Effect of dietary protein on plasma insulin-like growth factor-1, growth, and body composition in healthy term infants: a randomised, double-blind, controlled trial (Early Protein and Obesity in Childhood (EPOCH) study).

The effect of protein intake on growth velocity in infancy may be mediated by insulin-like growth factor-1 (IGF-1). This study aimed to determine the effects of formulae containing 1·8 (F1·8) or 2·7 g (F2·7) protein/418·4 kJ (100 kcal) on IGF-1 concentrations and growth. Healthy term infants were randomly assigned to receive F1·8 (n 74) or F2·7 (n 80) exclusively for the first 4 months of life. A group of breast-fed infants (n 84) was followed-up simultaneously (reference). Growth and body composition were measured at 0·5, 4, 6, 12, 36, 48 and 60 months of life. The IGF-1 concentrations at 4 months (primary outcome) were similar in the F1·8 (67·1 (sd 20·8) ng/l; n 70) and F2·7 (71·2 (sd 27·5) ng/l; n 73) groups (P=0·52). Both formula groups had higher IGF-1 concentrations than the breast-fed group at 4 and 9 months of age (P≤0·0001). During the first 60 months of life, anthropometric parameters in the F1·8 group were lower compared with the F2·7 group, and the differences were significant for head circumference from 2 to 60 months, body weight at 4 and 6 months and length at 9, 12 and 36 months of age. There were no significant differences in body composition between these two groups at any age. We conclude that, in formula-fed infants, although increased protein intake did not affect the IGF-1 concentration during the first 12 months of life, it did affect length and head circumference growth, suggesting that factors other than IGF-1 could play roles in determining growth velocity.

A Customizable Digital Cognitive Aid for Neonatal Resuscitation: A Simulation-Based Randomized Controlled Trial.

OBJECTIVE: Adherence to the International Liaison Committee on Resuscitation (ILCOR) algorithm optimizes the initial management of critically ill neonates. In this randomized controlled trial, we assessed the impact of a customizable sequential digital cognitive aid (DCA), adapted from the 2020 ILCOR recommendations, compared with a poster cognitive aid (standard of care [SOC]), on technical and nontechnical performance of junior trainees during a simulated critical neonatal event at birth. METHODS: For this prospective, bicentric video-recorded study, students were recruited on a voluntary basis, and randomized into groups of 3 composed of a pediatric resident and two midwife students. They encountered a simulated cardiac arrest at birth either (1) with DCA use and ILCOR algorithm poster displayed on the wall (intervention group) or (2) with sole ILCOR algorithm poster (poster cognitive aid [SOC]). Technical and nontechnical skills (NTS) between the two groups were assessed using a standardized scoring of videotaped performances. A neonate specific NTS score was created from the adult Team score. RESULTS: 108 students (36 groups of three) attended the study, 20 groups of 3 in the intervention group and 16 groups of 3 in the poster cognitive aid (SOC) group. The intervention group showed a significant improvement in the technical score (P < 0.001) with an average of 24/27 points (24.0 [23.5-25.0]) versus 20.8/27 (20.8 [19.9-22.5]) in poster cognitive aid (SOC) group. No nontechnical score difference was observed. Feedback on the application was positive. CONCLUSIONS: During a simulated critical neonatal event, use of a DCA was associated with higher technical scores in junior trainees, compared with the sole use of ILCOR poster algorithm.

Jacobsen and Beckwith-Wiedemann syndromes in a child with mosaicism for partial 11pter trisomy and partial 11qter monosomy.

We report on a child with Jacobsen syndrome (JBS, OMIM 147791) and abnormalities consistent with Beckwith-Wiedemann syndrome (BWS, OMIM 130650). The constitutional karyotype was apparently normal, but FISH analysis with probes specific for the short and long arms of chromosome 11 found 11qter deletion with 11pter trisomy in 80% of the cells studied. Array-CGH identified breakpoints in the 11p15.3 and 11q24.1 regions consistent with Jacobsen and Beckwith-Wiedemann syndromes. We suggest that this chromosome imbalance results from a pericentric inversion of chromosome 11 inherited from the father, with mosaicism resulting from meiotic recombination of a paternal inversion followed by mitotic recombination during the first embryonic divisions. This hypothesis is supported by the results of microsatellite marker analysis. Three previous cases of pericentric inversion and recombination of chromosome 11 have been reported. Our case is unusual in that it combines the Jacobsen and Beckwith-Wiedemann syndromes with mosaicism.

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.

Both extrauterine and intrauterine growth restriction impair renal function in children born very preterm.

