Objective: The objective of this study was to study the epidemiology of neonatal hypothermia in preterm infants using World Health Organization (WHO) temperature criteria. Result: In all, 56.2% of infants were hypothermic. Low birth weight, cesarean delivery and a low Apgar score were associated with hypothermia. Spontaneous labor, prolonged rupture of membranes and antenatal steroid administration were associated with decreased risk of hypothermia. Moderate hypothermia was associated with higher risk of intraventricular hemorrhage (IVH). Moderate and severe hypothermic conditions were associated with risk of death. Conclusion:Hypothermia by WHO criteria is prevalent in VLBW infants and is associated with IVH and mortality. Use of WHO criteria could guide the need for quality improvement projects targeted toward the most vulnerable infants.

In light of its pervasiveness and prevalence, more effective and aggressive treatments for bipolar depression are warranted to mitigate its profound impact upon individuals and society. Such studies could benefit by including metrics not only for mood outcomes, but also for illness burden.

IMPORTANCE To our knowledge, no study has previously evaluated whether individuals with bipolar depression enriched a priori on the basis of biochemical and/or phenotypic immuno-inflammatory activation would differentially respond to an anti-inflammatory agent for the treatment of depressive symptoms. OBJECTIVE To assess the antidepressant efficacy of adjunctive infliximab, a monoclonal antibody targeting tumor necrosis factor, in adults with bipolar I and bipolar II depression and inflammatory conditions. DESIGN, SETTING, AND PARTICIPANTS This 12-week, randomized, double-blind, placebo-controlled, parallel-group trial of 60 participants was conducted at 2 outpatient tertiary care sites in Canada and the United States. Eligible adults (aged 18-65 years) met DSM-5-defined criteria for bipolar I or bipolar II depression and exhibited pretreatment biochemical and/or phenotypic evidence of inflammatory activation. Participants were enrolled between October 1, 2015, and April 30, 2018. Data analysis was performed from May 1 through July 31, 2018, using modified intent-to-treat analysis. INTERVENTIONS Patients were randomized to receive 3 intravenous infusions of infliximab therapy or placebo at baseline and at weeks 2 and 6 of the 12-week study. MAIN OUTCOMES AND MEASURES The primary efficacy outcome was baseline-to-end point (ie, week-12) change in Montgomery-Asberg Depression Rating Scale (MADRS) total score. History of childhood maltreatment, as assessed by the Childhood Trauma Questionnaire, was used for exploratory analyses as 1 of several secondary outcomes. RESULTS A total of 60 participants were randomized to infliximab (n = 29 [48%]; mean [SD] age, 45.0 [11.7] years; 20 of 28 female [71%]) or to placebo (n = 31 [52%]; mean [SD] age, 46.8 [10.2] years; 26 of 30 female [87%]) across study sites. Overall baseline-to-end point change in MADRS total score was observed across treatment × time interaction (χ 2 = 10.33; P = .04); reduction in symptom severity was not significant at week 12 (relative risk, 1.09; 95% CI, 0.80-1.50; df= 1; P = .60). As part of a secondary analysis, a significant treatment × time × childhood maltreatment interaction was observed in which infliximab-treated individuals with childhood history of physical abuse exhibited greater reductions in MADRS total score (χ 2 = 12.20; P = .02) and higher response rates (Ն50% reduction in MADRS total score) (χ 2 = 4.05; P = .04). CONCLUSIONS AND RELEVANCE Infliximab did not significantly reduce depressive symptoms compared with placebo in adults with bipolar depression. Results from secondary analyses identified a subpopulation (ie, those reporting physical and/or sexual abuse) that exhibited a significant reduction in depressive symptoms with infliximab treatment compared with placebo.

Among outpatients with bipolar disorder, concurrent hypomanic symptoms observed during visits with depression were common, particularly in women. The DSM-5 diagnostic criteria for depression with mixed features may yield inadequate sensitivity to detect patients with mixed depression.