Better Control of Holder Pasteurization Results in Higher Retention of Human Milk Lactoferrin, IgA, and Lysozyme.

Background: Holder pasteurization is commonly used in milk banks. We previously reported that the pattern of temperature and time may be different according to the pasteurizer used. Aim: The aim of our study was to assess the variances in pasteurization using two different devices: a standard pasteurizer (Past STD) and an optimized pasteurizer (Past OPTI). Methods: Immunoglobulin A (IgA), lactoferrin (LF), and lysozyme (LZ) content were assessed before and after pasteurization of 24 donor human milk samples. The impact of the pasteurization device was evaluated by testing 50- to 200-mL samples. Results: Mean temperature and duration of the plateau were 1.5°C lower and 11 min shorter, respectively, with Past OPTI vs. Past STD. The loss of IgA, LF, and LZ was 17.6, 5.6, and 9.8% lower, respectively, with Past OPTI than with Past STD. Conclusions: Accurate control of temperature enabled better preservation of IgA, LF, and LZ in donor milk. Holder pasteurization should be optimized, and new techniques proposed to treat donor milk should be compared with Holder pasteurization performed with a well-controlled device under realistic conditions.

Early hypovolemic shock and abdominal distention due to neonatal splenic rupture: urgency of diagnosis and management.

Splenic rupture in the neonatal period is a rare condition that can be complicated by hemorrhagic shock. The symptoms are not very specific, rendering the diagnosis difficult and often delayed; sometimes only discovered at autopsy. We report five cases diagnosed in the Rhône-Alpes region of France. From these observations and from a review of the literature, the circumstances of the occurrence, the clinical signs, and the therapeutic possibilities are discussed. In the presence of severe anemia with pallor and abdominal distension, particularly in the context of a difficult birth, an abdominal ultrasound must be urgently performed and surgical management promptly considered. CONCLUSION: This pathology must be known to the neonatologist so that she/he can quickly evoke it, given that it can quickly become life-threatening. What is known: • Splenic rupture in the neonatal period is a rare condition that can be complicated by hemorrhagic shock and quickly lead to the death of the newborn. • The symptoms are not very specific, rendering the diagnosis difficult and often delayed. What is new: • This is the first publication bringing together as many clinical cases on the subject reporting in particular very serious cases to alert the clinician on this pathology and its diagnostic urgency. • We propose a clear therapeutic behavior to help the clinician in his daily practice.

Additional Protein Fortification Is Necessary in Extremely Low-Birth-Weight Infants Fed Human Milk.

In the present study, approximately one in three (49/152, 32.2%) extremely low-birth-weight infants were demonstrated to require additional protein intake to supplement the standard fortification to achieve satisfactory weight gain. This additional protein fortification also resulted in a rapid increase in length-for-age (P < 0.001) and head circumference-for-age (P = 0.02) z scores.

Probiotics and growth in preterm infants: A randomized controlled trial, PREMAPRO study.

BACKGROUND & AIMS: Recent studies have suggested that the gut microflora has metabolic effects. We aimed to evaluate postnatal growth in preterm infants who received different probiotic supplements, and to assess the safety of probiotic administration. METHODS: This prospective, randomized, double-blind, controlled trial was performed at three tertiary care neonatal units. Preterm infants were randomly assigned to receive daily supplementation over 4-6 weeks with placebo (group C) or probiotics (group P). Group P comprised three subgroups: P1 received Bifidobacterium lactis, P2 received Bifidobacterium longum, and P3 received B. lactis and B. longum. We assessed postnatal growth during the supplementation period and up to a corrected gestational age (GA) of 41 weeks when body composition was assessed using whole-body dual-energy X-ray absorptiometry. Aerobic and anaerobic blood cultures were performed on suspicion of late-onset sepsis. RESULTS: The study comprised 199 preterm infants with a mean GA of 29.1 ± 1.4 weeks and a mean birth weight of 1173 ± 210 g, who received a placebo (group C, n = 52) or probiotics (group P, n = 147) from the first week of life. At the end of the supplementation period, no statistically significant differences were seen between the groups in relation to the mean body weight (group C = 1906 ± 23 g, group P = 1875 ± 14 g, p = 0.25), length, or head circumference. The incidence rates of necrotizing enterocolitis and late-onset sepsis were similar in the two groups. At the corrected GA of 41 weeks, there were no differences between the groups with respect to anthropometric measurements or body composition analysis. CONCLUSIONS: Preterm infants receiving Bifidobacterium supplements did not exhibit better postnatal growth compared with those who received placebo treatment. No adverse effects were associated with probiotic administration. Registered under ClinicalTrials.gov Identifier no. NCT01379417.

