Characteristics and Outcomes of Patients With Pregnancy-Related End-Stage Kidney Disease.

Importance: The incidence of pregnancy-related acute kidney injury is increasing and is associated with significant maternal morbidity including progression to end-stage kidney disease (ESKD). Little is known about characteristics and long-term outcomes of patients who develop pregnancy-related ESKD. Objectives: To examine the characteristics and clinical outcomes of patients with pregnancy-related ESKD and to investigate associations between pre-ESKD nephrology care and outcomes. Design, Setting, and Participants: This was a cohort study of 183 640 reproductive-aged women with incident ESKD between January 1, 2000, and November 20, 2020, from the US Renal Data System and maternal data from births captured in the US Centers for Disease Control and Prevention publicly available natality data. Data were analyzed from December 2022 to June 2023. Exposure: Pregnancy-related primary cause of ESKD, per International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes reported at ESKD onset by the primary nephrologist on Centers for Medicare and Medicaid Services form 2728. Main Outcomes Measures: Multivariable Cox proportional hazards and competing risk models were constructed to examine time to (1) mortality, (2) access to kidney transplant (joining the waiting list or receiving a live donor transplant), and (3) receipt of transplant after joining the waitlist. Results: A total of 341 patients with a pregnancy-related primary cause of ESKD were identified (mean [SD] age 30.2 [7.3]). Compared with the general US birthing population, Black patients were overrepresented among those with pregnancy-related ESKD (109 patients [31.9%] vs 585 268 patients [16.2%]). In adjusted analyses, patients with pregnancy-related ESKD had similar or lower hazards of mortality compared with those with glomerulonephritis or cystic kidney disease (adjusted hazard ratio [aHR], 0.96; 95% CI, 0.76-1.19), diabetes or hypertension (aHR, 0.49; 95% CI, 0.39-0.61), or other or unknown primary causes of ESKD (aHR, 0.60; 95% CI, 0.48-0.75). Despite this, patients with pregnancy-related ESKD had significantly lower access to kidney transplant compared with those with other causes of ESKD, including (1) glomerulonephritis or cystic kidney disease (adjusted subhazard ratio [aSHR], 0.51; 95% CI, 0.43-0.66), (2) diabetes or hypertension (aSHR, 0.81; 95% CI, 0.67-0.98), and (3) other or unkown cause (aSHR, 0.82; 95% CI, 0.67-0.99). Those with pregnancy-related ESKD were less likely to have nephrology care or have a graft or arteriovenous fistula placed before ESKD onset (nephrology care: adjusted relative risk [aRR], 0.47; 95% CI, 0.40-0.56; graft or arteriovenous fistula placed: aRR, 0.31; 95% CI, 0.17-0.57). Conclusion and Relevance: In this study, those with pregnancy-related ESKD had reduced access to transplant and nephrology care, which could exacerbate existing disparities in a disproportionately Black population. Increased access to care could improve quality of life and health outcomes among these young adults with high potential for long-term survival.

Clinical and economic evaluation of a proteomic biomarker preterm birth risk predictor: cost-effectiveness modeling of prenatal interventions applied to predicted higher-risk pregnancies within a large and diverse cohort.

