Mammalian embryogenesis requires rapid growth and proper metabolic regulation1. Midgestation features increasing oxygen and nutrient availability concomitant with fetal organ development2,3. Understanding how metabolism supports development requires approaches to observe metabolism directly in model organisms in utero. Here we used isotope tracing and metabolomics to identify evolving metabolic programmes in the placenta and embryo during midgestation in mice. These tissues differ metabolically throughout midgestation, but we pinpointed gestational days (GD) 10.5–11.5 as a transition period for both placenta and embryo. Isotope tracing revealed differences in carbohydrate metabolism between the tissues and rapid glucose-dependent purine synthesis, especially in the embryo. Glucose’s contribution to the tricarboxylic acid (TCA) cycle rises throughout midgestation in the embryo but not in the placenta. By GD12.5, compartmentalized metabolic programmes are apparent within the embryo, including different nutrient contributions to the TCA cycle in different organs. To contextualize developmental anomalies associated with Mendelian metabolic defects, we analysed mice deficient in LIPT1, the enzyme that activates 2-ketoacid dehydrogenases related to the TCA cycle4,5. LIPT1 deficiency suppresses TCA cycle metabolism during the GD10.5–GD11.5 transition, perturbs brain, heart and erythrocyte development and leads to embryonic demise by GD11.5. These data document individualized metabolic programmes in developing organs in utero.

Objective Obstructive sleep apnea (OSA) is prevalent in children with sickle cell disease (SCD). We compared the demographic, clinical, and polysomnographic characteristics of children with and without SCD. Methods This retrospective chart review included children with SCD (n = 89) and without SCD (n = 192) ages 1–18 years referred for polysomnography (PSG) for OSA. Results Children with SCD were predominantly African American when compared to the non‐SCD group (95% vs. 28%, p < 0.001). The non‐SCD group had a higher BMI z‐score (1.3 vs. 0.1, p < 0.001) and a higher percentage of patients classified as obese (52% vs. 13%, p < 0.001). In children with SCD, 43% had severe OSA and 5.6% had no OSA. In the non‐SCD group, 67% had severe OSA and 4.7% had no OSA. The SCD compared to the non‐SCD group had a lower mean apnea‐hypopnea index (AHI) (13.6 vs. 22.4, p = 0.006) but a higher percent sleep time below 90% oxygen saturation (10.5% vs. 3.5%, p < 0.001). Predicted probability for severe OSA in children with SCD decreased with increasing age (OR = 0.81, 95% CI: 0.70–0.93). Conclusion Children with SCD referred for PSG are at risk for severe OSA. Compared with the non‐SCD group, most children were African American with lower rates of obesity and lower AHIs but longer periods of nocturnal hypoxemia. Likelihood for severe OSA decreased with increasing age for the SCD group. Level of Evidence 3, retrospective comparative study Laryngoscope, 133:1766–1772, 2023