Unbound free fatty acids from preterm infants treated with intralipid decouples unbound from total bilirubin potentially making phototherapy ineffective.

Extremely low birth weight (ELBW; <1,000 g) infants have poor outcomes, often compromised by bilirubin neurotoxicity. We measured unbound bilirubin (Bf) and unbound free fatty acid (FFAu) levels in 5 ELBW infants in a trial examining the effects of pharmacologic ductal closure on infants treated with Intralipid infusion (3 g/kg/day). The levels for all infants (mean ± SD) were: total serum bilirubin (TSB) 4.6 ± 1.7 mg/dl, FFAu 376 ± 496 nM, and Bf 42 ± 30 nM. Of the 3 infants who died, 2 had TSB <5.9 mg/dl but FFAu >580 nM and Bf >75 nM. Multiple regression revealed a major effect on Bf levels due to FFAu, indicating that Intralipid elevated levels of FFAu and Bf. Indomethacin or ibuprofen reduced Bf levels, most likely by reducing FFAu levels through lipase inhibition. Because displacement of Bf by FFAu decouples Bf from TSB, phototherapy may not reduce the risk of bilirubin or FFAu toxicity in Intralipid-treated ELBW infants.

Effects of bilirubin on neutrophil responses in newborn infants.

BACKGROUND: Newborns are susceptible to inflammatory diseases due to defects in clearing activated immune cells from tissues. Therefore, mechanisms have likely evolved to protect neonates from leukocyte-mediated cytotoxicity. Bilirubin has antioxidant activity, and it is possible that it also exerts effects on cellular immune responses in jaundiced infants. OBJECTIVES: We hypothesize that bilirubin increases expression of antioxidant genes and decreases production of inflammatory proteins in neonatal neutrophils. METHODS: Neutrophils were isolated from umbilical cord blood, and from adults for comparison, and treated with bilirubin (10-300 µmol/l, equivalent to unbound bilirubin 3-40 nmol/l), in the presence or absence of lipopolysaccharide (LPS). Expression of genes for antioxidant enzymes [superoxide dismutase (SOD), heme-oxygenase-1 (HO-1)] and heme-dependent enzymes involved in inflammation [NADPH oxidase-1 (NOX-1), cyclooxygenase-2 (COX-2)] was measured by PCR. Inflammatory cytokines were measured by bead array analysis using flow cytometry. RESULTS: We found that LPS induced production of interleukin (IL)-8, IL-1ß, and macrophage inhibitory protein-1ß (MIP-1ß). Bilirubin increased basal production of IL-8 and IL-1ß, but downregulated LPS-induced generation of IL-8 and MIP-1ß. It also upregulated SOD and HO-1 gene expression. We observed an unexpected bilirubin-induced increase in gene expression of NOX-1 in LPS-activated cells, and of COX-2 in both resting and activated cells. CONCLUSIONS: These findings suggest that bilirubin suppresses inflammation and increases antioxidant enzyme generation in activated neonatal neutrophils. The unexpected increases in NOX-1 and COX-2 expression may represent an early response, with physiologic effects mitigated by increased antioxidant activity. Further studies will be needed to define levels of bilirubin that optimize its protective effects, while minimizing potential inflammatory toxicity.

Sirtuin1 in tracheal aspirate leukocytes: possible role in the development of bronchopulmonary dysplasia in premature infants.

OBJECTIVE: To study the association between Sirtuin1 (Sirt1), a class III histone deacetylator, in tracheal aspirate (TA) leukocytes and the development of bronchopulmonary dysplasia (BPD) in premature infants and modulation of Sirt1 with dexamethasone (Dex) use. DESIGN/METHODS: Serial TA samples were collected on days 1, 3, 5 and 7 from ventilated premature neonates. Sirt1 was localized by immunocytochemistry and quantified on a scale of 0-4 by blinded observers. BPD was defined as the need of supplemental oxygen at 36 weeks postmenstrual age (PMA). RESULTS: A total of 130 TA samples were collected from 51 infants (mean ± SD: GA 25.5 ± 1.4 w, BW 762 ± 174 g). Eleven infants survived without BPD and 40 infants died before 36 weeks PMA or developed BPD. Sirt1 was localized in the cytoplasm and nuclei of mononuclear (MONO) as well as polymorphonuclear cells. Sirt1 was significantly more localized in the nuclei of MONO cells in infants without BPD compared to infants who developed BPD or died before 36 weeks PMA. Twenty six infants received Dex. There was no significant change in Sirt1 localization with steroid therapy. CONCLUSIONS: Lower Sirt1 in TA leukocytes is associated with the development of BPD or death in premature infants. Dex use had no effect on Sirt1.

