Maternal Glucose Values Research Articles

Maternal Glycemia During Pregnancy and Early Offspring Development: A Prospective Birth Cohort Study.

The association of maternal gestational diabetes mellitus (GDM) with neurodevelopmental outcomes remains controversial and evidence that maternal increasing levels of glucose during pregnancy associated with the risk for impaired neurodevelopment were limited. To identify the continuous association of increasing maternal glucose levels with neurodevelopmental disorders in offspring and explore the potential contribution of cord metabolites to this association. The prospective birth cohort study included 1036 mother-child pairs. Primary predictors were maternal exposure GDM and maternal glucose values at a 75-g oral-glucose-tolerance test at 24 to 28 weeks during pregnancy. Primary neurodevelopmental outcomes at 12 months in offspring were assessed by the Ages and Stages Questionnaires, Third Edition (ASQ-3). Maternal GDM was associated with failing the communication domain in offspring in the adjusted models [relative risk (RR) with 95% CI: 1.97 (1.11, 3.52)]. Increasing levels of fasting plasma glucose (FPG), 1-h plasma glucose (1-h PG) and 2-h plasma glucose (2-h PG) with 1 SD change were at higher risks in failing the personal social domain of ASQ-3 [RRs with 95% CI for FPG: 1.49 (1.09, 2.04); for 1-h PG: 1.70 (1.27, 2.29); for 2-h PG: 1.36 (1.01, 1.84)]. The linear association was also demonstrated. Compared with girls, boys exposed to higher maternal glucose levels were inclined to the failure of the personal social domain. Mediation analysis showed the contribution of maternal GDM to failure of communication domain mediated by C-peptide. Maternal glucose levels below those diagnostic of diabetes are continuously associated with impaired neurodevelopment in offspring at 12 months.

Association of glucose metabolism and blood pressure during pregnancy with subsequent maternal blood pressure.

The goal of this study was to examine associations of measures of maternal glucose metabolism and blood pressure during pregnancy with blood pressure at follow up in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. The HAPO Follow-Up Study included 4747 women who had a 75-g oral glucose tolerance test (OGTT) at ~28 weeks’ gestation. Of these, 4572 women who did not have chronic hypertension during their pregnancy or other excluding factors, had blood pressure evaluation 10–14 years after the birth of their HAPO child. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP) and hypertension (SBP ≥140 and/or DBP≥90 or treatment for hypertension) at follow-up.Blood pressure during pregnancy was associated with all blood pressure outcomes at follow-up independent of glucose and insulin sensitivity during pregnancy. The sum of glucose z-scores was associated with blood pressure outcomes at follow-up but associations were attenuated in models that included pregnancy blood pressure measures. Associations with SBP were significant in adjusted models, while associations with DBP and hypertension were not. Insulin sensitivity during pregnancy was associated with all blood pressure outcomes at follow-up, and although attenuated after adjustments, remained statistically significant (hypertension OR 0.79, 95%CI 0.68– 0.92; SBP beta −0.91, 95% CI −1.34– −0.49; DBP beta −0.50, 95% CI −0.81– −0.19).In conclusion, maternal glucose values at the pregnancy OGTT were not independently associated with maternal blood pressure outcomes 10–14 years postpartum; however, insulin sensitivity during pregnancy was associated independent of blood pressure, BMI and other covariates measured during pregnancy.

476: Hyperglycemia and adverse pregnancy outcomes in twins: do the HAPO findings apply to twin pregnancies?

In 2008, the HAPO study demonstrated in singleton pregnancies that maternal hyperglycemia, even less severe than in diabetes, was associated with adverse pregnancy outcomes. Our objective was to determine if hyperglycemia in twin pregnancies without gestational diabetes mellitus (GDM) is associated with an increased risk of adverse pregnancy outcomes. Retrospective cohort study of twin pregnancies in a single MFM practice between 2005 and 2019 who underwent two-step GDM screening at 24-28 weeks. We excluded women with pregestational or gestational diabetes. We examined the association between maternal glycemia and adverse pregnancy outcomes. Glycemia was defined as the 1-hour GCT in all women, and each of the four values of the 3-hour GTT in women who failed the GCT (≥130 mg/dL). Primary outcomes were preeclampsia, cesarean delivery, and neonatal hypoglycemia in either twin. Statistical tests used included Pearson correlation, Student’s t-test, chi-square for trend, and linear regression. 847 women underwent a GCT and 246 women underwent a GTT. Increasing maternal glucose levels had no positive association with adverse outcomes. Women with preeclampsia, cesarean delivery, and neonatal hypoglycemia did not have higher mean GCT or GTT values than women without these outcomes. On Pearson correlation, none of the GCT or GTT values were associated with adverse outcomes, aside from a negative correlation between the fasting GTT value and neonatal hypoglycemia. There was no increased risk of adverse outcomes with increasing quartiles of the GCT or GTT values (figure). Increasing fasting GTT was negatively associated with neonatal hypoglycemia. In women with twin pregnancies without GDM, increasing maternal glucose levels are not associated with adverse outcomes. In contrast, increased maternal glucose values may be associated with a decreased risk of neonatal hypoglycemia. This suggests that the diagnosis and treatment of GDM in twin pregnancies need to be revisited, as the recommendations come from data in singleton pregnancies which may not be applicable to twins.

409: Novel maternal glycemic indices during labor and the risk of significant neonatal hypoglycemia in T1DM

While it is well accepted that glycemic control during pregnancy is important in order to reduce the risk for maternal and neonatal complications, the optimal management of blood glucose levels during labor and delivery is still a matter of controversy. This is especially true among women with type I diabetes mellitus (T1DM). Thus, the aim of our study was to determine if there is an association between maternal glucose control indices during labor and neonatal hypoglycemia. A historical prospective study pertaining 37 women with T1DM managed during pregnancy and delivery with an insulin pump and continuous glucose monitoring. Data regarding maternal glucose levels during active labor, pregnancy and neonatal outcome were collected. The relationship between maternal glucose control indices during active labor and neonatal hypoglycemia requiring IV glucose treatment was determined. The prevalence of neonatal hypoglycemia requiring IV dextrose was 40.5% (15/37). Maternal glucose variability indices during active labor were higher in mothers of neonates requiring IV dextrose than in mothers of neonates not requiring IV intervention (glucose standard deviation 25.5±13 vs. 14.7±6.7 mg/dL, respectively, p=0.007; maternal glucose IQR 37.3±24.3 vs. 21.6±10.7 mg/dl, respectively, p=0.03). For every 1 unit (1 mg/dl) increase in maternal glucose SD there was a 1.12 (CI 1.03-1.23, p= 0.01) greater odds for neonatal hypoglycemia requiring IV glucose treatment. This relationship persisted after adjustment for maternal age, pregestational BMI, gestational age at delivery, birth weight, and neonatal gender. In addition, maternal maximal glucose values were higher among infants requiring IV glucose (162.8±48.9 vs. 131.3±29.5 mg/dl respectively, p=0.03). Finally, there was a negative correlation between maternal maximum glucose value and neonatal lowest glucose value (p= 0.03, r= -0.34). Nonetheless, the mean and minimum maternal glucose values were not significantly different. To the best of our knowledge this is the first study to determent the association between intrapartum glucose variability indices and neonatal hypoglycemia in parturient with T1DM. There is a relationship between maternal glucose variability and excursions during active labor and risk for neonatal hypoglycemia requiring IV glucose treatment. These results highlight the clinical importance of tight glycemic control during labor in patients with T1DM.

Changing perspectives in pre-existing diabetes and obesity in pregnancy: maternal and infant short- and long-term outcomes.

