Richard J. Schanler's research while affiliated with Hofstra Northwell School of Medicine and other places

Objective The objective of this multi-center study was to compare, in infants ≤1250 g birth weight (BW) with neurodevelopmental assessment at 18–22 months of corrected age (CA), whether their neurodevelopmental outcomes differed based on exposure to an exclusive human milk-based (HUM) or to a bovine milk-based fortifier and/or preterm formula (BOV). Study Design Retrospective multi-center cohort study of infants undergoing neurodevelopmental assessment as to whether HUM or BOV exposure related to differences in outcomes of infants at 18–22 months CA, using the Bayley Scales of Infant Development III (BSID-III). BSID-III cognitive, language, and motor scores were adjusted for BW, sex, study site, and necrotizing enterocolitis. Results 252 infants from 6 centers were included. BSID-III cognitive scores were higher in the HUM group (96.5 ± 15.1 vs 89.6 ± 14.1, adjusted p = 0.0001). Mean BSID-III language scores were 85.5 ± 15.0 in HUM and 82.2 ± 14.1 in BOV (adjusted p = 0.09). Mean BSID-III motor scores were 92.9 ± 11.7 in HUM and 91.4 ± 14.6 in BOV (adjusted p = 0.32). Conclusion In this cohort of infants undergoing neurodevelopmental assessment, infants receiving HUM diet had significantly higher cognitive BSID-III scores at 18–22 months CA. Further investigation is needed of this potential for HUM to positively influence infant cognitive outcomes.

Background: Iron (Fe) is essential for growth, but optimal intake is controversial. Our NICU practice was to supplement 2 mg/kg/d Fe for all preterm infants receiving human milk when they achieved full feeding volume. Adjusting Fe supplementation based on ferritin levels is thought to better address physiologic requirements. Our objective was to assess the impact of therapeutic monitoring of ferritin levels on the initiation and dosing of iron supplementation, hematocrit, transfusions, and oxygen radical diseases in preterm infants. Methods: Preterm infants (< 32 weeks gestation, n = 100) were included. Ferritin was measured when full feeds were achieved, and then every 2 weeks. Fe was started at 2 mg/kg/d or continued at current dose for ferritin 40-300μg/L, increased by 1-2 mg/kg/d for < 40μg/L, or discontinued for > 300μg/L. Outcomes were compared with a historical control group. Results: Ferritin levels were not predictable by dietary or transfusion histories. Using the ferritin protocol, 70% of infants received Fe at the time of full feeds, compared to 100% of controls. In contrast, all infants received Fe 4 weeks later, compared to 87% of controls. Mean age at Fe initiation increased (14.8±6.3 to 21.0±11.76 days). Peak doses were higher, with 32% receiving > 2 mg/kg day by 6 weeks, with fewer transfusions. The incidence of bronchopulmonary dysplasia and necrotizing enterocolitis did not change. Conclusion: An iron protocol based on ferritin levels results in later initiation, higher doses, and fewer transfusions, without increasing oxygen radical diseases.

Background: Nasal continuous positive airway pressure (CPAP) introduces positive pressure of air into both the trachea and stomach, which may affect gastric emptying. The rate of gastric emptying can be estimated by ultrasound (US) in neonates by two validated techniques: "antral cross-sectional area" (ACSA, 2-dimensional estimate of the surface area at the gastric antrum), and "spheroid gastric volume" (spheroid, 3-dimensional estimate of the stomach volume). Objective: To compare gastric emptying rates in neonates on machine-derived nasal CPAP (MD-nCPAP, Avea and RAM cannula) with those on bubble CPAP (bCPAP, Fisher Paykel and Babi.Plus nasal prongs). Methods: Ultrasound measurements of the amount of the milk in the stomach were performed before feeding and at 1, 2, and 3 hours after the start of feeding, using both the ACSA and spheroid methods. Rates of gastric emptying were calculated during the "early" (1-2 hours) and "late" (2-3 hours) phases after feeding. Results: We recruited 32 infants (25-34 weeks gestational age, full enteral tube feedings, on nasal CPAP). Seventeen infants were treated with MD-nCPAP [median birth weight 1015 g (IQR: 870 to 1300), gestational age 28 weeks (IQR: 27 to 29), postnatal age 20 days (IQR: 14 to 28)], while 15 infants were treated with bCPAP [median birth weight 960 g (IQR: 855 to 1070), gestational age 27 weeks (IQR: 26 to 28), postnatal age 17 days (IQR: 15 to 25)]. Gastric emptying rates (% emptied/min) were significantly faster in the "early" compared to the "late" phase for all infants. There were no significant differences in the rates of gastric emptying (either "early" or "late") or volumes of gastric residuals between infants receiving MD-nCPAP or bCPAP, measured by either method. Although no feeding intolerance was seen in either group, the volumes of residual gastric contents measured by both methods were higher than the volumes traditionally considered abnormal when obtained by gastric tube aspiration. Conclusions: Gastric emptying is faster during the "early" compared to the "late" phase. Gastric emptying rates are not different in infants receiving MD-nCPAP vs bCPAP. The presence of large residual gastric contents in infants who are tolerating feedings challenges the value of traditional gastric aspiration for the assessment of feeding tolerance in infants.

