Growth trajectory during the first 1000 days and later overweight in very preterm infants.

OBJECTIVE: To identify the characteristics of early life growth associated with later overweight or obesity (OWO) in very preterm population. DESIGN: Length, weight and body mass index (BMI) were prospectively recorded from three prospective, population-based cohorts with 5 years (Loire Infant Follow-up Team (LIFT), EPIPAGE2 (Etude EPIdémiologique sur les Petits Ages GEstationnels 2)) and 15 years (EPIPAGEADO, Etude EPIdémiologique sur les Petits Ages GEstationnels-Adolescents) of follow-up. Missing data were imputed. SETTING: Regional (LIFT), national (EPIPAGE2) and multiregional (EPIPAGEADO) cohorts in France. PATIENTS: Eligible infants born before 33 weeks of gestation in 1997 (EPIPAGEADO), between 2003 and 2014 (LIFT), and in 2011 (EPIPAGE2). MAIN OUTCOME MEASURES: OWO was determined as BMI Z-score >85th percentile of the WHO reference curves at 5 years (LIFT, EPIPAGE2) and 15 years (EPIPAGEADO). RESULTS: In EPIPAGEADO, LIFT and EPIPAGE2, BMI Z-scores were known for 302 adolescents, 1016 children and 2022 children, respectively. In EPIPAGEADO, OWO was observed in 42 (13.9%, 95% CI 10.5 to 18.3) adolescents. In multivariable models, birthweight Z-score, increase in weight Z-score during neonatal hospital stay and increase in BMI between discharge and at 2 years of corrected age were positively associated with OWO at 15 years (adjusted OR (aOR)=3.65, 95% CI 1.36 to 9.76; aOR=3.82, 95% CI 1.42 to 10.3; and aOR=2.55, 95% CI 1.72 to 3.78, respectively, by Z-score), but change in length Z-score during neonatal hospital stay was negatively associated (aOR=0.41, 95% CI 0.21 to 0.78, p=0.007). These four associations with OWO assessed at 5 years were confirmed in the LIFT and EPIPAGE2 cohorts. CONCLUSIONS: Change in length Z-score during hospitalisation, a putative proxy of quality of neonatal growth, was negatively associated with risk of later OWO when change in BMI between discharge and at 2 years was included in the multivariable model.

Neonatal growth velocity of preterm infants: The weight Z-score change versus Patel exponential model.

BACKGROUND: Different methods are used to assess the growth of preterm infants during neonatal hospital stay. The primary objective was to compare two methods for assessing growth velocity: g/kg/d according to the Patel exponential model (EM) and change in weight z-score (ZS) according to Fenton curves. The secondary objective was to highlight factors influencing the level of agreement between the two methods. METHODS: Preterm infants born before 33 weeks were included. Growth velocity was computed by EM and ZS methods and linear regression was used to predict what growth velocity by EM method would be obtained using the ZS method. Differences between EM growth velocity and EM growth velocity predicted by ZS method were then used to assess the level of agreement between the two methods. A difference between -2 and +2 g/kg/day was considered as fair agreement, greater than ± 4 g/kg/day as poor agreement, and as disagreement otherwise. RESULTS: Among the 3954 children included, we observe a fair agreement in 2471 children (62.5%), a poor agreement in 1278 (32.3%) and a disagreement in 205 children (5.2%). Birth weight and gestational age explained 31% and 25%, respectively, of the variance in the difference between the two methods. CONCLUSIONS: In more than a third of enrolled children, the two methods for measuring growth velocity disagreed substantially. As variation of weight Z-score takes into account infant gestational age and gender, it could be more suitable to analyze a population of preterm infants with a wide range of gestational age.

In Preterm Infants, Length Growth below Expected Growth during Hospital Stay Predicts Poor Neurodevelopment at 2 Years.

