Insulin treatment in diabetic pregnancy

Abstract

Pregnancy in women with diabetes is associated with increased risk of obstetric complications and neonatal morbidity and mortality. The 1989 St Vincent declaration set out a series of targets for improving quality of life in people with diabetes. For women, the declaration stated as a 5-year goal that the outcome of pregnancy should approximate that of the nondiabetic pregnancy [1]. Since then, a number of large, population-based studies have investigated the impact of the declaration on pregnancy outcomes among women with both pregestational (types 1 and 2) and gestational diabetes. The most recent is the Confidential Enquiry into Maternal and Child Health (CEMACH) [2]. This large survey of the outcomes of pregnancy complicated by both type 1 and type 2 diabetes comprised an extensive descriptive survey of all women with pregestational diabetes who gave birth in England, Wales and Northern Ireland in the calendar year from 1 March 2002. The results, along with those from other countries [3][4][5], demonstrate that the objectives of the St Vincent declaration remain unfulfilled. Moreover, it is estimated that up to one in four women with pregestational diabetes have a poor pregnancy outcome [6]. Risks include fetal and neonatal loss, congenital malformations, preterm delivery, macrosomia, pre-eclampsia, Caesarean section and maternal mortality [3,4,[6][7][8][9][10].Many studies assessing the risk of adverse outcomes in diabetic pregnancy have focused on women with type 1 diabetes [3,4,7], but type 2 diabetes is also a growing concern. The number of new cases of type 2 diabetes is increasing and, due to the increasing prevalence of obesity, the disease is now being recognised in adolescents and young adults. Pregnancy outcomes in those with type 2 diabetes are as poor as or worse than those with type 1 diabetes [11,12]. In the CEMACH, type 2 diabetes represented 27.2% of all pregnancies complicated by diabetes. The results of the survey found that rates of perinatal mortality and prevalence of congenital abnormalities are similar between infants of women with type 1 and type 2 diabetes (Table 1) [10,13].Between 2 and 12% of pregnant women develop gestational diabetes [14], which can result in macrosomia, shoulder dystocia, birth injuries and neonatal hypoglycaemia as well as increased perinatal mortality [15]. For the mother, gestational diabetes is a very strong predictor for the development of permanent diabetes later in life. Fetal and neonatal lossAmong women with diabetes, pregnancy loss remains significantly higher than in the nondiabetic maternity population. A lack of information on the rate of early fetal loss in the general population precludes accurate quantification of the increased risk of this outcome among diabetic Insulin treatment in diabetic pregnancy R E V I E W A R T I C L E DIABETES/METABOLISM RESEARCH AND REVIEWS Diabetes Metab Res Rev 2008; 24(Suppl 2): S3-S20

Progression of diabetic retinopathy during pregnancy in women with type 2 diabetes

“…This underlines the importance of lowering HbA 1c before pregnancy. Strict metabolic control is of uppermost importance for the outcome of pregnancy, since the occurrence of preeclampsia, preterm delivery and stillbirth is related to poor metabolic control [20][21][22][23]. The prevalence of perinatal mortality tended to be lower in this cohort than in previous observations from our centre [5].…”

Adverse pregnancy outcomes in women with diabetes

“…The most common fetal adverse outcomes found in pregnancies of women with diabetes are fetal and neonatal loss, a great variety of congenital abnormalities and malformations, premature delivery (delivery occurring before 37 weeks’ gestation), fetal growth acceleration and macrosomia (defined as a birth weight above 4 kg and/or >90th percentile weight for gestational age or large for gestational age) which are associated with several obstetric complications like birth trauma, hypertrophic miocardiopathy, stillbirth, respiratory distress syndrome, neonatal hypoglycemia, hypocalcemia, hyperbilirubinemia and polycythemia; maternal complications are pregnancy induced hypertension, pre-eclampsia, hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, Cesarean section, hypoglycemia and the worsening of any degree of a pre-existing renal insufficiency and retinopathy [20,21]. …”

“…The major congenital malformations among offspring of women with diabetes are found in the following systems: cardiovascular (cardiac transposition of the great arteries, ventricular septal defect, coarctation of the aorta, atrial septal defect, asymmetric septal hypertrophy), central nervous system (neural tube defects, including anencephaly, microcephaly and isolated hydrocephalus), gastrointestinal (duodenal atresia, anorectal atresia, hypoplastic left colon), musculoskeletal (talipes, arthrogryposis), urinary tract (uretal duplication, cystic kidney, renal dysgenesis, hydronephrosis), caudal regression syndrome, cleft lips and palate anomalies [9,20]. These major congenital abnormalities are an important contributory factor for the high mortality rates found in infants of women with diabetes [8].…”

Insulin analogues in the treatment of diabetes in pregnancy

“…Besides hyperglycemia, high levels of other metabolic fuels, such as some aminoacids and free fatty acids, might as well increase fetal insulin secretion and lead to macrosomia (10). The rates of macrosomia are 3.5-4.5 times greater among infants of women with pregestational diabetes than those found in infants born to non-diabetic mothers (11).…”

“…Important safety concerns with the use of the new insulin analogues in pregnancy have been their capacity of causing mitogenicity, immunogenicity, transplacental passage of the antibody-analogue complex and, finally, an increased risk of teratogenicity and embryotoxicity (10,21,59).…”