Low caloric intake and high fluid intake during the first week of life are associated with the severity of bronchopulmonary dysplasia in extremely low birth weight infants.

OBJECTIVE: To study whether there is an association between nutritional intake during the first week of life and severity of bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants. METHODS: In a retrospective cohort study, medical records of all ELBW infants admitted to our Neonatal Intensive Care Unit (2010-2017) were reviewed for infants' demographics, clinical characteristics, nutritional intake during their first week of life, and BPD risk factors. RESULTS: During the study period 226 infants were identified of whom 67% (151/226) had moderate-severe BPD and the rest served as controls. Overall infants with moderate-severe BPD were younger, smaller, and spent more time on mechanical ventilation than their controls [(mean±standard deviation) 24.7±1.7 vs. 26.8±2.0 weeks gestational age (p < 0.001); 678±154 vs. 837±129 grams (p < 0.001); and 37.9±23.6 vs. 13.7±15.3 days (p < 0.001) respectively]. During the first week of life, the average caloric, carbohydrate, protein and lipid intakes were significantly lower, and the average fluid intake was significantly higher in the moderate-severe BPD than the control group. After adjustment for confounders, fluid intake, and days on mechanical ventilation were significantly associated with moderate-severe BPD with an odds ratio [OR (95% confidence interval)] of 1.03 (1.01-1.04), and 1.05 (1.03-1.07) respectively. Daily caloric intake was associated with an increased risk for moderate-severe BPD [OR: 0.94 (0.91-0.97)]. CONCLUSION: Low caloric intake, and high fluid intake during the first week of life are associated with the severity of BPD in ELBW infants.

Enteral fish oil supplementation in the resolution of parenteral nutrition associated cholestasis.

OBJECTIVE: To analyze safety, tolerance and efficacy of enteral omega-3 fatty acids (FAs) in the resolution of Parenteral Nutrition Associated Cholestasis (PNAC) and postnatal growth among preterm neonates. STUDY DESIGN: This is a single center retrospective case-control study of all neonates born less than 32 weeks of gestation and developed PNAC (Direct bilirubin >2 mg/dl). Infants who received enteral omega-3 FAs supplementation (1 g/Kg/d) served as cases and were compared with gestational age, gender and direct bilirubin level matched controls who did not receive enteral omega-3 FAs supplementation. RESULTS: A total of 48 infants were analyzed, 24 who received enteral omega-3 fatty acids were matched with 24 controls. The omega-3 FAs and control groups were similar in gestational age (weeks) and birth weight (gram). Overall there were no differences between the two groups in infants' demographics or clinical characteristics including risk factors for the development of PNAC. Infants who received enteral omega-3 FAs had significantly fewer days of cholestasis (p = 0.025) and a higher average daily weight gain (grams/day) (p = 0.011) than their controls. In a linear regression analysis with days of cholestasis as the dependent variable and Ursodeoxycholic acid (UDCA) and Omega-3 FAs as independent variables, enteral omega-3 FAs remained associated with a shorter duration of cholestasis, p < 0.001. CONCLUSION: Enteral fish oil is inexpensive, safe & well tolerated in preterm neonates with no contraindications to enteral feeding. Enteral omega-3 FAs are easy to administer and help in rapid resolution of PNAC while promoting postnatal weight gain in preterm infants.

Slow enteral feeding decreases risk of transfusion associated necrotizing enterocolitis.

BACKGROUND: Necrotizing Enterocolitis (NEC) is a multifactorial condition where PRBC transfusion is associated with necrotizing enterocolitis (TANEC) in about a third of all cases of NEC. We have investigated the role of feeding practices in incidence of TANEC. We sought to compare infants diagnosed with TANEC versus infants diagnosed with classic NEC and investigated the effects of a standardized slow enteral feeding (SSEF) protocol on TANEC incidence as well as the effects of SSEF on growth of infants with NEC. METHODS: We conducted a retrospective cohort study, where medical records of infants born in a tertiary care neonatal intensive care unit (level IIIb) from January 1997 to May 2014 with birth weight < 1500 grams and gestational age≤34 weeks with NEC stage IIa or greater according to the modified Bell's staging were reviewed. RESULTS: During the study period, 111 infants developed NEC, and 41/111 (37%) were diagnosed with TANEC. Infants with TANEC were smaller, more premature, had higher SNAPPE scores and were more anemic prior to transfusion compared with infants with 'classic NEC'. The severity of NEC did not differ between the two groups, however, infants with TANEC had worse outcomes and longer NICU stays. Introduction of SSEF protocol, led to a significant decrease in TANEC. There was no difference in weight and head circumference of infants in the two groups at 2 years corrected age. CONCLUSION: SSEF led to a significant reduction in the incidence of TANEC without impairing growth at 2 years corrected age.

