Being overweight or obese was associated with an increased risk of still birth, large for gestational age, macrosomia, admission to the neonatal intensive care unit and LBW, while being underweight was associated with an increased risk of preterm birth, small for gestational age, and LBW. Women of childbearing age should maintain a normal body mass index before pregnancy.

This is the first natural history study of the primary symptoms of SDB across a key 6-year period in the development of SDB symptoms. Snoring rates are higher and spike earlier than previously reported. Symptoms are dynamic, suggesting the need for early and continued vigilance in early childhood.

No abstract

WHAT'S KNOWN ON THIS SUBJECT: Sleep-disordered breathing is associated with neurobehavioral morbidity in children. Prior related research has generally been cross-sectional or short (ie, 1-2 years) follow-up studies of a single symptom (ie, snoring, obstructive sleep apnea, mouth breathing), with limited control for confounders.WHAT THIS STUDY ADDS: Sleep-disordered breathing was assessed as a trajectory of combined symptoms from 6 months to 69 months, in more than 11 000 children. Sleep-disordered breathing was associated with 40% and 60% more behavioral difficulties at 4 and 7 years, respectively. abstract OBJECTIVES: Examine statistical effects of sleep-disordered breathing (SDB) symptom trajectories from 6 months to 7 years on subsequent behavior. METHODS:Parents in the Avon Longitudinal Study of Parents and Children reported on children' s snoring, mouth breathing, and witnessed apnea at $2 surveys at 6, 18, 30, 42, 57, and 69 months, and completed the Strengths and Difficulties Questionnaire at 4 (n = 9140) and 7 (n = 8098) years. Cluster analysis produced 5 "Early" (6-42 months) and "Later" (6-69 months) symptom trajectories ("clusters"). Adverse behavioral outcomes were defined by top 10th percentiles on Strengths and Difficulties Questionnaire total and subscales, at 4 and 7 years, in multivariable logistic regression models. RESULTS:The SDB clusters predicted 20% to 100% increased odds of problematic behavior, controlling for 15 potential confounders. Early trajectories predicted problematic behavior at 7 years equally well as at 4 years. In Later trajectories, the "Worst Case" cluster, with peak symptoms at 30 months that abated thereafter, nonetheless at 7 years predicted hyperactivity (1.85 [1.30-2.63]), and conduct (1.60 [1.18-2.16]) and peer difficulties (1.37 [1.04-1.80]), whereas a "Later Symptom" cluster predicted emotional difficulties (1.65 [1.21-2.07]) and hyperactivity (1.88 [1.42-2.49]) . The 2 clusters with peak symptoms before 18 months that resolve thereafter still predicted 40% to 50% increased odds of behavior problems at 7 years. CONCLUSIONS:In this large, population-based, longitudinal study, early-life SDB symptoms had strong, persistent statistical effects on subsequent behavior in childhood. Findings suggest that SDB symptoms may require attention as early as the first year of life. Pediatrics 2012;129:e857-e865

Background Multiple myeloma (MM) is characterized by expression of the cell surface protein B-cell maturation antigen (BCMA), a validated target for therapeutic intervention. REGN5458 is a BCMA x CD3 bispecific antibody (Ab) that binds to both BCMA and CD3, thereby targeting MM cells with T-cell effector function via BCMA. Previously, we presented data showing REGN5458 has an acceptable safety profile with evidence of clinical efficacy in heavily pre-treated patients with RRMM. Here we describe the updated safety and response durability in a Phase 1 trial of REGN5458 monotherapy in patients with RRMM (NCT03761108). Methods The primary objectives of the Phase 1 portion of the study are to determine the safety, tolerability, and occurrence of dose-limiting toxicities (DLTs) of REGN5458. Key secondary objectives include assessment of objective response rate (ORR), duration of response (DOR), minimum residual disease (MRD) status, pharmacokinetics (PK), and pharmacodynamics. Enrollment into the Phase 1 portion follows a standard 4+3 dose escalation design. Enrolled patients must have progressive MM after ≥3 prior lines of systemic therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 Ab. Treatment consists of weekly doses of REGN5458, followed by a maintenance phase administered every 2 weeks. Response assessments are according to modified International Myeloma Working Group criteria. MRD is assessed by flow cytometry. Results As of the June 15, 2020 data cut-off, 45 patients were treated with REGN5458. The median age at enrollment was 64.0 years (range, 41−81), of which 14 (31.1%) patients were >70 years. As per Revised International Staging System, 60.0% and 22.2% of patients were stage 2 and 3, respectively. Patients had a median of 5.0 (range, 2−17) prior lines of systemic therapy; 32 patients (71.1%) received a prior autologous stem cell transplant. All patients were refractory to an anti-CD38 Ab; 6.7% were triple-refractory, 33.3% were quad-refractory, and 53.3% were penta-refractory. REGN5458 was escalated in cohorts from 3−96 mg over six dose levels. The median duration of follow-up was 2.37 months (range, 0.7−12.3). The most common treatment-related adverse events (TRAEs) include cytokine release syndrome (CRS; 37.8%), fatigue (17.8%), nausea (17.8%), and myalgias (13.3%). CRS occurred primarily during the initial doses and was Grade (Gr) 1 in 88.2% of patients. No patients had Gr >3 CRS. Infusion-related reactions occurred in 6.7% of patients. Infection-related adverse events (AEs) occurred in 46.7% of patients (Gr ≥3 20%). Gr >3 treatment-related neurological events occurred in one patient (Gr 3 syncope 130 days after first infusion). Four patients discontinued due to AE with one patient having a TRAE (also DLT) of Gr 4 acute kidney injury. One patient had a DLT due to transient Gr 3 liver transaminases associated with CRS. Upon recovery, the patient continued study drug and has achieved ongoing partial remission. Gr >3 TRAEs occurred in 28.9% of patients, with the most common being anemia (8.9%) and lymphopenia (6.7%). Serious TRAEs occurred in 22.2% of patients, with the most common due to CRS (11.1%). Gr 5 AEs (all unrelated to study drug) occurred in three patients: two sepsis and one COVID-19. ORR was 35.6% across all dose levels (60% in highest dose level), with 81.3% of responders achieving at least a very good partial response; 31.3% had a complete response (CR) or stringent CR. A total of 43.8% of responders had a DOR >4 months and 18.8% had a DOR >8 months. The ORR in patients with extramedullary plasmacytomas was 16.7%. Additional efficacy, PK, and biomarker data will be available at the time of presentation. Conclusions In this updated analysis of the first-in-human study, REGN5458 continues to show an acceptable safety profile and durable efficacy in heavily pre-treated patients with RRMM. Enrollment in the Phase 1 dose escalation portion is ongoing, and the Phase 2 portion of the study is recruiting. Disclosures Madduri: Janssen: Consultancy, Honoraria; Foundation Medicine: Consultancy, Honoraria; Legend: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Kinevant: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; AbbVie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Brayer:Janssen: Consultancy; Bristol-Myers Squibb, WindMIL Therapeutics: Research Funding; Bristol-Myers Squibb, Janssen, Amgen: Speakers Bureau. Zonder:Prothena: Consultancy; BMS: Consultancy, Research Funding; Caelum: Consultancy; Oncopeptide: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Janssen: Consultancy, Other: Personal fees; Alnylam: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Intellia: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Celgene: Research Funding. Bensinger:Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Regeneron Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau. Li:Regeneron Pharmaceuticals, Inc: Current Employment, Current equity holder in publicly-traded company. Xu:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Adriaens:Regeneron Pharmaceuticals, Inc: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: Dosing regime that mitigates cytokine release syndrome for therapeutic antibodies (status: pending). Chokshi:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Zhang:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Boyapati:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Sharma:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Seebach:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Sirulnik:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Weinreich:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Yancopoulos:Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Dhodapkar:Amgen: Membership on an entity's Board of Directors or advisory committees, Other; Kite: Membership on an entity's Board of Directors or advisory committees, Other; Janssen: Membership on an entity's Board of Directors or advisory committees, Other; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Other; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Other; Lava Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other. Lentzsch:Mesoblast: Divested equity in a private or publicly-traded company in the past 24 months; Caelum Biosciences: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Celularity: Consultancy, Other; Janssen: Consultancy; Karyopharm: Research Funding; Magenta: Current equity holder in private company. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy. OffLabel Disclosure: The data described in the abstract will report on use of REGN5458 in a first-in-human trial in patients with multiple myeloma.