Faculty Bibliography

Obesity has been associated with non-Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome-wide association studies of European ancestry (N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.18, 95% confidence interval (95% CI): 1.05-1.33, p = .005]. This finding was consistent with Mendelian randomization analyses, which demonstrated a similar increased risk of DLBCL with higher genetically determined BMI (OR_{per SD} = 1.12, 95% CI: 1.02-1.23, p = .03). No significant associations were observed with other NHL subtypes. Our study demonstrates a positive link between a genetically determined BMI and an increased risk of DLBCL, providing additional support for increased adiposity as a risk factor for DLBCL.

OBJECTIVE:To determine whether administration of antenatal corticosteroids to patients with twin gestations at risk for late preterm delivery is associated with reduced risk for neonatal respiratory morbidity compared with unexposed twins. METHODS:This was a multicenter, retrospective cohort study in a large, urban health network (2013-2022) of patients with twin gestations at risk for preterm delivery between 34 0/7 and 36 6/7 weeks of gestation. Patients were excluded if they received antenatal corticosteroids before 34 weeks of gestation or had pregestational diabetes, single-twin death before 34 weeks, or oral steroid exposure during pregnancy. Neonates were excluded if they had major congenital anomalies. The primary outcome was a composite of neonatal respiratory morbidity requiring respiratory support within 72 hours of birth, including continuous positive airway pressure (CPAP) or high-flow nasal cannula for 2 hours or more, supplemental oxygen of 30% for 2 hours or more, extracorporeal membrane oxygenation, mechanical ventilation, and fetal or neonatal death. Secondary outcomes included neonatal hypoglycemia and indications for neonatal intensive care unit (NICU) admission. Adjusted and unadjusted relative risks with 95% CIs were calculated. RESULTS:During the study period, 366 twin gestations and 722 patient-neonate dyads were included: 162 gestations (321 neonates) in the exposed group and 204 (401 neonates) in the unexposed group. There was no difference in the composite outcome of respiratory morbidity in those exposed to antenatal corticosteroids (23.4% vs 20.4%, P=.40, adjusted relative risk [RR] 1.00, 95% CI, 0.71-1.42). The composite was driven mostly by rates of CPAP use (21.2% vs 18.5%, P=.41, adjusted RR 1.05, 95% CI, 0.73-1.53) and high-flow nasal cannula use (6.2% vs 2.2%, P=.02, RR 2.77, 95% CI, 1.16-6.66). Antenatal corticosteroid exposure was associated with a lower risk of need for supplemental oxygen (0.6% vs 3.5%, P=.02, RR 0.18, 95% CI, 0.04-0.79) and mechanical ventilation (0.6% vs 3.2%, P=.03, RR 0.19, 95% CI, 0.04-0.87). Although antenatal corticosteroids exposure was not associated with higher rates of hypoglycemia (44.2% vs 41.7%, P=.57, adjusted RR 0.99, 95% CI, 0.82-1.19), exposure was associated with a higher risk of having hypoglycemia as the only indication for NICU admission (10.3% vs 5.2%, P=.03, RR 1.96, 95% CI, 1.07-3.59). CONCLUSION/CONCLUSIONS:In a large, multicenter, network-wide retrospective cohort study of patients with twin gestations at risk for late preterm birth, antenatal corticosteroid use was not associated with a decrease in overall respiratory morbidity but was associated with a decreased risk of need for supplemental oxygen and mechanical ventilation, as well as a higher risk of NICU admission for hypoglycemia. These results underscore the ongoing need to elucidate the risks and benefits of late preterm antenatal corticosteroids for patients with twin gestations at risk for late preterm birth.

BACKGROUND:The approach to prevent eclampsia in the postpartum period utilizes magnesium sulfate but there is no evidence-based standard to guide duration. OBJECTIVES/OBJECTIVE:To assess the cost-effectiveness of an abbreviated 12-hour postpartum magnesium sulfate regimen compared with a standard 24-hour regimen. STUDY DESIGN/METHODS:A decision-analytic model was constructed to compare a 12-hour regimen with a 24-hour regimen in a theoretical cohort of 45,800 patients with preeclampsia with severe features. Probabilities, costs, and utilities were derived from the literature. Primary outcomes included incremental cost per quality-adjusted life-year (QALY), cases of eclampsia, magnesium toxicity, and maternal death. The cost-effectiveness threshold was $100,000 per QALY. RESULTS:A 12-hour regimen in this theoretical cohort of 45,800 postpartum patients compared with a 24-hour regimen resulted in 86 more cases of eclampsia (398 vs 312) and 0.37 more deaths (10.87 vs 10.50). However, there were 656 fewer cases of magnesium toxicity (2089 vs 2745). Overall, a 12-hour regimen was a dominant strategy that resulted in decreased costs of $21.5 million and increased effectiveness of 17 QALYs. CONCLUSION/CONCLUSIONS:In our study, an abbreviated duration of postpartum magnesium sulfate prophylaxis for patients with preeclampsia with severe features was a dominant strategy (lower costs, better outcomes) and cost-effective compared with the standard 24-hour regimen.

BACKGROUND/OBJECTIVES/OBJECTIVE:Approximately half of male cancer survivors experience infertility following cancer treatment, which can lead to psychosocial distress. The aim of this study was to identify support needs and reflections on the decision-making process related to sperm banking among adolescent male cancer survivors and their caregivers at 1 year post-diagnosis. METHODS:As part of a randomized controlled trial testing a family-centered sperm banking decision-making intervention, males diagnosed with cancer (12-25 years old) and their caregivers completed semi-structured interviews 1 year post-diagnosis. Thematic analysis was conducted by three independent coders (κ = 0.80) and focused on two interview questions: (1) Is there anything you wish you would have known or done before making the [sperm banking] decision? and (2) What information or support do you think is needed regarding your/your son's future fertility goals? RESULTS:Qualitative interviews with adolescents (n = 20) and caregivers (n = 18) revealed three primary themes: (1) satisfaction with information received at diagnosis, but retrospective desire for more decision-making time; (2) current desire for additional fertility-related support; (3) potential need for future fertility-related support. CONCLUSION/CONCLUSIONS:Despite satisfaction with the oncofertility consultation at diagnosis, clinical teams should prioritize fertility education moving forward and allow additional time for sperm banking decision-making (when possible) at diagnosis. Counseling gaps can lead to uncertainty, unplanned pregnancies, and adverse mental health outcomes. Thus, it is important to revisit issues surrounding fertility and family planning after treatment, particularly among adolescents transitioning to adulthood.

BACKGROUND:Physical exam indicated-cerclage is an intervention offered to prolong pregnancy in the setting of painless cervical dilation prior to 24 weeks. One randomized clinical trial (RCT) showed an increased incidence of pregnancy prolongation by at least 28 days among participants who received perioperative indomethacin and cefazolin in the setting of a physical exam-indicated cerclage compared to those who did not receive those perioperative medications. Prospective studies suggest that prophylactic azithromycin may increase latency in the setting of cervical shortening, but this has not been studied in a controlled manner in patients undergoing physical exam-indicated cerclage. OBJECTIVE:The aim of our study is to determine whether the addition of perioperative azithromycin to cefazolin and indomethacin for physical exam-indicated cerclage increases latency to delivery compared to perioperative cefazolin and indomethacin alone. STUDY DESIGN/METHODS:This was an open-label multicenter RCT of individuals with singleton gestations who were undergoing a physical exam-indicated cerclage between December 2021 and September 2023 at four sites across the United States. The study was IRB approved and registered at clinicaltrials.gov (NCT05132829). Participants were randomized 1:1 via a computer-generated randomization sequence stratified by site to standard of care (cefazolin 1-2 gm IV and indomethacin 50mg preoperatively followed by 2 additional doses at 8 and 16 hours postoperatively, control arm) or standard of care plus azithromycin (azithromycin 1000mg IV in addition to cefazolin and indomethacin described in the control group, azithromycin arm). The primary outcome was gestational latency (days) from cerclage placement to delivery. Secondary outcomes include preterm birth, gestational age at delivery, chorioamnionitis, and neonatal morbidity and mortality. RESULTS:A total of 82 pregnant individuals were assessed for eligibility and 54 participants were randomized, 27 to control and 27 to the azithromycin arm. In the primary intention-to-treat analysis, the median gestational latency from cerclage placement to delivery did not differ between the intervention and control groups (92 [45-118] vs 85 [20-123] days p=0.93). Furthermore, there were no statistically significant differences found in any of the secondary obstetric or neonatal outcomes. CONCLUSION/CONCLUSIONS:A single perioperative dose of azithromycin in addition to standard of care cefazolin and indomethacin does not improve latency to delivery or other perinatal outcomes compared to standard of care alone in singleton gestations undergoing a physical exam-indicated cerclage.

Our objective was to examine the role of structural racism and economic disadvantage in perinatal health inequities using the Environmental influences on Child Health Outcomes Cohort. Participants' addresses were linked to area-level measures of life expectancy, education, unemployment, health insurance, jail rate, segregation, and housing cost burden. We created absolute measures to represent economic disadvantage and relative measures comparing values for Black or Latinx people to White people in the same area to represent structural racism. We used quantile G-computation to estimate the effects of a one-quartile increase in all exposures simultaneously on fetal growth and gestational age measures. A one-quartile increase in economic disadvantage was associated with a reduction in birthweight [(-25.65 grams, 95% CI (-45.83, -5.48)], but not gestational age [-0.02 weeks, 95% CI (-0.13, 0.09)]. With a one-quartile increase in Latinx-White structural racism, we observed reductions in birthweight [-80.83, 95% CI (-143.42, -18.23)) among Latinx participants. A one-quartile increase in Black-White structural racism was weakly associated with lower birthweight among Black participants [-15.70, 95% CI (-82.89, 51.48)] but was associated with higher birthweight among White participants [57.47, 95% CI (13.26, 101.67)]. Our findings suggest co-occurring forms of structural inequity likely influence racialized disparities in fetal growth outcomes.

OBJECTIVES/OBJECTIVE:Novel biologic agents targeting the neonatal Fc receptor (FcRn) offer a promising strategy to prevent cardiac neonatal lupus (cardiac-NL) in pregnant patients with high-titre anti-SSA/Ro52 kD or 60 kD autoantibodies via dual effects: reducing serum immunoglobin G (IgG) levels and inhibiting placental transfer. This study was initiated to assess the feasibility of FcRn blockade as prophylactic therapy for recurrent cardiac-NL. METHODS:A 34-year-old pregnant patient with systemic lupus erythematosus and 3 prior consecutive pregnancies complicated by neonatal lupus (1 cutaneous, 1 fatal cardiac-NL at 20 weeks, 1 cardiac-NL delivered at 32 weeks and neonatal cutaneous NL), each despite hydroxychloroquine 400 mg daily, was treated with weekly subcutaneous infusions of 560 mg rozanolixizumab (humanised IgG4 monoclonal antibody against FcRn) from gestational weeks 14 to 28 (to cover the vulnerable period of fetal cardiac injury) through a compassionate use designation. The patient performed home fetal heart rhythm monitoring thrice daily with weekly echocardiograms. RESULTS:Maternal anti-SSA/Ro52 kD and 60 kD autoantibodies, total IgG, and subclasses IgG1, 2, 3 decreased by about 65% at gestational week 22, with a return to near baseline levels by week 34. The pregnancy was uncomplicated, resulting in a spontaneous vaginal delivery of a healthy neonate at 37 weeks. At delivery, cord blood and maternal IgG levels were normal, obviating the need for rescue intravenous immune globulin. The neonate had a normal echocardiogram and electrocardiogram but developed a rash consistent with neonatal lupus at 5 weeks of life. There were no serious adverse events. CONCLUSIONS:The successful application of FcRn blockade to prevent recurrent cardiac-NL sets a precedent for a multicentre study.