OBJECTIVES: Preterm birth occurs in more than 10% of U.S. births and is the leading cause of U.S. neonatal deaths, with estimated annual costs exceeding $25 billion USD. Using real-world data, we modeled the potential clinical and economic utility of a prematurity-reduction program comprising screening in a racially and ethnically diverse population with a validated proteomic biomarker risk predictor, followed by case management with or without pharmacological treatment. METHODS: The ACCORDANT microsimulation model used individual patient data from a prespecified, randomly selected sub-cohort (N = 847) of a multicenter, observational study of U.S. subjects receiving standard obstetric care with masked risk predictor assessment (TREETOP; NCT02787213). All subjects were included in three arms across 500 simulated trials: standard of care (SoC, control); risk predictor/case management comprising increased outreach, education and specialist care (RP-CM, active); and multimodal management (risk predictor/case management with pharmacological treatment) (RP-MM, active). In the active arms, only subjects stratified as higher risk by the predictor were modeled as receiving the intervention, whereas lower-risk subjects received standard care. Higher-risk subjects' gestational ages at birth were shifted based on published efficacies, and dependent outcomes, calibrated using national datasets, were changed accordingly. Subjects otherwise retained their original TREETOP outcomes. Arms were compared using survival analysis for neonatal and maternal hospital length of stay, bootstrap intervals for neonatal cost, and Fisher's exact test for neonatal morbidity/mortality (significance, p < .05). RESULTS: The model predicted improvements for all outcomes. RP-CM decreased neonatal and maternal hospital stay by 19% (p = .029) and 8.5% (p = .001), respectively; neonatal costs' point estimate by 16% (p = .098); and moderate-to-severe neonatal morbidity/mortality by 29% (p = .025). RP-MM strengthened observed reductions and significance. Point estimates of benefit did not differ by race/ethnicity. CONCLUSIONS: Modeled evaluation of a biomarker-based test-and-treat strategy in a diverse population predicts clinically and economically meaningful improvements in neonatal and maternal outcomes.

Preterm birth, defined as delivery before 37 weeks' gestation, is the leading cause of illness and death in newborns. In the United States, more than 10% of infants are born prematurely, and this rate is substantially higher in lower-income, inner-city and Black populations. Prematurity associates with greatly increased risk of short- and long-term medical complications and can generate significant costs throughout the lives of affected children. Annual U.S. health care costs to manage short- and long-term prematurity complications are estimated to exceed $25 billion.Clinical interventions, including case management (increased patient outreach, education and specialist care), pharmacological treatment and their combination can provide benefit to pregnancies at higher risk for preterm birth. Early and sensitive risk detection, however, remains a challenge.We have developed and validated a proteomic biomarker risk predictor for early identification of pregnancies at increased risk of preterm birth. The ACCORDANT study modeled treatments with real-world patient data from a racially and ethnically diverse U.S. population to compare the benefits of risk predictor testing plus clinical intervention for higher-risk pregnancies versus no testing and standard care. Measured outcomes included neonatal and maternal length of hospital stay, associated costs and neonatal morbidity and mortality. The model projected improved outcomes and reduced costs across all subjects, including ethnic and racial minority populations, when predicted higher-risk pregnancies were treated using case management with or without pharmacological treatment. The biomarker risk predictor shows high potential to be a clinically important component of risk stratification for pregnant women, leading to tangible gains in reducing the impact of preterm birth.

Trends in Opioid and Psychotropic Prescription in Pregnancy in the United States From 2001 to 2015 in a Privately Insured Population : A Cross-sectional Study.

BACKGROUND: Opioid and psychotropic prescriptions are common during pregnancy. Little is known about coprescriptions of both medications in this setting. OBJECTIVE: To describe opioid prescription among women who are prescribed psychotropics compared with women who are not. DESIGN: Cross-sectional study. SETTING: U.S. commercial insurance beneficiaries from MarketScan (2001 to 2015). PARTICIPANTS: Pregnant women at 22 weeks' gestation or greater who were insured continuously for 3 months or more before pregnancy through delivery. MEASUREMENTS: Opioid prescription, dosage thresholds (morphine milligram equivalents [MME] of ≥50/day and ≥90/day), number of opioid agents (≥2), and duration (≥30 days) among those with and without prescription of psychotropics, from 2011 to 2015. RESULTS: Among 958 980 pregnant women, 10% received opioids only, 6% psychotropics only, and 2% opioids with coprescription of psychotropics. Opioid prescription was higher among women prescribed psychotropics versus those who were not (26.5% vs. 10.7%). From 2001 to 2015, psychotropic prescription overall increased from 4.4% to 7.6%, opioid prescription without coprescription of psychotropics decreased from 11.9% to 8.4%, and opioids with coprescription decreased from 28.1% to 22.0%. Morphine milligram equivalents of 50 or greater per day decreased for women with and without coprescription (29.6% to 17.3% and 22.8% to 18.5%, respectively); MME of 90 or greater per day also decreased in both groups (15.0% to 4.7% and 11.5% to 4.2%, respectively). Women prescribed opioids only were more likely to have an antepartum hospitalization compared with those with neither prescription, as were women with coprescription versus those prescribed psychotropics only. Compared with those prescribed opioids only, women with coprescriptions were more likely to exceed MME of 90 or greater per day and to be prescribed 2 or more opioid agents and for 30 days or longer. Number and duration of opioids increased with benzodiazepine and gabapentin coprescription. LIMITATION: Inability to determine appropriateness of prescribing or overdose events. CONCLUSION: Opioids are frequently coprescribed with psychotropic medication during pregnancy and are associated with antepartum hospitalization. A substantial proportion of pregnant women are prescribed opioids at doses that increase overdose risk and exceed daily recommendations. PRIMARY FUNDING SOURCE: None.