Climbing obesity rates in women have propelled the increasing prevalence of type 2 diabetes mellitus (T2DM) in pregnancy, and an increasing number of women with type 1 diabetes mellitus (T1DM) are also affected by obesity. Increasing recognition that an intrauterine environment characterized by obesity, insulin resistance, nutrient excess, and diabetes may be fueling the obesity epidemic in children has created enormous pressure to re-examine the conventional wisdom of our current approaches. Compelling data in pregnancies complicated by diabetes, in particular those accompanied by insulin resistance and obesity, support a fetal programming effect resulting in increased susceptibility to metabolic disease for the offspring later in life. Recent data also underscore the contribution of obesity, lipids, and lesser degrees of hyperglycemia on fetal fat accretion, challenging the wisdom of current gestational weight gain recommendations with and without diabetes. The risks of adverse pregnancy outcomes in T2DM are at least as high as in T1DM and there remains controversy about the ideal glucose treatment targets, the benefit of different insulin analogues, and the role of continuous glucose monitoring in T1DM and T2DM. It has become unmistakably evident that achieving optimal outcomes in mothers with diabetes is clearly impacted by ideal glycemic control but goes far beyond it. The intrauterine metabolic environment seems to have long-term implications on the future health of the offspring so that the effectiveness of our current approaches can no longer be simply measured by whether or not maternal glucose values are at goal.

Cognitive Function in Adult Offspring of Women with Gestational Diabetes–The Role of Glucose and Other Factors

ObjectiveWe aimed to evaluate cognitive function in adult offspring of women with diet-treated gestational diabetes and to study potential associations with maternal glucose values.Materials and MethodsIn 2003–2005 cognitive function was assessed in a cohort of 18–27 year old offspring of women with diet-treated gestational diabetes mellitus (n = 153) and offspring from the background population (n = 118). The main outcome measure was global cognitive score derived from Raven’s Progressive Matrices and three verbal subtests from the Weschler Adult Intelligence Scale. Maternal fasting- and 2-hour blood glucose values from the diagnostic oral glucose tolerance test were used as exposure variables.ResultsOffspring of women with gestational diabetes mellitus had a lower global cognitive score, than offspring from the background population (93.1 vs. 100.0, P<0.001). However, when adjusted for maternal age at delivery, parity, smoking during pregnancy, pre-pregnancy overweight, family social class, parental educational level, gender, birth weight, gestational age, perinatal complications and offspring age at follow-up, the difference was no longer statistically significant. Offspring global cognitive score decreased significantly with increasing maternal fasting glucose (β = −4.5, 95% CI −8.0 to −0.9, P = 0.01) and 2-hour glucose (β = −1.5, −2.9 to −0.2, P = 0.03) in univariate general linear models, but not when adjusted for family social class and parental educational level.ConclusionsLower cognitive test scores in adult offspring of women with diet-treated gestational diabetes were explained by well known predictors of cognitive function, but not by maternal hyperglycaemia during pregnancy. We find it reassuring that mild intrauterine hyperglycaemia does not seem to have adverse effect on offspring cognitive function.

Decelerated Early Growth in Infants of Overweight and Obese Mothers

To investigate the relationship between maternal prepregnancy body mass index and early infant growth and body composition. Prospective cohort study performed at a university hospital/surrounding community. Ninety-seven nondiabetic mothers with singleton, term, healthy infants completed study visits at 2 weeks and 3 months of age. Before pregnancy, 59 mothers were normal weight, 18 were overweight, and 20 were obese. Infant anthropometrics and body composition via air-displacement plethysmography were measured. Infant feeding information and maternal prepregnancy weight were self-reported. Additional data were obtained via self-report and the medical record. Main outcome measures were change in weight, length, fat-free mass, and fat mass from 2 weeks to 3 months of age. Analysis was done via multivariate linear regression. At 2 weeks, anthropometrics and body composition did not differ across maternal body mass index groups. At 3 months, infants of overweight or obese mothers had gained less weight (P = .02), grew less in length (P = .01), and gained less fat mass (P = .01). Adjustment for breastfeeding status and regression to the mean via conditional change variables did not alter the results. The results were not altered after adjusting for maternal glucose values from a 50-g glucose challenge and for maternal smoking in a subset including 80% of the women. Maternal overweight/obesity is associated with early deceleration in linear growth and adipose tissue accrual; replication of these findings is needed.

