The association between postpartum depressive symptoms and contraception.

BACKGROUND: Postpartum depression affects 10% to 20% of birthing people and is associated with changes in healthcare use. Little is known about the association between postpartum depressive symptoms and choice to use contraception; however, both untreated or undertreated depression and short interpregnancy intervals pose substantial perinatal health risks. OBJECTIVE: This study aimed to evaluate whether postpartum depressive symptoms are associated with changes in decisions to use any method of contraception. STUDY DESIGN: This retrospective cohort study included birthing people who delivered between 2017 and 2022 and were referred to a collaborative care program for mental healthcare. Through this program, birthing people with mental health conditions have access to specialized perinatal mental healthcare and prospective symptom monitoring via a patient registry. Postpartum depressive symptoms are assessed via the Patient Health Questionnaire-9, and scores were stratified by severity according to clinical cutoffs. Contraceptive method choice was determined by documentation in the electronic health record and dichotomized as "none" if the participant declined all forms of contraception both at delivery and at the postpartum visit. Bivariable and multivariable analyses were performed. RESULTS: Of the 1871 participants that met the inclusion criteria, 160 (8.5%) had postpartum Patient Health Questionnaire-9 scores of >14, representing moderately severe or worse depressive symptoms, and 43 (2.3%) had severe (Patient Health Questionnaire-9 of >19) depressive symptoms. Birthing people with higher Patient Health Questionnaire-9 scores were more likely to have medical comorbidities; to have a higher body mass index; to self-identify as Black, Native Hawaiian or Pacific Islander, or Hispanic or Latina; and to have a preterm delivery and less likely to be married or nulliparous than those with Patient Health Questionnaire-9 scores of ≤14. There was no difference in any other sociodemographic or clinical characteristics. The choice to use any contraceptive method decreased with increasing depressive symptoms in bivariable and multivariable analyses, reaching statistical significance in birthing people with severe depressive symptoms (adjusted odds ratio, 2.92; 95% confidence interval, 1.46-5.84). CONCLUSION: Severe perinatal depressive symptoms are associated with a declination of any form of postpartum contraception. This finding becomes increasingly relevant as abortion access continues to be threatened across the United States, compounding the potential effect of opting not to use contraception.

The association between the COVID-19 pandemic and postpartum care provision.

BACKGROUND: The COVID-19 pandemic led to a rapid transformation in the healthcare system to mitigate viral exposure. In the perinatal context, one change included altering the prenatal visit cadence and increasing the utilization of telehealth methods. Whether this approach had inadvertent negative implications for postpartum care, including postpartum depression screening and contraceptive utilization, is unknown. OBJECTIVE: This study aimed to examine whether preventative health service utilization, including postpartum depression screening and contraceptive utilization, differed during the COVID-19 pandemic when compared with the prepandemic period. STUDY DESIGN: This retrospective cohort study included all pregnant patients who received prenatal care at 1 of 5 academic obstetrical practices and who delivered at Northwestern Memorial Hospital either before (delivery from September 1, 2018, to January 1, 2019) or during (delivery from February 1, 2020, to May 15, 2020) the COVID-19 pandemic. Completion of postpartum depression screening was assessed by reviewing standardized fields in the documentation associated with the screening in the electronic health record system. The method of contraception used was ascertained from the postpartum clinical documentation. Patients were classified as initiating long-acting reversible contraception use if they received NEXPLANON (etonogestrel implant) or an intrauterine device during the hospitalization for delivery or within 3 months following delivery. Bivariable and multivariable analyses were performed. RESULTS: Of the 2375 pregnant patients included in this study, 1120 (47%) delivered during the COVID-19 pandemic. Pregnant patients who delivered during the COVID-19 pandemic were significantly less likely to have undergone postpartum depression screening (45.5% vs 86.2%; P<.01); this association persisted after adjusting for potential confounders (adjusted odds ratio, 0.13; 95% confidence interval, 0.11-0.16). Pregnant patients who delivered during the COVID-19 pandemic also were significantly less likely to initiate long-acting reversible contraception use within 3 months of delivery (13.5% vs 19.6%; adjusted odds ratio, 0.67; 95% confidence interval, 0.53-0.84). CONCLUSION: The onset of the COVID-19 pandemic was associated with a decrease in the completion of postpartum depression screenings and fewer patients initiating long-acting reversible contraception use overall. These results can inform adaptations in healthcare delivery in the midst of the ongoing COVID-19 pandemic.

Loss of H3K36 Methyltransferase SETD2 Impairs V(D)J Recombination during Lymphoid Development.

Repair of DNA double-stranded breaks (DSBs) during lymphocyte development is essential for V(D)J recombination and forms the basis of immunoglobulin variable region diversity. Understanding of this process in lymphogenesis has historically been centered on the study of RAG1/2 recombinases and a set of classical non-homologous end-joining factors. Much less has been reported regarding the role of chromatin modifications on this process. Here, we show a role for the non-redundant histone H3 lysine methyltransferase, Setd2, and its modification of lysine-36 trimethylation (H3K36me3), in the processing and joining of DNA ends during V(D)J recombination. Loss leads to mis-repair of Rag-induced DNA DSBs, especially when combined with loss of Atm kinase activity. Furthermore, loss reduces immune repertoire and a severe block in lymphogenesis as well as causes post-mitotic neuronal apoptosis. Together, these studies are suggestive of an important role of Setd2/H3K36me3 in these two mammalian developmental processes that are influenced by double-stranded break repair.

Inhibition of MEK and ATR is effective in a B-cell acute lymphoblastic leukemia model driven by Mll-Af4 and activated Ras.

Infant B-cell acute lymphoblastic leukemias (B-ALLs) that harbor MLL-AF4 rearrangements are associated with a poor prognosis. One important obstacle to progress for this patient population is the lack of immunocompetent models that faithfully recapitulate the short latency and aggressiveness of this disease. Recent whole-genome sequencing of MLL-AF4 B-ALL samples revealed a high frequency of activating RAS mutations; however, single-agent targeting of downstream effectors of the RAS pathway in these mutated MLL-r B-ALLs has demonstrated limited and nondurable antileukemic effects. Here, we demonstrate that the expression of activating mutant N-Ras G12D cooperates with Mll-Af4 to generate a highly aggressive serially transplantable B-ALL in mice. We used our novel mouse model to test the sensitivity of Mll-Af4/N-Ras G12D leukemia to small molecule inhibitors and found potent and synergistic preclinical efficacy of dual targeting of the Mek and Atr pathways in mouse- and patient-derived xenografts with both mutations in vivo, suggesting this combination as an attractive therapeutic opportunity that might be used to treat patients with these mutations. Our studies indicate that this mouse model of Mll-Af4/N-Ras B-ALL is a powerful tool to explore the molecular and genetic pathogenesis of this disease subtype, as well as a preclinical discovery platform for novel therapeutic strategies.