Predictors of Low Uptake of Prenatal Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Immunization in Privately Insured Women in the United States.

OBJECTIVE: To examine the uptake of prenatal tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) immunization among pregnant women in the United States. METHODS: Using MarketScan data, we conducted a historical cohort study among pregnant women with employer-based commercial insurance in the United States who delivered between January 1, 2010, and December 31, 2014. We examined temporal trends of uptake, predictors of uptake, and timing of Tdap immunization. RESULTS: Among 1,222,384 eligible pregnancies in 1,147,711 women, receipt of prenatal Tdap immunization increased from 0.0% of women who delivered in January 2010 to 9.8% who delivered in October 2012 (the date of the recommendation by the Advisory Committee on Immunization Practices for Tdap during every pregnancy) to 44.4% who delivered in December 2014. Among women who received Tdap during pregnancy, the majority were immunized between 27 weeks and 36 6/7 weeks of gestation per the Advisory Committee on Immunization Practices recommendation. In multivariable analyses among women who delivered between November 2012 and December 2014, rates of prenatal Tdap immunization were lower for women younger than 25 years of age (eg, 20-24 compared with 30-34 years rate ratio [RR] 0.83, 95% confidence interval [CI] 0.85-0.88), with other children (eg, three compared with zero children: RR 0.86, 95% CI 0.84-0.88), residing in the South compared with the Midwest (RR 0.81, 95% CI 0.80-0.82), or with emergency department visits in early pregnancy (RR 0.93, 95% CI 0.92-0.95). The proportion of pregnant women who received prenatal Tdap increased with increasing gestational age at birth. CONCLUSION: By the end of 2014, fewer than half of pregnant women in the United States were receiving prenatal Tdap immunization. Implementation and dissemination strategies are needed to increase Tdap coverage among pregnant women, especially those who are young, have other children, or reside in the South.

Severe preeclampsia and maternal self-report of oral health, hygiene, and dental care.

BACKGROUND: Maternal periodontal disease diagnosed by a detailed oral health examination is associated with preeclampsia. Our objective was to measure the association between maternal self-report of oral symptoms/problems, oral hygiene practices, and/or dental service use before or during pregnancy and severe preeclampsia. METHODS: A written questionnaire was administered to pregnant females at the time of prenatal ultrasound and outcomes were ascertained by chart abstraction. The χ(2) test compared maternal oral symptoms/problems, hygiene practices, and dental service use between females with severe preeclampsia versus normotensive females. Multivariable logistic regression was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for severe preeclampsia. RESULTS: A total of 48 (10%) of 470 females reported ≥2 oral symptoms/problems in the 6 months before pregnancy and 77 (16%) since pregnancy. Fifty-one (11%) reported previous periodontal treatment. Twenty-eight (6%) of 470 developed severe preeclampsia. Females with a history of periodontal treatment were more likely to develop severe preeclampsia (aOR = 3.71; 95% CI = 1.40 to 9.83) than females without a history of periodontal treatment. Self-reported oral health symptoms/problems, oral hygiene practices, or dental service use before or during pregnancy were not associated with severe preeclampsia when considered in the context of other maternal risk factors. CONCLUSION: Maternal self-report of previous periodontal treatment before pregnancy is associated with severe preeclampsia.

Knowledge and beliefs regarding oral health among pregnant women.

