Prescription Medication Use in Pregnancy in People with Disabilities: A Population-Based Cohort Study.

Background: Individuals with disabilities may require specific medications in pregnancy. The prevalence and patterns of medication use, overall and for medications with known teratogenic risks, are largely unknown. Methods: This population-based cohort study in Ontario, Canada, 2004-2021, comprised all recognized pregnancies among individuals eligible for public drug plan coverage. Included were those with a physical (n = 44,136), sensory (n = 13,633), intellectual or developmental (n = 2,446) disability, or multiple disabilities (n = 5,064), compared with those without a disability (n = 299,944). Prescription medication use in pregnancy, overall and by type, was described. Modified Poisson regression generated relative risks (aRR) for the use of medications with known teratogenic risks and use of ≥2 and ≥5 medications concurrently in pregnancy, comparing those with versus without a disability, adjusting for sociodemographic and clinical factors. Results: Medication use in pregnancy was more common in people with intellectual or developmental (82.1%), multiple (80.4%), physical (73.9%), and sensory (71.9%) disabilities, than in those with no known disability (67.4%). Compared with those without a disability (5.7%), teratogenic medication use in pregnancy was especially higher in people with multiple disabilities (14.2%; aRR 2.03, 95% confidence interval [CI]: 1.88-2.20). Furthermore, compared with people without a disability (3.2%), the use of ≥5 medications concurrently was more common in those with multiple disabilities (13.4%; aRR 2.21, 95% CI: 2.02-2.41) and an intellectual or developmental disability (9.3%; aRR 2.13, 95% CI: 1.86-2.45). Interpretation: Among people with disabilities, medication use in pregnancy is prevalent, especially for potentially teratogenic medications and polypharmacy, highlighting the need for preconception counseling/monitoring to reduce medication-related harm in pregnancy.

The association between reproductive history and abdominal adipose tissue among postmenopausal women: results from the Women's Health Initiative.

STUDY QUESTION: What is the association between reproductive health history (e.g. age at menarche, menopause, reproductive lifespan) with abdominal adiposity in postmenopausal women? SUMMARY ANSWER: Higher visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) tissue levels were observed among women with earlier menarche, earlier menopause, and greater parity. WHAT IS KNOWN ALREADY: Postmenopausal women are predisposed to accumulation of VAT and SAT. Reproductive health variables are known predictors of overall obesity status in women, defined by BMI. STUDY DESIGN, SIZE, DURATION: This study is a secondary analysis of data collected from the baseline visit of the Women's Health Initiative (WHI). The WHI is a large prospective study of postmenopausal women, including both a randomized trial and observational study. There were 10 184 women included in this analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected from a reproductive health history questionnaire, dual-energy x-ray absorptiometry scans, and anthropometric measures at WHI baseline. Reproductive history was measured via self-report, and included age at menarche, variables related to pregnancy, and age at menopause. Reproductive lifespan was calculated as age at menopause minus age at menarche. Statistical analyses included descriptive analyses and multivariable linear regression models to examine the association between reproductive history with VAT, SAT, total body fat, and BMI. MAIN RESULTS AND THE ROLE OF CHANCE: Women who reported early menarche (<10 years) or early menopause (<40 years) had the highest levels of VAT. Adjusted multivariable linear regression results demonstrate women who experienced menarche >15 years had 23 cm2 less VAT (95% CI: -31.4, -14.4) and 47 cm2 less SAT (95% CI: -61.8, -33.4) than women who experienced menarche at age 10 years or earlier. A similar pattern was observed for age at menopause: compared to women who experienced menopause <40 years, menopause at 50-55 years was associated with 19.3 cm2 (95% CI: -25.4, -13.3) less VAT and 27.4 cm2 (-29.6, 10.3) less SAT. High parity (>3 pregnancies) was also associated with VAT and SAT. For example, adjusted beta coefficients for VAT were 8.36 (4.33, 12.4) and 17.9 (12.6, 23.2) comparing three to four pregnancies with the referent, one to two pregnancies. LIMITATIONS, REASONS FOR CAUTION: The WHI reproductive health history questionnaire may be subject to poor recall owing to a long look-back window. Residual confounding may be present given lack of data on early life characteristics, such as maternal and pre-menarche characteristics. WIDER IMPLICATIONS OF THE FINDINGS: This study contributes to our understanding of reproductive lifespan, including menarche and menopause, as an important predictor of late-life adiposity in women. Reproductive health has also been recognized as a sentinel marker for chronic disease in late life. Given established links between adiposity and cardiometabolic outcomes, this research has implications for future research, clinical practice, and public health policy that makes use of reproductive health history as an opportunity for chronic disease prevention. STUDY FUNDING/COMPETING INTEREST(S): HRB and AOO are supported by the National Institute of Health National Institute of Aging (R01AG055018-04). JWB reports royalties from 'ACSM'S Body Composition Assessment Book' and consulting fees from the WHI. The remaining authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Use of Latent Class Analysis to Predict Intensive Care Unit Admission and Mortality in Children with a Major Congenital Anomaly.

