Sharon Groh-Wargo

Lipid Needs of Preterm Infants: Updated Recommendations

Long-chain polyunsaturated fatty acids (LCPUFAs) are of nutritional interest because they are crucial for normal development of the central nervous system and have potential long-lasting effects that extend beyond the period of dietary insufficiency. Here we review the recent literature and current recommendations regarding LCPUFAs as they pertain to preterm infant nutrition. In particular, findings that relate to fetal accretion, LCPUFA absorption and metabolism, effects on development, and current practices and recommendations have been used to update recommendations for health care providers. The amounts of long-chain polyunsaturated fatty acids (LCPUFAs) used in early studies were chosen to produce the same concentrations as in term breast milk. This might not be a wise approach for preterm infants, however, particularly for very and extremely preterm infants, whose requirements for LCPUFAs and other nutrients exceed what is normally provided in the small volumes that they are able to tolerate. Recent studies have reported outcome data in preterm infants fed milk with a docosahexaenoic acid (DHA) content 2-3 times higher than the current concentration in infant formulas. Overall, these studies show that providing larger amounts of DHA supplements, especially to the smallest infants, is associated with better neurologic outcomes in early life. We emphasize that current nutritional management might not provide sufficient amounts of preformed DHA during the parenteral and enteral nutrition periods and in very preterm/very low birth weight infants until their due date, and that greater amounts than used routinely likely will be needed to compensate for intestinal malabsorption, DHA oxidation, and early deficit. Research should continue to address the gaps in knowledge and further refine adequate intake for each group of preterm infants.

Body Composition in Preterm Infants Who Are Fed Long-Chain Polyunsaturated Fatty Acids: A Prospective, Randomized, Controlled Trial

The objective of this study was to evaluate growth and body composition of premature infants who were fed formulas with arachidonic acid (ARA; 20:4n6) and docosahexaenoic acid (DHA; 22:6n3) to 1 y of gestation-corrected age (CA). Preterm infants (750–1800 g birth weight and <33 wk gestational age) were assigned within 72 h of first enteral feeding to one of three formulas: control (n = 22), DHA+ARA from fish/fungal oil [DHA+ARA(FF); n = 20], or DHA+ARA from egg/fish oil [DHA+ARA(EF); n = 18]. Human milk feeding was allowed on the basis of the mothers choice. Infants were fed breast milk and/or preterm formulas with or without 0.26% DHA and 0.42% ARA to term CA followed by breast milk or postdischarge preterm formulas with or without 0.16% DHA and 0.42% ARA to 12 mo CA. Body composition was measured by dual-energy x-ray absorptiometry. There were no significant differences among the three study groups at any time point in weight, length, or head circumference. Bone mineral content and bone mineral density did not differ among groups. At 12 mo CA, infants who were fed DHA+ARA-supplemented formulas had significantly greater lean body mass (p < 0.05) and significantly less fat mass (p < 0.05) than infants who were fed the unsupplemented control formula. The DHA+ARA-supplemented formulas supported normal growth and bone mineralization in premature infants who were born at <33 wk gestation. Preterm formulas that had DHA+ARA at the levels and ratios in this study and were fed to 1 y CA led to increased lean body mass and reduced fat mass by 1 y of age.

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.

Metabolic Bone Disease: A Continued Challenge in Extremely Low Birth Weight Infants

BACKGROUND Metabolic bone disease (MBD) is an important prematurity-related morbidity, but remains inadequately investigated in extremely low birth weight (ELBW) infants, the group most at risk. The objective was to describe the incidence and associated risk factors of MBD in ELBW infants. METHODS Retrospective analysis of all ELBW infants admitted between January 2005 and December 2010 who survived > 8 weeks. MBD was defined as the presence of osteopenia or rickets in radiographs. RESULTS Of the 230 infants included in the study, 71 (30.9%) developed radiological evidence of MBD (cases) of which 24/71 (33.8%) developed spontaneous fractures. MBD and fractures were noted at mean postnatal ages of 58.2 ± 28 and 100.0 ± 61 days, respectively. Compared with controls, cases were smaller at birth (664.6 ± 146 g vs 798.1 ± 129 g), more premature (25.0 ± 1.8 vs 26.4 ± 1.9 weeks), more frequently associated with mechanical ventilation, chronic lung disease, parenteral nutrition days, cholestasis, furosemide, postnatal steroids, and antibiotics use (all P < .01). Cases had lower average weekly intake of calcium, phosphorous, vitamin D, protein, and calories during the first 8 weeks of life compared with controls. Cases with MBD, compared with controls, had higher mortality (14.1 vs 4.4%) and longer hospital stay (140.2 ± 51 vs 101.0 ± 42 days; P < .01). CONCLUSIONS MBD remains an important morbidity in ELBW infants despite advances in neonatal nutrition. Further research is needed to optimize the management of chronic lung disease and early nutrition in ELBW infants.

