Drivers of variation in postpartum opioid prescribing across hospitals participating in a statewide maternity care quality collaborative.

BACKGROUND: We describe variation in postpartum opioid prescribing across a statewide quality collaborative and assess the proportion due to practitioner and hospital characteristics. METHODS: We assessed postpartum prescribing data from nulliparous, term, singleton, vertex births between January 2020 and June 2021 included in the clinical registry of a statewide obstetric quality collaborative funded by Blue Cross Blue Shield of Michigan. Data were summarized using descriptive statistics. Mixed effect logistic regression and linear models adjusted for patient characteristics and assessed practitioner- and hospital-level predictors of receiving a postpartum opioid prescription and prescription size. Relative contributions of practitioner and hospital characteristics were assessed using the intraclass correlation coefficient. RESULTS: Of 40,589 patients birthing at 68 hospitals, 3.0% (872/29,412) received an opioid prescription after vaginal birth and 87.8% (9812/11,177) received one after cesarean birth, with high variation across hospitals. In adjusted models, the strongest patient-level predictors of receiving a prescription were cesarean birth (aOR 899.1, 95% CI 752.8-1066.7) and third-/fourth-degree perineal laceration (aOR 25.7, 95% CI 17.4-37.9). Receiving care from a certified nurse-midwife (aOR 0.63, 95% CI 0.48-0.82) or family medicine physician (aOR 0.60, 95%CI 0.39-0.91) was associated with lower prescribing rates. Hospital-level predictors included receiving care at hospitals with <500 annual births (aOR 4.07, 95% CI 1.61-15.0). A positive safety culture was associated with lower prescribing rates (aOR 0.37, 95% CI 0.15-0.88). Much of the variation in postpartum prescribing was attributable to practitioners and hospitals (prescription receipt: practitioners 25.1%, hospitals 12.1%; prescription size: practitioners 5.4%, hospitals: 52.2%). DISCUSSION: Variation in postpartum opioid prescribing after birth is high and driven largely by practitioner- and hospital-level factors. Opioid stewardship efforts targeted at both the practitioner and hospital level may be effective for reducing opioid prescribing harms.

Outcomes of Elective Induction of Labor at 39 Weeks from a Statewide Collaborative Quality Initiative.

OBJECTIVE: This article evaluates the impact of adopting a practice of elective induction of labor (eIOL) at 39 weeks among nulliparous, term, singleton, vertex (NTSV) pregnancies in a statewide collaborative. STUDY DESIGN: We used data from a statewide maternity hospital collaborative quality initiative to analyze pregnancies that reached 39 weeks without a medical indication for delivery. We compared patients who underwent an eIOL versus those who experienced expectant management. The eIOL cohort was subsequently compared with a propensity score-matched cohort who were expectantly managed. The primary outcome was cesarean birth rate. Secondary outcomes included time to delivery and maternal and neonatal morbidities. Chi-square test, t-test, logistic regression, and propensity score matching methods were used for analysis. RESULTS: In 2020, 27,313 NTSV pregnancies were entered into the collaborative's data registry. A total of 1,558 women underwent eIOL and 12,577 were expectantly managed. Women in the eIOL cohort were more likely to be ≥35 years old (12.1 vs. 5.3%, p < 0.001), identify as white non-Hispanic (73.9 vs. 66.8%, p < 0.001), and be privately insured (63.0 vs. 61.3%, p = 0.04). When compared with all expectantly managed women, eIOL was associated with a higher cesarean birth rate (30.1 vs. 23.6%, p < 0.001). When compared with a propensity score-matched cohort, eIOL was not associated with a difference in cesarean birth rate (30.1 vs. 30.7%, p = 0.697). Time from admission to delivery was longer for the eIOL cohort compared with the unmatched (24.7 ± 12.3 vs. 16.3 ± 11.3 hours, p < 0.001) and matched (24.7 ± 12.3 vs. 20.1 ± 12.0 hours, p < 0.001) cohorts. Expectantly managed women were less likely to have a postpartum hemorrhage (8.3 vs. 10.1%, p = 0.02) or operative delivery (9.3 vs. 11.4%, p = 0.029), whereas women who underwent an eIOL were less likely to have a hypertensive disorder of pregnancy (5.5 vs. 9.2%, p < 0.001). CONCLUSION: eIOL at 39 weeks may not be associated with a reduced NTSV cesarean delivery rate. KEY POINTS: · Elective IOL at 39 weeks may not be associated with a reduced NTSV cesarean delivery rate.. · The practice of elective induction of labor may not be equitably applied across birthing people.. · Further research is needed to identify best practices to support people undergoing labor induction..

Considering environmental exposures to per- and polyfluoroalkyl substances (PFAS) as risk factors for hypertensive disorders of pregnancy.

Hypertensive disorders of pregnancy (HDP), including preeclampsia and gestational hypertension, lead to significant maternal morbidity and in some cases, maternal mortality. Environmental toxicants, especially those that disrupt normal placental and endothelial function, are emerging as potential risk factors for HDP. Per- and polyfluoroalkyl substances (PFAS) are a large group of ubiquitous chemicals found in consumer products, the environment, and increasingly in drinking water. PFAS have been associated with a multitude of adverse health effects, including dyslipidemia, hypertension, and more recently, HDP. In this review, we present epidemiological and mechanistic evidence for the link between PFAS and HDP and recommend next steps for research and prevention efforts. To date, epidemiological studies have assessed associations between only ten of the thousands of PFAS and HDP. Positive associations between six PFAS (PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonic acid; PFHxS, perfluorohexane sulfonic acid; PFHpA, perfluoroheptanoic acid; PFBS, perfluorobutanesulfonic acid; and PFNA, perfluoronanoic acid) and risk for HDP have been reported in some, but not all, studies. PFAS disrupt placental and immune function, cause oxidative stress, and disrupt lipid metabolism. These physiological disruptions may be mechanisms through which PFAS can lead to HDP. Overall, limited epidemiological evidence and plausible mechanisms support PFAS as risk factors for HDP. More research is needed in diverse, well-powered cohorts that assess exposures to as many PFAS as possible. Such research should consider not only individual PFAS but also the totality of exposures to PFAS and other environmental chemicals. Pregnant women may be a group that is vulnerable to PFAS exposure, and as such HDP risk should be considered by policymakers setting PFAS exposure limits. In the interim, medical and public health professionals in regions with PFAS contamination could provide short-term solutions in the form of patient-level prevention, increased monitoring, and early intervention for HDP.

Gestational hypertension and progression towards preeclampsia in Northern Ethiopia: prospective cohort study.

BACKGROUND: Preeclampsia (PE) is one of the main causes of medical complication of pregnancy and is the main cause of perinatal mortality and morbidity. It is one of the top causes of maternal mortality in Ethiopia. Also known as transient hypertension, gestational hypertension (GH) is increased blood pressure during pregnancy without proteinuria, which is expected to return to normal by the 12th-week postpartum visit. PE is GH with proteinuria and /or other systemic manifestations. Evidence from high income countries show that GH significantly progresses towards PE. To our knowledge, this is the first study on the progression of GH towards PE in an African setting. The objective of this study is, therefore, to assess the incidence of GH, progression towards PE and factors associated with progression in Ethiopia. METHODS: This is a prospective cohort study conducted at Ayder Comprehensive Specialized Hospital (ACSH) and Mekelle General Hospital (MGH), the largest referral centers in Northern Ethiopia. Two hundred and forty women with GH were enrolled and followed up until delivery. Clinical and laboratory data at initial presentation and at follow-up were compared among women who progressed towards PE and who remained with the diagnosis of GH. Logistic regression analysis was employed to model the combined effects of the clinical and laboratory data as significant predictors of progression from GH to PE. RESULT: The incidence of GH in this study was 6 % (4.9-8.5). The rate of progression was 17.1 % (13.4-23.8). Previous history of GH, anemia during pregnancy, previous second-trimester spontaneous abortion were significant predictors of progression. CONCLUSIONS: There is a high rate of progression of GH towards PE. In a resource-limited setting where predictive and diagnostic tools are scarce, clinical profile of women should be taken into consideration for prediction and diagnosis of PE.

New persistent opioid use after acute opioid prescribing in pregnancy: a nationwide analysis.