BACKGROUND: Racial or ethnic and economic disparities exist in terms of oral diseases among pregnant women and children. The authors hypothesized that women of a racial or ethnic minority have less oral health knowledge than do women not of a racial or ethnic minority. Therefore, the authors conducted a study to assess and compare maternal oral health knowledge and beliefs and to determine if maternal race and ethnicity or other maternal factors contributed to women's knowledge or beliefs. METHODS: The authors administered a written oral health questionnaire to pregnant women. The authors calculated the participants' knowledge and belief scores on the basis of correct answers or answers supporting positive oral health behaviors. They conducted multivariable analysis of variance to assess associations between oral health knowledge and belief scores and characteristics. RESULTS: The authors enrolled 615 women in the study, and 599 (97.4 percent) completed the questionnaire. Of 599 participants, 573 (95.7 percent) knew that sugar intake is associated with caries. Almost one-half (295 participants [49.2 percent]) did not know that caries and periodontal disease are oral infections. Median (interquartile range) knowledge and belief scores were 6.0 (5.5-7.0) and 6.0 (5.0-7.0), respectively. Hispanic women had median (interquartile range) knowledge and belief scores significantly lower than those of white or African American women (6.0 [4.0-7.0] versus 7.0 [6.0-7.0] versus 7.0 [6.0-7.0], respectively [P < .001]; and 5.0 [4.0-6.0] versus 6.0 [5.0-7.0] versus 6.0 [5.0-7.0], respectively [P < .001]). Multivariable analysis of variance results showed that being of Hispanic ethnicity was associated significantly with a lower knowledge score, and that an education level of eighth grade or less was associated significantly with a lower belief score. CONCLUSIONS: Pregnant women have some oral health knowledge. Knowledge varied according to maternal race or ethnicity, and beliefs varied according to maternal education. Including oral health education as a part of prenatal care may improve knowledge regarding the importance of oral health among vulnerable pregnant women, thereby improving their oral health and that of their children. CLINICAL IMPLICATIONS: Including oral health education as a part of prenatal care should be considered.

Routine antenatal thrombophilia screening in high-risk pregnancies: a decision analysis.

Thrombophilias have been implicated in complications related to ischemic placental disease including recurrent pregnancy loss, intrauterine fetal demise, preeclampsia, fetal growth restriction, placental abruption, and preterm delivery. Maternal screening and treatment may lower the recurrence of these outcomes. Our objective was to estimate if antenatal screening for thrombophilias with the intention to offer treatment among women with a prior adverse pregnancy outcome (APO) is preferable to no screening. A decision-analytical model was constructed for pregnant women with prior APO, comparing screening for thrombophilia with intention to treat with no screening. Values obtained from previously published studies include probability of positive test: 0.3 (0.1 to 0.6); good outcome with treatment: 0.9 (0.3 to 0.99); no thrombophilia, good outcome: 0.75 (0.5 to 0.9); test negative, thrombophilia positive: 0.05 (0.01 to 0.1); test negative, thrombophilia positive, good outcome: 0.75 (0.5 to 0.9); thrombophilia/test negative, good outcome: 0.98 (0.5 to 0.99). Sensitivity analyses were run over a wide range of assumptions. Thrombophilia screening with intention to treat in women with prior APO associated with ischemic placental disease is the strategy of choice compared with no testing over a wide range of assumptions. Sensitivity analyses support this to be robust. Women with poor pregnancy history related to placental ischemic disease may benefit from thrombophilia screening and treatment in a subsequent pregnancy.

Oral hygiene practices and dental service utilization among pregnant women.

