Prematurity should not prevent genetic testing for neonatal diabetes
American Academy of Pediatrics
Reason for embargo
BACKGROUND: Hyperglycemia in premature infants is usually thought to reflect inadequate pancreatic development rather than monogenic neonatal diabetes. No studies, to our knowledge, have investigated the prevalence of monogenic forms of diabetes in preterm infants. METHODS: We studied 750 patients with diabetes diagnosed before 6 months of age. We compared the genetic etiology and clinical characteristics of 146 preterm patients born <37 weeks and compared them with 604 born ≥37 weeks. RESULTS: A genetic etiology was found in 97/146 (66%) preterm infants compared with 501/604 (83%) born ≥37weeks, P < .0001. Chromosome 6q24 imprinting abnormalities (27% vs 12%, P = .0001) and GATA6 mutations (9% vs 2%, P = .003) occurred more commonly in preterm than term infants while mutations in KCNJ11 were less common (21 vs 34%, P = .008). Preterm patients with an identified mutation were diagnosed later than those without an identified mutation (median [interquartile range] 35 [34 to 36] weeks vs 31 [28 to 36] weeks, P < .0001). No difference was seen in other clinical characteristics of preterm patients with and without an identified mutation including age of presentation, birth weight, and time to referral. CONCLUSIONS: Patients with neonatal diabetes due to a monogenic etiology can be born preterm, especially those with 6q24 abnormalities or GATA6 mutations. A genetic etiology is more likely in patients with less severe prematurity (>32 weeks). Prematurity should not prevent referral for genetic testing as 37% have a potassium channel mutation and as a result can get improved control by replacing insulin with sulphonylurea therapy.
REJB was funded by Diabetes UK, through funding from a Clinical Training Fellowship, and the National Institute of Health Research from an Academic Clinical Lectureship award. IKT and DJGM are supported by the Wessex CRN, NIHR Wellcome Trust Clinical Research Facility, Southampton, and Diabetes UK. BS and MS are supported by the NIHR Exeter Clinical Research Facility. The genetic testing was funded by the Wellcome Trust. ATH and SE are Wellcome Trust Senior Investigators. ATH is an NIHR Senior Investigator.
This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.
Vol. 138 No. 3, e20153926
Place of publication