OBJECTIVE: To define major congenital anomaly (CA) subgroups and assess outcome variability based on defined subgroups. STUDY DESIGN: This population-based cohort study used registries in Denmark for children born with a major CA between January 1997 and December 2016, with follow-up until December 2018. We performed a latent class analysis (LCA) using child and family clinical and sociodemographic characteristics present at birth, incorporating additional variables occurring until age of 24 months. Cox proportional hazards regression models estimated hazard ratios (HRs) of pediatric mortality and intensive care unit (ICU) admissions for identified LCA classes. RESULTS: The study included 27 192 children born with a major CA. Twelve variables led to a 4-class solution (entropy = 0.74): (1) children born with higher income and fewer comorbidities (55.4%), (2) children born to young mothers with lower income (24.8%), (3) children born prematurely (10.0%), and (4) children with multiorgan involvement and developmental disability (9.8%). Compared with those in Class 1, mortality and ICU admissions were highest in Class 4 (HR = 8.9, 95% CI = 6.4-12.6 and HR = 4.1, 95% CI = 3.6-4.7, respectively). More modest increases were observed among the other classes for mortality and ICU admissions (Class 2: HR = 1.7, 95% CI = 1.1-2.5 and HR = 1.3, 95% CI = 1.1-1.4, respectively; Class 3: HR = 2.5, 95% CI = 1.5-4.2 and HR = 1.5, 95% CI = 1.3-1.9, respectively). CONCLUSIONS: Children with a major CA can be categorized into meaningful subgroups with good discriminative ability. These groupings may be useful for risk-stratification in outcome studies.

Teen Pregnancy and Risk of Premature Mortality.

Importance: Unintentional injury, suicide, and homicide are leading causes of death among young females. Teen pregnancy may be a marker of adverse life experiences. Objective: To evaluate the risk of premature mortality from 12 years of age onward in association with number of teen pregnancies and age at pregnancy. Design, Setting, and Participants: This population-based cohort study was conducted among all females alive at 12 years of age from April 1, 1991, to March 31, 2021, in Ontario, Canada (the most populous province, which has universal health care and data collection). The study period ended March 31, 2022. Exposures: The main exposure was number of teen pregnancies between 12 and 19 years of age (0, 1, or ≥2). Secondary exposures included how the teen pregnancy ended (birth or miscarriage vs induced abortion) and age at first teen pregnancy. Main Outcomes and Measures: The main outcome was all-cause mortality starting at 12 years of age. Hazard ratios (HRs) were adjusted for year of birth, comorbidities at 9 to 11 years of age, and area-level education, income level, and rurality. Results: Of 2 242 929 teenagers, 163 124 (7.3%) experienced a pregnancy at a median age of 18 years (IQR, 17-19 years). Of those with a teen pregnancy, 60 037 (36.8%) ended in a birth (of which 59 485 [99.1%] were live births), and 106 135 (65.1%) ended in induced abortion. The median age at the end of follow-up was 25 years (IQR, 18-32 years) for those without a teen pregnancy and 31 years (IQR, 25-36 years) for those with a teen pregnancy. There were 6030 deaths (1.9 per 10 000 person-years [95% CI, 1.9-2.0 per 10 000 person-years]) among those without a teen pregnancy, 701 deaths (4.1 per 10 000 person-years [95% CI, 3.8-4.5 per 10 000 person-years]) among those with 1 teen pregnancy, and 345 deaths (6.1 per 10 000 person-years [95% CI, 5.5-6.8 per 10 000 person-years]) among those with 2 or more teen pregnancies; adjusted HRs (AHRs) were 1.51 (95% CI, 1.39-1.63) for those with 1 pregnancy and 2.14 (95% CI, 1.92-2.39) for those with 2 or more pregnancies. Comparing those with vs without a teen pregnancy, the AHR for premature death was 1.25 (95% CI, 1.12-1.40) from noninjury, 2.06 (95% CI, 1.75-2.43) from unintentional injury, and 2.02 (95% CI, 1.54-2.65) from intentional injury. Conclusions and Relevance: In this population-based cohort study of 2.2 million female teenagers, teen pregnancy was associated with future premature mortality. It should be assessed whether supports for female teenagers who experience a pregnancy can enhance the prevention of subsequent premature mortality in young and middle adulthood.