BACKGROUND: In preterm infants, neonatal weight growth is associated with neurodevelopmental outcome but is a poor indicator of growth quality. OBJECTIVE: The aim of this work was to measure the relationship between neonatal length growth and the 2-year neurological outcome in preterm infants. METHODS: A total of 2,403 infants enrolled in the LIFT cohort with gestational age less than 34 weeks were studied. Neonatal observed length growth (OLG) was calculated as the change in length Z-score between birth and discharge. Expected length growth (ELG) was estimated based on gestational age, birth weight Z-score, birth length Z-score, gender, and observed neonatal weight growth. The difference between OLG and ELG (∆OLG-ELG) was calculated as OLG - ELG, and infants were ranked into 3 classes depending on their ∆OLG-ELG (≤-0.5, -0.49 to 0.49, ≥0.50 Z-score). We explored the relationship between ∆OLG-ELG and 2-year neurodevelopmental outcome (n = 2,036), and, in a subgroup (n = 85), between ∆OLG-ELG and body composition at discharge. RESULTS: ELG was strongly predicted from the above-mentioned parameters (R2 = 0.73, p = 0.001). OLG correlated closely with gestational age (p = 0.001) but ∆OLG-ELG did not (p = 1.0). OLG was not associated with a 2-year nonoptimal outcome after adjustment for gestational age, but ∆OLG-ELG ≤-0.5 was; the crude and adjusted odds ratios were 1.63 and 1.56, respectively. ∆OLG-ELG correlated negatively with fat mass (R2 = 0.29, p = 0.006) before and after adjustment for gestational age. CONCLUSION: ∆OLG-ELG is a marker of neonatal growth that does not depend on gestational age, and may reflect quality of growth. A ∆OLG-ELG ≤-0.5 Z-score is associated with a higher risk for 2-year nonoptimal neurodevelopmental outcome.

Deficit of Fat Free Mass in Very Preterm Infants at Discharge is Associated with Neurological Impairment at Age 2 Years.

Preterm infants have a deficit of fat-free mass accretion during hospitalization. This study suggests that z score of fat-free mass at discharge is associated with neurologic outcome (P = .003) at 2 years of age, independent of sex, gestational age, and birth weight z score. Interventions to promote quality of growth should be considered.

Determinants of body composition in preterm infants at the time of hospital discharge.

BACKGROUND: Preterm infants have a higher fat mass (FM) percentage and a lower fat-free mass (FFM) than do term infants at the time of hospital discharge. OBJECTIVE: We determined perinatal and nutritional factors that affect the body composition of preterm infants at discharge. DESIGN: A total of 141 preterm infants born at <35 wk of gestation and admitted to Nantes University Hospital Neonatology Unit over a period of 2 y were enrolled. Nutritional intake and growth were monitored during hospitalization. Body composition was assessed by using air-displacement plethysmography at discharge. FFM was compared with reference data in term infants according to sex and gestational age. RESULTS: Linear regression produced an excellent model to predict absolute FFM from perinatal characteristics and nutrition (R(2) = 0.82) but not the FM percentage (R(2) = 0.24). Gestational and postnatal ages played an equal role in absolute FFM accretion, as did the initial growth (between birth and day 5) and growth between day 5 and discharge. Antenatal corticosteroid treatment slightly reduced FFM accretion. As concerns nutritional intake, a higher protein:energy ratio at days 10 and 21 was significantly associated with decreased risk of an FFM deficit when preterm infants were compared with reference values for term infants. Boys had higher risk of an FFM deficit than did girls. CONCLUSION: The initial growth and quality of nutrition were significantly associated with absolute FFM accretion during a hospital stay in preterm infants. This trial was registered at clinicaltrials.gov as NCT01450436.

Air-displacement plethysmography for determining body composition in neonates: validation using live piglets.

INTRODUCTION: Air-displacement plethysmography (ADP) was developed as a noninvasive tool to assess body composition, i.e., the proportion of fat mass (%FM) and lean body mass. The results of previous studies comparing ADP with labeled water dilution in infants and with chemical analysis in phantoms have validated the ADP approach indirectly. We assessed the precision and accuracy of measurements of % FM proportions in live animals, using ADP in comparison with biochemical analyses. METHODS: Three groups of 12 piglets each underwent four consecutive body composition assessments at 2, 7, and 21 d and were euthanized to determine whole-body lipid content by direct chemical analysis. RESULTS: The average body weights were 1,490, 2,210, and 5,610 g at d2, d7, and d21, respectively. The mean %FM values determined by biochemical analysis and ADP were 8.63 ± 4.08% and 8.01 ± 4.03%, respectively. Linear regression and Bland-Altman analyses indicated good agreement for %FM. The root mean square coefficient of variation (RMS-CV) for ADP was 17.9%, with a better precision in the higher fat mass range. DISCUSSION: Despite its relatively poor precision in the low range of %FM, ADP measures fat mass with reasonable precision and accuracy in the range of body weight encountered in low-birth-weight infants.