Determinants of birth weight in boys and girls

AbstractBoys are heavier at birth than girls, but girls have higher fat mass at birth than boys. Insulin action may play an important role of this different distribution. Animal models have shown that female offspring are more sensitive to maternal feeding and glucose values during pregnancy and weaning than male offspring. Newborn girls have higher insulin and proinsulin concentrations and total proinsulin‐to‐insulin ratios in cord blood than boys, despite lighter birth weight. In a cohort of 522 newborn above 37 gestational weeks we split between the sexes and studied associations between birth weights, parental anthropometrics and fasting maternal plasma glucose and insulin levels. Boys weighed 184g more than girls, they were 1.1 cm longer and head circumference differed by 0.86 (all p values &lt;0.01). Multiple linear regressions showed that parity, maternal body mass index, gestational age and maternal birth weight were associated with birth weight for both sexes, whereas maternal weight gain in pregnancy and maternal fasting plasma glucose at week 30‐32 were significantly associated with birth weight for girls only. The effect of fasting plasma glucose on birth weight in girls was twice as high as in boys (B=162, 95% CI 33.4‐291, p=0.01). Paternal birth weight was significantly associated with birth weight of boys, but no such association was seen for girls. This supports the notion that there is a genetic regulation along the male line. Girls may be more sensitive to intrauterine environment and maternal glucose values, as these have a stronger influence on birth weight of girls.

Maternal Lipids as Strong Determinants of Fetal Environment and Growth in Pregnancies With Gestational Diabetes Mellitus

OBJECTIVE—To determine the contribution of maternal glucose and lipids to intrauterine metabolic environment and fetal growth in pregnancies with gestational diabetes mellitus (GDM).RESEARCH DESIGN AND METHODS—In 150 pregnancies, serum triglycerides (TGs), cholesterol, free fatty acids (FFAs), glycerol, insulin, and glucose were determined in maternal serum and cord blood during the 3rd trimester. Maternal glucose values came from oral glucose tolerance testing and glucose profiles. Measurements of fetal abdominal circumference (AC) were performed simultaneously with maternal blood sampling and birth weight, and BMI and neonatal fat mass were obtained following delivery.RESULTS—Maternal TGs and FFAs correlated with fetal AC size (at 28 weeks: triglycerides, P = 0.001; FFAs, P = 0.02), and at delivery they correlated with all neonatal anthropometric measures (FFA: birth weight, P = 0.002; BMI, P = 0.001; fat mass, P = 0.01). After adjustment for confounding variables, maternal FFAs and TGs at delivery remained the only parameters independently related to newborns large for gestational age (LGA) (P = 0.008 and P = 0.04, respectively). Maternal FFA levels were higher in mothers with LGA newborns than in those with appropriate for gestational age (AGA) newborns (362.8 ± 101.7 vs. 252.4 ± 10.1, P = 0.002). Maternal levels of TGs, FFAs, and glycerol at delivery correlated with those in cord blood (P = 0.003, P = 0.004, and P = 0.005, respectively). Fetal triglyceride and cholesterol levels were negatively correlated with newborn birth weight (P = 0.001), BMI (P = 0.004), and fat mass (P = 0.001). TGs were significantly higher in small for gestational age (SGA) newborns compared with AGA or LGA newborns, while insulin-to-glucose ratio and FFAs were the highest in LGA newborns.CONCLUSIONS—In well-controlled GDM pregnancies, maternal lipids are strong predictors for fetal lipids and fetal growth. Infants with abnormal growth seem to be exposed to a distinct intrauterine environment compared with those with appropriate growth.

What proportion of birth weight is attributable to maternal glucose among infants of diabetic women?

This study was undertaken to determine the proportion of birth weight attributable to glucose concentrations of diabetic mothers. Data of diabetic women who used insulin were eligible for analysis if the women had been treated during pregnancy for at least 12 weeks, and had recorded at least 50% of 4 daily glucose checks (fasting and 1-hour postprandial) until the last office visit before delivery. The independent association between maternal glucose values and demographics and birth weight percentiles for gestational age and gender were analyzed by multiple regression methods. Data of 90 diabetic women were analyzed. Only third-trimester glucose concentrations were associated with birth weight. Prepregnancy body mass index was also selected in the models, including second- and/or third-trimester glucose. Together, these variables explained 18% of the variance in birth weight percentiles. Maternal glycemia during third-trimester and prepregnancy body mass index are independent predictors of birth weight in pregnancies complicated by insulin-requiring gestational or type 2 diabetes.

