Neonatal and Obstetrical Outcomes of Pregnancies Complicated by Alloimmunization.

BACKGROUND AND OBJECTIVES: Despite advances in the prevention of rhesus (Rh)(D) alloimmunization, alloantibodies to Rh(D) and non-Rh(D) red blood cell antigens continue to be detected in ∼4% of US pregnancies and can result in hemolytic disease of the fetus and newborn (HDFN). Recent reports on HDFN lack granularity and are unable to provide antibody-specific outcomes. The objective of this study was to calculate the frequency of alloimmunization in our large hospital system and summarize the outcomes based on antibody specificity, titer, and other clinical factors. METHODS: We identified all births in a 6-year period after a positive red blood cell antibody screen result during pregnancy and summarized their characteristics and outcomes. RESULTS: A total of 707 neonates were born after a positive maternal antibody screen result (3.0/1000 live births). In 31 (4%), the positive screen result was due to rhesus immune globulin alone. Of the 676 neonates exposed to alloantibodies, the direct antibody test (DAT) result was positive, showing antigen-positivity and evidence of HDFN in 37% of those tested. Neonatal disease was most severe with DAT-positive anti-Rh antibodies (c, C, D, e, E). All neonatal red blood cell transfusions (15) and exchange transfusions (6) were due to anti-Rh alloimmunization. No neonates born to mothers with anti-M, anti-S, anti-Duffy, anti-Kidd A, or anti-Lewis required NICU admission for hyperbilirubinemia or transfusion. CONCLUSIONS: Alloimmunization to Rh-group antibodies continues to cause a majority of the severe HDFN cases in our hospital system. In neonates born to alloimmunized mothers, a positive DAT result revealing antigen-positivity is the best predictor of anemia and hyperbilirubinemia.

SMOFlipid vs Intralipid 20%: Effect of Mixed-Oil vs Soybean-Oil Emulsion on Parenteral Nutrition-Associated Cholestasis in the Neonatal Population.

BACKGROUND: Parenteral nutrition (PN) is critical for the growth and development of premature neonates who are unable to reach nutrition goals enterally. Using soybean-oil emulsions in PN is a risk factor for cholestasis, leading to alternative dosing strategies including a reduction in total lipid prescribed. Recently, SMOFlipid has been utilized with the goal of avoiding cholestasis while maintaining energy intake. The aim of our study was to compare the incidence of PN-associated cholestasis (PNAC) in patients admitted to the neonatal intensive care unit (NICU) who received either Intralipid 20% or SMOFlipid. METHODS: This single-center, retrospective study evaluated all NICU patients who received PN for ≥14 days. Patients who received SMOFlipid were compared with those who received Intralipid. The primary end point was incidence of PNAC. Secondary end points included (1) prevalence of elevated liver function tests; (2) effect on select laboratory parameters; (3) development of PNAC by age; and (4) incidence of retinopathy of prematurity. RESULTS: A total of 136 neonates were included. Nine of 55 patients (16.4%) in the Intralipid group and 2 of 81 patients (2.5%) in the SMOFlipid group developed cholestasis, defined as direct bilirubin > 2 mg/dL or direct bilirubin > 20% of total bilirubin, when total bilirubin is >5 mg/dL, on or before 30 days post initiation of PN (P = .007). CONCLUSION: Use of SMOFlipid as the lipid emulsion component of PN may be beneficial in prevention of PNAC in NICU patients that are receiving PN for ≥2 weeks.

Intrauterine growth restriction combined with a maternal high-fat diet increases hepatic cholesterol and low-density lipoprotein receptor activity in rats.

Intrauterine growth restriction (IUGR) and maternal consumption of a high-saturated-fat diet (HFD) increase the risk of hypercholesterolemia, a leading cause of morbidity and mortality. Many pregnant women eat a HFD, thus exposing the fetus to a HFD in utero. The cumulative effect of in utero exposure to IUGR and a HFD on offspring cholesterol levels remains unknown. Furthermore, little is known about the mechanism through which IUGR and maternal HFD consumption increase cholesterol. We hypothesize that IUGR combined with a maternal HFD would increase offspring serum and hepatic cholesterol accumulation via alteration in levels of key proteins involved in cholesterol metabolism. To test our hypothesis we used a rat model of surgically induced IUGR and fed the dams a regular diet or a HFD HFD-fed dams consumed the same kilocalories as regular diet-fed dams, with no difference between surgical intervention groups. In the offspring, IUGR combined with a maternal HFD increased hepatic cholesterol levels, low-density lipoprotein (LDL) receptor protein levels, and Ldlr activity in female rat offspring at birth and both sexes at postnatal day 14 relative to non-IUGR offspring both from regular diet- and HFD-fed dams. These findings suggest that IUGR combined with a maternal HFD increases hepatic cholesterol accumulation via increased LDL cholesterol uptake into the liver with resulting persistent increases in hepatic cholesterol accumulation.

Improved mortality rate for congenital diaphragmatic hernia in the modern era of management: 15 year experience in a single institution.

BACKGROUND/PURPOSE: Mortality rates with congenital diaphragmatic hernia (CDH) have remained at approximately 30% for the last 2 decades. Therapies targeting pulmonary hypertension (PHTN) have not been systematically studied in this population, but are increasingly used. We hypothesized that incremental changes in treatments for PHTN have improved mortality for CDH infants. METHODS: Prospective data from 1998 to 2013 on all liveborn CDH patients treated at our institution were retrospectively analyzed. Based on management of PHTN, 4 eras were identified for comparison. Logistic and linear regression were used to compare characteristics. The primary outcome of death prior to discharge was analyzed by multivariable Cox regression modeling. RESULTS: The study included 192 infants who met inclusion criteria. Length of stay increased, whereas rates of primary repair decreased, suggesting a sicker cohort in the most recent eras. Analysis of mortality across 4 eras showed no difference. By post-hoc analysis, ECMO availability was associated with mortality reduction for eras 3-4 versus 1-2 (HR=0.27, p<0.001). CONCLUSIONS: Improved survival at our institution may be related to recent introduction of ECMO and more aggressive approaches to pulmonary hypertension. Further systematic studies of these PHTN therapies in this specific population are warranted.

Combination of intrauterine growth restriction and a high-fat diet impairs cholesterol elimination in rats.

BACKGROUND: Intrauterine growth restriction (IUGR) increases the risk of adult-onset hypercholesterolemia. High-fat diet (HFD) consumption potentiates IUGR-induced increased cholesterol. Cholesterol is converted to bile acids by Cyp7a1 in preparation for excretion. We hypothesized that IUGR rats fed a HFD will have increased cholesterol, decreased Cyp7a1 protein levels, and decreased bile acids compared to control rats fed a HFD. METHODS: At day 21, IUGR and control pups were placed on one of three diets: a regular chow or one of two HFDs containing 1% or 2% cholesterol. Cholesterol levels and hepatic Cyp7a1 protein levels were quantified a postnatal week 28. RESULTS: Both HFDs increased serum cholesterol levels in control rats, and HFD fed IUGR rats had further increased serum cholesterol up to 35-fold. Both HFDs increased hepatic cholesterol levels, and IUGR further increased hepatic cholesterol levels up to fivefold. IUGR decreased hepatic Cyp7a1 protein up to 75%, and hepatic bile acids up to 54%. CONCLUSION: IUGR increased cholesterol and bile acids and decreased Cyp7a1 protein in rats fed a HFD without changing food intake. These findings suggest that IUGR increases the vulnerability of HFD fed rats to hypercholesterolemia via decreased cholesterol conversion to bile acids.