Mental health of caregivers of children with medical complexity: group-based trajectory modelling.

OBJECTIVE: To describe the mental health trajectories of caregivers of children with medical complexity (CMC) and explore child characteristics associated with below-average caregiver mental health. DESIGN: A secondary analysis of prospectively collected data from 123 caregivers of children aged <16 years with medical complexity from a multicentre randomised trial conducted from December 2016 to June 2021. MAIN OUTCOME MEASURE: The Patient-Reported Outcomes Measurement Information System Global Mental Health Scale was used to measure caregivers' self-reported mental health well-being. Group-based trajectory analysis was used to identify clusters of caregivers with similar changes in mental health across 24 months. Logistic regression was used to identify child-related predictors of mental health among caregivers. RESULTS: A final model with three distinct groups was selected, corresponding to caregivers with average (n=39), moderately below-average (n=65) and severely below-average (n=19) mental health scores, all with stable trajectories and high posterior probabilities (>90%). Moderately and severely below-average caregiver mental health groups, merged into one group, were associated with a greater number of child medical technology devices (adjusted OR (aOR) 1.44, 95% CI 1.01 to 2.04), gross motor difficulties (aOR 3.51, 95% CI 1.02 to 12.05) and worse child emotional (aOR 0.93, 95% CI 0.87 to 0.99) and psychological well-being (aOR 0.93, 95% CI 0.88 to 0.99). CONCLUSION: Most caregivers of CMC reported persistently below-average mental health. The intensity of caregiving, as indicated by medical technology and child functional needs, is a potential risk factor for below-average caregiver mental health. Future design and evaluation of interventions focused on support for caregivers of CMC are warranted.

Differences in maternal-newborn ABO blood groups and risk of serious infant infection.

BACKGROUND: During pregnancy, various maternal IgG antibodies are transferred to the developing fetus, some of which may protect the newborn against infection. If a mother and her fetus have different ABO blood groups, then transferred maternal antibodies may plausibly protect the infant against infection. AIM: To determine if maternal-newborn ABO blood group incongruence vs. congruence is associated with a lower risk of serious infection in the infant. DESIGN: Retrospective population-based cohort. METHODS: We used linked patient-level datasets for all singleton hospital livebirths from 2008-2022 in Ontario, Canada, with known maternal and newborn ABO blood groups. We used a dichotomous exposure state, either ABO blood group congruent (N = 114,507) or incongruent (N = 43,074). The main outcome of interest was the risk of serious infant infection within 27 days, and from 28-365 days, after birth. Cox proportional hazard models generated hazard ratios and 95% confidence intervals, and were adjusted for maternal age, world region of origin, residential income quintile, and gestational age at birth. RESULTS: Relative to maternal-newborn congruency, incongruent ABO blood group was associated with aHR of 0.88 (95% CI 0.80 to 0.97) for serious neonatal infection within 27 days of birth, and 0.93 (95% CI 0.90 to 0.96) for serious infection between 28-365 days after birth. CONCLUSIONS: Maternal-newborn ABO incongruence may be associated with a lower relative risk of a serious infant infection within 27 days, and from 28 to 365 days, after birth.

History of multifetal gestation and long-term maternal mortality.

