Ann Anderson-Berry

Risk Factors Associated with Development of Persistent Coagulase-Negative Staphylococci Bacteremia in the Neonate and Associated Short-Term and Discharge Morbidities

Background: Coagulase-negative staphylococci (CoNS) are the most common cause of late-onset sepsis in neonatal intensive care unit settings. Historically, authors have questioned the clinical significance of these bacteremia episodes. Recently, clusters of CoNS bacteremia associated with significant morbidity have been reported. The frequency and importance of these clusters of bacteremia and their associated morbidity remains unclear. Objective: We studied a prolonged cluster of 52 cases of persistent CoNS bacteremia in a level III neonatal intensive care unit to clarify risk factors, morbidity and outcomes associated with persistent CoNS bacteremia. Study Design: A retrospective case-control study of infants with CoNS bacteremia >48 h after initiation of appropriate antibiotics and gestational age-matched control infants was performed. We reviewed patient characteristics prior to and during bacteremia, and outcomes at discharge or death. Results: Persistently infected infants were significantly more likely to have greater duration of exposure to parenteral nutrition, hydrocortisone, antibiotics, and mechanical ventilation prior to infection. Persistently infected infants were significantly more likely than controls to experience feeding intolerance and to require inotropic support, increased respiratory support, and blood product transfusion during bacteremia. Infants with persistent CoNS bacteremia took longer to achieve full enteral feeds, had higher rates of chronic lung disease and increased length of stay compared to controls. No significant difference in mortality was noted. Conclusions: Persistent CoNS bacteremia is associated with clinically significant morbidity including feeding intolerance, respiratory failure, blood transfusion and chronic lung disease in this patient population. This impacts hospital course, increases length of stay and impacts medical needs after discharge. During this study, CoNS bacteremia was difficult to clinically eradicate despite in vitro antibiotic susceptibility.

Comparison of the effect of two human milk fortifiers on clinical outcomes in premature infants.

The use of human milk fortifiers (HMF) helps to meet the high nutritional requirements of the human milk-fed premature infant. Previously available powdered products have not met the protein requirements of the preterm infant population and many neonatologists add powder protein modulars to help meet protein needs. The use of powdered products is discouraged in neonatal intensive care units (NICU) due to concern for invasive infection. The use of a commercially available acidified liquid product with higher protein content was implemented to address these two concerns. During the course of this implementation, poor growth and clinically significant acidosis of infants on Acidified Liquid HMF (ALHMF) was observed. The purpose of this study was to quantify those observations by comparing infant outcomes between groups receiving the ALHMF vs. infants receiving powdered HMF (PHMF). A retrospective chart review compared outcomes of human milk-fed premature infants <2000 g receiving the ALHMF (n = 23) and the PHMF (n = 46). Infant growth, enteral feeding tolerance and provision, and incidence of necrotizing enterocolitis (NEC), metabolic acidosis, and diaper dermatitis were compared between the two groups. No infants were excluded from this study based on acuity. Use of ALHMF resulted in a higher incidence of metabolic acidosis (p = 0.002). Growth while on HMF as measured in both g/kg/day (10.59 vs. 15.37, p < 0.0001) and in g/day (23.66 vs. 31.27, p = 0.0001) was slower in the ALHMF group, on increased mean cal/kg/day (128.7 vs. 117.3, p = 0.13) with nearly twice as many infants on the ALHMF requiring increased fortification of enteral feedings beyond 24 cal/ounce to promote adequate growth (48% vs. 26%, p = 0.10). Although we were not powered to study NEC as a primary outcome, NEC was significantly increased in the ALHMF group. (13% vs. 0%, p = 0.03). Use of a LHMF in an unrestricted NICU population resulted in an increase in clinical complications within a high-acuity NICU, including metabolic acidosis and poor growth. Although further research is needed to assess outcomes among infants with a variety of clinical acuities, gestational ages, and weights to confirm these findings, based on this experience, caution is urged to avoid potential risks.

Parenteral nutrition additive shortages: the short-term, long-term and potential epigenetic implications in premature and hospitalized infants.