OBJECTIVE: To evaluate the association between opioid prescribing during pregnancy and new persistent opioid use in the year following delivery. MATERIALS AND METHODS: This nationwide retrospective cohort study included patients aged 12-55 years in Optum's deidentified Clinformatics Data Mart Database who were undergoing vaginal delivery or cesarean delivery from 2008 to 2016, with continuous enrollment from 2 years before birth to 1 year postdischarge. Women were included if they were opioid naive in pregnancy (ie, did not fill an opioid prescription 2 years to 9 months before delivery) and did not undergo a procedure within the year after discharge. The exposure was filling an opioid prescription in pregnancy. The primary outcome was new persistent opioid use, defined as a pharmacy claim for ≥1 opioid prescription between 4 and 90 days postdischarge and ≥1 prescription between 91 and 365 days postdischarge. Clinical and demographic covariates were included. Analyses included descriptive statistics and multivariable logistic regression, adjusting for clinical and demographic covariates. RESULTS: Of 158,425 childbirths identified, 101,013 (63.8%) were by vaginal delivery and 57,412 (36.2%) cesarean delivery. Among all patients, 6.0% (9429) filled an opioid prescription during pregnancy. The factors associated with filling an opioid in pregnancy were having a nondelivery procedure in pregnancy (adjusted odds ratio, 9.60; 95% confidence interval, 8.81-10.47) and having an emergency room visit during pregnancy (adjusted odds ratio, 2.48; 95% confidence interval, 2.37-2.59). Of women who received an opioid in pregnancy, 4% (379) developed new persistent opioid use. The factors most associated with new persistent opioid use were receiving an opioid prescription during pregnancy (adjusted odds ratio, 3.45; 95% confidence interval, 3.04-3.92) and filling a peripartum opioid prescription (1 week prior to 3 days postdischarge) adjusted odds ratio, 2.28, 95% confidence interval (2.02-2.57). Though having a procedure during pregnancy was associated with increased receipt of an opioid prescription, it was also associated with reduced new persistent opioid use (adjusted odds ratio, 0.72; 95% confidence interval, 0.52-0.99). CONCLUSION: Women who receive an opioid prescription during pregnancy are more likely to experience new persistent opioid use. Maternity care providers must balance pain management in pregnancy with potential risks of opioids.

Risk Factors, Etiologies, and Screening Tools for Sepsis in Pregnant Women: A Multicenter Case-Control Study.

BACKGROUND: Given the significant morbidity and mortality of maternal sepsis, early identification is key to improve outcomes. This study aims to evaluate the performance characteristics of the systemic inflammatory response syndrome (SIRS), quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA), and maternal early warning (MEW) criteria for identifying cases of impending sepsis in parturients. The secondary objective of this study is to identify etiologies and risk factors for maternal sepsis and to assess timing of antibiotics in patients diagnosed with sepsis. METHODS: Validated maternal sepsis cases during the delivery hospitalization from 1995 to 2012 were retrospectively identified at 7 academic medical centers in the United States and Israel. Control patients were matched by date of delivery in a 1:4 ratio. The sensitivity and specificity of SIRS, qSOFA, and MEW criteria for identifying sepsis were calculated. Data including potential risk factors, vital signs, laboratory values, and clinical management were collected for cases and controls. RESULTS: Eighty-two sepsis cases during the delivery hospitalization were identified and matched to 328 controls. The most common causes of sepsis were the following: chorioamnionitis 20 (24.4%), endometritis 19 (23.2%), and pneumonia 9 (11.0%). Escherichia coli 12 (14.6%), other Gram-negative rods 8 (9.8%), and group A Streptococcus 6 (7.3%) were the most commonly found pathogens. The sensitivities and specificities for meeting criteria for screening tools were as follows: (1) SIRS (0.93, 0.63); (2) qSOFA (0.50, 0.95); and (3) MEW criteria for identifying sepsis (0.82, 0.87). Of 82 women with sepsis, 10 (12.2%) died. The mortality rate for those who received antibiotics within 1 hour of diagnosis was 8.3%. The mortality rate was 20% for the patients who received antibiotics after >1 hour. CONCLUSIONS: Chorioamnionitis and endometritis were the most common causes of sepsis, together accounting for about half of cases. Notable differences were observed in the sensitivity and specificity of sepsis screening tools with the highest to lowest sensitivity being SIRS, MEW, and qSOFA criteria, and the highest to lowest specificity being qSOFA, MEW, and SIRS. Mortality was doubled in the cohort of patients who received antibiotics after >1 hour. Clinicians need to be vigilant to identify cases of peripartum sepsis early in its course and prioritize timely antibiotic therapy.

