Impact of Size for Gestational Age on Multivariate Analysis of Factors Associated with Necrotizing Enterocolitis in Preterm Infants: Retrospective Cohort Study.

OBJECTIVE: Necrotizing enterocolitis (NEC) primarily affects preterm, especially small for gestational age (SGA), infants. This study was designed to (1) describe frequency and timing of NEC in SGA versus non-SGA infants and (2) assess whether NEC is independently associated with the severity of intrauterine growth failure. STUDY DESIGN: Retrospective cohort study of infants without severe congenital malformations born <33 weeks' gestational age (GA) carried out from 2009 to 2021. The frequency and time of NEC were compared between SGA and non-SGA infants. Multivariate logistic regression was used to assess whether NEC was independently associated with intrauterine growth restriction. Severe growth restriction was defined as birth weight Z-score < -2. RESULTS: Among 2,940 infants, the frequency of NEC was higher in SGA than in non-SGA infants (25/268 [9.3%] vs. 110/2,672 [4.1%], respectively, p < 0.001). NEC developed 2 weeks later in SGA than non-SGA infants. In multivariate analysis, the adjusted odds of NEC increased with extreme prematurity (<28 weeks' GA) and with severe but not moderate growth restriction. The adjusted odds of NEC increased with urinary tract infection or sepsis within a week prior to NEC, were lower in infants fed their mother's own milk until discharge, and did not change over five epochs. NEC was independently associated with antenatal steroid (ANS) exposure in infants with birth weight (BW) Z-score < 0. CONCLUSION: NEC was more frequent in SGA than in non-SGA infants and developed 2 weeks later in SGA infants. NEC was independently associated with severe intrauterine growth failure and with ANS exposure in infants with BW Z-score < 0. KEY POINTS: · We studied 2,940 infants <33 weeks' GA.. · We assessed NEC.. · NEC was more frequent in SGA infants.. · NEC occurred 2 weeks later in SGA infants.. · NEC was associated with severe growth restriction..

Role of zinc in neonatal growth and brain growth: review and scoping review.

This manuscript includes (1) a narrative review of Zinc as an essential nutrient for fetal and neonatal growth and brain growth and development and (2) a scoping review of studies assessing the effects of Zinc supplementation on survival, growth, brain growth, and neurodevelopment in neonates. Very preterm infants and small for gestational age infants are at risk for Zinc deficiency. Zinc deficiency can cause several complications including periorificial lesions, delayed wound healing, hair loss, diarrhea, immune deficiency, growth failure with stunting, and brain atrophy and dysfunction. Zinc is considered essential for oligodendrogenesis, neurogenesis, neuronal differentiation, white matter growth, and multiple biological and physiological roles in neurobiology. Data support the possibility that the critical period of Zinc delivery for brain growth in the mouse starts at 18 days of a 20-21-day pregnancy and extends during lactation and in human may start at 26 weeks of gestation and extend until at least 44 weeks of postmenstrual age. Studies are needed to better elucidate Zinc requirement in extremely low gestational age neonates to minimize morbidity, optimize growth, and brain growth, prevent periventricular leukomalacia and optimize neurodevelopment. IMPACT: Zinc is essential for growth and brain growth and development. In the USA, very preterm small for gestational age infants are at risk for Zinc deficiency. Data support the possibility that the critical period of Zinc delivery for brain growth in the mouse starts at 18 days of a 20-21-day pregnancy and extends during lactation and in human may start at 26 weeks' gestation and extend until at least 44 weeks of postmenstrual age. Several randomized trials of Zinc supplementation in neonates have shown improvement in growth when using high enough dose, for long duration in patients likely to or proven to have a Zinc deficiency. Studies are needed to better elucidate Zinc requirement in extremely low gestational age neonates to minimize morbidity, optimize growth and brain growth, prevent periventricular leukomalacia and optimize neurodevelopment.

Follow-up of a randomized trial optimizing neonatal nutrition in preterm very low birthweight infants: growth, serum adipokines, renal function and blood pressure.

OBJECTIVE: The primary objectives were to compare body mass index (BMI) Z-score (Z), systolic blood pressure (SBP), serum leptin:adiponectin (L:A) ratio and estimated glomerular filtration rate (eGFR) at ~3 years adjusted age between two arms of a randomized controlled trial (RCT) comparing two modes of human milk fortification for very low-birthweight infants in the neonatal intensive care unit. STUDY DESIGN: Follow-up of RCT at 33-48 months. RESULTS: Follow-up data are available in 82/120 infants. Infants in the experimental arm have anthropometric data consistent with central obesity and higher serum L:A ratio (sensitivity analysis adjusting for sex and using all available data), but have similar eGFR and SBP at follow-up compared with controls. Serum L:A ratio is strongly correlated with anthropometric measurements suggesting central obesity. CONCLUSIONS: Infants in the experimental arm have central obesity and higher serum L:A ratio compared with controls. Notably, serum L:A ratio is strongly correlated with weight gain. TRIAL REGISTRATION: This randomized controlled trial was registered at ClinicalTrials.gov NCT02372136.