Nutrition support practitioners are currently dealing with shortages of parenteral nutrition micronutrients, including multivitamins (MVI), selenium and zinc. A recent survey from the American Society of Enteral and Parenteral Nutrition (ASPEN) indicates that this shortage is having a profound effect on clinical practice. A majority of respondents reported taking some aggressive measures to ration existing supplies. Most premature infants and many infants with congenital anomalies are dependent on parenteral nutrition for the first weeks of life to meet nutritional needs. Because of fragile health and poor reserves, they are uniquely susceptible to this problem. It should be understood that shortages and rationing have been associated with adverse outcomes, such as lactic acidosis and Wernicke encephalopathy from thiamine deficiency or pulmonary and skeletal development concerns related to inadequate stores of Vitamin A and D. In this review, we will discuss the current parenteral shortages and the possible impact on a population of very low birth weight infants. This review will also present a case study of a neonate who was impacted by these current shortages.

Vitamin D Status and Associations in Newborn Formula-Fed Infants during Initial Hospitalization

BACKGROUND Evidence suggests that adequate vitamin D status in infancy plays a role in improving bone health and preventing disease, including type 1 diabetes, infections, and asthma. The objective of this study was to provide newborn hospitalized infants with American Academy of Pediatrics recommendations of 400 IU/day vitamin D-3 and measure the effect on serum 25(OH)D levels. DESIGN This trial was conducted August 2009 to June 2010. Infants were randomized to a control were measured from cord blood, every 7 days, and at discharge. Intact parathyroid hormone was measured at discharge. PARTICIPANTS/SETTING Fifty-two infants <32 weeks gestational age who received formula feedings during their neonatal intensive care unit hospitalization. STATISTICAL ANALYSIS Patient characteristics for each treatment group were summarized using descriptive statistics. The Mann-Whitney test was used to compare continuous variables, and categorical variables were compared using the χ(2) test or Fishers exact test. The Pearson correlation coefficient was used to look at associations between continuous variables. RESULTS The mean cord blood level for all participants was 17.6±7.0 ng/mL. White infants had significantly higher 25(OH)D levels than non-white infants (P=0.0003). The mean 25(OH)D level at discharge of the supplemented group was 23.1±7.0 ng/mL (57.66±17.47 nmol/L), the mean 25(OH)D level of the unsupplemented group was 17.8±4.7 ng/mL (44.43±11.3 nmol/L), (P=0.007). Serum 25(OH)D showed a positive correlation with serum calcium in the first week of life (r=0.44, P=0.003) and negative correlation with parathyroid hormone levels at discharge (r=-0.35, P=0.02). CONCLUSIONS In newborn hospitalized infants, vitamin D-3 supplementation of 400 IU/day increased mean 25(OH)D levels from 17 ng/mL at birth to 23.1 ng/mL at discharge. Lower 25(OH)D levels were correlated with hypocalcemia during the first week of life, and elevated parathyroid hormone levels at discharge.

Relations between feeding intolerance and stress biomarkers in preterm infants.

Objectives: Feeding intolerance (FI) in preterm infants is common but the etiology remains unclear. This study examined FI as a stress-related disease involving brain–gut interactions and tested the model of allostatic load and complications of prematurity. Specific aims were to describe demographic/medical variables and biomarker levels at each time and over time for the sample; describe/compare variables and biomarker levels at each time for infants with/without FI; and compare biomarker interquartile/interpercentile distributions between infants with/without FI. Methods: Preterm infants <32 weeks’ gestation were recruited. The primary outcome was FI by day 7 defined as a feeding withheld, discontinued, or decreased because the infant was not tolerating enteral feedings. Allostatic load was operationalized using cortisol and 8-hydroxydeoxyguanosine (8-OHdG) from cord blood and from saliva and urine on days 1, 7, and 14. Descriptive statistics and comparative analyses were performed. Results: Seven of 31 infants enrolled met criteria for FI. Infants with FI had lower median urinary cortisol on day 1 (P = 0.007) and trended to have lower cortisol in the cord blood (P = 0.056). Interquartile distributions were significantly different between infants with/without FI for urinary cortisol on day 1 (P = 0.034) and trended for differences in 8-OHdG on day 14 (P = 0.087). Interpercentile distributions were significantly different in salivary cortisol on day 14 (P = 0.034) and trended for differences in 8-OHdG on day 1 (P = 0.079). Conclusions: Results support further testing of the model in a larger sample; investigation of the cellular mechanisms associated with the stress and the free radical/antioxidant systems; and inclusion of prenatal factors.