Assessing Maternal and Fetal Risks Associated with Prolonged Induction of Labor.

OBJECTIVE: To assess whether prolonged induction of labor was associated with increased maternal or neonatal morbidity. STUDY DESIGN: We performed a retrospective cohort study of women undergoing induction of labor at a single institution. We included women with singletons ≥ 36 weeks with initial cervical dilation ≤4 cm. Prolonged induction of labor was defined as lasting > 36 hours from the time of initial method to delivery. A 2-to-1 propensity score-matched analysis was performed between women with and those without prolonged induction of labor. Maternal outcomes were cesarean delivery, chorioamnionitis, endometritis, postpartum hemorrhage, severe perineal laceration, and length of postpartum admission. Neonatal outcomes included Apgar scores, umbilical artery pH, and neonatal intensive care admission. RESULTS: Among 2,021 women, 407 (20.1%) had a prolonged induction. In unadjusted analyses, prolonged induction of labor was associated with increased cesarean delivery and chorioamnionitis. After 2-to-1 propensity score matching, there were 267 women with prolonged induction and 424 controls. Women with prolonged induction of labor had higher rates of cesarean delivery (35.6 vs. 16%, p < 0.001), chorioamnionitis (14.2 vs. 4.7%, p < 0.001), endometritis (6.4 vs. 1.9%, p = 0.002), and postpartum hemorrhage (18.8 vs. 11.9%, p = 0.008). There were no significant differences in neonatal outcomes. CONCLUSION: Overall length of induction impacts maternal outcome.

Normal Range for Maternal Lactic Acid during Pregnancy and Labor: A Systematic Review and Meta-Analysis of Observational Studies.

OBJECTIVE: This article systematically reviews the literature to establish the normal range of lactic acid in healthy pregnant women. STUDY DESIGN: Ovid MEDLINE, Embase.com, and Clinicaltrials.gov were searched to identify studies that reported maternal lactic acid in healthy pregnant women. Pooled aggregate means and two standard deviations for each time period were computed using the inverse variance weighting technique. Analyses were performed separately for 1st, 2nd, and 3rd trimesters, scheduled cesarean delivery, early labor, active labor, 2nd stage of labor, and delivery. RESULTS: Overall, 22 studies met the inclusion criteria. There were 1,193 patients, and 2,008 observations identified. All time periods had maternal venous lactic acid aggregate means and two-standard-deviation ranges less than 4 mmol/L. Outside of labor, all ranges were less than 2 mmol/L. All labor periods had a range higher than 2 mmol/L. While the pooled ranges were less than 4 mmol/L, many individual studies reported ranges > 4 mmol/L during labor. CONCLUSION: This meta-analysis suggests that venous lactic acid levels can be used as a screening tool in pregnant women just as the test would be used in nonpregnant women, except that elevations may be seen during labor, especially later in labor when there is maximal skeletal muscle contraction.

Use of a novel electronic maternal surveillance system to generate automated alerts on the labor and delivery unit.

BACKGROUND: Maternal early warning systems reduce maternal morbidity. We developed an electronic maternal surveillance system capable of visually summarizing the labor and delivery census and identifying changes in clinical status. Automatic page alerts to clinical providers, using an algorithm developed at our institution, were incorporated in an effort to improve early detection of maternal morbidity. We report the frequency of pages generated by the system. To our knowledge, this is the first time such a system has been used in peripartum care. METHODS: Alert criteria were developed after review of maternal early warning systems, including the Maternal Early Warning Criteria (MEWC). Careful consideration was given to the frequency of pages generated by the surveillance system. MEWC notification criteria were liberalized and a paging algorithm was created that triggered paging alerts to first responders (nurses) and then managing services due to the assumption that paging all clinicians for each vital sign triggering MEWC would generate an inordinate number of pages. For preliminary analysis, to determine the effect of our automated paging algorithm on alerting frequency, the paging frequency of this system was compared to the frequency of vital signs meeting the Maternal Early Warning Criteria (MEWC). This retrospective analysis was limited to a sample of 34 patient rooms uniquely capable of storing every vital sign reported by the bedside monitor. RESULTS: Over a 91-day period, from April 1 to July 1, 2017, surveillance was conducted from 64 monitored beds, and the obstetrics service received one automated page every 2.3 h. The most common triggers for alerts were for hypertension and tachycardia. For the subset of 34 patient rooms uniquely capable of real-time recording, one vital sign met the MEWC every 9.6 to 10.3 min. Anecdotally, the system was well-received. CONCLUSIONS: This novel electronic maternal surveillance system is designed to reduce cognitive bias and improve timely clinical recognition of maternal deterioration. The automated paging algorithm developed for this software dramatically reduces paging frequency compared to paging for isolated vital sign abnormalities alone. Long-term, prospective studies will be required to determine its impact on patient outcomes.

