Research of glycemic variability of patients with gestational diabetes mellitus and its relationship with infant birth weight and adverse pregnancy outcomes

Abstract

Objective To analyze the glycemic variability in patients with gestational diabetes mellitus (GDM) by using continuous glucose monitoring system (CGMS) and to explore the relationship between GDM glycemic variability and infant birth weight and maternal and neonatal adverse pregnancy outcomes. Methods From April 2011 to August 2012, 189 cases of patients with GDM who were ready to regularly receive prenatal examination in the Department of Obstetrics of Guangdong Women and Children Hospital were enrolled in this study. All the GDM patients in this research met the GDM diagnostic criteria recommended by American Diabetes Association. They were instructed to wear the CGMS for 72 consecutive hours in the first week of this study. After four weeks of individual glucose control following strictly with doctors' advice, all the patients wear the CGMS for 72 consecutive hours for the second time in the fifth week of this study The parameters of glycemic variability which included mean blood glucose (MBG), the standard deviation of blood glucose (SDBG), mean amplitude of glycemic excursions (MAGE), and the mean of daily differences (MODD) were measured in the first and fifth weeks of this study. The maternal and neonatal adverse pregnancy outcomes and infant birth weight were collected. The relationship between infant birth weight and GDM patients' age, height, pregnancy history, body weight before pregnancy, fasting blood glucose level, oral glucose tolerance test (OGTT) 1 h glucose (OGTT-GLU1h), OGTT 2 h glucose (OGTT-GLU2h) and level of glycosylated hemoglobin A1c (HbA1c) on OGTT day, and MBG, SDBG, MAGE, MODD in the first and fifth weeks of this study were analyzed by multiple linear regression analysis. The relationship between maternal and neonatal adverse pregnancy outcomes and those above indexes of GDM patients in the first and fifth weeks of this study were analyzed by multiple logistic regression analysis. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Guangdong Women and Children Hospital. Results ①The MBG, SDBG, MAGE, MODD, duration of hyperglycemia level (≥7.8 mmol/L) and duration of hypoglycemia level (≤3.3mmol/L) of GDM patients in the fifth week of this study were (5.7±0.7) mmol/L, (1.1±0.4) mmol/L, (2.4±0.9) mmol/L, (1.2±0.3) mmol/L, 60 min/d (0-380 min/d) and 0 min/d (0~270 min/d) respectively, which all were significantly lower than those (6.1±0.9) mmol/L, (1.3±0.4) mmol/L, (3.1±0.9) mmol/L, (1.5±0. 4) mmol/L, 100 min/d (0~760 min/d) and 0 min/d (0~470 min/d) in the first week of this study respectively, and all the differences were statistically significant (χ2=4.197, P<0.001; χ2=7.028, P<0.001; χ2=7.691, P<0.001; χ2=12.986, P<0.001; Z=-4.992, P<0.001; Z=-2.601, P=0.009). ②189 women with GDM delivered 186 living infants, as 1 woman miscarried and 2 women experienced intrauterine fetal death. The average birth weight of infants was (3 345±508) kg. The maternal adverse pregnancy outcomes included: 1(0.5%) miscarriage, 2 (1.1%) intrauterine fetal deaths, 19(10.1%) combined with preeclampsia, 88(46.6%) primary cesarean delivery, 36(19.0%) repeat cesarean delivery. The neonatal adverse pregnancy outcomes included: 1(0.5%) obstetric trauma, 20(10.8%) macrosomia, 48(25.8%) large for gestational age, 5(2.7%) small for gestational age, 26(14.0%) combined with hypoglycemia, 18(9.7%) combined with hyperbilirubinemia, 11(5.9%) combined with respiratory distress syndrome. In total, 92(49.5%) infants suffered adverse pregnancy outcomes. ③MBG in the first week and MAGE in the fifth week were strongly associated with infant birth weight (b=104.709, P=0.013; b=87.804, P=0.035). ④MBG in the first week of GDM patients and primipara were independent risk factors for primary cesarean delivery (OR=1.728, 95% CI: 1.160-2.573, P=0.007; OR=5.208, 95% CI: 2.677-10.133, P=0.000). MAGE and MBG in the first week of GDM patients were independent risk factors for large or small for gestational age (OR=1.632, 95% CI: 1.137-2.343, P=0.008; OR=1.992, 95% CI: 1.269-3.128, P=0.003). MAGE, MBG in the first week and MAGE in the fifth week of GDM patients were independent risk factors for macrosomia (OR=1.800, 95% CI: 1.107-2.925, P=0.018; OR=1.987, 95% CI: 1.038-3.803, P=0.038; OR=1.885, 95% CI: 1.063-3.341, P=0.030). MAGE in the first week of GDM patients was independent risk factor for neonatal adverse pregnancy outcome (OR=1.452, 95% CI: 1.050-2.008, P=0.024). Conclusions Abnormal glycemic variability in patients with GDM may lead to maternal and neonatal adverse pregnancy outcomes. Therefore, seven times of measurements for glucose levels per day may be not enough for GDM. Monitoring for glycemic variability is also recommended. Key words: Diabetes, gestational; Glycemic variability; Pregnancy outcome; Continuous glucose monitoring system