BACKGROUND: Multifetal gestation could be associated with higher long-term maternal mortality because it increases the risk of pregnancy complications such as preeclampsia and preterm birth, which are in turn linked to postpartum cardiovascular risk. OBJECTIVES: We examined whether spontaneously conceived multifetal versus singleton gestation was associated with long-term maternal mortality in a racially diverse U.S. METHODS: We ascertained vital status as of 2016 via linkage to the National Death Index and Social Security Death Master File of 44,174 mothers from the Collaborative Perinatal Project (CPP; 1959-1966). Cox proportional hazards models with maternal age as the time scale assessed associations between history of spontaneous multifetal gestation (in the last CPP observed pregnancy or prior pregnancy) and all-cause and cardiovascular mortality, adjusted for demographics, smoking status, and preexisting medical conditions. We calculated hazard ratios (HR) for all-cause and cause-specific mortality over the study period and until age 50, 60, and 70 years (premature mortality). RESULTS: Of eligible participants, 1672 (3.8%) had a history of multifetal gestation. Participants with versus without a history of multifetal gestation were older, more likely to have a preexisting condition, and more likely to smoke. By 2016, 51% of participants with and 38% of participants without a history of multifetal gestation had died (unadjusted all-cause HR 1.14, 95% confidence interval [CI] 1.07, 1.23). After adjustment for smoking and preexisting conditions, a history of multifetal gestation was not associated with all-cause (adjusted HR 1.00, 95% CI 0.93, 1.08) or cardiovascular mortality (adjusted HR 0.99, 95% CI 0.87, 1.11) over the study period. However, history of multifetal gestation was associated with an 11% lower risk of premature all-cause mortality (adjusted HR 0.89, 95% CI 0.82, 0.96). CONCLUSIONS: In a cohort with over 50 years of follow-up, history of multifetal gestation was not associated with all-cause mortality, but may be associated with a lower risk of premature mortality.

Patterns of multiple chronic conditions in pregnancy: Population-based study using latent class analysis.

BACKGROUND: Adults with multiple chronic conditions (MCC) are a heterogeneous population with elevated risk of future adverse health outcomes. Yet, despite the increasing prevalence of MCC globally, data about MCC in pregnancy are scarce. OBJECTIVES: To estimate the population prevalence of MCC in pregnancy and determine whether certain types of chronic conditions cluster together among pregnant women with MCC. METHODS: We conducted a population-based cohort study in Ontario, Canada, of all 15-55-year-old women with a recognised pregnancy, from 2007 to 2020. MCC was assessed from a list of 22 conditions, identified using validated algorithms. We estimated the prevalence of MCC. Next, we used latent class analysis to identify classes of co-occurring chronic conditions in women with MCC, with model selection based on parsimony, clinical interpretability and statistical fit. RESULTS: Among 2,014,508 pregnancies, 324,735 had MCC (161.2 per 1000, 95% confidence interval [CI] 160.6, 161.8). Latent class analysis resulted in a five-class solution. In four classes, mood and anxiety disorders were prominent and clustered with one additional condition, as follows: Class 1 (22.4% of women with MCC), osteoarthritis; Class 2 (23.7%), obesity; Class 3 (15.8%), substance use disorders; and Class 4 (22.1%), asthma. In Class 5 (16.1%), four physical conditions clustered together: obesity, asthma, chronic hypertension and diabetes mellitus. CONCLUSIONS: MCC is common in pregnancy, with sub-types dominated by co-occurring mental and physical health conditions. These data show the importance of preconception and perinatal interventions, particularly integrated care strategies, to optimise treatment and stabilisation of chronic conditions in women with MCC.

Adverse perinatal events and maternal interpregnancy weight change: A population-based observational study.

OBJECTIVE: Mothers whose newborn experiences adversity may neglect their own health to care for their affected infant or following a perinatal death. Weight gain after pregnancy is one measure of maternal self-care. We measured interpregnancy weight gain among women whose child had an adverse perinatal event. METHODS: This population-based observational study included 192 154 primigravid women with two consecutive singleton births in Ontario, Canada. Outcomes included net weight gain, and adjusted odds ratios (aOR) of moving to a higher body mass index (BMI) category between pregnancies, comparing women whose child did versus did not experience either a perinatal death, prematurity, severe neonatal morbidity, major congenital anomaly, or severe neurologic impairment. RESULTS: Perinatal death was associated with a +3.5 kg (95% confidence interval [CI]: 2.1-4.9) net higher maternal weight gain in the subsequent pregnancy. Relative to term births, preterm birth <32 weeks (+3.2 kg, 95% CI: 1.9-4.6), 32-33 weeks (+1.8 kg, 95% CI: 0.7-2.8) and 34-36 weeks (+0.9 kg, 95% CI: 0.6-1.3) were associated with higher net weight gain. Having an infant with severe neonatal morbidity was associated with a +1.2 kg (95% CI: 0.3-2.1) weight gain. Likewise, the aOR of moving to a higher BMI category was 1.27 (95% CI, 1.14-1.42) following a perinatal death, 1.21 (95% CI: 1.04-1.41) after a preterm birth <32 weeks, and 1.11 (95% CI: 1.02-1.22) with severe neonatal morbidity. CONCLUSION: Greater interpregnancy weight gain, and movement to a higher BMI category, are each more likely in a woman whose first-born was affected by certain major adverse perinatal events.

ABO and Rh blood groups and risk of infection: systematic review and meta-analysis.

BACKGROUND: Persons with non-O and Rh-positive blood types are purported to be more susceptible to infection, including SARS-CoV-2, but there remains uncertainty about the degree to which this is so for both non-viral and viral infections. METHODS: We systematically reviewed Embase and PubMed from January 1st 1960 to May 31st 2022. English-language publications were selected that separately investigated the relation between ABO and/or Rh blood group and risk of SARS-CoV-2 and non-SARS-CoV-2 infection. Pooled odds ratios (ORp) and 95% confidence intervals (CI) were then generated for each. RESULTS: Non-O blood groups had a higher ORp for SARS-CoV-2 than O blood groups, both within 22 case-control studies (2.13, 95% CI 1.49- 3.04) and 15 cohort studies (1.89, 95% CI 1.56- 2.29). For non-SARS-CoV-2 viral infections, the respective ORp were 1.98 (95% CI 1.49-2.65; 4 case-control studies) and 1.87 (95% CI 1.53-2.29; 12 cohort studies). For non-viral infections, the ORp were 1.56 (95% CI 0.98-2.46; 13 case-control studies) and 2.11 (95% CI 1.67-6.67; 4 cohort studies). Rh-positive status had a higher ORp for SARS-CoV-2 infection within 6 case-control studies (13.83, 95% CI 6.18-30.96) and 6 cohort studies (19.04, 95% CI 11.63-31.17), compared to Rh-negative persons. For Rh status, non-SARS-CoV-2 infections, the ORp were 23.45 (95% CI 16.28-33.76) among 7 case-control studies, and 9.25 (95% CI 2.72-31.48) within 4 cohort studies. High measures of heterogeneity were notably observed for all analyses. CONCLUSIONS: Non-O and Rh-positive blood status are each associated with a higher risk of SARS-CoV-2 infection, in addition to other viral and non-viral infections.

Levothyroxine initiation and the risk of pregnancy loss among pregnant women with subclinical hypothyroidism: An observational study emulating a target trial.

BACKGROUND: While the benefits of levothyroxine are well-established for overt hypothyroidism, they are unclear for subclinical hypothyroidism (SCH) among pregnant women. OBJECTIVE: To estimate the effect of initiation of levothyroxine on pregnancy loss among women with SCH with an emulated target trial using observational data. METHODS: We emulated a target trial using the United Kingdom's Clinical Practice Research Datalink to account for the staggered timing of diagnosis and treatment of SCH and the time of entry of women into prenatal care. We emulated multiple nested trials (at each gestational week) and used an intention-to-treat approach to define levothyroxine use (≥1 prescription in the 7 days prior to trial entry), with eligible users matched to non-users (1:4) on time of diagnosis, gestational week of the first eligible trial and high-dimensional propensity score. Pregnancy losses included spontaneous abortion and stillbirth. A pooled logistic regression model with bootstrap resampling was used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Based on 159,177 eligible person-trials (5781 women), the matched cohort included 181 initiators and 640 non-initiators of levothyroxine, with 57 pregnancy losses occurring during follow-up. Overall, the mean age of women was 32.2 years (SD 5.4), 25% were obese, 8% had type 2 diabetes and about 50% were nulliparous. After matching, women who initiated levothyroxine versus not had higher thyroid-stimulating levels during pregnancy and were more likely to have a history of hypothyroidism. The cumulative incidence of pregnancy loss was lower in initiators versus non-initiators of levothyroxine. The adjusted HR for pregnancy loss was 0.87 (95% CI 0.22, 1.56). CONCLUSIONS: Although our assessment of the effect of initiation of levothyroxine for SCH in pregnancy precludes any definitive conclusions due to wide confidence intervals, this study illustrates the feasibility of using the target trial emulation framework to examine the effectiveness of medication use in pregnancy.