ALG3-CDG: Report of two siblings with antenatal features carrying homozygous p.Gly96Arg mutation.

Congenital disorders of glycosylation (CDG) are a group of inborn errors of metabolism presenting with heterogeneous multisystemic clinical manifestations. To date, more than 60 different types of CDG have been reported. ALG3-CDG is very rare, with only nine patients described so far. We report two affected siblings presenting prenatally with skeletal abnormalities associated with dysmorphic features, cerebellar vermis hypoplasia, corpus callosum agenesis, hepatic fibrosis and poor prognosis. This is the first detailed report of an affected fetus including clinical, radiographic and pathological findings. The patients showed some clinical features previously unreported in ALG3-CDG, such as bone dysplasia, cataract, corneal opacities, and pons hypoplasia. Both patients were homozygous for the previously unreported p.Gly96Arg mutation of the ALG3 gene. One patient showed chondrodysplasia punctata (CDP), which has not been previously reported in CDG. An exhaustive genetic and metabolic assessment, performed in order to rule out other possible causes of CDP, showed abnormally raised levels of anti-nuclear antibodies in the mother who, nevertheless, did not show any clinical sign of autoimmune disease during a 7 years follow-up. We speculate that the observed CDP may be explained by the maternal anti-nuclear antibodies; alternatively, a possible link to the underlying metabolic disorder cannot be ruled out. In conclusion, we report the clinical, pathological, biochemical and molecular characterization of two further patients affected by ALG3-CDG, expanding the phenotypic spectrum of this very rare disease.

Gut microbiota in preterm infants with gross blood in stools: A prospective, controlled study.

OBJECTIVE: Gross blood in stools is a peculiar entity in preterm infants, but little is known about its etiology. As gut microbiota can be distorted in preterm infants, we aimed to evaluate the gut microbiota in infants with gross blood in stools. STUDY DESIGN: In a prospective, controlled, single-center study, we enrolled all infants born before 34 weeks of gestational age presenting gross blood in stools that was either completely isolated or associated with mild clinical symptoms or radiological signs. Each case was paired with two controls who were hospitalized in the same unit and were matched for gestational age and birth weight. The diversity of the gut microbiota was analyzed using 16S rRNA gene PCR and temporal temperature gel electrophoresis. We calculated a diversity score corresponding to the number of operational taxonomic units present in the microbiota. RESULTS: Thirty-three preterm infants with gross blood in stools were matched with 57 controls. Clinical characteristics were similar in cases and controls. There was no statistically significant difference in the diversity score between the two groups, but microbiota composition differed. The proportion of infants with Escherichia coli was significantly higher in cases than in controls (p=0.045) and the opposite pattern occurred for Staphylococcus sp. (p=0.047). CONCLUSION: Dysbiosis could be a risk factor for gross blood in stools in preterm infants. Additional, larger studies are needed to confirm the implications of the presence of different genotypes of E. coli and to evaluate preventive actions such as the prophylactic use of probiotics and/or prebiotics.

Risk factors of mild rectal bleeding in very low birth weight infants: a case control study.

BACKGROUND: Mild rectal bleeding (MRB) is a particular clinical entity different from necrotizing enterocolitis, which significantly influences neonatal care in preterm infants. We aimed to determine the risk factors and to evaluate prospectively the clinical course of MRB. METHODS: We consecutively included in a case-control study all infants with birth weight ≤ 1500 g or gestational age ≤ 32 weeks admitted to our unit, and presenting MRB, defined as either isolated or associated with mild clinical or radiological signs. We matched each Case with two Controls. Clinical data before, after and at time of MRB were collected, together with stool cultures at time of MRB (or at similar postnatal age in Controls). Multiple logistic regression analysis was performed to determine independent risk factors for the development of MRB. RESULTS: During 4 years, among 823 very low birth weight (VLBW) infants admitted to our unit, 72 (8.8%) had MRB. The median duration of rectal bleeding was 1.1 [1-2] days and the fasting period lasted 2.9 [2-10] days. A relapse occurred in 24% of cases. In multivariate analysis, only hypertension during pregnancy (p = 0.019), growth restriction at onset of bleeding (p = 0.026), and exposure to ibuprofen (p = 0.003) were independent risk factors for MRB. In Cases there were more infants with Clostridium Difficile in stools than in Controls (p = 0.017). CONCLUSION: Hypertension during pregnancy, even without intrauterine growth restriction, appeared to carry the same risk for MRB as exposure to ibuprofen and extrauterine growth restriction.

