Standard Compared With Extended Red Blood Cell Antigen Matching for Prevention of Subsequent Hemolytic Disease of the Fetus and Newborn: A Systematic Review.

OBJECTIVE: To systematically review and meta-analyze alloimmunization among recipients of red blood cells (RBCs) matched for ABO blood type and Rhesus D (ABO+D) antigen compared with those also matched for c, E, and Kell (cEK). DATA SOURCES: Four online databases (Medline, Scopus, EMBASE, ClinicalTrials.gov) were searched from March 28, 2023, to April 1, 2024. The search protocol was peer reviewed and published on PROSPERO (CRD42023411620). METHODS OF STUDY SELECTION: Studies reporting alloimmunization as the primary outcome among recipients of RBCs matched for ABO+D or additional cEK matching were included. Patients transfused with unmatched RBCs or a mixture of matching regimens were excluded. Risk of bias was assessed with Cochrane Tool to Assess Risk of Bias in Cohort Studies and Tool for Risk of Bias. Random-effects meta-analysis was used to combine effect estimates. TABULATION, INTEGRATION, AND RESULTS: Ten studies met criteria. Risk of bias was low. Overall, 91,221 patients were transfused, of whom 40,220 (44.1%) received additional cEK-matched RBCs. The overall rate of alloimmunization was 6.2% (95% CI, 2.5-14.9%) for ABO+D-only matching and 1.9% (95% CI, 0.7-5.1%) when cEK was added. Time of follow-up antibody testing ranged from 6 to 18 months after transfusion. Additional cEK match was associated with significantly less alloimmunization compared with standard ABO+D match (odds ratio [OR] 0.37, 95% CI, 0.20-0.69). This association remained when chronically transfused patients were excluded (OR 0.65, 95% CI, 0.54-0.79) and for alloimmunization to c, E, or K antigens only (OR 0.29, 95% CI, 0.18-0.47). CONCLUSION: Additional cEK RBC matching protocols were associated with lower odds of recipient alloimmunization. Given severe sequelae of alloimmunization in pregnancy, routine cEK matching for transfusion in people with pregnancy potential younger than age 50 years in the United States merits consideration. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023411620.

Suboptimally Controlled Diabetes in Pregnancy: A Review to Guide Antepartum and Delivery Management.

Importance: Diabetes mellitus is one of the most common complications in pregnancy with adverse maternal and neonatal risks proportional to the degree of suboptimal glycemic control, which is not well defined. Literature guiding providers in identifying and managing patients at highest risk of complications from diabetes is lacking. Objective: This article reviews the definition, epidemiology, and pathophysiology of suboptimal control of diabetes in pregnancy, including "diabetic fetopathy"; explores proposed methods of risk stratification for patients with diabetes; outlines existing antepartum management and delivery timing guidelines; and guides direction for future research. Evidence Acquisition: Original research articles, review articles, and professional society guidelines on diabetes management in pregnancy were reviewed. Results: The reviewed available studies demonstrate worsening maternal and neonatal outcomes associated with suboptimal control; however, the definition of suboptimal based on parameters followed in pregnancy such as blood glucose, hemoglobin A1c, and fetal growth varied from study to study. Studies demonstrating specific associations of adverse outcomes with defined suboptimal control were reviewed and synthesized. Professional society recommendations were also reviewed to summarize current guidelines on antepartum management and delivery planning with respect to diabetes in pregnancy. Conclusions: The literature heterogeneously characterizes suboptimal glucose control and complications related to this during pregnancy in individuals with diabetes. Further research into antepartum management and delivery timing for patients with varying levels of glycemic control and at highest risk for diabetic complications is still needed.

Predictors of Breastfeeding among Women Admitted with Severe Preeclampsia before 34 Weeks.

