Long-term endocrine outcome of small for gestational age infants born to mother with and without gestational diabetes mellitus

Objective
Small for gestational age (SGA) infants and infants born to mothers with gestational diabetes mellitus (GDM) are at an increased risk for significant morbidity and mortality, mainly metabolic disorders. We aimed to question the long-term endocrine morbidity of SGA infants born to mothers with GDM compared to SGA infants born to non- diabetic mothers.

Study Design
A population-based cohort study was performed to assess the risk for endocrine morbidity among children born SGA to mothers with GDM compared to SGA infants born to non- diabetic mothers. The main outcome evaluated was endocrine morbidity of the offspring up to the age of 18 years, predefined in a set of ICD 9 codes. Endocrine morbidity included thyroid disease, insulin and non-insulin dependent diabetes mellitus, hypoglycemia, childhood obesity, parathyroid hormone disease, adrenal disease and sex hormone disease. All SGA infants born between the years 1991-2014 and discharged alive from the hospital were included in the study. Multiple pregnancies, infants with congenital malformations or chromosomal abnormalities and mothers lacking prenatal care were excluded from the analysis. Kaplan-Meier survival curve was constructed to compare cumulative endocrine morbidity. A Cox proportional hazards model was conducted to control for confounders.

Results
During the study period, 9312 newborn infants met the inclusion criteria, of them 259 SGA infants were born to mothers with GDM and 9053 SGA offspring were born to mother without GDM. Long-term endocrine morbidity was comparable between the groups (0.8% in children born to mothers with GDM vs. 0.5% in children born to non-diabetic mothers, p=0.62; Table). Likewise, the Kaplan-Meier survival curve did not demonstrate a significantly higher cumulative incidence of endocrine morbidity in offspring of women with GDM (Figure, log rank test p=0.67). In a Cox regression model, while controlling for ethnicity, hypertensive disorders, preterm birth, and maternal age, delivery of an SGA neonate to mother with GDM was not associated with long-term endocrine morbidity of the offspring (adjusted HR 1.2, 95% confidence interval 0.27-5.00, p=0.82).

Conclusion
SGA infants born to mothers with GDM are not at an increased risk for long-term endocrine morbidity as compared with SGA infants born to non- diabetic mothers.