Systematic Literature Review of Basal Bolus Insulin Analogue Therapy during Pregnancy

The maternal, fetal and neonatal complications of having diabetes during pregnancy, whether pre-gestational (PGDM) or gestational (GDM), have been well-established in the literature, prompting recommendations that women achieve and maintain strict glycemic control before and during pregnancy [1]. DMassociated maternal complications include progression of retinopathy, nephropathy, hypertension, and preeclampsia. DMassociated fetal and neonatal complications include congenital malformations, stillbirth, macrosomia, shoulder dystocia, intrauterine growth restriction (IUGR) [2,3]. Poor glycemic control (glycated hemoglobin (A1c) ≥7%) in the first trimester (T1) is associated with an increased rate of major congenital malformations and spontaneous abortions. In the third trimester (T3), poor glycemic control is associated with increased rate of preterm birth, preeclampsia and perinatal mortality [2,4]. However, simply targeting A1c levels is inadequate to prevent such complications. Insulin requirements vary throughout pregnancy: increasing in early pregnancy (for mean requirement of 0.7 units/ kg), may decrease in the second half of T1, likely due to nausea and vomiting, then increase in second trimester (T2) (mean 0.8 units/kg) and T3 (mean 0.9-1.0 units/kg), and lastly, either plateaus or decreases beyond 32 weeks’ gestation [5]. Insulin dosing must be continually managed and altered on an individual basis. Therefore, stringent glycemic control during pregnancy strives to minimize glucose excursions throughout the day [6].