Gestational weight change in a diverse pregnancy cohort and mortality over 50 years: a prospective observational cohort study.

BACKGROUND: High weight gain in pregnancy is associated with greater postpartum weight retention, yet long-term implications remain unknown. We aimed to assess whether gestational weight change was associated with mortality more than 50 years later. METHODS: The Collaborative Perinatal Project (CPP) was a prospective US pregnancy cohort (1959-65). The CPP Mortality Linkage Study linked CPP participants to the National Death Index and Social Security Death Master File for vital status to 2016. Adjusted hazard ratios (HRs) with 95% CIs estimated associations between gestational weight gain and loss according to the 2009 National Academy of Medicine recommendations and mortality by pre-pregnancy BMI. The primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular and diabetes underlying causes of mortality. FINDINGS: Among 46 042 participants, 20 839 (45·3%) self-identified as Black and 21 287 (46·2%) as White. Median follow-up time was 52 years (IQR 45-54) and 17 901 (38·9%) participants died. For those who were underweight before pregnancy (BMI <18·5 kg/m2; 3809 [9·4%] of 40 689 before imputation for missing data]), weight change above recommendations was associated with increased cardiovascular mortality (HR 1·84 [95% CI 1·08-3·12]) but not all-cause mortality (1·14 [0·86-1·51]) or diabetes-related mortality (0·90 [0·13-6·35]). For those with a normal pre-pregnancy weight (BMI 18·5-24·9 kg/m2; 27 921 [68·6%]), weight change above recommendations was associated with increased all-cause (HR 1·09 [1·01-1·18]) and cardiovascular (1·20 [1·04-1·37]) mortality, but not diabetes-related mortality (0·95 [0·61-1·47]). For those who were overweight pre-pregnancy (BMI 25·0-29·9 kg/m2; 6251 [15·4%]), weight change above recommendations was associated with elevated all-cause (1·12 [1·01-1·24]) and diabetes-related (1·77 [1·23-2·54]) mortality, but not cardiovascular (1·12 [0·94-1·33]) mortality. For those with pre-pregnancy obesity (≥30·0 kg/m2; 2708 [6·7%]), all associations between gestational weight change and mortality had wide CIs and no meaningful relationships could be drawn. Weight change below recommended levels was associated only with a reduced diabetes-related mortality (0·62 [0·48-0·79]) in people with normal pre-pregnancy weight. INTERPRETATION: This study's novel findings support the importance of achieving healthy gestational weight gain within recommendations, adding that the implications might extend beyond the pregnancy window to long-term health, including cardiovascular and diabetes-related mortality. FUNDING: National Institutes of Health.

Accuracy of aspirin prophylaxis for preeclampsia prevention documentation within a large administrative dataset.

BACKGROUND: Low-dose aspirin prophylaxis is recommended for women at risk of preeclampsia. Capturing aspirin prophylaxis within administrative databases can be challenging since it is an over-the-counter medication. The Better Outcome Registry and Network (BORN) database, a perinatal health registry in Ontario, Canada, includes a formal variable that captures aspirin prophylaxis for preeclampsia. This variable has not been formally validated. OBJECTIVES: To assess the accuracy of the aspirin prophylaxis variable in the BORN database against an electronic medical record (EMR). METHODS: This validation study comprised 200 randomly selected women who had a livebirth at St. Michael's Hospital (SMH) in Toronto, Ontario, from January 2018 to July 2022. Recorded aspirin prophylaxis in pregnancy and maternal sociodemographic characteristics were independently extracted by two abstractors. Accuracy of aspirin prophylaxis use in the BORN database was compared to that in the SMH EMR, expressed as sensitivity, specificity, positive (PPV) and negative predictive values (NPV), Cohen's kappa (κ), and overall percent agreement, with 95% confidence intervals (CI). Sensitivity analyses were performed to account for missing or unclear aspirin prophylaxis use. RESULTS: Among 200 women, 24 (12.0%) received aspirin prophylaxis - 12.5% within the SMH EMR and 8.0% in the BORN database. Women using aspirin were older (37.0 vs 33.0 years) and had higher median gravidity (3 vs. 2). Sensitivity and specificity of the BORN aspirin prophylaxis variable were 62.5% (95% CI 40.6, 81.2) and 100.0% (95% CI 97.3, 100.0), respectively. The corresponding positive and negative predictive values were 100.0% (95% CI 78.2, 100.0), and 93.8% (95% CI 88.6, 97.1), respectively. Cohen's κ was 0.74 (95% CI 0.58, 0.90), and overall percent agreement was 94.4% (95% CI 87.1, 100.0). CONCLUSIONS: Aspirin use within the BORN database, based on a standard variable field, appears accurate enough for the potential use in epidemiological studies of aspirin prophylaxis for preeclampsia or as a covariate in related studies.