Malondialdehyde adduct to hemoglobin: a new marker of oxidative stress suitable for full-term and preterm neonates.

Oxidative stress may play a central role in the onset of many diseases during the neonatal period. Malondialdehyde (MDA) is a marker of lipid peroxidation. The aim of this study was to evaluate a new marker, the malondialdehyde adduct to hemoglobin (MDA-Hb), which is measured in red blood cells (RBCs) and thus does not require that an additional blood sample be drawn. In this prospective study, we first adapted the measurement method previously described to Hb solutions obtained from washed RBCs and then evaluated the suitability of the method for use in neonates. MDA-Hb concentrations were measured by liquid chromatography-mass spectrometry. We compared the concentrations of MDA-Hb between preterm and term neonates. Erythrocyte samples were collected at birth from 60 healthy neonates (29 full-term and 31 preterm), as well as from 50 preterm neonates with uncomplicated postnatal evolution during the first months of life. We found a significantly higher MDA-Hb concentration at birth in preterm neonates (P = 0.002). During the first months of life, MDA-Hb concentrations were 9.4 nanomol/g Hb in hospitalized preterm neonates. MDA-Hb could be used to assess oxidative stress in preterm neonates. Together with clinical variables, it could be a useful marker for oxidative stress exposition in these higher risk patients.

Adduct of malondialdehyde to hemoglobin: a new marker of oxidative stress that is associated with significant morbidity in preterm infants.

Preterm infants (PT) are particularly exposed to oxidative stress (OS), and a blood-sparing marker, the malondialdehyde adduct to hemoglobin (MDA-Hb), may be useful to accurately assess OS-related neonatal morbidity. In a prospective study, MDA-Hb concentrations were assessed in two groups of PT, one with and one without severe neonatal morbidity as estimated by a composite index of severe morbidity (ISM). All PT born in a single tertiary care NICU (<32 weeks and birth weight <1500 g) were consecutively included. MDA-Hb and blood glutathione (GSH) concentrations were measured by liquid chromatography-mass spectrometry during the first 6 weeks of life. Linear regressions and a multilevel model were fitted to study the relationship between MDA-Hb or GSH and ISM. Of the 83 PT (mean ± SD: 28.3 ± 2 weeks, 1089 ± 288 g), 21% presented severe neonatal morbidity. In the multivariate model, MDA-Hb concentrations were significantly higher in the ISM+ group than in the ISM- group during the first 6 weeks of life (P = 0.009). No significant difference in GSH concentrations was observed between groups (P = 0.180). MDA-Hb is a marker of interest for estimating oxidative stress in PT and could be useful to evaluate the impact of strategies to improve perinatal outcomes.

Postnatal steroids in extremely low birth weight infants: betamethasone or hydrocortisone?

AIM: To compare the efficacy and tolerance of betamethasone (BTM) and hydrocortisone (HC) in weaning extremely low birth weight (ELBW) infants with bronchopulmonary dysplasia (BPD) from the ventilator. METHODS: Monocentric, retrospective, cohort analysis based on prospective, standardized collection of data between 2005 and 2011 in ELBW receiving postnatal steroids (PS) after the second week of life. We used BTM for the first 4 years, and thereafter HC. We compared extubation rates, growth, glycaemia and blood pressure. RESULTS: Sixty-seven infants received PS: 35 BTM and 32 HC. Most infants (83% BTM vs. 72% HC) were extubated during treatment (p = 0.281). During PS, the need for insulin was similar. Mean arterial blood pressure was similar at day 3 of PS, but was significantly lower in infants treated by BTM 30 days after the end of treatment. The z-scores for body weight and head circumference indicated significantly greater loss in BTM than HC group. This persisted only for body weight after adjustment for differences in energy intake and corticosteroid dose. CONCLUSION: Our study suggests that HC may be as efficient as BTM in facilitating the extubation of ELBW infants, without short-term adverse effects. Blood pressure monitoring and investigation of long-term neurodevelopment are nevertheless needed.

Extremely low birthweight infants: how neonatal intensive care unit teams can reduce postnatal malnutrition and prevent growth retardation.

