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      Modelling predictive gender- and gestation-specific weight reference centiles for preterm infants using a population-based cohort study

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          Abstract

          We aimed to model longitudinal data to create predictive growth charts for weight in preterm infants from birth till discharge, that took into account the differing growth rates post-birth when compared to in-utero growth and therefore was more representative of the data than the UK1990 reference charts. Data from birth until discharge (or death), was collected and rigorously cleaned for all infants born at <32 weeks of gestation over a 4-year period. Means and standard deviations from the UK1990 reference charts were used to compute standard deviation scores (SDS) for our cohort. 2/3rd of the data was randomly selected and used to create gestation and gender-specific predictive weight centile lines through novel application of mixed modelling methods. The remaining 1/3rd of the data was used to test model fit by comparing expected vs actual weights for the new model with those predicted by the UK1990 model. Data from 1,510 preterm infants was analysed. 1067 of these were used to produce the predictive model. Weekly SDS were significantly lower than predicted throughout hospital stay for all gestation groups when compared with UK1990 data. The test data (n = 539) fitted the new centile lines substantially better than those modelled by the UK1990 centile lines. Mixed modelling of longitudinal data produced new predictive references for weight centiles of preterm infants. A large population-based prospective study is needed to produce representative longitudinal reference growth charts using these methods.

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          Longitudinal growth of hospitalized very low birth weight infants.

          The interpretation of growth rates for very low birth weight infants is obscured by limited data, recent changes in perinatal care, and the uncertain effects of multiple therapies. To develop contemporary postnatal growth curves for very low birth weight preterm infants and to relate growth velocity to birth weight, nutritional practices, fetal growth status (small- or appropriate-for-gestational-age), and major neonatal morbidities (chronic lung disease, nosocomial infection or late-onset infection, severe intraventricular hemorrhage, and necrotizing enterocolitis). Large, multicenter, prospective cohort study. Growth was prospectively assessed for 1660 infants with birth weights between 501 to 1500 g admitted by 24 hours of age to 1 of the 12 National Institute of Child Health and Human Development Neonatal Research Network centers between August 31, 1994 and August 9, 1995. Infants were included if they survived >7 days (168 hours) and were free of major congenital anomalies. Anthropometric measures (body weight, length, head circumference, and midarm circumference) were performed from birth until discharge, transfer, death, age 120 days, or a body weight of 2000 g. To obtain representative data, nutritional practices were not altered by the study protocol. Postnatal growth curves suitable for clinical and research use were constructed for body weight, length, head circumference, and midarm circumference. Once birth weight was regained, weight gain (14.4-16.1 g/kg/d) approximated intrauterine rates. However, at hospital discharge, most infants born between 24 and 29 weeks of gestation had not achieved the median birth weight of the reference fetus at the same postmenstrual age. Gestational age, race, and gender had no effect on growth within 100-g birth weight strata. Appropriate-for-gestational age infants who survived to hospital discharge without developing chronic lung disease, severe intraventricular hemorrhage, necrotizing enterocolitis, or late onset-sepsis gained weight faster than comparable infants with those morbidities. More rapid weight gain was also associated with a shorter duration of parenteral nutrition providing at least 75% of the total daily fluid volume, an earlier age at the initiation of enteral feedings, and an earlier age at achievement of full enteral feedings. These growth curves may be used to better understand postnatal growth, to help identify infants developing illnesses affecting growth, and to aid in the design of future research. They should not be taken as optimal. Randomized clinical trials should be performed to evaluate whether different nutritional management practices will permit birth weight to be regained earlier and result in more rapid growth, more appropriate body composition, and improved short- and long-term outcomes.
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            Growth failure in the preterm infant: can we catch up?