Outcomes in oligohydramnios: the role of etiology in predicting pulmonary morbidity/mortality.

Objective Early-onset oligohydramnios is typically secondary to renal-urinary anomalies (RUA) or preterm premature rupture of membranes (PPROM). We compared neonatal pulmonary outcomes between these etiologies. Methods We conducted a retrospective cohort study of women with oligohydramnios identified before 24 completed weeks of gestation attributed to either PPROM or RUA. Patients were excluded if other fetal anomalies were noted. Respiratory morbidity was assessed by the need for oxygen at 36 corrected weeks or at hospital discharge. Results Of 116 eligible patients, 54 chose elective pregnancy termination. A total of 39.5% of PPROM (n=17/43) and 36.8% of RUA (n=7/19) pregnancies experienced pre-viable loss (P=1.00). Significantly fewer PPROM live births resulted in neonatal mortality (26.9% vs. 75.0%, P<0.01). There was no difference in respiratory morbidity (57.9% vs. 66.6%, P=1.00). The collective incidence of respiratory mortality and morbidity was not different between etiologies (P=0.06). Conclusion This analysis suggests that the prognoses for oligohydramnios due to pre-viable PPROM vs. renal anomalies are similarly grave, though RUA infants experienced a higher rate of neonatal respiratory mortality.

A Double-Blind, Randomized, Placebo-Controlled Trial of 17 Alpha-hydroxyprogesterone Caproate in the Management of Preterm Premature Rupture of Membranes.

OBJECTIVE: The objective of this study was to evaluate whether weekly administration of 17 α-hydroxyprogesterone caproate (17-OHPC) increases the number of women who achieve 34 weeks of gestation after preterm premature rupture of membranes (PPROM). STUDY DESIGN: We conducted a multicenter double-blind, randomized controlled trial of 17-OHPC versus placebo among women with PPROM. Women with singleton pregnancy, clinically confirmed PPROM, and without evidence of active infection or major fetal malformation between 240/7 and 320/7 weeks of pregnancy were offered enrollment. Women received weekly injections of 17-OHPC versus placebo until 340/7 weeks of gestation or delivery. The remainder of care was per hospital protocol. The primary outcome was achievement of 34 weeks of gestation. Secondary outcomes included length of latency and maternal and fetal outcomes. RESULTS: In this study, 21 women were enrolled. Eleven women received placebo and 10 received 17-OHPC. The study was closed prematurely secondary to poor enrollment. None of the women remained pregnant until 34 weeks of gestation. The median latency periods were 8 and 14.5 days for the placebo and 17-OHPC groups, respectively (p = 0.14). There were no differences in maternal or neonatal outcomes. CONCLUSION: We did not identify any benefit from administration of 17-OHPC in pregnancies complicated by PPROM.

Maternal leukocytosis after antenatal corticosteroid administration: a systematic review and meta-analysis.