BACKGROUND: Daily oral hygiene and regular dental visits are important components of oral health care. The authors' objective in this study was to examine women's oral hygiene practices and use of dental services during pregnancy. METHODS: The authors developed a written oral health questionnaire and administered it to 599 pregnant women. They collected demographic information, as well as data on oral hygiene practices and use of dental services during pregnancy. They used chi2 and multivariable logistic regression models to assess associations between oral hygiene practice and dental service use during pregnancy and to identify maternal predictor variables. RESULTS: Of the 599 participants, 83 percent (n=497) reported brushing once or twice per day. Twenty-four percent (n=141) reported flossing at least once daily; Hispanic women were more likely to floss than were white or African American women (28 percent [52 of 183] versus 22 percent [54 of 248] versus 19 percent [23 of 121], respectively, P<.001). Seventy-four percent (n=442) of the participants reported having received no routine dental care during pregnancy. Hispanic women were significantly less likely than were black or white women to receive routine dental care during pregnancy (13 percent versus 21 percent versus 36 percent, respectively, P<.001). The authors found that being older than 36 years, being of Hispanic race or ethnicity, having an annual income of less than $30,000, flossing infrequently and receiving no dental care when not pregnant were significantly associated with lack of routine dental care during pregnancy (adjusted odds ratios, 95 percent confidence intervals: 2.56 [1.33-4.92]; 2.19 [1.11-4.29]; 2.02 [1.12-3.65]; 1.86 [1.13-3.07]; and 4.35 [2.5-7.69], respectively). A woman's lack of receiving routine dental care when not pregnant was the most significant predictor of lack of receiving dental care during pregnancy. CONCLUSION: Racial, ethnic and economic disparities related to oral hygiene practices and dental service utilization during pregnancy exist. CLINICAL IMPLICATIONS: Medical and dental care providers who treat women of reproductive age and pregnant women need to develop policy strategies to address this population's access barriers to, and use of, dental care services.

Periodontal disease early in pregnancy is associated with maternal systemic inflammation among African American women.

BACKGROUND: Maternal periodontal disease is a chronic oral infection with local and systemic inflammatory responses and may be associated with adverse pregnancy outcomes. This study determined whether maternal periodontal disease in early pregnancy is associated with elevated serum C-reactive protein (CRP) levels and whether maternal race influences the relationship between maternal periodontal disease and systemic inflammatory responses. METHODS: A secondary analysis of prospectively collected data from the Oral Conditions and Pregnancy study was conducted. Healthy women at <26 weeks of gestation underwent an oral health examination and had blood collected. Periodontal disease was categorized by clinical criteria, and maternal serum was analyzed for CRP levels using highly sensitive enzyme-linked immunosorbent assay kits. An elevated CRP level was defined as >75th percentile. Demographic and medical data were obtained from the women's charts. Chi-square and multivariable logistic regression models were used to determine maternal factors associated with an elevated CRP. An adjusted odds ratio (OR) for elevated CRP levels was calculated and stratified by race and periodontal disease category. RESULTS: The median (interquartile) CRP level was 4.8 (0.6 to 15.7) microg/ml, and an elevated CRP level (>75th percentile) was 15.7 microg/ml. African American race and moderate/severe periodontal disease were significantly associated with elevated CRP levels. When stratified by race, moderate/severe periodontal disease remained associated with an elevated CRP level among African American women (adjusted OR: 4.0; 95% confidence interval [CI]: 1.2 to 8.5) but not among white women (adjusted OR: 0.9; 95% CI: 0.2 to 3.6) after adjusting for age, smoking, parity, marital status, insurance status, and weight. CONCLUSION: Among African American women, moderate/severe periodontal disease is associated with elevated CRP levels early in pregnancy.

Projected benefits of universal or scheduled antepartum corticosteroids to prevent neonatal morbidity: a decision analysis.

OBJECTIVE: The purpose of this study was to compare strategies of corticosteroid administration for the prevention of neonatal morbidity and death. STUDY DESIGN: A Markov decision model compared 3 strategies of antepartum corticosteroid administration: (1) to all pregnant women (universal), (2) to all pregnant women with a previous preterm delivery (high risk), and (3) to women who had preterm labor symptoms that placed them at risk for delivery within 7 days (current). A second model with addition of a "rescue" arm to capture women who remained undelivered was also created. RESULTS: Compared with the current strategy, the universal strategy would result in roughly 1000 fewer cases of respiratory distress syndrome and > 3 million more women would receive corticosteroids annually. The addition of a rescue arm further reduces morbidity and mortality rates. CONCLUSION: A universal strategy of corticosteroid administration confers potential benefit for the prevention neonatal morbidity or death over the current strategy but requires that a large number of women be treated.