Hyperbilirubinemia and neurodevelopmental outcome of very low birthweight infants: results from the LIFT cohort.

BACKGROUND: Bilirubin-related neurotoxicity is an important clinical issue in very low birthweight (VLBW) infants, and the existing literature is inconsistent. OBJECTIVE: To analyze the relationship between maximal serum unconjugated bilirubin levels (SBL) and neurodevelopmental outcome at 2-year corrected age in VLBW infants. METHODS: Phototherapy was initiated in all infants born before 33 weeks of gestation, according to Maisels' recommendations. Neurodevelopmental assessment at 2-year corrected age was performed in all infants that survived. SBLs collected during the first week of life were used to define three tertiles of max-SBL. The first tertile corresponded to infants with the lowest max-SBL. RESULTS AND CONCLUSIONS: A total of 724 infants were included in the study, and among them, 631 (87%) were evaluated at two years old. The infants of the first tertile were younger and smaller than the infants of the other two tertiles, in accordance with Maisels' recommendations for very small infants. No difference in the risk of impaired functional outcome among the three groups was observed. However, among infants weighing less than 1001 g, those in the third tertile had a poorer neurodevelopmental prognosis as compared to those in the second tertile (adjusted odds ratio = 6.8, 95% CI: 1.2-36.7, p = 0.03). Considering the results obtained, we propose 196 µmol/L (11.5 mg/dL) when birthweight varies between 1001 and 1500 g, and 170 µmol/L (9.9 mg/dL) when birthweight is less than 1001 g, as recommended max-SBLs (defined as maximal levels of 95(th) percentile curves of SBLs in infants with an optimal outcome). When Maisels' recommendations were applied, max SBLs were higher in 8% of infants weighing 1001-1500 g and in 15% of infants weighing less than 1001 g. Our data seems to validate Maisels' recommendations in the overall population of infants born before 33 weeks of gestation, but not in infants weighing less than 1001 g.

Non-invasive exploration of neonatal gastric epithelium by using exfoliated epithelial cells.

BACKGROUND & AIMS: In preterm infants, exfoliated gastric epithelial cells can be retrieved from aspirates sampled through the naso-gastric feeding tube. Our aims were to determine (1) whether the recovery of exfoliated cells is feasible at any time from birth through the removal of the nasogastric tube, (2) whether they can be grown in culture in vitro, and (3) whether the physiological state of exfoliated cells expressing H+/K+ -ATPases reflects that of their counterparts remaining in situ at the surface of the gastric epithelium in neonatal rat pups. METHODS: In infants, gastric fluid aspirates were collected weekly after birth or every 3 hours over 24-h periods, and related to clinical parameters (Biocollection PROG/09/18). In rat pups submitted to a single fasting/refeeding cycle, we explored circadian exfoliation with the cellular counter-parts in the gland. All samples were analyzed by confocal imaging and Enzyme-Linked Immunosorbent Assay. RESULTS: Epithelial cells were identified by microscopy using membrane-bound anti-H+/K+ ATPases antibody, assessed for nucleus integrity, and the expression of selected proteins (autophagy, circadian clock). On 34 infants, the H+/K+-ATPase-positive cells were consistently found quiescent, regardless of gestational age and feeding schedule from day-5 of life to the day of removal of the naso-gastric tube. By logistic regression analysis, we did find a positive correlation between the intensity of exfoliation (cellular loss per sample) and the postnatal age (p<0.001). The H+/K+ ATPase-positive cells established in culture retained the expression of a biomarker of progenitor status (Pouf5F1-Oct4). In rat pups, the expression pattern of Survivin in H+/K+ ATPase-positive exfoliated cells paralleled that observed in cells remaining at the surface of the gastric gland. CONCLUSIONS: Tracking parietal cells can improve clinical monitoring and understanding of the autophagic death via the phosphatidylinositol 3-kinase/Akt/survivin pathway.