies between March 2020 and March 2022 in Quebec, Canada. The main exposure was Covid-19 infection, including the severity, period of infection (antepartum, peripartum), and circulating variant (wildtype, alpha, delta, omicron). The outcome was severe maternal morbidity during pregnancy up to 42 days postpartum. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between Covid-19 infection and severe maternal morbidity using adjusted log-binomial regression models. RESULTS: Covid-19 infection was associated with twice the risk of severe maternal morbidity compared with no infection (RR 2.02, 95% CI 1.76-2.31). Risks were elevated for acute renal failure (RR 3.01, 95% CI 1.79-5.06), embolism, shock, sepsis, and disseminated intravascular coagulation (RR 1.35, 95% CI 0.95-1.93), and severe hemorrhage (RR 1.49, 95% CI 1.09-2.04). Severe antepartum (RR 13.60, 95% CI 10.72-17.26) and peripartum infections (RR 20.93, 95% CI 17.11-25.60) were strongly associated with severe maternal morbidity. Mild antepartum infections also increased the risk, but to a lesser magnitude (RR 3.43, 95% CI 2.42-4.86). Risk of severe maternal morbidity was around 3 times greater during circulation of wildtype and the alpha and delta variants, but only 1.2 times greater during omicron. CONCLUSIONS: Covid-19 infection during pregnancy increases risk of life-threatening maternal morbidity, including renal, embolic, and hemorrhagic complications. Severe Covid-19 infection with any variant in the antepartum or peripartum periods all increase the risk of severe maternal morbidity.

Risk of recurrent severe maternal morbidity: a population-based study.

BACKGROUND: Severe maternal morbidity is a composite indicator of maternal health and obstetrical care. Little is known about the risk of recurrent severe maternal morbidity in a subsequent delivery. OBJECTIVE: This study aimed to estimate the risk of recurrent severe maternal morbidity in the next delivery after a complicated first delivery. STUDY DESIGN: We analyzed a population-based cohort study of women with at least 2 singleton hospital deliveries between 1989 and 2021 in Quebec, Canada. The exposure was severe maternal morbidity in the first hospital-recorded delivery. The study outcome was severe maternal morbidity at the second delivery. Log-binomial regression models adjusted for maternal and pregnancy characteristics were used to generate relative risks and 95% confidence intervals comparing women with and without severe maternal morbidity at first delivery. RESULTS: Among 819,375 women, 43,501 (3.2%) experienced severe maternal morbidity in the first delivery. The rate of severe maternal morbidity recurrence at second delivery was 65.2 vs 20.3 per 1000 in women with and without previous severe maternal morbidity (adjusted relative risk, 3.11; 95% confidence interval, 2.96-3.27). The adjusted relative risk for recurrence of severe maternal morbidity was greatest among women who had ≥3 different types of severe maternal morbidity at their first delivery, relative to those with none (adjusted relative risk, 5.50; 95% confidence interval, 4.26-7.10). Women with cardiac complication at first delivery had the highest risk of severe maternal morbidity in the next delivery. CONCLUSION: Women who experience severe maternal morbidity have a relatively high risk of recurrent morbidity in the subsequent pregnancy. In women with severe maternal morbidity, these study findings have implications for prepregnancy counseling and maternity care in the next pregnancy.

The effect of maternal hypertension and maternal mental illness on adverse neonatal outcomes: A mediation and moderation analysis in a U.S. cohort of 9 million pregnancies.