AIM: To evaluate the impact of an improved nutritional policy for extremely low birthweight (ELBW) infants on nutritional deficits and postnatal growth. METHOD: We compared two groups of 37 ELBW infants, born before and after the introduction of an improved nutritional policy in April 2006. Group A (born 2005 to early 2006) and group B (born 2009) stayed in a French neonatal intensive care unit (NICU) for at least 7 weeks. Optimal energy and protein intakes were 120 and 3.5 g/kg/day, respectively, and used to calculate cumulative deficits. Delta z-scores for weight, length and head circumference were calculated between birth and 36 weeks of postmenstrual age (PMA). The improved nutritional policy focused on earlier and higher parenteral intake of lipids and proteins, earlier and higher human milk fortification and earlier transition to preterm formula. RESULTS: The two groups did not differ in gestational age and birthweight. However, protein and energy deficits were significantly reduced in group B. Between birth and 36 weeks of PMA, delta z-scores were significantly reduced for length (p = 0.012) but not for weight (p = 0.09) or head circumference (p = 0.83). CONCLUSION: Higher parenteral intake and close attention to enteral feeding reduced nutritional deficits and linear growth restriction in infants admitted to a French NICU.

Dietary glutamate is almost entirely removed in its first pass through the splanchnic bed in premature infants.

Breast milk glutamate is a potential gluconeogenic substrate. However, in piglets, most dietary glutamate undergoes first pass extraction by the gut, limiting its contribution to glucose formation. The objectives of the study were to determine in preterm infants, whether dietary glutamate increases plasma [glutamate] in a dose-dependent fashion and whether glutamate carbon appears in plasma glucose to an appreciable extent. Five enterally fed infants (31 +/- 0 wk; 1555 +/- 131 g) (mean +/- SE) were studied twice (postnatal age 10 +/- 1 d and 17 +/- 1 d, respectively), while receiving an intragastric infusion of glutamate (labeled to 4% +/- by [U-13C] glutamate) at 2.4 (study 1) and 4.8 micromol/kg/min (study 2) for 1.5 h (n=2) or 5 h (n=3). Plasma [glutamate] was 82 +/- 8 microM at baseline, and 84 +/- 11 and 90 +/- 13 microM after glutamate supplementation at 2.4 and 4.8 micromol/kg/min, respectively, values not different from baseline. Plasma [glutamate] was not affected by the duration of the glutamate infusion (1.5 versus 5 h). Plasma 13C glucose enrichment was only 0.3% (after 5 h ingestion of glutamate labeled to 4%) indicating insignificant contribution of dietary glutamate carbon to glucose. Thus, in premature infants, splanchnic extraction is the major fate of dietary glutamate, which is not a significant gluconeogenic substrate in these infants.

Hyperglycemia is a risk factor for early death and morbidity in extremely low birth-weight infants.

OBJECTIVES: The objectives of this study were to determine the prevalence of hyperglycemia in extremely low birth-weight infants and to determine whether hyperglycemia increases the risk of early adverse outcomes (death or intraventricular hemorrhage of grade 3 or 4) and/or affects the length of hospital stay among survivors without intraventricular hemorrhage. METHODS: The charts of all extremely low birth-weight infants (n = 93) admitted to Texas Children's Hospital (Houston, TX) during 2001 were reviewed. The highest daily blood glucose concentrations, highest dopamine infusion rates, highest daily percentage of inspired oxygen, and mean blood sodium concentrations were averaged over the first week of life or before death or occurrence of grade 3 or 4 intraventricular hemorrhage. Among survivors without severe intraventricular hemorrhage, the time ratio for blood glucose concentrations of >150 mg/dL was calculated. RESULTS: More than 50% of the infants had persistent blood glucose concentrations of >150 mg/dL during their first week of life. Early adverse outcomes were associated with the average highest daily blood glucose concentration through interaction with the Clinical Risk Index for Babies score and with the average highest daily percentage of inspired oxygen. The length of hospital stay was associated with the time ratio for blood glucose concentrations of >150 mg/dL through interaction with birth weight and the average highest daily percentage of inspired oxygen. CONCLUSION: These data confirm the high prevalence of hyperglycemia among parenterally fed, extremely low birth-weight infants and show that high blood glucose concentrations increase the risk of early death and grade 3 or 4 intraventricular hemorrhage and the length of hospital stay among survivors without intraventricular hemorrhage, which suggests that prevention and treatment of hyperglycemia may improve the outcomes of extremely low birth-weight infants.