Dr. David Barker first popularized the concept of fetal origins of adult disease (FOAD). Since its inception, FOAD has received considerable attention. The FOAD hypothesis holds that events during early development have a profound impact on one’s risk for development of future adult disease. Low birth weight, a surrogate marker of poor fetal growth and nutrition, is linked to coronary artery disease, hypertension, obesity, and insulin resistance. Clues originally arose from large 20th century, European birth registries. Today, large, diverse human cohorts and various animal models have extensively replicated these original observations. This review will focus on the pathogenesis related to FOAD and examines Dr. David Barker’s landmark studies, along with additional human and animal model data. Implications of the FOAD extend beyond the low birth weight population and include babies exposed to stress, both nutritional and non-nutritional, during different critical periods of development, which ultimately result in a disease state. By understanding FOAD, health care professionals and policy makers will make this issue a high healthcare priority and implement preventative measures and treatment for those at higher risk for chronic diseases.

Background Studies have suggested that when intravenous (IV) soybean oil (SO) is replaced with fish oil (FO), direct hyperbilirubinemia is more likely to resolve. The necessary duration of FO has not been established. This study seeks to determine if 24 weeks of FO is an effective and safe therapy for intestinal failure associated liver disease (IFALD). Materials and Methods This is a clinical trial using patients with IFALD between the ages of 2 weeks and 18 years. SO was replaced with FO (1 g/kg/day) in 10 subjects who were receiving the majority of their calories from parenteral (PN). Subjects were compared to 20 historical controls receiving SO. SO for both groups was prescribed by the primary medical team at variable doses. The primary outcome was time to reversal of cholestasis. Secondary outcomes were death, transplant, and full enteral feeds. Safety measurements included growth, essential fatty acid deficiency, and laboratory markers to assess bleeding risk. Results The Kaplan-Meier method estimates that 75% in the FO group will experience resolution of cholestasis by 17 weeks vs. 6% in the SO group (p < 0.0001). When compared to the SO group, the FO group had decreased serum direct bilirubin concentrations at weeks 8 (p=0.03), 12, 16, 20 and 24 (p< 0.0001). While length Z-score at the end of the study increased in the FO group compared to baseline (p=0.03), there were no significant differences in other outcomes. Conclusions A limited duration of FO appears to be safe and effective in reversing IFALD.

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Background Neonates with gastrointestinal disorders (GD) are at high risk for parenteral nutrition associated liver disease (PNALD). Soybean-based intravenous lipid emulsions (S-ILE) have been associated with PNALD. This study’s objective was to determine if a lower dose when compared to a higher dose of S-ILE prevents cholestasis without compromising growth. Material and Methods This multi-center randomized controlled pilot study enrolled subjects with GD who were ≤ 5 days of age to a low dose (approximately 1 g/kg/day) (LOW) or control dose of S-ILE (approximately 3 g/kg/day) (CON). The primary outcome was cholestasis (direct bilirubin (DB) > 2 mg/dL) after the first seven days of age. Secondary outcomes included growth, PN duration, and late onset sepsis. Results Baseline characteristics were similar between the LOW (n=20) and CON groups (n=16). When the LOW group was compared to the CON group, there was no difference in cholestasis (30% vs. 38%, p=0.7) or secondary outcomes. However, mean (±SE) DB rate of change over the first eight weeks (0.07±0.04 vs. 0.3±0.09 mg/dL/week, p=0.01) and entire study (0.008±0.03 vs. 0.2±0.07 mg/dL/week, p=0.02) was lower in the LOW group when compared to the CON group. Conclusion In neonates with GD who received a lower dose of S-ILE, DB increased at a slower rate in comparison to neonates who received a higher dose of S-ILE. Growth was comparable between the groups. This study demonstrates a need for a larger, randomized controlled trial comparing two different S-ILE doses for cholestasis prevention in neonates at risk for PNALD.