The Association Of Blood Glucose With Pregnant Outcomes In Patients With Normal OGTT

[BACKGROUND]In women with normal pregnancy, blood glucose presents its unique characteristics with increasing gestational age. as early as the mid-estrogen and progestin.During the first and second trimester, due to increased maternal glucose utilization of fetus and increased renal blood flow and glomerular filtration rate of women, the level of blood glucose decreased with the progress of pregnancy, mainly presenting with lower fasting blood glucose. While during the third trimester, the pruduction of anti-insulin hormones, such as placental lactogen, estrogen and progesterone, cortisol, and placental insulin enzymes, was increasing. In order to maintain normal glucose levels, insulin need be correspondingly increased, present with insulin resistance. After delivery, the secretion of insulin-resistant hormones within the placenta rapidly disappeared, causing hypoglycemia. During pregnancy, due to the existence of physiological insulin resistance, pregnant women presented with varying degrees of impaired glucose tolerance.Gestational diabetes diabetes mellitus (GDM) as an independent type of diabetes, the incidence of GDM is significant differences amongst races, from1%to14%. Prevalence of GDM in the United States was2%-8%. However, Ma et al reported incidence in the Kunming city was11.6%. The hyperglycemia environment during pregnancy was associated with not only the increased complications of pregnant women and risk of postpartum type2diabetes, but also the increase risk of complications for newborns and children. The common complications of pregnant women with GDM included pre-eclampsia, premature labor, polyhydramnios, cesarean section and infections, while fetal and neonatal complications contained fetal macrosomia, fetal distress, fetal malformations, neonatal hypoglycemia and newborn hyperbilirubinemia. The effects of GDM on maternal and neonatal complications is closely related to the severity of diabetes, duration of disease and control level of pregnancy blood glucose.The impact of GDM on maternal and fetus have been defined. However, for pregnant women with blood glucose yet reaching the level of GDM diagnosis, the effect of mild hyperglycemia on maternal and fetus remained undefined.To investigate the association of impaired glucose tolerance with pregnant outcome diabetes during pregnancy, from July2000to April2006. the study (Hyperglycemia and Adverse Pregnancy Outcomes,HAPO) sponsored by National Institutes of Health was conducted. HAPO study, from15centers,9countries,25505pregnant women received75g of oral glucose tolerance test (OGTT) between24to32weeks of gestation. Fasting plasma glucose (FPG) and postprandial1h and2h glucose were screened, participants with FPG<5.8mmol/L and postprandial2-hour blood glucose <11.1mmol/L were considered to be normal blood glucose, and a total of23316cases of pregnant women were enrolled. The four primary outcomes were birth weight above the90th percentile for gestational age, primary cesarean delivery, clinical neonatal hypoglycemia, and cord-blood serum C-peptide level above the90th percentile, while Secondary outcomes were premature delivery, shoulder dystocia or birth injury, need for intensive neonatal care, hyperbilirubinemia and preeclampsia. HAPO study indicated strong, continuous associations of maternal glucose levels below those diagnostic of diabetes with increased maternal and fetal complications, and there were no obvious thresholds at which risks increased. Based on HAPO study results, In determining the recommendations for diagnostic thresholds. associations with>90th percentiles of birth weight, cord C-peptide, and percent body were used to select glucose concentrations as potential diagnostic threshold values. Mean values for FPG,1-h, and2-h OGTT plasma glucose concentrations(4.5,7.4, and6.2mmol/l, respectively.) for the entire study cohort should be used as reference. These thresholds are the average