A single-center prospective cohort study was designed to identify alterations of renal function during childhood in children born prematurely. A cohort of 143 such babies born over a 4-year period (birth weight less than 1000 g and/or less than 30 weeks of gestation) was prospectively included at birth. A mailing was sent to all parents to propose renal evaluation. Among the 50 included children, 23 had intra-uterine and 16 had extrauterine growth retardation. When comparing both of these groups to 11 children with appropriate pre- and postnatal growth at a mean follow-up of 7.6 years, both groups of growth-restricted children had slightly but significantly lower glomerular filtration rates, measured by inulin clearance, although both groups were still within the normal range for their ages. There were no differences for other renal parameters, neonatal therapies or complications, except for postnatal corticosteroid exposure. Children with extrauterine growth restriction were found to have significantly lower protein-energy intake during their first week of life than the intrauterine growth-restricted or the normotrophic children. Our study found that children with either intra- or extrauterine growth retardation are at risk of decreased glomerular filtration rates during childhood. Extrauterine growth restriction represents a new risk factor for long-term renal impairment in premature children.

Ocular anomalies associated with interstitial deletion of chromosome 2q31: case report and review.

We describe a newborn girl with multiple malformations associated with an interstitial deletion of chromosome 2q (q24q32). Clinical findings included growth retardation, microcephaly, facial malformations, common atrioventricular canal, digital anomalies of both hands and feet, and ovarian hypoplasia. Bilateral ocular anomalies included down-slanting palpebral fissures, blepharophimosis, microphthalmia, uveal coloboma, and corneal opacity. Chromosomal segment 2q31 may play a major role in the development of the eye and its adnexa.

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.

In situ simulation training for neonatal resuscitation: an RCT.

OBJECTIVES: High-fidelity simulation is an effective tool in teaching neonatal resuscitation skills to professionals. We aimed to determine whether in situ simulation training (for ∼80% of the delivery room staff) improved neonatal resuscitation performed by the staff at maternities. METHODS: A baseline evaluation of 12 maternities was performed: a random sample of 10 professionals in each unit was presented with 2 standardized scenarios played on a neonatal high-fidelity simulator. The medical procedures were video recorded for later assessments. The 12 maternities were then randomly assigned to receive the intervention (a 4-hour simulation training session delivered in situ for multidisciplinary groups of 6 professionals) or not receive it. All maternities were evaluated again at 3 months after the intervention. The videos were assessed by 2 neonatologists blinded to the pre-/postintervention as well as to the intervention/control groups. The performance was assessed using a technical score and a team score. RESULTS: After intervention, the median technical score was significantly higher for scenarios 1 and 2 for the intervention group compared with the control group (P = .01 and 0.004, respectively), the median team score was significantly higher (P < .001) for both scenarios. In the intervention group, the frequency of achieving a heart rate >90 per minute at 3 minutes improved significantly (P = .003), and the number of hazardous events decreased significantly (P < .001). CONCLUSIONS: In situ simulation training with multidisciplinary teams can effectively improve technical skills and teamwork in neonatal resuscitation.

Effects of lipid-supplemented total parenteral nutrition on fatty liver disease in a premature neonatal piglet model.

BACKGROUND: Routine total parenteral nutrition (TPN) in neonatal care can result in hepatic dysfunction in 40-60% of patients, most commonly as fatty liver, but little work has been conducted on the underlying mechanisms causing hepatic dysfunction. OBJECTIVE: To use a piglet model for the premature human neonate on TPN, supplemented with lipid emulsions, to investigate hepatic responses. METHOD: Piglets were delivered 2 days prematurely. Six control piglets were fed enterally (E), whilst twelve animals were maintained on TPN. TPN piglets received the standard TPN solution plus the lipid emulsion as either ClinOleic(R) (C, n = 6) or Intralipid(R) (I, n = 6). Hepatic lipid content and the fatty acid composition of liver triacylglyercol (TAG) as well as hepatic lipase (HL) activity were determined. Lipoprotein lipase (LPL) activity was measured in the liver, muscle and adipose tissue. The plasma concentrations of choline, bilirubin, TAG and non-esterified fatty acids (NEFA) were also measured. RESULTS: Liver lipid was significantly increased in piglets on TPN and the tissue fatty acid profiles reflected the lipid emulsion. HL and LPL activities were reduced in liver but LPL increased in adipose tissue during TPN. Plasma concentrations of choline, bilirubin, TAG and NEFA were similar across the treatments. CONCLUSIONS: The results suggest fatty liver occurs in neonates receiving TPN and the source of the accumulated lipid appears to be the lipid emulsion used. The factors regulating lipase activity during TPN require further study. The piglet can be used as a model for neonatal TPN.

The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations.

This paper reviews current knowledge on the role of the long-chain polyunsaturated fatty acids (LC-PUFA), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, 20:4n-6), in maternal and term infant nutrition as well as infant development. Consensus recommendations and practice guidelines for health-care providers supported by the World Association of Perinatal Medicine, the Early Nutrition Academy, and the Child Health Foundation are provided. The fetus and neonate should receive LC-PUFA in amounts sufficient to support optimal visual and cognitive development. Moreover, the consumption of oils rich in n-3 LC-PUFA during pregnancy reduces the risk for early premature birth. Pregnant and lactating women should aim to achieve an average daily intake of at least 200 mg DHA. For healthy term infants, we recommend and fully endorse breastfeeding, which supplies preformed LC-PUFA, as the preferred method of feeding. When breastfeeding is not possible, we recommend use of an infant formula providing DHA at levels between 0.2 and 0.5 weight percent of total fat, and with the minimum amount of AA equivalent to the contents of DHA. Dietary LC-PUFA supply should continue after the first six months of life, but currently there is not sufficient information for quantitative recommendations.

Growth in extremely low birth weight infants up to three years.

OBJECTIVE: To evaluate postnatal growth of extremely low birth weight infants (ELBW, <1,000 g) until 36 months of corrected age (CA), and to relate growth outcome to anthropometric parameters at birth, sex, fetal growth status (small or appropriate for gestational age--SGA/AGA), period of admission and major perinatal events. STUDY DESIGN/METHOD: Weight (Wt), height (Ht) and head circumference (HC) were assessed in 159 ELBW infants. Data were standardized with Z-scores following Usher and McLean and Sempe growth curves. Uni- and multivariate statistical analysis were performed. RESULTS: The mean birth weight was 851.2+/-116.5 g. Z-scores decreased from birth to term, at a deeper rate for AGA than for SGA infants (p<0.005 for Ht, Wt, and HC). Between term and 36 months, growth was better in SGA compared with AGA infants (p=0.003 for Ht). Multivariate analysis showed that anthropometric parameters at birth were positive determinants for Wt, Ht and HC at term, and also for Wt and Ht at 36 months CA (Z-scores). Oxygen therapy after 36 weeks of post-conceptional age was a negative determinant influencing growth at 36 months CA (Z-scores). CONCLUSIONS: Significant catch-up growth took place between birth and 36 months, which was greater for SGA than for AGA infants. Anthropometric parameters at birth and oxygen therapy at 36 weeks post-conceptional age are the main predictive factors for growth at 36 months CA.

Oral vitamin A, E and D supplementation of pre-term newborns either breast-fed or formula-fed: a 3-month longitudinal study.

BACKGROUND: In contrast to the studies of vitamin A and E status in children, adolescents and adults, information on preterm infants is scarce. In the present investigation we examined the vitamin A, D and E status of pre-term infants at birth, and verified whether, at 1 and 3 months, breast or formula feeding affected the plasma concentration of those vitamins while being supplemented with Uvesterol ADEC. PATIENTS AND METHODS: In this prospective study, 2 groups of consecutively recruited preterm newborns fed either breast milk or formula received 3000 IU of vitamin A, 5 IU of vitamin E and 1000 IU of vitamin D daily. Vitamin A and E were measured by high performance liquid chromatography and spectrophotometry. 25-hydroxyvitamin D, a surrogate marker for vitamin D status, was measured by radioimmunoassay, and retinol binding-protein concentration was measured by immunonephelometry. RESULTS: At birth, formula-fed and breast-milk fed infants had similar plasma concentrations of vitamin A (0.75 +/- 0.20 and 0.64 +/- 0.21 micromol/L, ns), 25-hydroxyvitamin D (34.4 +/- 25.6 and 47.5 +/- 26.7 nmol/L, ns) and vitamin E (9.5 +/- 3.2 and 8.4 +/- 3.3 micromol/L, ns). Vitamins A and E, and retinol binding-protein concentrations steadily increased with time in both groups of infants without attaining, at 3 months, values considered normal in term infants and in young children. At 3 months of age, concentrations of 25-hydroxyvitamin D reached values comparable to those observed in term infants. CONCLUSION: Plasma concentrations of vitamins A and E and of retinol binding-protein steadily increased during the the study without reaching full repletion values. At the conclusion of the study, the type of nutrition did not affect plasma vitamin concentrations.