OBJECTIVE: Patients with severe preeclampsia (sPREX) face barriers to successful breastfeeding (BF), including an increased risk of maternal and newborn complications, prematurity, and low birth weight. Patients with early-onset sPREX (before 34 weeks' gestation) may be at even greater risk, yet there are little data available on factors associated with BF challenges in this population. We describe rates of BF initiation at hospital discharge and BF continuation at postpartum (PP) visit and identify factors associated with BF noninitiation and BF cessation among patients admitted with early-onset sPREX. STUDY DESIGN: Retrospective cohort study of women with sPREX admitted at less than 34 weeks' gestation to a single tertiary center (2013-2019). Demographic, antepartum, and delivery characteristics were evaluated. Factors associated with BF noninitiation at maternal discharge and with BF cessation at routine PP were assessed. Patients with intrauterine or neonatal demise and those missing BF data were excluded. Bivariate statistics were used to compare characteristics and Poisson regression was used to estimate relative risks (RR). RESULTS: Of 255 patients with early-onset sPREX, 228 (89.4%) had BF initiation at maternal hospital discharge. Initiation of BF occurred less frequently among patients with tobacco use in pregnancy (7.5 vs. 37.0%, χ 2, p < 0.001, RR: 0.69 [95% confidence interval, CI: 0.52-0.92]). At 6 weeks' PP, 159 of 199 (79.9%) patients had BF continuation. Maternal age under 20 years (1.9 vs. 17.5%, χ 2, p = 0.01, RR: 0.36 [95% CI: 0.14-0.91]) and experiencing maternal morbidity (25.2 vs. 45.0%, χ 2, p = 0.01, RR: 0.80 [95% CI: 0.66-0.96]) were associated with BF cessation at the PP visit. CONCLUSION: Among patients with early sPREX, tobacco use in pregnancy was associated with noninitiation of BF at discharge, whereas young maternal age and maternal morbidity were associated with cessation of BF by routine PP visit. Further research is needed on how to support BF in this population, especially among patients with these associated factors. KEY POINTS: · Tobacco use was associated with BF noninitiation in patients with early preeclampsia.. · Maternal age < 20 and maternal morbidity were associated with BF cessation by PP visit.. · BF support for patients with risk factors is important for BF success PP..

High rates of venous thromboembolism among deliveries complicated by cancer.

BACKGROUND: Venous thromboembolism (VTE) risk is increased independently by both cancer and pregnancy. OBJECTIVES: To estimate VTE risk in the postpartum period among patients delivering with a cancer diagnosis, stratified by cancer type and delivery route. METHODS: We performed a retrospective cohort study utilizing the large, all-payer Nationwide Readmissions Database from October 2015 through December 2020. We identified delivery hospitalizations, cancer diagnoses, and VTE using patient demographics and diagnosis codes. The primary outcome was VTE incidence at 42 and 330 days from delivery admission date, comparing patients with and without cancer diagnoses. A secondary analysis included VTE risk stratified by cancer diagnosis and delivery route. Outcomes were compared using inverse probability-weighted survival curves. RESULTS: The study population included 9 793 503 delivery hospitalizations (weighted estimate, 18 207 346), with a weighted estimate of 10 428 (0.06%) pregnant patients with cancer. Individuals with cancer were older, with higher rates of comorbid conditions, than those without cancer. VTE incidence in individuals with cancer at 42 and 330 days was 1.11% and 2.19%, respectively, vs 0.11% and 0.14%, respectively, in those without cancer. At 330 days, this finding was significant in both unadjusted (relative risk, 15.52; 95% CI, 11.54-19.51) and adjusted (relative risk, 9.68; 95% CI, 7.18-12.18) models. Stratification by cancer type and delivery route demonstrated elevated VTE risk across cancer types, with cesarean delivery conferring a greater risk. CONCLUSION: Cancer in pregnancy confers excess thromboembolic risk extending beyond the immediate postpartum period. Further study is needed to identify optimal VTE prophylactic strategies for this population.

Maternal morbidity and mortality among patients with cancer at time of delivery.