A Comparison of Nutritional Antioxidant Content in Breast Milk, Donor Milk, and Infant Formulas

Human milk is the optimal food for human infants, including infants born prematurely. In the event that a mother of a hospitalized infant cannot provide breast milk, donor milk is considered an acceptable alternative. It is known that the macronutrient composition of donor milk is different than human milk, with variable fat content and protein content. However, much less is known about the micronutrient content of donor milk, including nutritional antioxidants. Samples of breast milk from 12 mothers of infants hospitalized in the Newborn Intensive Care Unit until were collected and analyzed for concentrations of nutritional antioxidants, including α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein + zeaxanthin, retinol, and α-tocopherol. Additionally, a homogenized sample of donor milk available from a commercial milk bank and samples of infant formulas were also analyzed. Concentrations of nutritional antioxidants were measured using high-performance liquid chromatography. Compared to breast milk collected from mothers of hospitalized infants, commercially available donor milk had 18%–53% of the nutritional antioxidant content of maternal breast milk. As donor milk is becoming a common nutritional intervention for the high risk preterm infant, the nutritional antioxidant status of donor milk–fed premature infants and outcomes related to oxidative stress may merit further investigation.

Serum Retinol Concentrations, Race, and Socioeconomic Status in of Women of Childbearing Age in the United States

Background: Vitamin A is an essential nutrient during pregnancy and throughout the lifecycle due to its role in the development of critical organ systems. Because maternal tissue is progressively depleted of vitamin A to supply fetal demands, women who become pregnant while possessing marginal vitamin A reserves are at increased risk of vitamin A inadequacy as pregnancy progresses. Few studies have assessed the relationship between socioeconomic factors and retinol status in women of childbearing age. Methods: We used the National Health and Nutrition Examination Survey (NHANES) to assess the relationship between serum retinol concentrations and socioeconomic factors in women of childbearing age. Women 14–45 years of age (n = 3170) from NHANES cycles 2003–2004 and 2005–2006 were included. Serum retinol concentrations were divided into categories according to World Health Organization criteria. All statistical procedures accounted for the weighted data and complex design of the NHANES sample. A p-value of < 0.05 was considered statistically significant. Results: The poverty score and race were significantly associated with vitamin A status after adjustment for confounders. Odds of retinol concentrations of <1.05 µmol/L were 1.85 times higher for those of lower socioeconomic status when compared to those of higher status (95% CI: 1.12–3.03, p = 0.02), and 3.1 times higher for non-Hispanic blacks when compared to non-Hispanic whites (95% CI: 1.50–6.41, p = 0.002). Dietary intakes of retinol activity equivalents were significantly lower in groups with higher poverty scores (p = 0.004). Conclusion There appear to be disparities in serum vitamin A levels in women of childbearing age related to income and race in the United States.

Dynamics of Vitamin D Metabolism in Maternal-Fetal Dyads.

