title: Fetal macrosomia and neonatal hyperinsulinemic hypoglycemia associated with transplacental transfer of sulfonylurea in a mother with KCNJ11-related neonatal diabetes.
abstract: OBJECTIVE
  Sulfonylureas (SUs) are effective at controlling glycemia in permanent neonatal diabetes mellitus (PNDM) caused by KCNJ11 (Kir6.2) mutations.
  
  
  METHODS
  We report the case of a woman with PNDM who continued high doses of glibenclamide (85 mg/day) during her pregnancy. The baby was born preterm, and presented with macrosomia and severe hyperinsulinemic hypoglycemia requiring high-rate intravenous glucose infusion.
  
  
  RESULTS
  Postnatal genetic testing excluded a KCNJ11 mutation in the baby. Glibenclamide was detected in both the baby's blood and the maternal milk.
  
  
  CONCLUSIONS
  We hypothesize that high doses of glibenclamide in the mother led to transplacental passage of the drug and overstimulation of fetal β-cells, which resulted in severe hyperinsulinemic hypoglycemia in the neonate (who did not carry the mutation) and contributed to fetal macrosomia. We suggest that glibenclamide (and other SUs) should be avoided in mothers with PNDM if the baby does not carry the mutation or if prenatal screening has not been performed, while glibenclamide may be beneficial when the fetus is a PNDM carrier.
authors.affiliation: Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Myngheer
authors.affiliation: Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
authors.forename: Karel
authors.initials: K
authors.lastname: Allegaert
authors.affiliation: University of Exeter Medical School, Exeter, U.K.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hattersley
authors.affiliation: University of Exeter Medical School, Exeter, U.K.
authors.forename: Tim
authors.initials: T
authors.lastname: McDonald
authors.affiliation: University Laboratory of Physiology, Oxford, Oxford, U.K.
authors.forename: Holger
authors.initials: H
authors.lastname: Kramer
authors.affiliation: University Laboratory of Physiology, Oxford, Oxford, U.K.
authors.forename: Frances M
authors.initials: FM
authors.lastname: Ashcroft
authors.affiliation: Department of Obstetrics/Gynaecology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Verhaeghe
authors.affiliation: Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
authors.affiliation: Department of Development and Regeneration, KU Leuven, Leuven, Belgium Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium kristina.casteels@uzleuven.be.
authors.forename: Kristina
authors.initials: K
authors.lastname: Casteels
mesh_terms: D000328:Adult; D044903:Congenital Hyperinsulinism / Q000139:chemically induced* / Q000175:diagnosis; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005320:Fetal Macrosomia / Q000139:chemically induced* / Q000175:diagnosis; D005905:Glyburide / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D007231:Infant, Newborn; D008431:Maternal-Fetal Exchange; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D011247:Pregnancy; D000099161:Kcnj11 Channel
chemical_list: D005905:Glyburide; D007004:Hypoglycemic Agents; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel