Risk of Adverse Neonatal Events in Pregnancies Complicated by Severe Maternal Morbidity.

OBJECTIVE: To investigate the risk of adverse neonatal events after a pregnancy complicated by severe maternal morbidity. STUDY DESIGN: We analyzed a population-based cohort of deliveries in Quebec, Canada, between 2006 and 2021. The main exposure measure was severe maternal morbidity, comprising life-threatening conditions such as severe hemorrhage, cardiac complications, and eclampsia. The outcome included adverse neonatal events such as very preterm birth (gestational age <32 weeks), bronchopulmonary dysplasia, hypoxic ischemic encephalopathy, and neonatal death. Using log-binomial regression models, we estimated adjusted relative risks (RRs) and 95% confidence intervals (CIs) for the association between severe maternal morbidity and adverse neonatal events. RESULTS: Among 1 199 112 deliveries, 29 992 (2.5%) were complicated by severe maternal morbidity and 83 367 (7.0%) had adverse neonatal events. Severe maternal morbidity was associated with 2.96 times the risk of adverse neonatal events compared with no morbidity (95% CI 2.90-3.03). Associations were greatest for mothers who required assisted ventilation (RR 5.86, 95% CI 5.34-6.44), experienced uterine rupture (RR 4.54, 95% CI 3.73-5.51), or had cardiac complications (RR 4.39, 95% CI 3.98-4.84). Severe maternal morbidity was associated with ≥3 times the risk of neonatal death and hypoxic-ischemic encephalopathy and ≥10 times the risk of very preterm birth and bronchopulmonary dysplasia. CONCLUSIONS: Severe maternal morbidity is associated with an elevated risk of adverse neonatal events. Better prevention of severe maternal morbidity may help reduce burden of severe neonatal 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.

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.

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.

Impact of COVID-19 Pandemic on Dispensing of Cardiovascular Drugs in Norway: An Interrupted Time Series Study.

INTRODUCTION: The COVID-19 pandemic resulted in changes in prescription patterns and fillings for certain medications, but little is known about its impact on the dispensing of cardiovascular drugs. METHODS: Trends in dispensing of cardiovascular drugs before and during the pandemic were examined using a population-based cohort in Norway. Using interrupted time series analyses and considering March 1, 2020 as the interruption point, the impact of the pandemic on defined daily dose dispensing of prescribed cardiovascular drugs was estimated in a population of adults with and without pre-existing cardiovascular disease from January 2018 to December 2021. All data were analyzed in 2023. RESULTS: In a total of 4,053,957 adults, 690,910 (17.0%) had pre-existing cardiovascular disease. Prior to the pandemic, there was a significant monthly increase in any cardiovascular drug dispensing among those with pre-existing cardiovascular disease (0.30 defined daily dose per month per adult), including prescription of diuretics, calcium channel blockers, and lipid-modifying agents. After controlling for preinterruption trends, there was a slight decrease in level change immediately after the start of the pandemic (2.5 defined daily dose per month per adult) but an increase in the postinterruption trend (0.06 defined daily dose per month per adult) for dispensing of cardiovascular prescriptions, although these changes were not significant. CONCLUSIONS: Although the COVID-19 pandemic did not appear to result in significant changes in patterns of cardiovascular drug dispensing in Norway, continued access to cardiovascular drugs remains important to prevent further related morbidity.

Severe maternal morbidity and risk of cardiovascular disease: Recent advances.

Pregnancy complications including severe maternal morbidity have been linked with an increased risk of cardiovascular disease, and provide opportunities to identify women who would benefit from prevention. Severe maternal morbidity comprises life-endangering complications around the time of pregnancy and delivery. Literature on the relationship between severe maternal morbidity and cardiovascular disease is increasing at a rapid pace. Studies have shown that severe preeclampsia or eclampsia and severe hemorrhage are associated with cardiovascular disease later in life. Proposed pathways include endothelial damage, hypercoagulability, and impaired cardiac function that are induced or exacerbated by severe pregnancy complications that elevate cardiovascular risks. However, less is known about other types of severe maternal morbidity that may influence the risk of cardiovascular disease. Other research gaps include a need to better understand the pathways and mechanisms linking severe maternal morbidity with cardiovascular disease, the potential for cardiovascular recovery after severe cardiovascular events during pregnancy, and disparities in the occurrence of cardiovascular disease after severe maternal morbidity.

Assessment and validation of the Community Maternal Danger Score algorithm.

BACKGROUND: High rates of maternal mortality in low-and-middle-income countries (LMICs) are associated with the lack of skilled birth attendants (SBAs) at delivery. Risk analysis tools may be useful to identify pregnant women who are at risk of mortality in LMICs. We sought to develop and validate a low-cost maternal risk tool, the Community Maternal Danger Score (CMDS), which is designed to identify pregnant women who need an SBA at delivery. METHODS: To design the CMDS algorithm, an initial scoping review was conducted to identify predictors of the need for an SBA. Medical records of women who delivered at the Federal Medical Centre in Makurdi, Nigeria (2019-2020) were examined for predictors identified from the literature review. Outcomes associated with the need for an SBA were recorded: caesarean section, postpartum hemorrhage, eclampsia, and sepsis. A maternal mortality ratio (MMR) was determined. Multivariate logistic regression analysis and area under the curve (AUC) were used to assess the predictive ability of the CMDS algorithm. RESULTS: Seven factors from the literature predicted the need for an SBA: age (under 20 years of age or 35 and older), parity (nulliparity or grand-multiparity), BMI (underweight or overweight), fundal height (less than 35 cm or 40 cm and over), adverse obstetrical history, signs of pre-eclampsia, and co-existing medical conditions. These factors were recorded in 589 women of whom 67% required an SBA (n = 396) and 1% died (n = 7). The MMR was 1189 per 100,000 (95% CI 478-2449). Signs of pre-eclampsia, obstetrical history, and co-existing conditions were associated with the need for an SBA. Age was found to interact with parity, suggesting that the CMDS requires adjustment to indicate higher risk among younger multigravida and older primigravida women. The CMDS algorithm had an AUC of 0.73 (95% CI 0.69-0.77) for predicting whether women required an SBA, and an AUC of 0.85 (95% CI 0.67-1.00) for in-hospital mortality. CONCLUSIONS: The CMDS is a low-cost evidence-based tool that uses 7 risk factors assessed on 589 women from Makurdi. Non-specialist health workers can use the CMDS to standardize assessment and encourage pregnant women to seek an SBA in preparation for delivery, thus improving care in countries with high rates of maternal mortality.

Development and internal validation of a model to predict type 2 diabetic complications after gestational diabetes.

Gestational diabetes mellitus (GDM) increases the risk of early-onset type 2 diabetes, which further exacerbates the risk of developing diabetic complications such as kidney, circulatory, and neurological complications. Yet, existing models have solely focused on the prediction of type 2 diabetes, and not of its complications, which are arguably the most clinically relevant outcomes. Our aim was to develop a prediction model for type 2 diabetic complications in patients with GDM. Using provincial administrative data from Quebec, Canada, we developed a model to predict type 2 diabetic complications within 10 years among 90,143 women with GDM. The model was internally validated and assessed for discrimination, calibration, and risk stratification accuracy. The incidence of diabetic complications was 3.8 (95% confidence interval (CI) 3.4-4.3) per 10,000 person-years. The final prediction model included maternal age, socioeconomic deprivation, substance use disorder, gestational age at delivery, severe maternal morbidity, previous pregnancy complications, and hypertensive disorders of pregnancy. The model had good discrimination [area under the curve (AUROC) 0.72 (95% CI 0.69-0.74)] and calibration (slope ≥ 0.9) to predict diabetic complications. In the highest category of the risk stratification table, the positive likelihood ratio was 8.68 (95% CI 4.14-18.23), thereby showing a moderate ability to identify women at highest risk of developing type 2 diabetic complications. Our model predicts the risk of type 2 diabetic complications with moderate accuracy and, once externally validated, may prove to be a useful tool in the management of women after GDM.

Black-White Inequality in Outcomes of In Vitro Fertilization: a Systematic Review and Meta-analysis.

This study aims to systematically review disparities in outcomes of in vitro fertilization between Black and White patients. We searched CINAHL, Cochrane Library, EMBASE, Global Health, PsycINFO, PubMed, and Web of Science for observational studies published before August 2021. Outcomes included implantation, clinical pregnancy, spontaneous abortion, and live birth following in vitro fertilization in Black versus White patients. We used random-effects models for meta-analysis and the Mantel-Haenszel method to calculate unadjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between race and in vitro fertilization outcomes, comparing Black relative to White patients. We used the generic inverse variance method to calculate adjusted ORs. Nine observational studies met eligibility criteria, including 696 Black and 7,458 White patients. All were retrospective studies of US cohorts. In unadjusted meta-analyses, Black patients had a greater likelihood of spontaneous abortion (OR 2.08, 95% CI 1.59-2.71) and lower likelihood of live birth (OR 0.67, 95% CI 0.47-0.95) compared with White patients but no difference in implantation (OR 0.95, 95% CI 0.32-2.77) or clinical pregnancy (OR 0.78, 95% CI 0.54-1.12). In adjusted meta-analyses, Black patients had lower odds of live birth (OR 0.57, 95% CI 0.43-0.75) and no difference in clinical pregnancy (OR 0.87, 95% CI 0.51-1.48). This meta-analysis suggests that in vitro fertilization services achieve similar pregnancy rates in Black and White patients. However, Black patients have more spontaneous abortions and fewer live births, suggesting there may be disparities in the quality of achieved pregnancies or other factors associated with pregnancy loss. Systematic review registration: PROSPERO (ID CRD42021256250).

Racial and Ethnic Disparities in the Perinatal Health of Infants Conceived by ART.

BACKGROUND AND OBJECTIVES: Although racial and ethnic disparities in adverse birth outcomes have been well documented, it is unknown whether such disparities diminish in women who use medically assisted reproduction (MAR). We examined differences in the association between maternal race and ethnicity and adverse birth outcomes among women who conceived spontaneously and those who used MAR, including assisted reproduction technology (ART), eg, in-vitro fertilization, and also non-ART MAR, eg, fertility drugs. METHODS: We conducted a population-based retrospective cohort study using data on all singleton births (N = 7 545 805) in the United States from 2016 to 2017. The outcomes included neonatal and fetal death, preterm birth, and serious neonatal morbidity, among others. Modified Poisson regression was used to estimate adjusted rate ratios (aRR) and 95% confidence intervals (CI) and to assess the interactions between race and ethnicity and mode of conception. RESULTS: Overall, 93 469 (1.3%) singletons were conceived by MAR. Neonatal mortality was twofold higher among infants of non-Hispanic Black versus non-Hispanic White women in the spontaneous-conception group (aRR = 1.9, 95% CI: 1.8-1.9), whereas in the ART-conception group, neonatal mortality was more than fourfold higher in infants of non-Hispanic Black women (aRR = 4.1, 95% CI: 2.9-5.9). Racial and ethnic disparities between Hispanic versus non-Hispanic White women were also significantly larger among women who conceived using MAR with regard to preterm birth (<34 weeks) and perinatal mortality. CONCLUSIONS: Compared to women who conceived spontaneously, racial and ethnic disparities in adverse perinatal outcomes were larger in women who used MAR. More research is needed to identify preventive measures for reducing risks among vulnerable women who use medically assisted reproduction.

COVID-19 vaccine hesitancy in Africa: a scoping review.

BACKGROUND: Vaccination against the novel coronavirus is one of the most effective strategies for combating the global Coronavirus disease (COVID-19) pandemic. However, vaccine hesitancy has emerged as a major obstacle in several regions of the world, including Africa. The objective of this rapid review was to summarize the literature on COVID-19 vaccine hesitancy in Africa. METHODS: We searched Scopus, Web of Science, African Index Medicus, and OVID Medline for studies published from January 1, 2020, to March 8, 2022, examining acceptance or hesitancy towards the COVID-19 vaccine in Africa. Study characteristics and reasons for COVID-19 vaccine acceptance were extracted from the included articles. RESULTS: A total of 71 articles met the eligibility criteria and were included in the review. Majority (n = 25, 35%) of the studies were conducted in Ethiopia. Studies conducted in Botswana, Cameroun, Cote D'Ivoire, DR Congo, Ghana, Kenya, Morocco, Mozambique, Nigeria, Somalia, South Africa, Sudan, Togo, Uganda, Zambia, Zimbabwe were also included in the review. The vaccine acceptance rate ranged from 6.9 to 97.9%. The major reasons for vaccine hesitancy were concerns with vaccine safety and side effects, lack of trust for pharmaceutical industries and misinformation or conflicting information from the media. Factors associated with positive attitudes towards the vaccine included being male, having a higher level of education, and fear of contracting the virus. CONCLUSIONS: Our review demonstrated the contextualized and multifaceted reasons inhibiting or encouraging vaccine uptake in African countries. This evidence is key to operationalizing interventions based on facts as opposed to assumptions. Our paper provided important considerations for addressing the challenge of COVID-19 vaccine hesitancy and blunting the impact of the pandemic in Africa.

Place-specific factors associated with adverse maternal and perinatal outcomes in Southern Mozambique: a retrospective cohort study.

OBJECTIVES: To identify and measure the place-specific determinants that are associated with adverse maternal and perinatal outcomes in the southern region of Mozambique. DESIGN: Retrospective cohort study. Choice of variables informed by literature and Delphi consensus. SETTING: Study conducted during the baseline phase of a community level intervention for pre-eclampsia that was led by community health workers. PARTICIPANTS: A household census identified 50 493 households that were home to 80 483 women of reproductive age (age 12-49 years). Of these women, 14 617 had been pregnant in the 12 months prior to the census, of which 9172 (61.6%) had completed their pregnancies. PRIMARY AND SECONDARY OUTCOME MEASURES: A combined fetal, maternal and neonatal outcome was calculated for all women with completed pregnancies. RESULTS: A total of six variables were statistically significant (p≤0.05) in explaining the combined outcome. These included: geographic isolation, flood proneness, access to an improved latrine, average age of reproductive age woman, family support and fertility rates. The performance of the ordinary least squares model was an adjusted R2=0.69. Three of the variables (isolation, latrine score and family support) showed significant geographic variability in their effect on rates of adverse outcome. Accounting for this modest non-stationary effect through geographically weighted regression increased the adjusted R2 to 0.71. CONCLUSIONS: The community exploration was successful in identifying context-specific determinants of maternal health. The results highlight the need for designing targeted interventions that address the place-specific social determinants of maternal health in the study area. The geographic process of identifying and measuring these determinants, therefore, has implications for multisectoral collaboration. TRIAL REGISTRATION NUMBER: NCT01911494.

The Impact of a History of Adverse Childhood Experiences on Breastfeeding Initiation and Exclusivity: Findings from a National Population Health Survey.

BACKGROUND: Exclusive breastfeeding is strongly recommended by the World Health Organization. Given the low rate of exclusive breastfeeding in Canada and the increasing reports of a history of adverse childhood experiences, this study sought to investigate the association between a history of adverse childhood experiences and breastfeeding initiation and breastfeeding. MATERIALS AND METHODS: Data used for this study were based on the 2011-2012 Canadian Community Health Survey, collected using a cross-sectional survey. The outcome measures were breastfeeding initiation and exclusive breastfeeding for 6 months or more. History of adverse childhood experiences was the main explanatory variable. Multivariable logistic regression models were developed to investigate the effect on breastfeeding initiation and on exclusive breastfeeding in women who gave birth within 5 years before when the surveys were conducted. RESULTS: The study sample included 697 and 633 women for analyses on breastfeeding initiation and breastfeeding, respectively. The proportion of women with breastfeeding initiation and exclusive breastfeeding for up to 6 months in this study were 96.8% and 42.8%, respectively. After controlling for age and highest level of education, having a history of adverse childhood experiences was not significantly associated with breastfeeding initiation (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.10-1.87), but mothers with such history were less likely to exclusively breastfeed for up to 6 months compared with those without (OR 0.53, 95% CI 0.31-0.90). CONCLUSIONS: These findings suggest the need for more breastfeeding monitoring programs beyond the hospital environment to provide more support to Canadian mothers, especially those who have experienced adverse childhood experiences or trauma in the past.