Background: In the neonatal intensive care unit (NICU) expressed mothers' milk usually is stored frozen until used. We found that when human milk was stored at -20°C for up to 9 months there were reduced bacterial counts and pH, increased free fatty acids, but unchanged immune proteins. Antioxidant protection is an important benefit of human milk. Few studies have evaluated long-term effects of cold storage on the antioxidant capacity of human milk. We hypothesized that the antioxidant capacity of human milk is affected adversely by long-term storage at -20°C. Objective: To study the impact of long-term cold storage on the oxidative capacity of human milk and the biological impact of these changes on macromolecular constituents of human milk. Methods: Freshly expressed milk was obtained from mothers in the NICU, stored at -20°C for 6 months, and compared with the baseline. Paired samples were analyzed for glutathione, hydrogen peroxide (H2O2), 8-isoprostane, catalase, and superoxide dismutase. Results: There was no change in H2O2 concentration between baseline and 6 months. Significant reductions from baseline in both catalase and superoxide dismutase concentrations and activities, total glutathione, oxidized glutathione, reduced glutathione, and the ratio of reduced to oxidized glutathione were observed (p < 0.05). There was a significant increase in 8-isoprostane concentrations (p < 0.001). Conclusion: These data indicate significant changes in antioxidant capacity of human milk, including oxidation of macromolecules, after storage at -20°C for 6 months. The clinical implication of these findings may explain the nonuniform protection against oxidant disease in preterm infants fed human milk.

Background: Nasal CPAP introduces positive pressure of air into both trachea and stomach, which may affect gastric emptying. The rate of gastric emptying can be estimated by US by two validated techniques: “antral cross-sectional area” (2-dimensional estimate of the surface area at the gastric antrum), and “spheroid gastric volume” (3-dimensional estimate of the stomach content volume). No study examined gastric emptying rate in infants on bubble CPAP (bCPAP). Objective: To compare gastric emptying rates in neonates on machine-derived nasal CPAP (MD-nCPAP) with those on bCPAP. Methods: Ultrasound measurements of the amount of milk in the stomach were performed before feeding and at 1, 2, and 3 hours after the start of feeding, using both the ACSA and spheroid methods. Rates of gastric emptying were calculated during the “early” (1-2 hours) and “late” (2-3 hours) phases after feeding. Results: We recruited 32 infants (25-34 weeks gestational age). Seventeen infants were treated with MD-nCPAP [median birth weight 1015 g (IQR: 870 to 1300), gestational age 28 weeks (IQR: 27 to 29), postnatal age 20 days (IQR: 14 to 28)], while 15 infants were treated with bCPAP [median birth weight 960 g (IQR: 855 to 1070), gestational age 27 weeks (IQR: 26 to 28), postnatal age 17 days (IQR: 15 to 25)]. Gastric emptying rates (% emptied/min) were significantly faster in the “early” compared to the “late” phase for all infants. There were no significant differences in the rates of gastric emptying (either “early” or “late”) or volumes of gastric residuals between infants receiving MD-nCPAP or bCPAP, measured by either method. Conclusions: Gastric emptying is faster during the “early” compared to the “late” phase. Gastric emptying rates are not different in infants receiving MD-nCPAP vs bCPAP.