Assessment and Prediction of Cardiovascular Contributions to Severe Maternal Morbidity.

Severe maternal morbidity (SMM) refers to any unexpected outcome directly related to pregnancy and childbirth that results in both short-term delivery complications and long-term consequences to a women's health. This affects about 60,000 women annually in the United States. Cardiovascular contributions to SMM including cardiac arrest, arrhythmia, and acute myocardial infarction are on the rise, probably driven by changing demographics of the pregnant population including more women of extreme maternal age and an increased prevalence of cardiometabolic and structural heart disease. The utilization of SMM prediction tools and risk scores specific to cardiovascular disease in pregnancy has helped with risk stratification. Furthermore, health system data monitoring and reporting to identify and assess etiologies of cardiovascular complications has led to improvement in outcomes and greater standardization of care for mothers with cardiovascular disease. Improving cardiovascular disease-related SMM relies on a multipronged approach comprised of patient-level identification of risk factors, individualized review of SMM cases, and validation of risk stratification tools and system-wide improvements in quality of care. In this article, we review the epidemiology and cardiac causes of SMM, we provide a framework of risk prediction clinical tools, and we highlight need for organization of care to improve outcomes.

Infant sex at birth and long-term maternal mortality.

BACKGROUND: Maternal adaptations may vary by foetal sex. Whether male infants influence long-term mortality in mothers remains uncertain. OBJECTIVE: The objective of the study was to examine whether male infants increase the risk of maternal mortality. METHODS: This study included pregnant women enrolled at 12 US sites from 1959 to 1966 in the Collaborative Perinatal Project (CPP). Collaborative Perinatal Project records were linked to the National Death Index and the Social Security Master Death File to ascertain deaths until 2016. Foetal sex was determined by infant sex at birth, defined as the total number of male or female infants in pregnancies prior to or during enrolment in the CPP. In secondary analyses, exposure was defined as infant sex at the last CPP delivery. Outcomes included all-cause and underlying causes of mortality. We used Cox proportional hazards models weighted by the number of prior live births and stratified our models by parity and race/ethnicity. RESULTS: Among 48,188 women, 50.8% had a male infant at their last registered CPP pregnancy and 39.0% had a recorded death after a mean follow-up of 47.8 years (SD 10.5 years). No linear association was found between the number of liveborn males and all-cause mortality (primipara women: HR 1.02, 95% CI 0.95, 1.09, multipara women, 1 prior live birth: HR 0.96, 95% CI 0.89, 1.03, multipara women, ≥2 prior live births: HR 0.97, 95% CI 0.85, 1.11). A similar trend was noted for cardiovascular- and cancer-related mortality. At the last delivery, women with a male infant did not have an increased risk of all-cause or cause-specific mortality compared to women with a female infant. These findings were consistent across racial/ethnic groups. CONCLUSIONS: Women who give birth to male infants, regardless of number, are not at increased risk of all-cause and cause-specific mortality. These findings suggest that giving birth to male infants may not independently influence the long-term health of women.

Hypertensive Disorders of Pregnancy in Black Women - Where Do We Go from Here?

In this issue of NEJM Evidence, Sheehy et al.1 report the results of a prospective cohort study that examined the association between hypertensive disorders of pregnancy (HDOP) and the risk of stroke among Black women in the United States. Using data from 42,924 participants in the Black Women's Health Study (BWHS) who were free of cardiovascular disease at baseline, they compared the rates of stroke between women with HDOP and those who did not have HDOP over a median follow-up of 22 years.