Although it is known that corticosteroid administration causes leukocytosis, the magnitude and length of time this leukocytosis persists is unknown during pregnancy. This study aimed to establish the expected range of maternal leukocytosis in healthy pregnant women at risk for preterm delivery after antenatal corticosteroid administration. PubMed, Embase and ClinicalTrials.gov were searched to identify the studies in healthy women at risk for preterm delivery without signs of clinical infection that reported white blood cell values preceding and after antenatal corticosteroid administration. The inverse variance weighting technique was used to calculate the weighted means and the standard deviation from the mean for each time period. Six studies met inclusion criteria and included 524 patients and 1406 observations. Mean ± standard deviation maternal white blood cell count values prior to antenatal corticosteroid administration and up to 24, 48, 72 and 96 hours after corticosteroid administration were 10.4 ± 2.4, 13.6 ± 3.6, 12.1 ± 3.0, 11.5 ± 2.9 and 11.1 ± 2.5 × 109/L, respectively. Leukocytosis in healthy, non-infected women is expected to peak 24 hours after antenatal corticosteroid administration and the magnitude of increase is small. Impact statement What is already known on this subject: While it is well known that administration of antenatal corticosteroids causes leukocytosis, it is currently unknown the magnitude and length of time the leukocytosis persists. What the results of this study add: This study establishes the expected range and the temporal progression and regression with antenatal corticosteroid administration in healthy pregnant women at risk for preterm delivery without clinical signs of infection. What the implications are of these findings for clinical practice and/or further research: Clinicians may wish to consider further investigation into the clinical cause, whether infectious or non-infectious, for absolute values and changes outside this range.

Maternal glucose response to betamethasone administration.

OBJECTIVE: This study aims to describe the pattern of maternal glucose response to betamethasone administration using a continuous glucose monitoring system. STUDY DESIGN: A prospective observational trial was conducted among women receiving clinically indicated betamethasone between 24 and 34 weeks gestation. At the time of initial betamethasone administration, a continuous glucose monitoring device was inserted which measured interstitial fluid glucose levels every 5 minutes. Glucose levels were monitored for 7 days, until delivery, or until hospital discharge, whichever came first. We recorded the percentage of time women spent above three glucose thresholds: 110, 144, and 180 mg/dL, respectively. RESULTS: A total of 17 women were enrolled at the time of betamethasone administration and data were available for 15 patients. There were 11 nondiabetic and 4 diabetic women. Both diabetic and nondiabetic women had the highest recorded blood glucose readings between 24 and 48 hours after the first injection of betamethasone. In that period, nondiabetic women spent 73, 40, and 17% of the time with blood glucose levels above the 110, 144, and 180 mg/dL thresholds, respectively. CONCLUSION: Nondiabetic women receiving betamethasone manifest significant hyperglycemia after betamethasone administration. If delivery is imminent, maternal glucose response to betamethasone may need to be monitored to prevent possible neonatal hypoglycemia.

High rate of preterm birth in pregnancies complicated by rheumatoid arthritis.

OBJECTIVE: To describe the outcomes of pregnancies complicated by rheumatoid arthritis (RA) and to estimate potential associations between disease characteristics and pregnancy outcomes. STUDY DESIGN: We reviewed all pregnancies complicated by RA delivered at our institution from June 2001 through June 2009. Fisher exact tests were used to calculate odds ratios. Univariable regression was performed using STATA 10.1 (StataCorp, College Station, TX). A p value of ≤ 0.05 was considered statistically significant. RESULTS: Forty-six pregnancies in 40 women were reviewed. Sixty percent of pregnancies had evidence of disease flare and 28% delivered prior to 37 weeks. We did not identify associations between preterm birth and active disease at conception or during pregnancy. In univariate analysis, discontinuation of medication because of pregnancy was associated with a significantly earlier gestational age at delivery (362/7 versus 383/7 weeks, p = 0.022). CONCLUSION: Women with RA may be at higher risk for preterm delivery.

Discover overlooked complications after preeclampsia using electronic health records.