Validation of mid-infrared spectroscopy for macronutrient analysis of human milk.

OBJECTIVE: Human milk has considerable variation in its composition. Hence, the nutrient profile is only an estimate and can result in under- or over-estimation of the intake of preterm infants. Mid-infrared (MIR) spectroscopy is an evolving technique for analyzing human milk but needs validation before use in clinical practice. STUDY DESIGN: Human milk samples from 35 mothers delivering at 35 weeks to term gestation were analyzed for macronutrients by MIR spectroscopy and by standard laboratory methods using Kjeldahl assay for protein, Mojonnier assay for fat and high-pressure liquid chromatography assay for lactose. RESULTS: MIR analysis of the macronutrients in human milk correlated well with standard laboratory tests with intraclass correlation coefficients of 0.997 for fat, 0.839 for protein and 0.776 for lactose. Agreement between the two methods was excellent for fat, and moderate for protein and lactose (P<0.001). CONCLUSIONS: This methodological paper provides evidence that MIR spectroscopy can be used to analyze macronutrient composition of human milk. Agreement between the methodologies varies by macronutrient.

Standardized slow enteral feeding protocol reduces necrotizing enterocolitis in micropremies.

BACKGROUND: Compared to early enteral feeds, delayed introduction and slow enteral feeding advancement to reduce necrotizing enterocolitis (NEC) is not well studied in micropremies (<750g birth weight). METHODS: Pre-post case control study. Micropremies who followed a standardized slow enteral feeding (SSEF) protocol (September 2009 to March 2015) were compared with a similar group of historical controls (PreSSEF, January 2003 to July 2009). Enteral feeding withheld for first 10-14 days and advanced at <10 ml/kg/day in the SSEF group. RESULTS: Ninety-two infants in the SSEF group were compared with 129 PreSSEF group. Birth weight and gestational age in SSEF and PreSSEF were similar. Breast milk initiation rate was higher in SSEF (87.0 vs. 72.0%, p = 0.01) compared to PreSSEF, but were similar at full enteral feeds. Compared with PreSSEF, feeding initiation day, full enteral feeding day, parenteral nutrition days, and total central line days were longer in SSEF. There was significant reduction in NEC (1.1 vs. 16.2%, p < 0.01), surgical NEC (0.0 vs. 7.8%, p < 0.01) and NEC/death (7.6 vs. 29.5%, p < 0.01), in SSEF compared to PreSSEF. SSEF, compared to PreSSEF, had more cholestasis (41.8 vs 28.8%, p = 0.04), higher peak serum alkaline phosphatase (638 vs. 534 IU/dL, p < 0.01), but similar rates of late-onset sepsis (39.1 vs 43.4%, p = 0.53). In infants who survived to discharge, SSEF had higher discharge weight, lower extra-uterine growth restriction, and similar length of stay, compared to PreSSEF. CONCLUSIONS: A SSEF protocol significantly reduces the incidence of NEC and combined NEC/death in micropremies.

Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial.

OBJECTIVES: A randomized, masked, controlled trial was conducted to assess effects of supplementing premature infant formulas with oils containing the long-chain polyunsaturated fatty acids, arachidonic acid (AA; 20:4 n6), and docosahexaenoic acid (DHA; 22:6 n3) on growth, visual acuity, and multiple indices of development. METHODS: Infants (N = 470) with birth weights 750 to 1800 g were assigned within 72 hours of the first enteral feeding to 1 of 3 formula groups with or without long-chain polyunsaturated fatty acids: 1) control (N = 144), 2) AA+DHA from fish/fungal oil (N = 140), and 3) AA+DHA from egg-derived triglyceride (egg-TG)/fish oil (N = 143). Infants were fed human milk and/or Similac Special Care with or without 0.42% AA and 0.26% DHA to term corrected age (CA), then fed human milk or NeoSure with or without 0.42% AA and 0.16% DHA to 12 months' CA. Infants fed exclusively human milk to term CA (EHM-T; N = 43) served as a reference. RESULTS: Visual acuity measured by acuity cards at 2, 4, and 6 months' CA was not different among groups. Visual acuity measured by swept-parameter visual-evoked potentials in a subgroup from 3 sites (45 control, 50 AA+DHA [fish/fungal]; 39 AA+DHA [egg-TG/fish]; and 23 EHM-T) was better in both the AA+DHA (fish/fungal; least square [LS] means [cycle/degree] +/- standard error [SE; octaves] 11.4 +/- 0.1) and AA+DHA (egg-TG/fish; 12.5 +/- 0.1) than control (8.4 +/- 0.1) and closer to that of the EHM-T group (16.0 +/- 0.2) at 6 months' CA. Visual acuity improved from 4 to 6 months' CA in all but the control group. Scores on the Fagan test of novelty preference were greater in AA+DHA (egg-TG/fish; LS means +/- SE, 59.4 +/- 7.7) than AA+DHA (fish/fungal; 57.0 +/- 7.5) and control (57.5 +/- 7.4) at 6 months' CA, but not at 9 months' CA. There were no differences in the Bayley Mental Development Index at 12 months' CA. However, the Bayley motor development index was higher for AA+DHA (fish/fungal; LS means +/- SE, 90.6 +/- 4.4) than control (81.8 +/- 4.3) for infants

