Fetal Growth In Diabetic Pregnancies Research Articles

In vivo: maternal betaine supplementation normalized fetal growth in diabetic pregnancy.

Diabetes alters maternal metabolism and can lead to aberrant fetal growth. In addition to insulin treatment, nutritional diet interventions are recommended for promoting fetal health against diabetes-induced adverse effects. Therefore, we conducted an in vivo study to investigate betaine efficacy on fetal development against maternal diabetes. Thirty-two dams were divided into four equal groups: control (C), betaine supplementation (BS), diabetic pregnancy (DP) and diabetic pregnancy plus betaine supplementation (DP + BS). Fasting blood sugar (FBS) and body weight (BW) were monitored during pregnancy. After physiological delivery, dams glycated hemoglobin (HbA1c) concentrations were measured, followed by fetal development indices including litter size (LS), neonatal weight (NW) and crown-rump (CR). Also, maternal oxidative status was assessed by evaluating glutathione (GSH) content, glutathione peroxidase (GSH-Px) and catalase (CAT) activities, and malondialdehyde (MDA) concentration in the erythrocytes. Betaine supplementation significantly alleviated FBS and tended to recover BW loss. It also significantly decreased HbA1c values in dams of DP + BS compared to DP group. Normalized fetal indices such as LS, NW and CR under betaine supplementation were associated with a significant increase in GSH content and GSH-Px activity, as well as decreased MDA concentrations in erythrocytes of dams in the DP + BS versus the DP group, indicating improved redox balance in the dams. We indicated for the first time that betaine supplementation improved the maternal glucose metabolism and redox balance associated with normalized fetal growth. Nevertheless, further studies are required to investigate the mechanisms through which betaine protects fetal growth in diabetic pregnancy.

Impact of aspirin on fetal growth in diabetic pregnancies according to White classification

Current US Preventive Services Task Force and other guidelines recommend low-dose aspirin for all pregnant women with pregestational diabetes mellitus to prevent preeclampsia and small-for-gestational-age birth. The Maternal-Fetal Medicine Units High-Risk Aspirin trial did not show a reduction in either preeclampsia or small-for-gestational-age birth in diabetic women. Our objective was to reassess the impact of aspirin on fetal growth in diabetic pregnancies overall and according to White classification. We hypothesized that aspirin improves fetal growth in pregnancies with vascular complications of diabetes at highest risk for poor fetal growth. We conducted secondary analysis of the cohort of diabetic women enrolled in the Maternal-Fetal Medicine Units High-Risk Aspirin trial. The impact of aspirin prophylaxis on birthweight was assessed in the overall cohort and in 2 groups categorized according to White classification as nonvascular (White class B, C, D) or vascular (White class R, F, RF). Birthweight was converted to Z-score normalized for gestational age at delivery and neonatal sex. Difference in birthweight Z-score between aspirin and placebo was tested with a 2-sample t test. The effect of vascular group, aspirin vs placebo randomization, and the interaction of the 2 on normalized birthweight percentile was estimated with linear regression with a multivariable model including covariates body mass index, tobacco use, race, and parity. The percentage of small and large-for-gestational-age newborns born to aspirin- vs placebo-treated women was compared between groups using Pearson exact χ2 analysis, and an adjusted model was estimated by logistic regression. All 444 women with pregestational diabetes and complete outcome data were included (53 vascular, 391 nonvascular). Aspirin was significantly associated with a higher birthweight Z-score (0.283; 95% confidence interval, 0.023-0.544) in the overall cohort (P=.03). In the adjusted model, the association of aspirin with higher birthweight Z-score was confined to neonates of women with nonvascular diabetes (0.341; 95% confidence interval, 0.677-0.006; P= .044). An opposite but nonsignificant effect was observed among neonates from women with vascular diabetes (-0.416; 95% confidence interval, -1.335 to 0.503; P= .6). This difference in the relationship of aspirin and birthweight Z-score by vascular group was significant at P= .046. Aspirin-randomized women with nonvascular diabetes had more large-for-gestational-age births than those treated with placebo (40.2 vs 26.6%; P= .005). Small-for-gestational-age births occurred at the same frequency with aspirin vs placebo randomization in the overall cohort (8% in each group) and in each vascular group. Inconsistent with our hypothesis, aspirin did not reduce small-for-gestational-age births in the overall cohort or either group. The increased incidence of large-for-gestational-age infants in aspirin-treated diabetic gestations is of potential concern given the known increased maternal and neonatal morbidity associated with macrosomia.