Background: Preeclampsia (PE) is a severe pregnancy complication characterized by hypertension and end-organ damage such as proteinuria. PE poses a significant threat to women's long-term health, including an increased risk of cardiovascular and renal diseases. Most previous studies have been hypothesis-based, potentially overlooking certain significant complications. This study conducts a comprehensive, non-hypothesis-based analysis of PE-complicated diagnoses after pregnancies using multiple large-scale electronic health records (EHR) datasets. Method: From the University of Michigan (UM) Healthcare System, we collected 4,348 PE patients for the cases and 27,377 patients with pregnancies not complicated by PE or related conditions for the controls. We first conducted a non-hypothesis-based analysis to identify any long-term adverse health conditions associated with PE using logistic regression with adjustments to demographics, social history, and medical history. We confirmed the identified complications with UK Biobank data which contain 443 PE cases and 14,870 non-PE controls. We then conducted a survival analysis on complications that exhibited significance in more than 5 consecutive years post-PE. We further examined the potential racial disparities of identified complications between Caucasian and African American patients. Findings: Uncomplicated hypertension, complicated diabetes, congestive heart failure, renal failure, and obesity exhibited significantly increased risks whereas hypothyroidism showed decreased risks, in 5 consecutive years after PE in the UM discovery data. UK Biobank data confirmed the increased risks of uncomplicated hypertension, complicated diabetes, congestive heart failure, renal failure, and obesity. Further survival analysis using UM data indicated significantly increased risks in uncomplicated hypertension, complicated diabetes, congestive heart failure, renal failure, and obesity, and significantly decreased risks in hypothyroidism. There exist racial differences in the risks of developing hypertension and hypothyroidism after PE. PE protects against hypothyroidism in African American postpartum women but not Cacausians; it also increases the risks of uncomplicated hypertension but less severely in African American postpartum women as compared to Cacausians. Interpretation: This study addresses the lack of a comprehensive examination of PE's long-term effects utilizing large-scale EHR and advanced statistical methods. Our findings underscore the need for long-term monitoring and interventions for women with a history of PE, emphasizing the importance of personalized postpartum care. Notably, the racial disparities observed in the impact of PE on hypertension and hypothyroidism highlight the necessity of tailored aftercare based on race.

Discover overlooked complications after preeclampsia using electronic health records.

Background: Preeclampsia (PE) is a severe pregnancy complication characterized by hypertension and end-organ damage such as proteinuria. PE poses a significant threat to women's long-term health, including an increased risk of cardiovascular and renal diseases. Most previous studies have been hypothesis-based, potentially overlooking certain significant complications. This study conducts a comprehensive, non-hypothesis-based analysis of PE-complicated diagnoses after pregnancies using multiple large-scale electronic health records (EHR) datasets. Method: From the University of Michigan (UM) Healthcare System, we collected 4,348 PE patients for the cases and 27,377 patients with pregnancies not complicated by PE or related conditions for the controls. We first conducted a non-hypothesis-based analysis to identify any long-term adverse health conditions associated with PE using logistic regression with adjustments to demographics, social history, and medical history. We confirmed the identified complications with UK Biobank data which contain 443 PE cases and 14,870 non-PE controls. We then conducted a survival analysis on complications that exhibited significance in more than 5 consecutive years post-PE. We further examined the potential racial disparities of identified complications between Caucasian and African American patients. Findings: Uncomplicated hypertension, complicated diabetes, congestive heart failure, renal failure, and obesity exhibited significantly increased risks whereas hypothyroidism showed decreased risks, in 5 consecutive years after PE in the UM discovery data. UK Biobank data confirmed the increased risks of uncomplicated hypertension, complicated diabetes, congestive heart failure, renal failure, and obesity. Further survival analysis using UM data indicated significantly increased risks in uncomplicated hypertension, complicated diabetes, congestive heart failure, renal failure, and obesity, and significantly decreased risks in hypothyroidism. There exist racial differences in the risks of developing hypertension and hypothyroidism after PE. PE protects against hypothyroidism in African American postpartum women but not Cacausians; it also increases the risks of uncomplicated hypertension but less severely in African American postpartum women as compared to Cacausians. Interpretation: This study addresses the lack of a comprehensive examination of PE's long-term effects utilizing large-scale EHR and advanced statistical methods. Our findings underscore the need for long-term monitoring and interventions for women with a history of PE, emphasizing the importance of personalized postpartum care. Notably, the racial disparities observed in the impact of PE on hypertension and hypothyroidism highlight the necessity of tailored aftercare based on race.

Placental transcriptome analysis of hypertensive pregnancies identifies distinct gene expression profiles of preeclampsia superimposed on chronic hypertension.