Cytokines in human milk.

Breast feeding improves the health of children. The greatest significance is to host defense, prevention of autoimmunity, and development of the digestive system; however, the underlying mechanisms for these effects are not well understood. Based on recent evidence that cytokines might be important in these processes, we have used ELISA to quantitate the cytokines in human colostrum, transitional, and mature milk from mothers delivering preterm or at term. We also used reverse transcription PCR to test breast milk cells for the production of cytokine mRNA. No significant (< 10 pg/ml) GM-CSF, SCF, LIF, MIP-1 alpha, IL-2, IL-4, IL-11, IL-12, IL-13, IL-15, sIL-2R, or IFN-gamma was detected. And, in contrast to earlier studies using bioassays or RIA, no significant IL-1 beta, TNF-alpha, or IL-6 was present; nor was IL-10, which had been tested using less specific antibodies. We did confirm the presence of high levels of M-CSF, which remained high throughout lactation. Human milk contained latent, but not free, TGF-beta 1, and especially TGF-beta 2, both of which may be activated by gastric acid pH. High levels of IL-1RA were detected, and like activated TGF-beta, may protect against autoimmunity. Chemokines, particularly GRO-alpha and MCP-1, but also RANTES and IL-8, were present and could protect against infection. Maternal cells in breast milk expressed mRNA for MCP-1 (20/20), IL-8 (14/20), TGF-beta 1 (14/16), TGF-beta 2 (4/6), M-CSF (9/12), IL-6 (6/12) and IL-1 beta (7/12), and may be a source of these cytokines. mRNA for IL-2, IL-10, IFN-gamma, TNF-alpha was not detected and only weak expression was found for RANTES (1/18). There was considerable variability between individual women, and women delivering preterm had lower levels of several cytokines in colostrum than women delivering at term. Yet, cytokine levels remained high months to years into lactation, providing immunological benefit to the breastfed infant/child.

The utility of a bilateral breast pumping system for mothers of premature infants.

Mothers of premature infants have difficulty maintaining their milk supply as a result of the separation that occurs between the mother and the baby. The hypothesis in the present investigation is that use of a bilateral (simultaneous) breast pumping system will increase the volume of milk expressed in these mothers. Thirty-two breastfeeding mothers of premature infants were randomly assigned to either the control (single) or the experimental (bilateral) breast pump group. Mothers pumped at least four times a day. Data collection included a daily milk production log, weekly serum prolactin levels, and a weekly State-Trait Anxiety Inventory (STAI). Participation lasted from four to six weeks. Data analysis included average STAI scores; average prolactin levels; and weekly averages for number of pumping sessions, hours of pumping, and milk production in milliliters. The two groups did not differ on several demographic characteristics, STAI scores, prolactin levels, number of pumping sessions per week, or weekly milk production. The amount of time spent pumping, however, was statistically less for mothers who used the bilateral pump (7.6 +/- 3.0 hours/week) versus those who used the single pump (11.1 +/- 3.1 hours/week) (p = .003). Although use of either the single pump or the bilateral electric pump resulted in similar milk production, the bilateral pump significantly reduced the time invested in pumping. Health professionals should advocate use of the bilateral pump for mothers of premature infants. Additional studies are needed to determine strategies for increasing milk production in this population.

Smoking alters the relationship between maternal zinc intake and biochemical indices of fetal zinc status.

Maternal smoking impairs fetal zinc status. This study was designed to clarify the effect of smoking on the relationship between maternal zinc intake and zinc status in mother and fetus. Zinc was measured with atomic-absorption spectroscopy. Statistical analyses consisted of descriptive statistics, simple correlations, and stepwise multiple regression. The results suggest that maternal plasma zinc, red blood cell zinc, and alkaline phosphatase at term are not related to maternal zinc intake. In the nonsmoking parturient both cord-vein plasma zinc and cord-vein alkaline phosphatase activity are positively related to maternal zinc intake. In the smoking parturient there is no relationship between maternal zinc intake and fetal zinc status except for a negative relation with cord-vein plasma zinc. Relations between maternal zinc intake and placental zinc can be shown with stepwise-multiple-regression techniques. The data suggests that maternal zinc intake is related not to maternal zinc status but to fetal zinc status in a normal pregnancy. The relation is altered in the pregnancy complicated by smoking.