Maternal obesity not maternal glucose values correlates best with high rates of fetal macrosomia in pregnancies complicated by gestational diabetes.

The current therapeutic strategies to reduce macrosomia rates in gestational diabetes (GDM) have focused on the normalizing of maternal glucose levels. The aim of our study was 1.) to compare maternal glycemic values with the presence of fetal macrosomia at different gestational ages (GA) and with LGA at birth in a cohort of women with glucose intolerance and standard diabetic therapy. 306 women with GDM and 97 with impaired glucose tolerance underwent ultrasound examinations at entry and, after initiation of therapy, monthly in addition to standard diabetic therapy. Measurements from the entry diagnostic oGTT, glucose profile and HbA1c and from subsequent glucose profiles obtained within 3 days of the ultrasound at 5 categories of GA age (20-23, 24-27 etc) were retrospectively compared between pregnancies with and without fetal macrosomia, defined as an abdominal circumference (AC) > or = 90th percentile. Maternal prepregnancy BMI was adjusted for and BMI > or = 30 kg/m2 was defined as obesity. At entry, neither the hourly oGTT values, HbA1c, nor the entry glucose profile differed significantly between pregnancies with and without fetal macrosomia. In a total of 919 pairs of ultrasound/glucose profiles there was no significant difference in glucose levels at every GA category neither in lean nor in obese woman except for the fasting glucose of 32-35 GA. The fetal macrosomia rate in each GA category and the rate of LGA were significantly higher in obese women: e.g. 14.5 vs 28% at diagnosis, 15.7 vs 26.7% at 32-35 weeks, 15.5 vs 25.0% at birth (p < 0.05 for each comparison). The association of maternal glucose values and fetal macrosomia was limited to the fasting glucose values between 32-35 weeks while maternal obesity appeared to be a strong risk factor for macrosomia throughout pregnancies with GDM. In obese women the high fetal macrosomia rate did not appear be normalized by therapy based on maternal euglycemia.

Toward universal criteria for gestational diabetes: The 75-gram glucose tolerance test in pregnancy

OBJECTIVES: The purpose of this study was to determine the distribution of values for the 75 gm glucose tolerance test in pregnancy and to define glucose intolerance by the relationship between maternal glucose values and neonatal macrosomia. STUDY DESIGN: A total 3505 unselected pregnant women were given a 75 gm, 2-hour glucose tolerance test. Diet or insulin therapy was offered only to patients with a fasting plasma glucose level ≥ 105 mg/dl or a 2-hour post-glucose-load value ≥ 200 mg/dl. Birth weights of live-born singletons delivered from 36 to 42 weeks whose mothers had a fasting plasma glucose level < 105 mg/dl and 2-hour post-glucose-load value < 200 mg/dl were used to calculate relationships between glucose levels and birth weights. RESULTS: At 24 to 28 weeks' gestation the mean and SD plasma glucose values were fasting 83.6 (8.9) mg/dl, 1 hour 128.4 (32.9) mg/dl, and 2 hour 108.4 (24.8) mg/dl. In a multiple logistic regression model the factors found to be statistically significantly associated with macrosomia were maternal race, parity, prepregnancy body mass index, weight gain, gestational age at testing, fasting plasma glucose level, and 2-hour post-glucose-load value. A positive association was found between maternal glucose values and birth weight percentiles. No clinically meaningful glucose threshold values relative to birth weight or macrosomia were found. CONCLUSION: In the absence of a meaningful threshold relationship between glucose tolerance test values and clinical outcome, criteria defining gestational diabetes will probably be established by consensus.

Oral Concurrent Session F OB Anesthesia and Pharmacology Medical Complications of Pregnancy

Oral Concurrent Session F OB Anesthesia and Pharmacology Medical Complications of Pregnancy