BACKGROUND: Individuals with cancer during pregnancy are a medically complex patient population that is anticipated to grow. A better understanding of this population and patterns of risk at time of delivery would offer an opportunity for providers to mitigate maternal morbidity. OBJECTIVE: This study aimed to estimate the prevalence in the United States of concurrent cancer diagnoses at time of delivery by cancer type and associated maternal morbidity and mortality. STUDY DESIGN: Using the National Inpatient Sample, we identified delivery-associated hospitalizations between 2007 and 2018. Concurrent cancer diagnoses were classified using the Clinical Classifications Software. Main outcomes included severe maternal morbidity, as defined by the Centers for Disease Control and Prevention indicators, and mortality during delivery hospitalization. We calculated adjusted rates for cancer diagnosis at time of delivery and adjusted odds ratios of severe maternal morbidity and maternal death during hospitalization using survey-weighted multivariable logistic regression models. RESULTS: In this sample of 9,418,761 delivery-associated hospitalizations, 63 per 100,000 deliveries had a concurrent cancer diagnosis (95% confidence interval, 60-66; national weighted estimate, 46,654,042). The most common cancer types were breast cancer (8.4 per 100,000 deliveries), leukemia (8.4 per 100,000 deliveries), Hodgkin lymphoma (7.4 per 100,000 deliveries), non-Hodgkin lymphoma (5.4 per 100,000 deliveries), and thyroid cancer (4.0 per 100,000 deliveries). Patients with cancer were at significantly higher risk for any severe maternal morbidity (adjusted odds ratio, 5.25; 95% confidence interval, 4.73-5.83) and maternal death (adjusted odds ratio, 67.5; 95% confidence interval, 45.1-101.4). Risks of hysterectomy (adjusted odds ratio, 16.92; 95% confidence interval, 13.96-20.52), acute respiratory distress (adjusted odds ratio, 12.76; 95% confidence interval, 9.92-16.42), sepsis (adjusted odds ratio, 11.91; 95% confidence interval, 8.68-16.32), and embolism (adjusted odds ratio, 11.12; 95% confidence interval, 6.94-17.82) were particularly heightened among patients with cancer. Patients with leukemia, specifically, had the highest risk of adverse maternal outcomes (adjusted rate, 113 per 1000 deliveries; 95% confidence interval, 91-135 per 1000) when evaluating risk by cancer type. CONCLUSION: Patients with cancer are at markedly increased risk of maternal morbidity and all-cause mortality during delivery-associated hospitalization. Risk is distributed unevenly within this population, with certain cancer types carrying unique risks for specific morbidity events.

Preterm Birth Rates and Racial Disparities during the COVID-19 Pandemic at a Single Institution in the Southeastern United States.

OBJECTIVE: The COVID pandemic has been associated with varied effects on preterm birth (PTB). We sought to compare rates of PTB during the pre- and post vaccination COVID periods with pre-pandemic PTB rates, stratified by race and ethnicity. STUDY DESIGN: Retrospective cohort comparing all deliveries over 20 weeks at a single tertiary center during "early" (March 2020-June 2020) versus "late" COVID (March 2021-June 2021), and "late" COVID versus pre-COVID (March to June 2014-2019). PTBs <37, <34, and <28 weeks were compared and stratified by race/ethnicity. RESULTS: A total of 16,483 deliveries occurred including 2,068 "early" COVID, 2,115 "late" COVID, and 12,300 pre-COVID. The PTB rate during "late" COVID was lower compared to "early" COVID (12.1 vs. 14.6%, p = 0.02). Rate of PTB <34 was also lower during "late" COVID (4.4 vs. 5.7%, p = 0.05). PTB <28 did not differ. When controlling for prior PTB, "late" COVID remained associated with a decreased risk of PTB compared to "early" COVID, adjusted odds ratio (aOR) of 0.82 (95% confidence interval [CI]: 0.68, 0.98). Although there was no difference in PTB among Hispanic individuals when comparing "late" COVID versus pre-COVID, when further subdivided, a small number of Hispanic Puerto Rican individuals had higher odds of PTB < 37 during "late" COVID versus pre-COVID (aOR = 4.29 [95% CI: 1.12, 16.4]). Additionally, White individuals had reduced odds of PTB <37 (aOR = 0.80 [95% CI: 0.65, 0.98]) during "late" COVID versus pre-COVID while the PTB rate was unchanged when comparing "late" COVID versus pre-COVID in all other racial and ethnic groups. CONCLUSION: During 2021, PTB rates decreased from rates observed in 2020 at the height of COVID restrictions. Among White birthing individuals, PTB decreased in 2021 compared to pre-COVID rates. This decrease was not observed in Black and Hispanic birthing individuals. These data highlight the continued racially disparate impact of the COVID-19 pandemic on PTB rates. KEY POINTS: · The COVID-19 pandemic has been associated with varied effects on the preterm birth (PTB) rate.. · PTB rates decreased in "late" COVID compared to "early" COVID.. · When stratified, PTB decreased among white individuals, but not in Black or Hispanic individuals..

Society for Maternal-Fetal Medicine Special Statement: Quality metric on the rate of postpartum diabetes screening after pregnancies with gestational diabetes mellitus.

As many as 1 in 3 patients with gestational diabetes mellitus have impaired glucose metabolism when screened postpartum. These patients have a 40% to 70% lifetime risk of progression to type 2 diabetes mellitus, but progression can be delayed or prevented by lifestyle interventions or medication. The American College of Obstetricians and Gynecologists and the American Diabetes Association recommend a glucose tolerance test at 4 to 12 weeks postpartum for all patients with gestational diabetes mellitus. Despite these recommendations, postpartum screening rates are typically <50%, representing a major healthcare "quality gap." The Society for Maternal-Fetal Medicine proposes a uniform metric that identifies the percentage of persons with gestational diabetes mellitus who completed a 75-g, 2-hour glucose tolerance test within 12 weeks after delivery. The metric is designed to be measured using diagnosis and procedure codes in payor claims data. Barriers to screening are discussed. Possible uses of the metric for quality improvement projects are outlined. Increasing the rate of postpartum diabetes screening should facilitate timely referral to implement lifestyle modifications, medication, and long-term follow-up. Use of the metric in financial incentive programs is discouraged at this time.

Survey of Obstetric Providers to Assess the Knowledge and Management of a Reported Penicillin Allergy in Pregnant Women.

OBJECTIVE: Penicillin allergy is the most commonly reported drug allergy in the United States; however, less than 10% of individuals labeled with a penicillin allergy are truly allergic. A reported penicillin allergy in pregnancy is associated with adverse maternal and perinatal outcomes. Despite recommendations for penicillin allergy testing in pregnancy, limited literature regarding obstetric providers' comfort and knowledge in addressing penicillin allergy and referral patterns exists. The objective of this study is to survey obstetric providers to assess their clinical practice patterns and baseline penicillin allergy knowledge, identify potential knowledge gaps in the management of pregnant patients with reported penicillin allergy, and measure the impact of an educational intervention on provider knowledge and practice patterns. STUDY DESIGN: An anonymous, electronic 23-question survey administered to all obstetric providers at a single academic medical center assessed obstetric provider characteristics, self-reported antibiotic practice patterns, and antibiotic allergy knowledge before (June 19, 2020) and after (September 16, 2020) a penicillin allergy educational intervention, which consisted of multiple small-group educational sessions and a culminating departmental educational session. Discrete knowledge comparison by provider type and experience level of pre- and postintervention was performed using chi-square tests. RESULTS: Of 277 obstetric providers invited, 124 (45%) responded preintervention and 62 (22%) postintervention. In total, 27% correctly identified the percentage of patients labeled penicillin allergic who would tolerate penicillins, 45% identified cephalosporin cross-reactivity, 59% understood penicillin allergies can wane, and 54% identified penicillin skin testing (PST) as a valid allergy verification tool. Among 48 respondents who attended educational sessions and responded postintervention, their knowledge of penicillin allergy waning (79% preeducation vs. 98% posteducation, p < 0.01) and PST as a valid tool for penicillin allergy verification (50% preeducation vs. 83% posteducation, p < 0.01) improved. CONCLUSION: Knowledge gaps related to penicillin allergy exist among obstetric providers. Educational initiatives may improve provider knowledge, help in the identification of patients requiring penicillin allergy evaluation, and reduce referral barriers. KEY POINTS: · Obstetric providers lack adequate knowledge of penicillin allergy.. · Educational interventions can improve discrete knowledge.. · Limited knowledge is a barrier to allergy referral for penicillin allergy delabeling..

Outpatient penicillin allergy evaluation during pregnancy and associated clinical outcomes.

BACKGROUND: Beta-lactam antibiotics are often clinically indicated in the peripartum period, posing a challenge for pregnant women who report a penicillin allergy. Allergy verification testing is rarely performed during pregnancy, even though most women do not have a true allergy. OBJECTIVE: This study aimed to evaluate a hospital-wide multidisciplinary program introduced in August 2020 to identify, refer, evaluate, and test pregnant women with unverified penicillin allergies and assess its association with maternal and neonatal outcomes. STUDY DESIGN: We conducted a retrospective cohort study at a large academic hospital of all pregnant women with a penicillin allergy documented in the electronic medical record who delivered from September 2020 to October 2021. Data were abstracted by medical record review. Women referred for penicillin allergy evaluation were compared with those who were not. Maternal outcomes were alternative antibiotic (clindamycin or vancomycin) use, postpartum infection, and maternal length of postpartum hospital stay. Neonatal outcomes were intensive care unit admission, postnatal blood draw, antibiotic treatment, and birth hospitalization length of hospital stay. Bivariate and multivariable analyses were performed. RESULTS: Of 689 women with a documented penicillin allergy, 232 (33.7%) were referred for allergy evaluation during the study period. Of those referred, 175 (75.4%) underwent allergy consultation, and of these patients, 167 (95.4%) were considered appropriate for allergy verification testing. Of note, 117 women (70.1%) underwent skin testing with or without graded oral amoxicillin drug challenge, and all but 1 woman (99.1%) were found to be penicillin tolerant. Moreover, 5 additional women were delabeled of their penicillin allergy based on history and pharmacy confirmation of penicillin tolerance subsequent to index reaction. Referred women had a 62% lower likelihood of receiving an alternative antibiotic than those who were not referred, and this significance persisted even after adjusting for potential confounders (adjusted odds ratio, 0.49; 95% confidence interval, 0.27-0.89). Other maternal and neonatal adverse outcomes were less frequent in those referred, but these associations did not reach statistical significance. CONCLUSION: This study documented the feasibility, safety, and clinical benefit of an outpatient penicillin allergy referral program for pregnant women. Referred patients were significantly less likely to receive alternative antibiotics; however, more patients are needed to assess whether there are additional clinical benefits.

Coronavirus disease 2019 pregnancy outcomes in a racially and ethnically diverse population.

Background: Older age and medical comorbidities are identified risk factors for developing severe coronavirus disease 2019. However, there are limited data on risk stratification, clinical and laboratory course, and optimal management of coronavirus disease 2019 in pregnancy. Objective: Our study aimed to describe the clinical course of coronavirus disease 2019, effect of comorbidities on disease severity, laboratory trends, and pregnancy outcomes of symptomatic and asymptomatic severe acute respiratory syndrome coronavirus 2-positive pregnant women. Study Design: This is a case series of pregnant and postpartum women who received positive test results for severe acute respiratory syndrome coronavirus 2 between March 3, 2020, and May 11, 2020, within 3 hospitals of the Yale New Haven Health delivery network. Charts were reviewed for basic sociodemographic and prepregnancy characteristics, coronavirus disease 2019 course, laboratory values, and pregnancy outcomes. Results: Of the 1567 tested pregnant and postpartum women between March 3, 2020, and May 11, 2020, 9% (n=141) had a positive severe acute respiratory syndrome coronavirus 2 result. Hispanic women were overrepresented in the severe acute respiratory syndrome coronavirus 2-positive group (n=61; 43.8%). In addition, Hispanic ethnicity was associated with a higher rate of moderate and severe diseases than non-Hispanic (18% [11/61] vs 3.8% [3/78], respectively; odds ratio, 5.5; 95% confidence interval, 1.46-20.7; P=.01). Of note, 44 women (31.2%) were asymptomatic, 37 of whom (26.2%) were diagnosed on universal screening upon admission for delivery. Moreover, 59% (n=83) were diagnosed before delivery, 36% (n=51) upon presentation for childbirth, and 5% (n=7) after delivery. Severe disease was diagnosed in 6 cases (4.3%), and there was 1 maternal death. Obese women were more likely to develop moderate and severe diseases than nonobese women (16.4% [9/55] vs 3.8% [3/79]; odds ratio, 4.96; 95% confidence interval, 1.28-19.25; P=.02). Hypertensive disorders of pregnancy were diagnosed in 22.3% of women (17/77) who delivered after 20 weeks' gestation. Higher levels of C-reactive protein during antepartum coronavirus disease 2019-related admission were more common in women with worse clinical course; however, this association did not reach statistical significance. Conclusion: Coronavirus disease 2019 in pregnancy may result in severe disease and death. Hispanic women were more likely to receive a positive test result for severe acute respiratory syndrome 2 than other ethnic groups. Obesity and Hispanic ethnicity represent risk factors for moderate and severe diseases.