Objectives To investigate the relationships between dietary intake and fecal concentrations of milk fat globule-epidermal growth factor 8 (MFG-E8), and between fecal concentrations of MFG-E8 and markers of intestinal inflammation in infants born preterm. Study design Fecal samples were collected daily and enteral feedings were sampled weekly. MFG-E8 in enteral feedings and feces, and cytokine concentrations in feces were quantified by enzyme-linked immunosorbent assay. Results Milk MFG-E8 concentrations were significantly greater in unfortified mother's own milk (MOM) and MOM with human milk fortifier than either donor human milk or preterm formula. MFG-E8 concentrations in fecal samples were positively correlated with MFG-E8 concentrations in respective milks. High MFG-E8 exposure (≥60 mL/kg/day of feedings that include MOM or MOM with human milk fortifier) was associated with lower concentrations of proinflammatory cytokines (interleukin-8, tumor necrosis factor-α, and monocyte chemoattractant protein-1) and higher concentrations of the anti-inflammatory cytokine interleukin-4 in feces, compared with low MFG-E8 exposure. Conclusions Infants born preterm who were fed MOM had greater concentrations of MFG-E8 and lower concentrations of proinflammatory cytokines in fecal samples than other diets or no feedings. These data further support the protective role of MOM, possibly because of MFG-E8, against intestinal inflammation.

Background: Fecal calprotectin, a recognized marker of intestinal inflammation, is derived from neutrophil migration to a site of inflammation. Introduction of bovine-based human milk fortifier containing intact protein in preterm infants is associated with an increase in fecal calprotectin suggestive of intestinal inflammation. Newer fortifiers contain protein hydrolysates in place of intact protein. Objective: To measure fecal calprotectin in human milk-fed preterm infants before and after human milk fortification using a fortifier containing hydrolyzed protein. Methods: Serial stool samples were collected from 24 infants beginning at the first week to 60 days postnatal age. To compare the effect of human milk fortification, samples collected before and after fortification were compared. Infant demographics, diet, postnatal morbidities, and maternal characteristics were recorded. Results: A total of 401 stool samples were collected from 24 study infants who had a birth weight of 993 ± 277 g (mean ± standard deviation), gestational age 27.5 ± 2.8 weeks, and fortifier initiation at 14 days. Median fecal calprotectin before and after fortification were similar. Calprotectin levels were not correlated with birth weight or gestational age but were inversely correlated with postnatal age (p = 0.005), use of fortifier (p < 0.001), receipt of antibiotics antenatally (p = 0.007) and postnatally (p = 0.008). After adjusting for postnatal age, calprotectin levels were significantly lower following receipt of fortifier (p < 0.001) and postnatal antibiotics (p < 0.001). Conclusions: The feeding of protein hydrolysate-containing human milk fortifiers does not appear to be associated with increases in a marker of intestinal inflammation.

Objectives Human milk supports the development of a beneficial newborn intestinal microflora. We have shown previously that human milk had reduced bacteria but unchanged nutrient composition when stored at −20 °C for up to nine months. We suspected declining bacterial colony counts were manifestations of bacterial dormancy and not failure of survival. We investigated differences in selected bacterial colony counts (lactobacillus, bifidobacteria, staphylococcus, streptococcus and enterococcus) in human milk stored for 2 and 12 weeks at −20 °C in either manual or automatic defrost freezers and whether reduced bacterial counts at 12 weeks were the result of dormancy or failure of survival. Methods Freshly expressed milk was obtained from mothers in the NICU, divided into aliquots and stored for 2 and 12 weeks at −20 °C in either automatic or manual defrost freezers. Subsequently, duplicate aliquots, one thawed and the other thawed and maintained at room temperature for 4 h, were plated to assess bacterial colony counts. Results Significant declines in bacterial colony counts were seen from 2 to 12 weeks freezer storage for all bacteria. There were no differences in colony counts between freezer types. Once thawed, no further bacterial growth occurred. Conclusions Short-term freezer storage for 12 weeks resulted bacterial killing. Type of freezer used for storage did not have an impact on bacterial survival. It is unknown whether the paucity of important probiotic bacteria in stored human milk has adverse effects on infants.

Preterm infants are increasingly diagnosed as having “extrauterine growth restriction” (EUGR) or “postnatal growth failure” (PGF). Usually EUGR/PGF is diagnosed when weight is <10th percentile at either discharge or 36–40 weeks postmenstrual age. The reasons why the phrases EUGR/PGF are unhelpful include, they: (i) are not predictive of adverse outcome; (ii) are based only on weight without any consideration of head or length growth, proportionality, body composition, or genetic potential; (iii) ignore normal postnatal weight loss; (iv) are usually assessed prior to growth slowing of the reference fetus, around 36–40 weeks, and (v) are usually based on an arbitrary statistical growth percentile cut-off. Focus on EUGR/PGF prevalence may benefit with better attention to nutrition but may also harm with nutrition delivery above infants’ actual needs. In this paper, we highlight challenges associated with such arbitrary cut-offs and opportunities for further refinement of understanding growth and nutritional needs of preterm neonates.