Association of Exclusive Breast Milk Intake and Outcomes in Infants With Uncomplicated Gastroschisis: A National Cohort Study.

BACKGROUND: Enteral feeding is an essential part of the management of infants with gastroschisis. We hypothesized that exclusive breast milk is associated with improved neonatal outcomes. METHODS: We conducted a retrospective review of infants with uncomplicated gastroschisis through the Canadian Pediatric Surgery Network (CAPSNet) and Canadian Neonatal Network (CNN). The primary outcome was time to full enteral feeds. RESULTS: We identified 411 infants with gastroschisis treated at CAPSNet centres from 2014 to 2022. 144 patients were excluded due to gestational age <32 weeks, birth weight <1500 g, other congenital anomalies, or complicated gastroschisis. Of the remaining 267 participants, 78% (n = 209) received exclusive breast milk diet in the first 28 days of life, whereas 22% (n = 58) received supplemental or exclusive formula. Infants who received exclusive breast milk experienced higher time to reach full enteral feeding (median 24 vs 22 days, p = 0.047) but were more likely to have undergone delayed abdominal closure (32% vs 17%, p = 0.03). After adjustment, there were no significant differences between groups in time to reach full enteral feeds, duration of parenteral nutrition, or length of stay. Infants who received supplemental or exclusive formula had a similar risk of necrotizing enterocolitis (4% vs 3%) but were less likely to transition to exclusive breast milk at discharge (73% vs 11%, p < 0.001). CONCLUSION: Early use of exclusive breast milk in infants with uncomplicated gastroschisis is associated with similar outcomes compared to supplemental or exclusive formula. Patients who received supplemental or exclusive formula were unlikely to transition to exclusive breastfeeding by discharge. LEVEL OF EVIDENCE: Level IIb (Individual Cohort Study).

Ionizable Lipid Nanoparticles for Therapeutic Base Editing of Congenital Brain Disease.

Delivery of mRNA-based therapeutics to the perinatal brain holds great potential in treating congenital brain diseases. However, nonviral delivery platforms that facilitate nucleic acid delivery in this environment have yet to be rigorously studied. Here, we screen a diverse library of ionizable lipid nanoparticles (LNPs) via intracerebroventricular (ICV) injection in both fetal and neonatal mice and identify an LNP formulation with greater functional mRNA delivery in the perinatal brain than an FDA-approved industry standard LNP. Following in vitro optimization of the top-performing LNP (C3 LNP) for codelivery of an adenine base editing platform, we improve the biochemical phenotype of a lysosomal storage disease in the neonatal mouse brain, exhibit proof-of-principle mRNA brain transfection in vivo in a fetal nonhuman primate model, and demonstrate the translational potential of C3 LNPs ex vivo in human patient-derived brain tissues. These LNPs may provide a clinically translatable platform for in utero and postnatal mRNA therapies including gene editing in the brain.

Use of breast milk in infants with uncomplicated gastroschisis: A retrospective cohort study.

BACKGROUND: Infants with gastroschisis often experience slow return of bowel function following closure. The purpose of this study was to determine whether exclusive breast milk is associated with decreased time to enteral autonomy. METHODS: We conducted a retrospective cohort study of infants with uncomplicated gastroschisis from a tertiary pediatric hospital. The primary outcome was enteral autonomy, defined as days from initiating enteral feeds to stopping parenteral nutrition. Secondary outcomes included days of parenteral nutrition, length of stay, positive culture, necrotizing enterocolitis, cholestasis, additional surgery, readmission, and mortality. RESULTS: We identified 100 infants with gastroschisis treated from 2005 to 2019. Twenty-five were excluded due to gestational age <32 weeks, birth weight <1500 g, or gastroschisis-associated complications (e.g., intestinal atresia). Seventy-five were included in the analysis. Mean gestational age was 36 weeks, 48% were female, and all were diagnosed antenatally. Sixty-five infants (87%) received exclusive maternal (n = 64) or donor (n = 1) breast milk, while 10 others (13%) were fed formula for 1-16 days (mean 7 days). Two infants received formula only. Demographics and gastroschisis prognostic scores were similar between groups. Infants who were given breast milk exclusively demonstrated decreased time to enteral autonomy (median 18 versus 25 days, p = 0.023) and shorter duration of parenteral nutrition (median 20 versus 26 days, p = 0.037). CONCLUSION: Exclusive breast milk may be associated with improved outcomes among infants with gastroschisis. Further research is needed to evaluate the economic impact of this association and explore possible confounders. These efforts may expand the role of donor breast milk for these patients.

Structural basis for salinity-induced alteration in oxygen binding by haemocyanin from the estuarine amphipod Chaetogammarus marinus (L.).

In the estuarine amphipod Chaetogammarus marinus, differences in O(2) binding by haemocyanins (Hc) could be related to natural and salinity-related quantitative variation in just one polypeptide subunit (band 2) and not to variations in any of the other seven bands present. Band 2 was always present, irrespective of salinity treatment, and naturally makes up 6%-36% of the total Hc. However, low salinity exposure (S=4 per thousand for 48-49 h, T=15 degrees C) was accompanied by an increase in the prevalence of greater concentrations of band 2 (i.e., range, 20%-36% of total Hc present) and a concomitant increase in Hc-O(2) affinity (half saturation [P(50)] decreased from 1.38 to 1.12 kPa at pH=7.81, T=15 degrees C). A similar salinity-related mechanism (that is, one band altering) has been shown previously for the blue crab Callinectes sapidus, although the functional consequences were different. In contrast with C. marinus, an increase in the proportion of one polypeptide subunit in C. sapidus resulted in a decrease in Hc-O(2) affinity. This study has confirmed that between-individual variation (quantitative rather than qualitative) in just one Hc subunit may have functional consequences, although the significance of such variation is difficult to interpret.