Compelling reasons to study the role of sex in the circadian system include the higher rates of sleep disorders in women than in men and evidence that sex steroids modulate circadian control of locomotor activity. To address the issue of sex differences in the circadian system, we examined daily and circadian rhythms in wheel-running activity, electrical activity within the suprachiasmatic nucleus, and PER2::LUC-driven bioluminescence of gonadally-intact adult male and female C57BL/6J mice. We observed greater precision of activity onset in 12-hour light, 12-hour dark cycle for male mice, longer activity duration in 24 hours of constant darkness for female mice, and phase-delayed PER2::LUC bioluminescence rhythm in female pituitary and liver. Next, in order to investigate whether sex differences in behavior are sex chromosome or gonadal sex dependent, we used the 4 core genotypes (FCG) mouse model, in which sex chromosome complement is independent of gonadal phenotype. Gonadal males had more androgen receptor expression in the suprachiasmatic nucleus and behaviorally reduced photic phase shift response compared with gonadal female FCG mice. Removal of circulating gonadal hormones in adults, to test activational vs organizational effects of sex revealed that XX animals have longer activity duration than XY animals regardless of gonadal phenotype. Additionally, we observed that the activational effects of gonadal hormones were more important for regulating activity levels in gonadal male mice than in gonadal female FCG mice. Taken together, sex differences in the circadian rhythms of activity, neuronal physiology, and gene expression were subtle but provide important clues for understanding the pathophysiology of the circadian system.

The objective of this narrative review was to synthesize the literature on human milk oligosaccharides (HMOs) and neurodevelopmental outcomes in human milk-fed infants. We conducted a scoping review of the literature indexed in PubMed reporting observational or interventional studies on HMO exposure in relation to psychometric measures in infants. Studies were characterized based on study design and definitions of HMO exposure and neurodevelopmental outcomes. Six studies were identified; all were observational in design, and five were conducted in full-term infants. Sample sizes ranged from 35–659 infants. HMOs were defined as individual concentrations or relative abundances assessed at 1 and/or 6 months of age. Studies accounted for differences in HMO exposure based on maternal secretor status. Neurodevelopmental outcomes were assessed between 6 and 24 months of age and included four domains. Studies in full-term infants reported that total and individual fucosylated and sialylated HMOs were positively associated with cognitive, language, and motor skill domains between 18 and 24 months of age, while the single study in preterm infants reported no statistically significant findings in the full cohort. The presence of a maternal secretor did not consistently alter the associations between HMO exposure and neurodevelopmental outcomes. Emerging evidence from observational studies suggests that HMO exposure may be beneficial for neurodevelopment in infants.

Background In some studies, the dose of intravenous soybean oil (SO) has been associated with a decreased incidence of intestinal failure–associated liver disease. The effect of lipid sparing on neurodevelopment (ND) and growth remains unknown. This study investigated the impact of SO dose on ND and growth over the first 2 years of age in preterm neonates. Materials and Methods This is a single-site prospective follow-up study. Neonates with a gestational age ≤29 weeks were randomized to low-dose (LOW) or standard-dose (CON) SO. Bayley Scales of Infant Development III and anthropometric measurements were collected at approximately 6, 12, and 24 months corrected gestational age. Results Subjects were premature, with a mean (±SD) gestational age of 28 ± 1 and 27 ± 1 weeks (P = .3) for LOW and CON, respectively. Thirty subjects completed follow-up (LOW = 15, CON = 15). There were no differences for ND and growth outcomes when LOW was compared with CON, with the exception of a higher 12-month follow-up cognitive scaled score in the LOW group (P = .02). Conclusion A reduced SO dose did not adversely affect ND or growth in this cohort of preterm neonates. However, larger studies are needed to determine the long-term safety of SO dose reduction before this strategy can be adopted.

Background: Intravenous fish oil (FO) treats pediatric intestinal failure associated liver disease (IFALD). There are concerns that a lipid emulsion composed of omega-3 fatty acids will cause an essential fatty acid deficiency (EFAD). This study’s objective was to quantify the risk for abnormal fatty acid concentrations in children treated with FO. Methods: Inclusion criteria for this prospective study was children with intestinal failure. Intravenous soybean oil (SO) was replaced with FO for no longer than 6 months. Serum fatty acids were analyzed using linear and logistic models, and compared to age-based norms to determine the percentage of subjects with low and high concentrations. Results: Subjects (n=17) started receiving FO at a median of 3.6 months of age (IQR 2.4-9.6 months). Over time, α-linolenic, linoleic, arachidonic and Mead acid decreased, while docosahexaenoic and eicosapentanoic acid increased (p<0.001 for all). Triene:tetraene ratios remained unchanged (p=1). Although subjects were 1.8 times more likely to develop a low linoleic acid while receiving FO vs. SO (95% CI 1.4-2.3, p<0.01), there was not a significant risk for low arachidonic acid. Subjects were 1.6 times more likely to develop high docosahexaenoic acid while receiving FO vs. SO; however this was not significant (95% CI 0.9-2.6, p=0.08). Conclusion: In this cohort of parenteral nutrition-dependent children, switching from SO to FO led to a decrease in essential fatty acid concentrations, but an EFAD was not evident. Low and high levels of fatty acids developed. Further investigation is needed to clarify if this is clinically significant. Trial Identifier: