Insulin in pregnancy and breastfeeding


Risk Factor: B
Class: Hormones/ Antidiabetic agents

Contents of this page:
Fetal Risk Summary
Breast Feeding Summary

Fetal Risk Summary

Insulin, a naturally occurring hormone, is the drug of choice for the control of diabetes mellitus in pregnancy. Because it is a very large molecule, it has been believed that insulin does not cross the human placenta. Research published in 1990, however, found that animal (bovine or porcine) insulin does cross the human placenta as an insulin-antibody complex, and that the amount of transfer directly correlated with the amount of anti-insulin antibody in the mother (1). Moreover, high concentrations of animal insulin in cord blood were significantly associated with the development of fetal macrosomia, suggesting that the transferred insulin had biologic activity and that the fetal condition was determined by factors other than the mother’s glycemic control (1). This latter conclusion has been challenged (2,3) and defended (4) and, at present, requires additional study. The results of the study do underscore the argument that immunogenic insulin should not be used in women who may become pregnant (1,2).

Infants of diabetic mothers are at risk for an increased incidence of congenital anomalies, 3 to 5 times that of normal controls (5,6,7,8,9,10,11 and 12). The rate of malformations appears to be related to maternal glycemic control in the 1st trimester of pregnancy, but the exact mechanisms causing structural defects are unknown. A 1996 review examined this issue and concluded that uncontrolled diabetes, occurring very early in gestation (i.e., before 8 weeks of gestation), causes an abnormal metabolic fuel state and that this condition leads to a number of processes, operating via a common pathway, that results in cell injury (11).

Congenital malformations are now the most common cause of perinatal death in infants of diabetic mothers (5,6). Not only is the frequency of major defects increased but also the frequency of multiple malformations (affecting more than one organ system) (5). Malformations observed in infants of diabetic mothers include the following (9,10,12,13 and 14): Caudal regression syndrome (includes anomalies of lower neural tube resulting in sacral agenesis and defects of lumbar vertebrae; defects of lower extremities, gastrointestinal and genitourinary tracts (15)) Femoral hypoplasia and unusual facies syndrome Spina bifida, hydrocephalus, other central nervous system defects Anencephalus Cardiovascular: transposition of great vessels, ventricular septal defect, atrial septal defect Anal and rectal atresia Renal: agenesis, multicystic dysplasia, ureter duplex Gastrointestinal: situs inversus, tracheoesophageal fistula, bowel atresias, imperforate anus, small left colon Infants of diabetic mothers may have significant perinatal morbidity, even when the mothers have been under close diabetic control (12). Perinatal morbidity in one series affected 65% (169/260) of the infants and included hypoglycemia, hyperbilirubinemia, hypocalcemia, and polycythemia (16).

In contrast to the data relating to the adverse fetal effects of poor maternal hyperglycemia control, animal studies have documented that short periods of hypoglycemia during early organogenesis are associated with malformations of the skeleton and heart (17,18 and 19), and reduced growth, including some major organs (20). Although hypoglycemia in humans has not been shown to be teratogenic (21,22), at least one author has concluded that this has not been adequately studied (23).

Breast Feeding Summary

Insulin is a naturally occurring constituent of the blood. It does not pass into breast milk.



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