Objectives: Metabolites of vitamin D in maternal–neonatal dyads remain relatively unexplored. The goal of this study was to evaluate concentrations of 25(OH)D3, 24,25(OH)2D3, and 3-epi-25(OH)D3 in maternal–infant pairs at delivery. Methods: Serum samples of maternal and infant cord blood were collected on 131 mother–infant pairs at delivery. Vitamin D metabolites were analyzed in triplicate using liquid chromatography-tandem mass spectrometry. Statistical analysis was conducted using the Fisher exact test, Wilcoxon rank sum test, and Spearman correlation coefficients. Results: Mean 25(OH)D3 concentrations in maternal and cord blood were 32.9 and 18.5 ng/mL, respectively; mean maternal and cord 24,25(OH)2D3 were 2.0 versus 1.1 ng/mL, respectively. Absolute concentrations of 3-epi-25(OH)D3 were similar in maternal and cord samples (2.4 vs 2.2 ng/mL), whereas the proportion of the total 25(OH)D as the 3-epimer was 6.5% in maternal samples and 10.5% in cord samples. This suggests that the fetus contributes significantly to 3-epi-25(OH)D3 production. In contrast, the ratio of 25(OH)D3:24,25(OH)2D3 was identical in maternal and cord samples (18.5) suggesting equivalent CYP24A1 activity in mother and fetus. Maternal and cord metabolite levels were highly correlated (r = 0.78, 0.90, 0.89 for 25(OH)D3, 24,25(OH)2D3, and 3-epi-25(OH)D3, respectively, P = 0.001 for all). Serum concentrations of all metabolites were lower in nonwhite infants compared with white infants. Maternal and cord concentrations of 25(OH)D3 were positively associated with birth weight (r = 0.21, P = 0.02; r = 0.25, P = 0.003, respectively). Conclusions: This data suggests that although maternal and cord concentrations of vitamin D metabolites are highly correlated, regulation of specific vitamin D metabolites in the mother and the neonate may be mediated independently.

Omega-3 Fatty Acid Intake of Pregnant Women and Women of Childbearing Age in the United States: Potential for Deficiency?

Omega-3 fatty acids play critical roles during fetal growth and development with increased intakes associated with improved maternal-fetal outcomes. Omega-3 fatty acid intake in Western diets is low, and the impact of socioeconomic factors on omega-3 fatty acid intake in pregnant women and women of childbearing age has not been reported. We used the National Health and Nutrition Examination Survey (NHANES) cycles 2003–2012 to assess the relationship between omega-3 fatty acid intake and socioeconomic factors in women of childbearing age. Out of 7266 eligible participants, 6478 were women of childbearing age, while 788 were identified as pregnant at the time of the survey. Mean EPA+DHA intake of the population was 89.0 mg with no significant difference between pregnant and non-pregnant women. By univariate and multivariate analyses adjusting for confounders, omega-3 fatty acid intake was significantly associated with poverty-to-income ratio, race, and educational attainment. Our results demonstrate that omega-3 fatty acid intake is a concern in pregnant women and women of childbearing age in the United States, and that socioeconomically disadvantaged populations are more susceptible to potential deficiencies. Strategies to increase omega-3 fatty acid intake in these populations could have the potential to improve maternal and infant health outcomes.

Comparison of a Powdered, Acidified Liquid, and Non-Acidified Liquid Human Milk Fortifier on Clinical Outcomes in Premature Infants.

We previously compared infant outcomes between a powdered human milk fortifier (P-HMF) vs. acidified liquid HMF (AL-HMF). A non-acidified liquid HMF (NAL-HMF) is now commercially available. The purpose of this study is to compare growth and outcomes of premature infants receiving P-HMF, AL-HMF or NAL-HMF. An Institutional Review Board (IRB) approved retrospective chart review compared infant outcomes (born < 2000 g) who received one of three HMF. Growth, enteral nutrition, laboratory and demographic data were compared. 120 infants were included (P-HMF = 46, AL-HMF = 23, NAL-HMF = 51). AL-HMF infants grew slower in g/day (median 23.66 vs. P-HMF 31.27, NAL-HMF 31.74 (p < 0.05)) and in g/kg/day, median 10.59 vs. 15.37, 14.03 (p < 0.0001). AL-HMF vs. NAL-HMF infants were smaller at 36 weeks gestational age (median 2046 vs. 2404 g, p < 0.05). However AL-HMF infants received more daily calories (p = 0.21) and protein (p < 0.0001), mean 129 cal/kg, 4.2 g protein/kg vs. P-HMF 117 cal/kg, 3.7 g protein/kg , NAL-HMF 120 cal/kg, 4.0 g protein/kg. AL-HMF infants exhibited lower carbon dioxide levels after day of life 14 and 30 (p < 0.0001, p = 0.0038). Three AL-HMF infants (13%) developed necrotizing enterocolitis (NEC) vs. no infants in the remaining groups (p = 0.0056). A NAL-HMF is the most optimal choice for premature human milk-fed infants in a high acuity neonatal intensive care unit (NICU).