Quality improvement project in a neonatal intensive care unit reduced the prevalence and duration of hypophosphatemia with significant and sustainable results.

BACKGROUND: Hypophosphatemia is associated with prolonged mechanical ventilation and may affect growth, bone mineralization, nephrocalcinosis, and mortality in preterm infants. Optimal nutrition practices may decrease risk for hypophosphatemia and improve outcome. METHODS: A quality improvement project was established to improve parenteral and enteral phosphorus intake with the goal to decrease prevalence and duration of hypophosphatemia in the first 14 days in infants <32 weeks' gestation. RESULTS: Among 406 preterm infants, the prevalence of moderate hypophosphatemia decreased from 44% to 19% (P < 0.01) over 4 years. The median duration of moderate hypophosphatemia decreased from 72 h (48-128) to 24 (24-53) (P < 0.01). Daily intakes of parenteral calcium and phosphorus on the fourth day of life increased from 1.5 to 2.5 mEq/kg/day (P < 0.01) and 0.6 to 1.3 mmol/kg/day (P < 0.01), respectively. The median postnatal age of first serum phosphorus concentration assessment decreased from 53 h (41-64) to 32 (24-40) (P < 0.01). CONCLUSION: During this quality improvement project, reduced prevalence and duration of hypophosphatemia in infants <32 weeks' gestation in the first 14 days of life was achieved through the optimization of parenteral and enteral phosphorus intake and improved response to acute hypophosphatemia.

Growth after implementing a donor breast milk program in neonates <33 weeks gestational age or birthweight <1500 grams: Retrospective cohort study.

BACKGROUND: Donor breast milk (DBM) feeding has been associated with less growth than formula in preterm infants. Zinc content in DBM is insufficient to support growth in preterm infants. OBJECTIVE: To compare growth from birth to discharge, macro- and micronutrient intake and the frequency of poor growth before (Epoch-1) and after (Epoch-2) implementing a DBM program. METHODS: Retrospective cohort study of 1069 infants born at < 33 weeks' gestational age or birthweight < 1500 g and fed using our adjustable feeding protocol with accurate serial length measurements. Growth was assessed by changes in Z-scores of weight, length and fronto-occipital circumference from birth to discharge. RESULTS: Growth did not decrease significantly in Epoch-2. However, energy and protein intake increased by 5% and frequency of zinc and vitamin D supplementation increased by >30%. CONCLUSIONS: DBM implementation did not significantly decrease growth from birth to discharge using our adjustable feeding protocol.

Antibiotic exposure and growth patterns in preterm, very low birth weight infants.

BACKGROUND: Antibiotic exposure in term infants has been associated with later obesity. Premature, very-low-birth-weight (birth weight ≤ 1500 g) infants in the neonatal intensive care unit frequently are exposed to antibiotics. Our hypothesis was that in preterm infants, there is a positive linear and dose-dependent relationship between antibiotic exposure and growth from birth through 12 months' corrected age. METHODS: Retrospective analysis of prospectively collected data of all antibiotic use among inborn, preterm (≤32 weeks' gestation), very-low-birth-weight infants admitted to the neonatal intensive care unit at Parkland Memorial Hospital and followed in the Low Birth Weight Clinic at Children's Medical Center, Dallas, TX. Antibiotic use was quantified by days of therapy which was compared with weight and length parameters at birth, 36 weeks' postmenstrual age, and 2, 4, 6, and 12 months' corrected age. The change in weight and length z-scores from birth to all subsequent age points was calculated. Stepwise multivariate regression analysis was performed to determine predictors of weight, length, and weight-for-length delta z-scores from birth to each subsequent age point. RESULTS: During the 18-month study, 161 infants received a median of 11 (IQR, 5.5-19.5) antibiotic days of therapy which was not associated with weight or length delta z-scores from birth through 12 months' corrected age. CONCLUSION: Association of prolonged antibiotic use and neonatal morbidities and mortality may override the potential association with increased weight gain in the NICU and beyond.

Zinc deficiency limiting head growth to discharge in extremely low gestational age infants with insufficient linear growth: a cohort study.

OBJECTIVE: To assess the relationship of size for age with zinc deficiency in extremely low gestational age (GA) infants (23-28 weeks, ELGANs) who had insufficient linear growth despite optimizing other nutrients and to analyze changes in fronto-occipital circumference (FOC), weight and length with zinc supplementation. STUDY DESIGN: Retrospective cohort study. RESULTS: Among 302 ELGANs, a serum zinc concentration was obtained in 52 with insufficient linear growth (17%). Zinc deficiency (serum concentration <0.74 mcg/ml) was diagnosed in 8 of 24 (33%) small for GA (SGA) compared to 35 of 278 (13%) non-SGA infants (P = 0.01). Zinc supplementation for >2 weeks improved FOC growth to discharge or 50 weeks postmenstrual age in infants with Zn deficiency. However, neither linear growth nor weight gain improved with Zn supplementation. CONCLUSION: Zinc deficiency was diagnosed in 14% ELGANs in this cohort. Zinc supplementation for >2 weeks improved FOC growth but not linear growth or weight gain.

Optimizing individual nutrition in preterm very low birth weight infants: double-blinded randomized controlled trial.

OBJECTIVE: In preterm neonates fed human milk, fortification may be adjusted by (1) optimization, based on growth rate and serum nutrient analyses, or (2) individualization, based on serial milk nutrient analyses. The primary aim was to determine whether individualized plus optimized nutrition (experimental) improves velocity of weight gain and linear growth from birth to endpoint (36 weeks postmenstrual age or discharge) when compared with optimized nutrition alone (controls). STUDY DESIGN: Double-blinded parallel group randomized trial in 120 neonates <29 weeks gestational age (GA) or <35 weeks and small for GA (birth weight < 10th centile). RESULT: Weight-gain velocity (13.1 ± 2.1, n = 57 controls, vs. 13.0 ± 2.6 g kg-1 day-1, n = 59 experimental, P = 0.87), linear growth (0.9 ± 0.2, n = 55, vs. 0.9 ± 0.2 cm week-1, n = 52, P = 0.90) and frequency of weight/length disproportion (2% vs. 2%, P = 0.98) were similar in both groups. CONCLUSIONS: Individualized plus optimized nutrition does not improve weight gain, linear growth, or weight/length disproportion at endpoint versus optimized nutrition alone.

Association of age of initiation and type of complementary foods with body mass index and weight-for-length at 12 months of age in preterm infants.

OBJECTIVE: To assess whether in very preterm infants (1) body mass index (BMI) Z-score and weight-for-length (WtFL) Z-score at 1 year of age and (2) head growth from discharge to 1 year are associated with breastfeeding at discharge and the age of onset and type of complementary foods. STUDY DESIGN: Observational cohort study. RESULTS: Infants started on only ready-made complementary (RMC) feedings at ≤26 weeks adjusted age had the highest adjusted BMI Z-score and WtFL Z-score at 1 year of age. Adjusted change in fronto-occipital circumference was highest in infants either discharged on breastmilk or receiving home-made complementary food with/without RMC (HMM) at ≤26 weeks adjusted age. CONCLUSIONS: Infants started on RMC ≤26 weeks adjusted age had the highest BMI Z-score and WtFL Z-score at 1 year. Head growth from discharge to 1 year was highest in infants either discharged on breastmilk or receiving HMM at ≤26 weeks adjusted age.

Correction to: Adjustable feedings plus accurate serial length measurements decrease discharge weight-length disproportion in very preterm infants: quality improvement project.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Adjustable feedings plus accurate serial length measurements decrease discharge weight-length disproportion in very preterm infants: quality improvement project.

BACKGROUND: Preterm very-low-birth-weight (≤1500 g) infants exhibit disproportionate weight-for-length growth in the Neonatal Intensive Care Unit. LOCAL PROBLEM: High frequency of body mass index (BMI) > 90th centile at discharge and 1-year postnatal age associated with elevated blood pressure and serum leptin in infancy and adolescence. METHODS: Single-institution quality improvement project in appropriately grown infants born at 230/7-286/7 weeks gestational age and discharged home. INTERVENTION: Adjustable feeding protocol based on valid serial length measurements (board or caliper). RESULTS: The average monthly percentage of weight-for-length disproportion at discharge decreased from 13% in Epoch 1 to 0% in Epoch 2 (P < 0.05). Although the average Z-score for BMI at discharge was lower in Epoch 2 versus Epoch 1 (P < 0.01), this was absent by 1 year follow-up (P = 0.91). CONCLUSIONS: Adjustable feedings plus use of accurate serial length measurements decreases weight-for-length disproportion at hospital discharge but not at 1 year.