glucose values at which odds for birth weight>90th percentile, cord C-peptide>90th percentile, and percent body fat reached1.75times the estimated odds ofthese outcomes at mean glucose values. Hence, the diagnostic thresholds of GDM were defined as FPG>5.1mmol/L,1hPG>10.0mmol/L, and2hPG>8.5mmol/L respectively. However, there were still undefined problem. For example, in the HAPO study did not give a specific threshold of elevated blood glucose, and not included pregnant women from mainland China, due to the habits and ethnic factors affecting the development of GDM. Therefore, on the basis of the HAPO study, we further explored the impact of blood glucose on adverse pregnancy outcomes in pregnant women with positvie50g GCT and negative75g OGTT from Guangzhou.[OBJECTIVE]To retrospectively analyse the association of blood glucose with pregnant outcomes and the glucose thresholds for adverse pregnant outcomes in women with normal OGTT from Guangzhou.[METHODS]1. All pregnant women were eligible to participate if they had one or more of the following inclusion criteria:l)between January2005to June2011, prenatal examination and delivery were taken at the Nanfang hospital;2) age greater than18years;3) singleton and first birth;4) gestational age matcted with weeks of gestation;5)50g glucose challenge test (GCT) was takan during24to32weeks of gestation, if1-hPG≥7.8mmol/L,75g OGTT should be carried out within a week, and the OGTT test was of the normal range (FPG<5.1mmol/L and1h PG<10.0mmol/L and2h PG <8.5mmol/L).2. All pregnant women were excluded if they had one or more of the following exclusion criteria:1) age youngter than18years;2) no ultrasonographic estimation between6and24weeks of gestational age;3) inability to complete the OGTT within32weeksof gestation;4) multiple pregnancy and multiple fetus;5) conception by means of gonadotropin ovulation induction or in vitro fertilization;6) diagnosis of diabetes before the current pregnancy;7) no history of liver disease, kidney disease, hypertension, coronary heart disease, connective tissue disease,and polycystic ovarian syndrome;8) no other pregnancy complications.3. We recorded the clinical characterists of women and fetus,including age, body mass index, arterial blood pressure, family history of diabetes, the detection time of the OGTT, OGTT result (fasting,1h and2h glucose value), the mode of delivery, gestational age, pre-eclampsia, intrauterine infection, birth weight, serum bilirubin level,1-minute Apgar score, need for pediatric care treatment.4. The present study analysed the following adverse pregnancy outcomes:1) birth weight above the90th percentile for gestational age;2) pre-eclampsia;3) intrauterine infection;4)1-minute Apgar scores;5) neonatal hyperbilirubinemia;6)need for neonatal care.5. statistical analysisStatistical software SPSS13.0was adopted, the odds ratio (OR) was analysed using logistic regression model for analysis; in all tests, p<0.05was considered statistically significant.[RESULTS]According to the inclusion and exclusion criteria of this study, a total of527pregnant women were enrolled, mean age was28±3.5years, mean FPG was4.4±0.3mmol/L, mean1hPG8.6±1.Ommol/L. mean2hPG7.1±1.0mmol/L.According to the blood glucose level, FPG,1hPG and2hPG were divided into four subgroups respectively, the difference between each sub-group of one standard deviation; for example, FPG:1subgroup≤4.Ommol/L,4.0<2subgroup≤4.3mmol/L4.3<3subgroup≤4.6mmol/L, and4.6<4subgroup≤5.0mmol/L;1hPG:1subgroup≤7.5mmol/L, and7.5<2subgroup≤8.5mmol/L, and8.5<3subgroup≤9.5mmol/L,9.5<4subgroup≤9.9mmol/L;2hPG:1subgroup≤6.Ommol/L, and6.0<2subgroup≤7.0mmol/L, and7.0<3subgroup≤8.0mmol/L, and8.0<4subgroup≤8.4mmol/L.With respect to the birth weight above the90th percentile for gestational age and neonatal hyperbilirubinemia in FPG,1hPG and2hPG, the frequency and OR of both complications were incereased with elevated blood glucose, and their OR values were greater than1with p<0.05. Therefore, elevated blood glucose may be the risk