Four-vessel umbilical cord associated with multiple congenital anomalies: a case report and literature review.

A case is described of a neonate with a four-vessel umbilical cord containing two arteries and two veins. This was due to a rare persistence of the caudal portion of the right umbilical vein. The infant had multiple congenital anomalies including a complete atrioventricular canal, an interrupted inferior vena cava, a double superior vena cava, a left ventricular hypoplasia, dextrocardia, situs ambiguous, and malrotation of the small bowel. The birth of an infant with a four-vessel cord mandates comprehensive work-up for associated anomalies. The literature is reviewed.

Early exclusive breastfeeding and maternal attitudes towards infant feeding in a population of new mothers in San Francisco, California.

BACKGROUND: Positive parental attitudes towards infant feeding are an important component in child nutritional health. Previous studies have found that participants in the Special Supplemental Women, Infants, and Children (WIC) Program have lower breastfeeding rates and attitudes that do not contribute towards healthy infant feeding in spite of breastfeeding and nutrition education programs targeting WIC participants. The objective of this study was to assess the frequency of exclusive breastfeeding in the early postpartum period and maternal attitudes towards breastfeeding in a population of mothers at two San Francisco hospitals and in relation to WIC participation status. METHODS: We interviewed women who had recently delivered a healthy newborn using a structured interview. RESULTS: A high percentage (79.8%) of our sample was exclusively breastfeeding at 1-4 days postpartum. We did not find any significant differences in rates of formula or mixed feeding by WIC participant status. Independent risk factors for mixed or formula feeding at 1-3 days postpartum included Asian/Pacific Islander ethnicity (odds ratio [OR] 2.90, 95% confidence interval [CI] 1.17-7.19). Being a college graduate was associated with a decreased risk of formula/mixed feeding (OR 0.28, 95% CI 0.10-0.79). We also found that thinking breastfeeding was physically painful and uncomfortable was independently associated with not breastfeeding (OR 1.41, 95% CI 1.06-1.89). CONCLUSIONS: Future studies should be conducted with Asian-Americans and Pacific Islanders to better understand the lower rates of exclusive breastfeeding in this population and should address negative attitudes towards breastfeeding such as the idea that breastfeeding is painful or uncomfortable.

Maternal knowledge of infant feeding guidelines and label reading behaviours in a population of new mothers in San Francisco, California.

The objective of this study was to evaluate the relationship between maternal nutrition knowledge and maternal socio-demographics including participation in the Special Supplemental Women, Infants and Children's (WIC) Program. A cross-sectional study of new mothers at two San Francisco hospitals was conducted using some of the American Academy of Pediatrics' guidelines in a structured questionnaire to assess maternal nutritional knowledge. Maternal nutritional attitudes towards product nutrient labels were also assessed in a questionnaire format. Logistic regression models were used to evaluate the odds of having high maternal nutrition knowledge and of infrequently reading nutrition labels. In multivariate logistic regression models, higher maternal nutrition knowledge (defined as answering all four nutrition questions correctly) was associated with higher income levels defined as > or =$25 000/year, odds ratio (OR) 10.03 95% confidence interval (CI) (1.51-66.74), and in linear models, higher nutritional knowledge was associated with having more children (P < 0.01), a higher income (P = 0.01) and not being a WIC participant (P < 0.01). Mothers with higher incomes were also more likely to read product nutritional labels OR 4.24, 95% CI (1.24-14.51), compared with mothers with lower incomes as were mothers with higher education levels OR 3.32, 95% CI (1.28-8.63). In San Francisco, lower income mothers are at greatest risk for low maternal nutrition knowledge and not reading product nutritional labels. Higher household income was independently associated with increased maternal nutrition knowledge and likelihood of reading nutritional labels. More comprehensive interventions need to target low-income mothers including current WIC participants to help close the nutritional advantages gap conferred by income and education.