BACKGROUND: While hypertensive disorders of pregnancy (HDP) coexist with maternal anxiety and depression, it is unclear how these conditions affect neonatal outcomes. We evaluated the prevalence as well as associations and potential mechanisms between HDP, maternal anxiety and depression, preterm birth (PTB), and small for gestational age (SGA). METHODS: We conducted a retrospective population-based study using the Healthcare Cost and Utilization Project (HCUP) database from 2004 to 2014. Preterm birth (<37 weeks), SGA (<10th percentile for gestational age and sex), HDP, and mental disorders (anxiety and depression) were extracted using the International Classification of Diseases, Ninth Revision (ICD-9). Mediation and moderation models were constructed separately to evaluate potential mechanisms between maternal anxiety and depression, HDP, and adverse neonatal outcomes. Multivariate logistic regressions were used to determine their associations. RESULTS: Of 9,097,355 pregnant women, the prevalence of HDP was 6.9 %, anxiety 0.91 %, depression 0.36 %, preterm birth 7.2 %, and SGA 2.1 %. Anxiety increased the probability of having HDP (OR = 1.242, 95 % CI 1.235-1.250), and HDP mediated the association between anxiety and preterm birth (mediation effect = 0.048, p-value<0.001). Depression significantly moderated the effect of HDP on preterm birth (moderation effect = -0.126, p-value = 0.027). HDP also mediated the association between anxiety and SGA (mediation effect = 0.042, p-value<0.001), but depression did not moderate the association between HDP and SGA (p-value = 0.29). CONCLUSION: Our study suggests that women with anxiety are more likely to have HDP, and HDP mediates the associations between anxiety and adverse neonatal outcomes. Depression moderates associations between HDP and preterm birth but not between HDP and SGA.

Study protocol for the sheMATTERS study (iMproving cArdiovascular healTh in new moThERS): a randomized behavioral trial assessing the effect of a self-efficacy enhancing breastfeeding intervention on postpartum blood pressure and breastfeeding continuation in women with hypertensive disorders of pregnancy.

BACKGROUND: Individuals with hypertensive disorders of pregnancy (HDP) have an elevated lifetime risk of chronic hypertension, metabolic syndrome, and premature cardiovascular disease. Because breastfeeding duration and exclusivity have been associated in observational studies with improved cardiovascular health, optimizing breastfeeding in those with HDP might be an unrealized cardio-prevention approach, in particular because individuals with HDP have more breastfeeding challenges. Breastfeeding supportive interventions targeting one's breastfeeding self-efficacy have been shown to improve breastfeeding rates. METHODS: We designed an open-label, multi-center 1:1 randomized behavioral trial to test whether a previously validated self-efficacy enhancing breastfeeding intervention can improve breastfeeding duration and/or exclusivity, and lower postpartum blood pressure at 12 months. Randomization is computer-generated and stratified by site (four hospitals in Montreal, Quebec and one hospital in Kingston, Ontario; all in Canada). Included are breastfeeding participants with HDP (chronic/gestational hypertension or preeclampsia) who delivered a live singleton infant at > 34 weeks, speak English or French, and have no contraindications to breastfeeding. Informed and written consent is obtained at hospitalization for delivery or a re-admission with hypertension within 1 week of discharge. Participants assigned to the intervention group receive a breastfeeding self-efficacy-based intervention delivered by a trained lactation consultant in hospital, with continued reactive/proactive support by phone or text message for up to 6 months postpartum. Regardless of group assignment, participants are followed for self-reported outcomes, automated office blood pressure, and home blood pressure at several time points with end of follow-up at 12 months. DISCUSSION: This study will assess whether an intensive nurse-led behavioral intervention can improve breastfeeding rates and, in turn, postpartum blood pressure - an early marker for atherosclerotic cardiovascular disease. If effective, this form of enhanced breastfeeding support, along with closer BP and metabolic surveillance, can be implemented broadly in individuals lactating after HDP. TRIAL REGISTRATION: ClinicalTrials.gov, # NCT04580927 , registered on Oct 9, 2020.

Fresh Compared With Frozen Embryo Transfer and Risk of Severe Maternal Morbidity: A Study of In Vitro Fertilization Pregnancies in Ontario, Canada.

OBJECTIVES: To quantify the risk of severe maternal morbidity (SMM) in fresh versus frozen-thawed embryo transfers (ETs) among pregnancies conceived by in vitro fertilization (IVF) and to assess SMM risk according to the number of fresh ETs prior to the index pregnancy. METHODS: Retrospective cohort study using the provincial birth registry in Ontario, Canada. We included 13 929 individuals aged 18-55 years who conceived via IVF between January 1, 2013, and March 5, 2018, and delivered a live or stillborn infant ≥20 weeks gestation. We compared the primary outcome, a composite of SMM or death, between fresh and frozen ETs. RESULTS: A total of 174 individuals who conceived via fresh ETs had SMM (30.7 per 1000), compared with 280 among individuals who received frozen ETs (33.9 per 1000); adjusted risk ratio (aRR) 0.85 (95% CI 0.70-1.04). Compared with frozen ET, fresh ET was associated with a lower risk of severe hemorrhage (aRR 0.63; 95% CI 0.48-0.82) but no difference in risk of preeclampsia. Among individuals with 1 (n = 211) or ≥2 (n = 88) prior fresh cycles, the risk of SMM was not increased compared with having no prior cycles; aRR 0.96 (95% CI 0.78-1.18) and 0.91 (95% CI 0.67-1.25), respectively. CONCLUSION: Fresh ET was associated with a lower risk of severe hemorrhage compared with frozen ET. These findings may be partly explained by the increased popularity of a freeze-all strategy, reserving fresh ETs for patients with fewer comorbidities.

Impact of Covid-19 on rates of gestational diabetes in a North American pandemic epicenter.

AIMS: We assessed the impact of Covid-19 on gestational diabetes rates in Quebec, the pandemic epicenter of Canada. METHODS: We conducted a population-based study of 569,686 deliveries in Quebec between 2014 and 2021. We measured gestational diabetes rates in wave 1 (March 1, 2020-August 22, 2020) and wave 2 (August 23, 2020-March 31, 2021), compared with the prepandemic period. We used interrupted time series regression to assess changes in gestational diabetes rates during each wave, and log-binomial regression models to estimate adjusted risk ratios (RR) and 95% confidence intervals (CI) for the association of the pandemic with gestational diabetes. We identified the types of patients that contributed to the change in gestational diabetes rates using Kitagawa's decomposition. RESULTS: Gestational diabetes rates were higher during the first (13.2 per 100 deliveries) and second waves (14.3 per 100 deliveries) than during the prepandemic period (12.4 per 100 deliveries). Risk of gestational diabetes increased both in wave 1 (RR 1.05, 95% CI 1.02-1.09) and wave 2 (RR 1.14, 95% CI 1.10-1.18), compared with the prepandemic period. However, most of the increase in gestational diabetes rates was driven by low-risk women without Covid-19 infections who were socioeconomically advantaged, had no comorbidity, and were 25-34 years of age. CONCLUSIONS: Gestational diabetes rates increased during the pandemic, mainly among women traditionally at low risk of hyperglycemia who did not have Covid-19 infections. Sudden widespread changes in screening or lifestyle can have a large impact on gestational diabetes rates in a population.

A retrospective study comparing postoperative opioid prescribing practices in an academic medical centre.

Background: In the midst of the North American opioid crisis, identifying and intervening on drivers of high-risk opioid prescriptions is an important step towards reducing iatrogenic harm. Objectives: We aimed to identify factors associated with variations in high-risk opioid discharge prescriptions, following select surgical procedures, to guide future quality improvement initiatives. Methods: This retrospective cohort study analyzed 1322 patients who underwent select open pelvic and open abdominal surgeries between January 1 and December 31, 2017, in a tertiary health care centre in Montreal. Results: Patients who underwent open abdominal surgeries were prescribed significantly higher daily doses of morphine milligram equivalents (MME) (45 mg; interquartile range, 30-60), than patients who underwent either a caesarean delivery (20 mg, 20-20) or a hysterectomy (30 mg, 22-30). After adjustment for multiple potential confounders, abdominal surgery was associated with 4 times the odds of receiving more than 50 MME at hospital discharge compared with pelvic surgeries (odds ratio, 3.96; 95% confidence interval, 1.31-11.97). The availability of postoperative preprinted order sets with fixed high doses of opioids was also highly associated with the outcome. Conclusion: In our institution, some surgeries were more likely to receive high-risk opioid prescriptions at discharge. Efforts to optimize safer prescribing practices should address the creation and/or updating of preprinted order sets to reflect current best practice guidelines. This initiative could be overseen by hospital pharmacy and therapeutics committees.

Association between Cardiorespiratory Fitness and Hypertensive Disorders of Pregnancy: A Systematic Review and Meta-Analysis.