factor of the birth weight above the90th percentile for gestational age and neonatal hyperbilirubinemia.With respect to transfer of neonatal intensive care treatment in FPG and1hPG, the frequency and OR of both complications were incereased with elevated blood glucose, and their OR values were greater than1with p>0.05. Hence, the elevated FPG and1hPG may not be the risk factors for transfer of neonatal intensive care treatment. OR values of the2hPG were less than1with p>0.05, therefore, elevated2hPG may not be the risk factors for transfer of neonatal intensive care treatment.With respect to pre-eclampsia in FPG,1hPG and2hPG, the frequency and OR of this complication were incereased with elevated blood glucose, and their OR values were greater than1with p>0.05. Therefore, blood glucose may not be the risk factor of the pre-eclampsia.With respect to intrauterine infection under the FPG,1hPG and2hPG, the frequency of this complication was incereased with elevated blood glucose, most of the OR were less than1amd p value was more than0.05. Therefore, elevated blood glucose may not be the risk factor of intrauterine infection.With respect to1minutes Agpar score<8under the FPG,1hPG and2hPG, the frequency of this complication was not linearly incereased with elevated blood glucose, and all p values were more than0.05. Therefore, elevated blood glucose may not be the risk factor of1minutes Agpar score<8. With respect to the birth weight above the90th percentile for gestational age, the lower limit of95%confidence interval of OR in the1st,2nd and3rd subgroups of FBG,1hPG and2hPG were less than1with p>0.05, the counterpart of the4th subgroup were greater than1with p<0.05. Therefore, FPG>4.6mmol/L,1hPG>9.5mmol/L and2hPG>8.0mmol/L may be the threshold for this complication.With respect to hyperbilirubinemia. the lower limit of95%confidence interval of OR in the1st and2nd subgroups of FBG and1hPG were less than1with p>0.05, the counterpart of the3rd and4th subgroups were greater than1with p<0.05. Therefore, FPG>4.3mmol/L,1hPG>5.5mmol/L may be the threshold for this complication. Meanwhile, the lower limit of95%confidence interval of OR in the1st,2nd and3rd subgroups of2hPG were less than1with p>0.05, the counterpart of the4th subgroup were greater than1with p<0.05. Therefore,2hPG>8.0mmol/L may be the threshold for this complication.With respect to transfer of neonatal intensive care treatment, the lower limit of95%confidence interval of OR in the1st,2nd and3rd subgroups of FBG and1hPG were less than1with p>0.05, the counterpart of the4th subgroup were greater than1with p<0.05. Therefore, FPG>4.6mmol/L and1hPG>9.5mmol/L may be the threshold for this complication.With respect to pre-eclampsia, intrauterine infection and1minute Agpar score <8, all the lower limit of95%confidence interval of OR were less than1with p>0.05, Therefore, the thresholds for these complication remained undefined.[CONCLUSION]1.For pregnant women with positive50g GCT and negative75g OGTT from Guangzhou, increased FPG,1hPG and2hPG may be the risk factors of the birth weight above the90th percentile for gestational age and neonatal hyperbilirubinemia.2. For pregnant women with positive50g GCT and negative75g OGTT from Guangzhou, increased FPG,1hPG and2hPG may not be the risk factors of the pre-eclampsia, intrauterine infection,1-minute Apgar scores<8and need for neonatal care.3. For pregnant women with positive50g GCT and negative75g OGTT from Guangzhou, the glucose thresholds for the birth weight above the90th percentile for gestational age may be FPG>4.6mmol/L.1hPG>9.5mmol/L and2hPG>8.0mmol/L, respectively.4. For pregnant women with positive50g GCT and negative75g OGTT from Guangzhou, the glucose thresholds for neonatal hyperbilirubinemia may be FPG>4.3mmol/L.1hPG>8.5mmol/L and2hPG>8.0mmol/L. respectively.5. For pregnant women with positive50g GCT and negative75g OGTT from Guangzhou, the glucose thresholds for need for neonatal intensive care may be FPG>4.6mmol/L and1hPG>9.5mmol/L, respectively.