Gestational Age and Age at Sampling Influence Metabolic Profiles in Premature Infants

Abstract

WHAT'S KNOWN ON THIS SUBJECT: Prematurely born infants commonly have abnormal metabolic screens.WHAT THIS STUDY ADDS: Both gestational and chronological age influence metabolic profiles used to screen for inborn errors of metabolism.abstract OBJECTIVE: To describe the influence that gestational age and chronological age have on amino acid and acylcarnitine profiles in an atrisk population of premature infants. METHODS:Metabolic profiles (15 amino acids and 35 acylcarnitines) were obtained by using standard newborn techniques on infants born between 23 and 31 completed weeks of gestation. The profiles were drawn within the first 24 hours after birth and on approximately days 7, 28, and 42 of life or at discharge. A single, central, contract laboratory analyzed and managed the samples. RESULTS:We studied 995 patients; none was subsequently diagnosed with an inborn error of metabolism. Of the 3579 samples, there were 257 (7.2%) amino acid or acylcarnitine alerts reported in 214 infants (21.5% of infants studied). Both gestational age and postbirth chronological age significantly influenced the metabolic profile. Twenty-nine percent of infants at 23 to 26 weeks' gestational age had an abnormal metabolic profile compared with 17% of infants at 29 to 31 weeks' gestational age (P , .01). On the day of birth, 12% of the profiles were abnormal compared with 2% on day 28 (P , .01). The highest rate of abnormal values occurred on day 7 in the infants 23 to 26 weeks' gestational age (21%).CONCLUSIONS: These results demonstrate the complexity of understanding the impact of immaturity and disease on metabolic profiles used to screen for inborn errors of metabolism. Dr Clark has contributed to the conception and design of the study. The article from first to final draft was written and edited by Dr Clark with the help of his co-authors who offered suggestions for improvement; Mrs Kelleher has contributed to the drafting and revising of the article for important intellectual content; Dr Chace has contributed to the conception and design of the study analysis and interpretation of data; Dr Spitzer has contributed to the conception and design of the study, analysis and interpretation of data, and critical revisions for important intellectual content; and all authors approved the final manuscript as submitted.This trial has been registered at www.clinicaltrials.gov (identifier NCT00865150). METHODS Study SubjectsWe included inborn infants between the gestational ages of 23 weeks and 0/7 days and 31 weeks and 0/7 days and excluded infants if they had major congenital anomalies. Parental consent was obtained for each subject. The protocol was approved by the Western Institutional Review Board and/or each site' s local institutional review board. Nutritional SupportFluid management and nutritional guidelines were used as per site specific protocol. Data on precisely what was received by the study subject and growth parameters were collected on postnatal days 1, 7, 28, and 42. Metabolic ProfilesAn experienced health care professional...

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“…It is possible that metabolic immaturity may contribute to dysfunctional FAO in premature neonates since false-positive newborn screens are more common in premature and low-birth-weight infants, 38 but this association has been found mainly for disorders of amino acid and hormone metabolism rather than FAO disorders. 39, 40 We do not yet know where dysfunctional FAO lies on the causal pathway for preterm birth.…”

Stopping Parenteral Nutrition for 3 Hours Reduces False Positives in Newborn Screening

“…6,9,[19][20][21][22][23] This study shows a new NBS blood collection, the 3-hour stop-PN protocol, can significantly reduce falsepositive AA results and the associated medical costs. The current study confirms and expands the results of a smaller study of the effect of holding AA containing PN by Morris et al 23 The current study includes a much larger sample size of VLBW infants (87 vs 413 in this study).…”

“…Several studies have identified factors associated with false-positive NBS, one of the most significant of which is prematurity and low BW. [6][7][8][9] Our study focused on AA results in NBS, which are among the most common false-positive NBS results. The false-positive rate for AA was 0.3% of total newborn infants, and approximately 90% of infants with false-positive AA results are VLBW infants.…”

“…6 Several studies have shown increased rates of false-positive NBS in preterm infants that are variously postulated to result from immature organ or endocrine function, underlying illness, transfusion, parenteral nutrition (PN), inappropriate cut-off values, and timing of NBS collection. [6][7][8][9] Over the past 15 years, most extremely premature infants are given PN containing amino acids (AAs) for prevention of catabolic state, nutritional deficiency, and growth restriction [10][11][12] prior to NBS blood collection at 24-48 hours of life. Recent reports demonstrate increased false-positive NBS results for hypermethioninemia in premature infants with PN, 13 and higher plasma AA concentrations in infants with early parenteral AA.…”

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“…Smoking at home, smoking during pregnancy, eczema, asthma and atopic family history did not show any correlation. For UBD only, a correlation with gestational age was found; however, gestational age is a well-known confounder, which does not exclude the value of UBD as severity marker [23].…”