Enteral nutrition support of the preterm infant in the neonatal intensive care unit.

The delivery of a preterm baby is a nutrition emergency. Growth and the accumulation of nutrient reserves are higher during the third trimester of pregnancy than at any other time during the life cycle. Enteral nutrition is the preferred mode of support and human milk the preferred source of enteral nutrition. Human milk is highly digestible and contains many anti-infective components, which confer a lower risk of infection. The mother of a preterm infant requires education, equipment, and encouragement to successfully initiate and sustain lactation. Human milk requires nutrient fortification to meet the protein and mineral needs of the rapidly growing preterm infant. Commercial human milk fortifiers are available. If human milk is unavailable or the volume is insufficient, preterm formulas are available. Preterm formulas have different sources of macronutrients and greater density of all nutrients than formulas intended for term newborns. Preterm infants benefit from early enteral feedings with slow but steady increases in feedings to achieve full support. Infants born at <35 weeks gestational age are supported with tube feedings. A transition to feedings at the breast or to bottle feedings is gradually made as the baby matures. Nutrient recommendations specific to the preterm infant are available. Special products and feeding strategies exist to respond to common medical conditions that can complicate nutrition management. Optimal nutrition care of the preterm infant offers the opportunity to improve outcomes for children.

Standardized Slow Enteral Feeding Protocol and the Incidence of Necrotizing Enterocolitis in Extremely Low Birth Weight Infants.

BACKGROUND Compared with early enteral feeds, the delayed introduction and slow advancement of enteral feedings to reduce the incidence of necrotizing enterocolitis (NEC) are not well studied in extremely low birth weight (ELBW) infants. OBJECTIVE To study the effects of a standardized slow enteral feeding (SSEF) protocol in ELBW infants. METHODS ELBW infants who followed an SSEF protocol (September 2009 to December 2012) were compared with a similar group of historical controls (January 2003 to July 2009). Short-term outcomes between the 2 groups were compared by propensity score (PS) analysis. RESULTS One hundred twenty-five infants in the SSEF group were compared with 294 historical controls. Compared with the controls, feeding initiation day, full enteral feeding day, parenteral nutrition (PN) days, and total central line days were longer in the SSEF group. There was no significant difference in overall NEC (5.6% vs 11.2%, respectively; P = .10) or surgical NEC (1.6% vs 4.8%, respectively; P = .17) between the SSEF group and controls. However, in infants with birth weight <750 g, NEC (2.1% vs 16.2%, respectively; P < .01) or combined NEC/death (12.8% vs 29.5%, respectively; P = .03) was significantly less in the SSEF group compared with controls. In infants who survived to discharge, there was no significant difference in the discharge weight or length of stay in PS-adjusted analysis. CONCLUSIONS An SSEF protocol significantly reduces the incidence of NEC and combined NEC/death in infants with birth weight <750 g. Despite taking longer to achieve full enteral feeding on this protocol, surviving ELBW infants demonstrated comparable weight gain at discharge without prolonging their hospital stay.

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.

Working group reports: evaluation of the evidence to support practice guidelines for nutritional care of preterm infants—the Pre-B Project

ABSTRACT The “Evaluation of the Evidence to Support Practice Guidelines for the Nutritional Care of Preterm Infants: The Pre-B Project” is the first phase in a process to present the current state of knowledge and to support the development of evidence-informed guidance for the nutritional care of preterm and high-risk newborn infants. The future systematic reviews that will ultimately provide the underpinning for guideline development will be conducted by the Academy of Nutrition and Dietetics’ Evidence Analysis Library (EAL). To accomplish the objectives of this first phase, the Pre-B Project organizers established 4 working groups (WGs) to address the following themes: 1) nutrient specifications for preterm infants, 2) clinical and practical issues in enteral feeding of preterm infants, 3) gastrointestinal and surgical issues, and 4) current standards of infant feeding. Each WG was asked to 1) develop a series of topics relevant to their respective themes, 2) identify questions for which there is sufficient evidence to support a systematic review process conducted by the EAL, and 3) develop a research agenda to address priority gaps in our understanding of the role of nutrition in health and development of preterm/neonatal intensive care unit infants. This article is a summary of the reports from the 4 Pre-B WGs.