Hypertensive disorders of pregnancy (HDP) are associated with future cardiovascular disease (CVD), which may be mediated by diminished cardiorespiratory fitness (CRF). In this systematic review and meta-analysis, we summarize evidence linking CRF with HDP before, during, and after pregnancy. We searched relevant databases to identify observational or randomized studies that measured CRF (VO2 max or peak, VO2 at anaerobic threshold, or work rate at peak VO2) in women with and without HDP. We pooled results using random effects models. Fourteen studies (n = 2406 women) reporting on CRF before, during, and after pregnancy were included. Before pregnancy, women who developed HDP had lower CRF (e.g., VO2max < 37 vs. ≥37 mL O2/min) than those without HDP (two studies, 811 women). VO2max at 14−18 weeks of pregnancy was marginally lower among women who developed preeclampsia vs. normotensive women (three studies, 275 women; mean difference 0.43 mL/kg/min [95% CI 0.97, 0.10]). Postpartum, there was a trend towards lower VO2peak in women with previous preeclampsia (three studies, 208 women; 0.26 mL/kg/min [−0.54, 0.02]). While exploratory, our findings raise the possibility that CRF can identify women at risk for HDP, and furthermore, that HDP confers a hit to a woman's cardiorespiratory reserve.

Black-White disparity in severe cardiovascular maternal morbidity: A systematic review and meta-analysis.

BACKGROUND: To synthesize existing evidence on Black-White disparities in the prevalence of severe cardiovascular maternal morbidity. METHODS: We searched MEDLINE, EMBASE, and CINAHL for observational studies published before July 31, 2021 that compared the risk of severe cardiovascular maternal morbidity between Black and White women. The outcome was severe cardiovascular maternal morbidity, including acute myocardial infarction, peripartum cardiomyopathy, and stroke during pregnancy, delivery, or postpartum. We extracted relevant information including adjusted and unadjusted effect estimates. We used random-effects models to estimate the pooled association between race and severe cardiovascular maternal morbidity, presented as odds ratios with 95% confidence intervals for the comparison of Black women relative to White women. RESULTS: We included 18 studies that met the eligibility criteria for systematic review and meta-analysis. All studies were conducted in the United States and included a total of 7,656,876 Black women and 26,412,600 White women. Compared with White women, Black women had an increased risk of any severe cardiovascular maternal morbidity (adjusted odds ratio, 1.90; 95% confidence interval, 1.54-2.33). Black women were at risk of acute myocardial infarction (adjusted odds ratio, 1.38; 95% confidence interval, 1.14-1.68), peripartum cardiomyopathy (adjusted odds ratio, 1.71; 95% confidence interval, 1.51-1.94), and stroke (adjusted odds ratio, 2.13; 95% confidence interval, 1.39-3.26). CONCLUSIONS: Black women have a considerably higher risk of severe cardiovascular maternal morbidity than White women, including acute myocardial infarction, peripartum cardiomyopathy, and stroke. Reducing inequality in adverse cardiovascular outcomes of pregnancy between Black and White women should be prioritized.

Attention-deficit hyperactivity disorder in children born to mothers with infertility: a population-based cohort study.