BACKGROUND: The pathogenesis of preeclampsia superimposed on chronic hypertension (SI) is poorly understood relative to preeclampsia (PreE) occurring in pregnant people without chronic hypertension. Placental transcriptomes in pregnancies complicated by PreE and SI have not been previously compared. METHODS: We identified pregnant people in the University of Michigan Biorepository for Understanding Maternal and Pediatric Health with hypertensive disorders affecting singleton, euploid gestations (N = 36) along with non-hypertensive control subjects (N = 12). Subjects were grouped as: (1) normotensive (N = 12), (2) chronic hypertensive (N = 13), (3) preterm PreE with severe features (N = 5), (4) term PreE with severe features (N = 11), (5) preterm SI (N = 3), or (6) term SI (N = 4). Bulk RNA sequencing of paraffin-embedded placental tissue was performed. The primary analysis assessed differential gene expression relative to normotensive and chronic hypertensive placentas, where Wald adjusted P values < 0.05 were considered significant. Unsupervised clustering analyses and correlation analyses were performed between conditions of interest, and a gene ontology was constructed. RESULTS: Comparing samples from pregnant people with hypertensive diseases to non-hypertensive controls, there were 2290 differentially expressed genes. The log2-fold changes in genes differentially expressed in chronic hypertension correlated better with term (R = 0.59) and preterm (R = 0.63) PreE with severe features than with term (R = 0.21) and preterm (R = 0.22) SI. A relatively poor correlation was observed between preterm SI and preterm PreE with severe features (0.20) as well as term SI and term PreE with severe features (0.31). The majority of significant genes were downregulated in term and preterm SI versus normotensive controls (92.1%, N = 128). Conversely, most term and preterm PreE with severe features genes were upregulated compared to the normotensive group (91.8%, N = 97). Many of the upregulated genes in PreE with the lowest adjusted P values are known markers of abnormal placentation (e.g., PAAPA, KISS1, CLIC3), while the downregulated genes with the greatest adjusted P values in SI have fewer known pregnancy-specific functions. CONCLUSIONS: We identified unique placental transcriptional profiles in clinically relevant subgroups of individuals with hypertension in pregnancy. Preeclampsia superimposed on chronic hypertension was molecularly distinct from preeclampsia in individuals without chronic hypertension, and chronic hypertension without preeclampsia, suggesting that preeclampsia superimposed on hypertension may represent a distinct entity.

Mediation effects of DNA methylation and hydroxymethylation on birth outcomes after prenatal per- and polyfluoroalkyl substances (PFAS) exposure in the Michigan mother-infant Pairs cohort.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are chemicals that are resistant to degradation and ubiquitous in our environments. PFAS may impact the developing epigenome, but current human evidence is limited to assessments of total DNA methylation. We assessed associations between first trimester PFAS exposures with newborn DNA methylation, including 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC). DNA methylation mediation of associations between PFAS and birth outcomes were explored in the Michigan Mother Infant Pairs cohort. Nine PFAS were measured in maternal first trimester blood. Seven were highly detected and included for analysis: PFHxS, PFOA, PFOS, PFNA, PFDA, PFUnDA, and MeFOSAA. Bisulfite-converted cord blood DNA (n = 141) and oxidative-bisulfite-converted cord blood (n = 70) were assayed on Illumina MethylationEPIC BeadChips to measure total DNA methylation (5-mC + 5-hmC) and 5-mC/5-hmC. Correcting for multiple comparisons, beta regressions were used to assess associations between levels of PFAS and total methylation, 5-mC, or 5-hmC. Nonlinear mediation analyses were used to assess the epigenetic meditation effect between PFAS and birth outcomes. RESULTS: PFAS was significantly associated with total methylation (q < 0.05: PFHxS-12 sites; PFOS-19 sites; PFOA-2 sites; PFNA-3 sites; PFDA-4 sites). In 72 female infants and 69 male infants, there were sex-specific associations between five PFAS and DNA methylation. 5-mC and 5-hmC were each significantly associated with thousands of sites for PFHxS, PFOS, PFNA, PFDA, PFUnDA, and MeFOSAA (q < 0.05). Clusters of 5-mC and 5-hmC sites were significant mediators between PFNA and PFUnDA and decreased gestational age (q < 0.05). CONCLUSIONS: This study demonstrates the mediation role of specific types of DNA methylation on the relationship between PFAS exposure and birth outcomes. These results suggest that 5-mC and 5-hmC may be more sensitive to the developmental impacts of PFAS than total DNA methylation.

Unicuspid Aortic Valve With Severe Aortic Stenosis and Progressive Heart Failure During Pregnancy.

A 39-year-old gravida 7 para 6 woman with unicuspid aortic valve and severe symptomatic stenosis was admitted to the hospital at 15 weeks gestation. We describe maternal cardiovascular complications and their implication on obstetric and fetal care. We also describe our multidisciplinary approach to caring for this complex patient.