The Association between Sickle Cell Disease and Postpartum Severe Maternal Morbidity.

OBJECTIVE: To compare the risk of severe maternal morbidity (SMM) from the delivery admission to 42 days' postdischarge among persons with sickle cell disease (SCD) to those without SCD. STUDY DESIGN: This retrospective cohort study included deliveries ≥20 weeks' gestation at an urban safety net hospital in Atlanta, GA from 2011 to 2019. The exposure was SCD diagnosis. The outcome was a composite of SMM from the delivery admission to 42 days' postdischarge. SMM indicators as defined by the Centers for Disease Control and Prevention were identified using the International Classification of Diseases, Ninth and Tenth Revisions (ICD-9/10) codes; transfusion of blood products and sickle cell crisis were excluded. RESULTS: Of N = 17,354 delivery admissions, n = 92 (0.53%) had SCD. Persons with SCD versus without SCD had an increased risk of composite SMM (15.22 vs. 2.29%, p < 0.001), acute renal failure (6.52 vs. 0.71%, p < 0.001), acute respiratory distress syndrome (4.35 vs. 0.17%, p < 0.001), puerperal cerebrovascular disorders (3.26 vs. 0.10%, p < 0.001), sepsis (4.35 vs. 0.42%, p < 0.01), air and thrombotic embolism (5.43 vs. 0.10%, p < 0.001), and ventilation (2.17 vs. 0.09%, p < 0.01). Ultimately, those with SCD had an approximately 6-fold higher incidence risk ratio of SMM, which remained after adjustment for confounders (adjusted incidence risk ratio [aIRR]: 5.96, 95% confidence interval [CI]: 3.4-9.19, p < 0.001). Persons with SCD in active vaso-occlusive crisis at the delivery admission had an approximately 9-fold higher risk of SMM up to 42 days' postdischarge compared with those with SCD not in crisis at the delivery admission (incidence: 25.71 vs. 8.77%, p < 0.05; aIRR: 8.92, 95% CI: 4.5-10.04, p < 0.05). Among those with SCD, SMM at the delivery admission was primarily related to renal and cerebrovascular events, whereas most postpartum SMM was related to respiratory events or sepsis. CONCLUSION: SCD is significantly associated with an increased risk of SMM during the delivery admission and through 42 days' postdischarge. Active crisis at delivery further increases the risk of SMM. KEY POINTS: · Sickle cell disease was associated with an approximately 6-fold increased risk of SMM.. · Active vaso-occlusive crisis at delivery was associated with an approximately 9-fold increased risk of SMM.. · 48% of SMM events in persons with SCD occurred postpartum and were respiratory- or sepsis-related..

Characterization of the inflammatory response to COVID-19 illness in pregnancy.

OBJECTIVE: Pregnant patients face greater morbidity and mortality from COVID-19 related illness than their non-pregnant peers. Previous research in non-pregnant patients established that poor clinical outcomes in SARS-CoV-2 positive patients admitted to the ICU were correlated with a significant increase in the proinflammatory markers interleukin (IL)-1ß, IL-6, IL-8, and IL-10. Importantly, high levels of these inflammatory markers have also been associated with adverse pregnancy outcomes, including spontaneous preterm birth, preeclampsia, and severe respiratory disease. STUDY DESIGN: This was a retrospective cohort study that compared the serum inflammatory cytokine profiles of pregnant patients with acute/post-acute SARS-CoV-2 infection to those with previous exposure. All subjects in both cohorts tested positive for SARS-CoV-2 antibodies; however, those in the acute/post-acute infection cohort had a documented positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) result within 30 days of serum sample collection. Serum samples were obtained during prenatal venipuncture from 13 to 39 weeks' gestation and the cohorts were matched by gestational age. The inflammatory cytokines interferon (IFN)-γ, IL-10, IL-1ß, IL-4, IL-6, IL-8, and tumor necrosis factor (TNF)-α were assayed from maternal serum using a standard ELISA assay and median cytokine concentrations were compared using the Mann-Whitney test. RESULTS AND DISCUSSION: We enrolled 50 non-Hispanic Black patients with confirmed COVID-19 infection who received prenatal care at Grady Memorial Hospital in Atlanta, Georgia. Those with acute/post-acute infection (n = 22) had significantly higher concentrations of SARS-CoV-2 antibody, IL-10, IL-1ß, and IL-8, while patients with previous exposure (n = 28) had significantly higher concentrations of IL-4. There were no significant inter-group differences in medical comorbidities. Pregnant patients with acute/post-acute SARS-CoV-2 infection had significantly higher serum concentrations of pro-inflammatory cytokines as compared to those with previous exposure, suggesting that, like in the non-pregnant population, SARS-CoV-2 infection alters the levels of circulating proinflammatory markers during pregnancy. The increased levels of cytokines may contribute to the adverse obstetric outcomes observed with COVID-19 illness.

Antiretroviral Options and Treatment Decisions During Pregnancy.

The majority of pediatric human immunodeficiency virus (HIV) infections are the result of vertical transmissions that occur during pregnancy, childbirth, and breastfeeding. The treatment of all pregnant persons living with HIV remains a global health initiative. Early and consistent use of antiretroviral therapy throughout pregnancy and childbirth drastically reduces the risk of perinatal transmission of HIV, resulting in fewer children living with the disease worldwide. Given that the maternal HIV viral load is the strongest predictor of perinatal transmission, suppressive antiretroviral treatment during pregnancy is the principal means to eliminate transmission of HIV from mother to child. With the use of combined antiretroviral therapy, typically with dual-nucleoside reverse transcriptase inhibitors plus an integrase strand transfer inhibitor or a ritonavir-boosted protease inhibitor, HIV-infected mothers can now achieve virologic suppression to undetectable levels and yield a perinatal transmission rate of less than 2%. Important considerations of HIV treatment in pregnancy include the safety and efficacy of antiretroviral drugs, altered pregnancy-related pharmacokinetics, potential for birth defects or adverse neonatal outcomes, and individualized delivery planning based on maternal viral load. This practical review article summarizes the options, considerations, and recommendations for antiretroviral treatment in pregnancy to reduce perinatal HIV transmission and optimize health outcomes for mothers and infants worldwide.

Characterization of the maternal serum inflammatory profile during pregnancy according to socioeconomic status.

PROBLEM: In pregnancy, lower socioeconomic status (SES) is associated with adverse outcomes, which is partly attributed to chronic inflammation. Our study compared the maternal serum cytokine profiles in patients with low and high SES. METHOD OF STUDY: This retrospective cohort study compared maternal serum cytokine profiles between Medicaid-insured patients who delivered at an urban safety-net hospital (low SES) and privately-insured patients who delivered at a community-based academic hospital (high SES) in Atlanta, GA (n = 32-33/group). Serum samples were obtained during prenatal venipuncture from 13 to 38 weeks' gestation and the cohorts were matched by gestational age. Interferon (IFN)-γ, Interleukin (IL)-10, IL-1ß, IL-4, IL-6, IL-8, and Tumor Necrosis Factor (TNF)-α were assayed from maternal serum samples using a standard ELISA assay. RESULTS: Median concentrations of IL-6, a promotor of chronic inflammation, were higher in the low SES group (0.85 vs. 0.49 pg/mL, p < .001), while median levels of IL-1ß, a potent monocyte activator, and TNF-α, a master regulator of acute inflammation, were lower in the low SES group (0.09 vs. 0.46 pg/mL, p < .001, and 1.23 vs. 1.58 pg/mL, p = .002, respectively) as compared to the high SES group. After adjusting for maternal age, obesity, hypertensive disorders, and gestational age at delivery, the differences in IL-6 and IL-1ß by SES persisted (p = .0002 and p < .0001, respectively). CONCLUSIONS: In this retrospective cohort study, there were significant differences in levels of pro-inflammatory cytokines during pregnancy for groups defined by SES, even after adjustment for confounding variables. Our data are foundational for further research to investigate SES-associated inflammation that may contribute to adverse pregnancy outcomes.

Inorganic Nitrite Supplementation Improves Endothelial Function With Aging: Translational Evidence for Suppression of Mitochondria-Derived Oxidative Stress.

[Figure: see text].