Preterm infant growth velocity calculations: A systematic review

The many different methods used to calculate preterm infant growth velocity make comparisons between studies and with published values difficult if not impossible. CONTEXT: Clinicians assess the growth of preterm infants and compare growth velocity using a variety of methods. OBJECTIVE: We determined the numerical methods used to describe weight, length, and head circumference growth velocity in preterm infants; these methods include grams/kilogram/day (g/kg/d), grams/day (g/d), centimeters/week (cm/week), and change in z scores. DATA SOURCES: A search was conducted in April 2015 of the Medline database by using PubMed for studies that measured growth as a main outcome in preterm neonates between birth and hospital discharge and/or 40 weeks’ postmenstrual age. English, French, German, and Spanish articles were included. The systematic review was conducted by using Preferred Reporting Items for Systematic Reviews and Meta-analyses methods. STUDY SELECTION: Of 1543 located studies, 373 (24%) calculated growth velocity. DATA EXTRACTION: We conducted detailed extraction of the 151 studies that reported g/kg/d weight gain velocity. RESULTS: A variety of methods were used. The most frequently used method to calculate weight gain velocity reported in the 1543 studies was g/kg/d (40%), followed by g/d (32%); 29% reported change in z score relative to an intrauterine or growth chart. In the g/kg/d studies, 39% began g/kg/d calculations at birth/admission, 20% at the start of the study, 10% at full feedings, and 7% after birth weight regained. The kilogram denominator was not reported for 62%. Of the studies that did report the denominators, the majority used an average of the start and end weights as the denominator (36%) followed by exponential methods (23%); less frequently used denominators included birth weight (10%) and an early weight that was not birth weight (16%). Nineteen percent (67 of 355 studies) made conclusions regarding extrauterine growth restriction or postnatal growth failure. Temporal trends in head circumference growth and length gain changed from predominantly cm/wk to predominantly z scores. LIMITATIONS AND CONCLUSIONS The lack of standardization of methods used to calculate preterm infant growth velocity makes comparisons between studies difficult and presents an obstacle to using research results to guide clinical practice.

Growth and Tolerance of Preterm Infants Fed a New Extensively Hydrolyzed Liquid Human Milk Fortifier

Objectives: This study was a comparison of growth and tolerance in premature infants fed either standard powdered human milk fortifier (HMF) or a newly formulated concentrated liquid that contained extensively hydrolyzed protein. Methods: This was an unblinded randomized controlled multicenter noninferiority study on preterm infants receiving human milk (HM) supplemented with 2 randomly assigned HMFs, either concentrated liquid HMF containing extensively hydrolyzed protein (LE-HMF) or a powdered intact protein HMF (PI-HMF) as the control. The study population consisted of preterm infants ⩽33 weeks who were enterally fed HM. Infants were studied from the first day of HM fortification until day 29 or hospital discharge, whichever came first. Results: A total of 147 preterm infants were enrolled. Noninferiority was observed in weight gain reported in the intent-to-treat (ITT) analysis was 18.2 and 17.5 g · kg−1 · day−1 for the LE-HMF and PI-HMF groups, respectively. In an a priori defined subgroup of strict protocol followers (n = 75), the infants fed LE-HMF achieved greater weight over time than those fed PI-HMF (P = 0.036). The LE-HMF group achieved greater linear growth over time compared to the PI-HMF (P = 0.029). The protein intake from fortified HM was significantly higher in the LE-HMF group compared with the PI-HMF group (3.9 vs 3.3 g · kg−1 · day−1, P < 0.0001). Both fortifiers were well tolerated with no significant differences in overall morbidity. Conclusions: Both fortifiers showed excellent weight gain (grams per kilograms per day), tolerance, and low incidence of morbidity outcomes with the infants who were strict protocol followers fed LE-HMF having improved growth during the study. These data point to the safety and suitability of this new concentrated liquid HMF (LE-HMF) in preterm infants. Growth with this fortifier closely matches the recent recommendations for a weight gain of >18 g · kg−1 · day−1.