Necrotizing enterocolitis: feeding in endemic and epidemic periods.

Aggressive feeding practices are thought to increase the incidence of necrotizing enterocolitis (NEC). Detailed feeding histories of the 39 cases occurring between January 1, 1984 and May 31, 1985 were compared with matched controls. The study period included a cluster (epidemic) of 11 cases diagnosed within 1 month. Data were analyzed collectively and separately for endemic and epidemic cases. Collectively, cases had greater average daily intake volume, maximum daily intake volume, intake volume on the day prior to diagnosis, and maximum daily caloric intake (all p less than 0.05) than controls. The only recorded parameter that differed in endemic cases vs controls was intake the day prior to diagnosis. In contrast, epidemic cases were fed significantly more volume, more calories, and faster than controls: average intake volume (62.5 +/- 27.2 vs 37.4 +/- 18.0 ml/kg/day); maximum intake volume (118.5 +/- 33.5 vs 76.4 +/- 38.8 ml/kg/day); intake day prior to diagnosis (109.8 +/- 30.9 vs 63.8 +/- 43.1 ml/kg/day); maximum daily increment (42.6 +/- 16.7 vs 26.7 +/- 16.4 ml/kg); maximum caloric intake (126.1 +/- 44.6 vs 77.3 +/- 50.0) (all p less than 0.01). Five of the feeding parameters were significantly less for the epidemic controls than the endemic controls, suggesting a general slowing of feeding during the NEC epidemic. In summary, the data suggest feeding patterns may have an impact on NEC especially during epidemic periods.

Neonatal metabolic acidosis: effect of chloride from normal saline flushes.

Metabolic Acidosis is a reported complication of total parenteral nutrition (TPN). A large number of infants receiving TPN in an NICU were noted to have metabolic acidosis. We evaluated the effect of lowering the chloride intake on the incidence of metabolic acidosis in low birth weight (LBW) infants on TPN. Standard TPN solutions were adjusted to provide about 2-3 mEq/kg/day chloride instead of 5-7 mEq/kg/day provided previously. Most infants on TPN received approximately another 1-3 mEq/kg/day from intravenous and arterial line flushes with normal saline. Ten infants who had been on the original TPN solutions were compared to 10 infants who were on the revised TPN solutions. Serum pH, bicarbonate, and base deficit were used to measure acidosis. Medical records were reviewed for the number of days the infants had abnormal values. Serum chloride levels were also recorded. While similar in gestational age, birth weight, age during study period, days on TPN, and days on orally supplemented parenteral nutrition, the group with higher chloride intake had significantly more days of metabolic acidosis. They also had significantly higher serum chlorides. It is concluded that a total chloride load in excess of 6 mEq/kg/day in LBW infants receiving TPN is associated with more metabolic acidosis. Also, if saline is used for clearing of intravenous and arterial lines, standard TPN solutions should be formulated with consideration of the total chloride load.

The effect of smoking on placental and fetal zinc status.

Previous studies have reported a cadmium/zinc interaction in cadmium-exposed pregnant animals that results in (1) increased placental cadmium levels, (2) increased placental zinc levels, and (3) decreased placental zinc transport. This study was carried out to determine whether zinc status would be affected in pregnant women exposed to cadmium through cigarette smoke. Atomic absorption spectroscopy was used to determine the levels of cadmium and zinc; 65 pregnant women who smoke and 84 who do not smoke were studied. Our data reveal that increased cadmium levels in pregnant women as the result of smoking increase placental zinc levels and decrease cord red blood cell zinc levels. Significantly higher levels of both cadmium and zinc were found in the placentas of pregnant women who smoke; moreover, stepwise multiple regression showed that maternal whole blood cadmium levels predicted placental zinc levels. In regard to cord blood, a significant 9% decrease in the red blood cell zinc level was observed in infants of mothers who smoke and this decrease was correlated with smoking activity, as evaluated by measuring plasma levels of thiocyanate. Also cord red blood cell zinc levels were found to correlate with placental zinc levels in nonsmokers but not in smokers. Overall, our data show that a cadmium/zinc interaction does take place in the maternal-fetal-placental unit of pregnant women who smoke and results in less favorable zinc status in the infants.