title: Insulin analogues in pregnancy and specific congenital anomalies: a literature review.
abstract: Insulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin. We performed a literature search for studies of pregnant women with pregestational diabetes using insulin analogues in the first trimester and information on congenital anomalies. The studies were analysed to compare the congenital anomaly rate among foetuses of mothers using insulin analogues with foetuses of mothers using human insulin. Of 29 studies, we included 1286 foetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 foetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn). The congenital anomaly rate was 4.84% and 4.29% among the foetuses of mothers using lispro and aspart. For glargine and detemir, the congenital anomaly rate was 2.86% and 3.47%, respectively. No studies on the use of insulin glulisine and degludec in pregnancy were found. There was no statistically significant difference in the congenital anomaly rate among foetuses exposed to insulin analogues (lispro, aspart, glargine or detemir) compared with those exposed to human insulin or Neutral Protamine Hagedorn insulin. The total prevalence of congenital anomalies was not increased for foetuses exposed to insulin analogues. The small samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies.
authors.affiliation: Department of Pharmacoepidemiology and Pharmacoeconomics, University of Groningen, Groningen, The Netherlands.
authors.forename: Josta
authors.initials: J
authors.lastname: de Jong
authors.affiliation: Paediatric Department, Hospital Lillebaelt, Kolding, Denmark.
authors.forename: Ester
authors.initials: E
authors.lastname: Garne
authors.affiliation: Department of Obstetrics and Women's Diseases, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Wender-Ozegowska
authors.affiliation: Congenital Anomaly Register and Information Service for Wales, Singleton Hospital, Swansea, UK.
authors.forename: Margery
authors.initials: M
authors.lastname: Morgan
authors.affiliation: Department of Pharmacoepidemiology and Pharmacoeconomics, University of Groningen, Groningen, The Netherlands.
authors.forename: Lolkje T W
authors.initials: LT
authors.lastname: de Jong-van den Berg
authors.affiliation: Department of Pharmacoepidemiology and Pharmacoeconomics, University of Groningen, Groningen, The Netherlands.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
mesh_terms: D000013:Congenital Abnormalities / Q000209:etiology*; D003920:Diabetes Mellitus / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D007328:Insulin / Q000009:adverse effects* / Q000031:analogs & derivatives*; D011247:Pregnancy
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin
keywords: congenital anomalies; diabetes; insulin analogues; pregnancy; review