            Postnatal growth failure is extremely common in the very low birth weight and extremely low birth weight infant. Recent data from the National Institute of Child and Human Development (NICHD) Neonatal Research Network indicates that 16% of extremely low birth weight infants are small for gestational age at birth, but by 36 weeks corrected age, 89% have growth failure. Follow-up at 18 to 22 months corrected age shows that 40% still have weights, lengths, and head circumferences less than the 10th percentile. Growth failure is associated with an increased risk of poor neurodevelopmental outcome. Inadequate postnatal nutrition is an important factor contributing to growth failure, as most extremely low birth weight infants experience major protein and energy deficits during the neonatal intensive care unit hospitalization, in spite of the fact that nutrition sufficient to support intrauterine growth rates can generally be provided safely. Aggressive nutritional support--parenteral and enteral--is well tolerated in the extremely low birth weight infant and is effective in improving growth. Continued provision of appropriate nutrition (premature formula or fortified human milk) is important throughout the neonatal intensive care unit stay. After discharge, nutrient-enriched postdischarge formula should be continued for approximately 9 months post-term. Exclusively breast-fed infants require additional supplementation/fortification postdischarge as well. Additional trials are needed to address a number of important questions concerning the role of nutrition and growth on ultimate development.
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              Monitoring the Postnatal Growth of Preterm Infants: A Paradigm Change.

              There is no consensus regarding how the growth of preterm infants should be monitored or what constitutes their ideal pattern of growth, especially after term-corrected age. The concept that the growth of preterm infants should match that of healthy fetuses is not substantiated by data and, in practice, is seldom attained, particularly for very preterm infants. Hence, by hospital discharge, many preterm infants are classified as postnatal growth-restricted. In a recent systematic review, 61 longitudinal reference charts were identified, most with considerable limitations in the quality of gestational age estimation, anthropometric measures, feeding regimens, and how morbidities were described. We suggest that the correct comparator for assessing the growth of preterm infants, especially those who are moderately or late preterm, is a cohort of preterm newborns (not fetuses or term infants) with an uncomplicated intrauterine life and low neonatal and infant morbidity. Such growth monitoring should be comprehensive, as recommended for term infants, and should include assessments of postnatal length, head circumference, weight/length ratio, and, if possible, fat and fat-free mass. Preterm postnatal growth standards meeting these criteria are now available and may be used to assess preterm infants until 64 weeks' postmenstrual age (6 months' corrected age), the time at which they overlap, without the need for any adjustment, with the World Health Organization Child Growth Standards for term newborns. Despite remaining nutritional gaps, 90% of preterm newborns (ie, moderate to late preterm infants) can be monitored by using the International Fetal and Newborn Growth Consortium for the 21st Century Preterm Postnatal Growth Standards from birth until life at home.
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                Author and article information

                Contributors
                chakrabortym@cardiff.ac.uk
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                4 March 2020
                4 March 2020
                2020
                : 10
                : 4032
                Affiliations
                [1 ]ISNI 0000 0001 0807 5670, GRID grid.5600.3, Department of Infection and Immunity, Cardiff University, ; Cardiff, UK
                [2 ]ISNI 0000 0004 0649 0274, GRID grid.415947.a, Neonatal Intensive Care Unit, Singleton Hospital, ; Swansea, UK
                [3 ]ISNI 0000 0000 9616 5600, GRID grid.461312.3, Neonatal Intensive Care Unit, Royal Gwent Hospital, ; Newport, UK
                [4 ]ISNI 0000 0001 0169 7725, GRID grid.241103.5, Regional Neonatal Intensive Care Unit, University Hospital of Wales, ; Cardiff, UK
                [5 ]ISNI 0000 0001 0807 5670, GRID grid.5600.3, Centre for Medical Education, School of Medicine, Cardiff University, ; Cardiff, UK
                Author information
                http://orcid.org/0000-0002-1721-6532
                Article
                60895
                10.1038/s41598-020-60895-6
                7055271
                32132590
                4555fe63-5090-4840-8a35-0e75ebbe63a8
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 25 September 2019
                : 17 February 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/100012068, Health and Care Research Wales (Ymchwil Iechyd a Gofal Cymru);
                Award ID: CTRA-16-04
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                neonatology,epidemiology
                Uncategorized
                neonatology, epidemiology

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