STUDY QUESTION: Is the risk of attention-deficit hyperactivity disorder (ADHD) increased in children born to mothers with infertility, or after receipt of fertility treatment, compared to mothers with unassisted conception? SUMMARY ANSWER: Infertility itself may be associated with ADHD in the offspring, which is not amplified by the use of fertility treatment. WHAT IS KNOWN ALREADY: Infertility, and use of fertility treatment, is common. The long-term neurodevelopmental outcome of a child born to a mother with infertility, including the risk of ADHD, remains unclear. STUDY DESIGN, SIZE, DURATION: This population-based cohort study comprised all singleton and multiple hospital births in Ontario, Canada, 2006-2014. Outcomes were assessed up to June 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Linked administrative datasets were used to capture all hospital births in Ontario, maternal health and pregnancy measures, fertility treatment and child outcomes. Included were all children born at ≥24 weeks gestation between 2006 and 2014, and who were alive at age 4 years. The main exposure was mode of conception, namely (i) unassisted conception (reference group), (ii) infertility without fertility treatment (history of an infertility consultation with a physician within 2 years prior to conception but no fertility treatment), (iii) ovulation induction (OI) or intrauterine insemination (IUI) and (iv) IVF or intracytoplasmic sperm injection (ICSI). The main outcome was a diagnosis of ADHD after age 4 years and assessed up to June 2020. Hazard ratios (HRs) were adjusted for maternal age, income quintile, rurality, immigration status, smoking, obesity, parity, any drug or alcohol use, maternal history of mental illness including ADHD, pre-pregnancy diabetes mellitus or chronic hypertension and infant sex. In addition, we performed pre-planned stratified analyses by mode of delivery (vaginal or caesarean delivery), infant sex, multiplicity (singleton or multiple), timing of birth (term or preterm <37 weeks) and neonatal adverse morbidity (absent or present). MAIN RESULTS AND THE ROLE OF CHANCE: The study included 925 488 children born to 663 144 mothers, of whom 805 748 (87%) were from an unassisted conception, 94 206 (10.2%) followed infertility but no fertility treatment, 11 777 (1.3%) followed OI/IUI and 13 757 (1.5%) followed IVF/ICSI. Starting at age 4 years, children were followed for a median (interquartile range) of 6 (4-8) years. ADHD occurred among 7.0% of offspring in the unassisted conception group, 7.5% in the infertility without fertility treatment group, 6.8% in the OI/IUI group and 6.3% in the IVF/ICSI group. The incidence rate (per 1000 person-years) of ADHD was 12.0 among children in the unassisted conception group, 12.8 in the infertility without fertility treatment group, 12.9 in the OI/IUI group and 12.2 in the IVF/ICSI group. Relative to the unassisted conception group, the adjusted HR for ADHD was 1.19 (95% CI 1.16-1.22) in the infertility without fertility treatment group, 1.09 (95% CI 1.01-1.17) in the OI/IUI group and 1.12 (95% CI 1.04-1.20) in the IVF/ICSI group. In the stratified analyses, these patterns of risk for ADHD were largely preserved. An exception was seen in the sex-stratified analyses, wherein females had lower absolute rates of ADHD but relatively higher HRs compared with that seen among males. LIMITATIONS, REASONS FOR CAUTION: Some mothers in the isolated infertility group may have received undocumented OI oral therapy, thereby leading to possible misclassification of their exposure status. Parenting behaviour, schooling and paternal mental health measures were not known, leading to potential residual confounding. WIDER IMPLICATIONS OF THE FINDINGS: Infertility, even without treatment, is a modest risk factor for the development of ADHD in childhood. The reason underlying this finding warrants further study. STUDY FUNDING/COMPETING INTEREST(S): This study was made possible with funding from the Canadian Institutes of Health Research, Grant number PJT 165840. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Time-related biases in perinatal pharmacoepidemiology: A systematic review of observational studies.

BACKGROUND: Time-related biases, such as immortal time and time-window bias, frequently occur in pharmacoepidemiologic research. However, the prevalence of these biases in perinatal pharmacoepidemiology is not well understood. OBJECTIVE: To describe the frequency of time-related biases in observational studies of medications commonly used during pregnancy (antibiotic, antifungal, and antiemetic drugs) via systematic review. METHOD: We searched Medline and EMBASE for observational studies published between January 2013 and September 2020 and examining the association between antibiotic, antifungal, or antiemetic drugs and adverse pregnancy outcomes, including spontaneous abortion, stillbirth, preterm delivery, small-for-gestational age, pre-eclampsia, and gestational diabetes. The proportion of studies with time-related biases was estimated overall and by type (immortal time bias, time-window bias). RESULTS: Our systematic review included 20 studies (16 cohort studies, 3 nested case-control studies, and 1 case-control study), of which 12 examined antibiotic, 6 antiemetic, and 2 anti-fungal drugs. Eleven studies (55%) had immortal time bias due to the misclassification of unexposed, event-free person-time between cohort entry and exposure initiation as exposed. No included study had time-window bias. The direction of effect varied for both studies with and without time-related bias, with many studies reporting very wide confidence intervals around the effect estimates, thus making the direction of effect less interpretable. However, studies with time-related bias were more likely to show protective or null associations compared with studies without time-related bias. CONCLUSION: Time-related biases occur frequently in observational studies of drug effects during pregnancy. The use of appropriate study design and analytical approaches is needed to prevent time-related biases and ensure study validity.