Macrosomia and the IGF System: A Short Review

Introduction: Macrosomia in diabetic pregnancy is an ubiquitous finding and implies both maternal and fetal issues. Its incidence surpasses other critical obstetrical morbidity in diabetic pregnancy with increased placental size and polyhydramnios as comorbidity. The studies on the underlying factors contributing to macrosomia have focused on growth stimuli like IGF, glycemia, and insulin and their effects on regional organ function. IGF-I and –II in maternal serum are associated with birth weight and the bioavailabiliy is modulated by IGF- binding-proteins (IGFBP) and phosporylated isoforms of IGFBP and the presence of proteases and IGF split products. Human placental growth hormone regulates the effect of IGF-I in pregnancy.Methods: The literature on the IGF system′s possible effect on fetal growth in diabetic pregnancy is reviewed before our current studies and updated with respect to later findings. Regulation on bioavailability by proteolysis and phosporylation is described. The review discusses briefly the studies on pregnant women with type 1 diabetes with respect to vasculopathy.Results: The data show good correlation of IGF-1/2 levels with birth weight. No such correlation with IGFBP-1 and -3 is found. Fetal growth deviation in diabetic pregnancy is not uniform. In first trimester, growth delay is documented in fetal growth curves compared to non-diabetic controls. Accordingly, a shift in IGF-IGFBP regulation in second trimester is found with less proteolysis of IGFBPs and relative increase in total binding capacity. In third trimester, free IGF further increases as IGFBP binding decreases by proteolysis and modulation. The first trimester values may be used as predictor of fetal weight at term. Diabetic women show a two- to threefold increase in the in vitro IGFBP-3 proteolytic activity during pregnancy as compared to post-partum values.Conclusions: Prominent proteolysis of binding proteins and the modulation by insulin account for the mechanism leading to macrosomia. The two factors combined guarantee the stimulation by more bioavailable IGF and the glycemic levels reveal whether insulin dose are optimal. Structural factors of diabetes i.e. microangiopathy further modulate the sum of effects on fetal growth. In contrast to macrosomia, fetal growth restriction is associated with prominent maternal vascular endothelial complications, such as overt nephropathy, proliferative retinopathy, preeclampsia, and hypertension. In parallel to the growth inhibition, stimulatory effects are exerted by the GH axis including the placental growth hormones and occur probably as compensatory mechanism, similar to the increased IGFBP-3 proteolysis in late pregnancy found in growth retardation. This influence may in part explain the disproportionate growth in different tissue components occurring in the various stages of diabetic pregnancy.

495: Impact of low-dose aspirin on fetal growth in diabetic pregnancies: the importance of white classification

495: Impact of low-dose aspirin on fetal growth in diabetic pregnancies: the importance of white classification

Fetal growth profiles of macrosomic and non‐macrosomic infants of women with pregestational or gestational diabetes

To assess fetal growth profiles in an unselected group of pregnant women with either type-1 diabetes (DM1), type-2 diabetes (DM2) or gestational diabetes (GDM), with emphasis on intergroup differences and development of disproportionate fetal growth and macrosomia. Second- and third-trimester longitudinal ultrasound measurements of fetal growth were made in 77 women with DM1, 68 women with DM2 and in 99 women with GDM. Altogether 897 ultrasound examinations were performed and 145 uncomplicated pregnancies with 843 ultrasound examinations were included as controls. Ultrasound data included head circumference (HC), abdominal circumference (AC), femur length (FL) and HC/AC ratio. The AC, but not HC and FL, evolved differently in diabetic pregnancies, with a smaller AC in early pregnancy and larger AC at term (significant for DM1 and DM2). The most striking differences were found for the HC/AC ratio, especially in DM1 pregnancies. HC/AC growth trajectories of both macrosomic and non-macrosomic fetuses differed from that of the controls, and the HC/AC ratio at term was lower in all diabetic subgroups except in non-macrosomic DM2 cases. We found altered (disproportionate) fetal growth in macrosomic and non-macrosomic fetuses of women with DM1, DM2 and GDM. This indicates that the abnormal intrauterine environment affects the majority of these infants. Growth profiles differed among these groups, the most prominent growth deviations being found in the fetuses of women with DM1. The latter was most probably caused by poor glucose control. In monitoring fetal growth in diabetic pregnancies the HC/AC ratio should be used to assess altered fetal growth.

Population Standards of Birth Weight Underestimate Fetal Growth Abnormalities in Diabetic Pregnancies

The objective of this study was to compare the frequency of abnormal fetal growth in women with diabetes mellitus (DM) using population-based birth weight (pop BW) percentiles compared with customized birth weight (cust BW) percentiles, which include adjustments for maternal race, parity, height, weight, and fetal sex. The study design comprised a retrospective cohort of singleton DM pregnancies delivered over a 1-year period (June 2007 to May 2008) from a single tertiary care university-based medical center. Inclusion criteria were gestational age >20 weeks at delivery, live birth, and absence of major chromosomal/structural abnormalities. Small for gestational age (SGA), <10th percentile, and large for gestational age (LGA), >90th percentile pregnancies were categorized based on pop BW or cust BW standards. There were significant differences in the rates of SGA (p < 0.004) and LGA (p < 0.001) between cust BW and pop BW methods. When comparing the two methods, pop BW did not identify 13/16 (81%) of SGA and 23/39 (59%) of LGA babies defined by cust BW methods. The use of cust BW calculation in a diabetic population identified a greater percentage of neonates with pathologic fetal growth compared with pop BW standards, suggesting that the population standard may underdiagnose abnormal fetal growth in diabetic pregnancies.

Maternal endothelial dysfunction and its association with abnormal fetal growth in diabetic pregnancy

Some authors consider the vascular endothelium to be a target organ in diabetes. However, there have only been a few studies of the function of the maternal endothelium during pregnancy in women with diabetes. We analysed the relationship between maternal vascular endothelial dysfunction and fetal growth in such pregnancies. Markers of endothelial dysfunction (serum concentration of sE-selectin and sVCAM-1) were measured at admission (baseline) and before delivery in 97 women with pregestational diabetes and a singleton pregnancy,. After delivery, the group with pregestational diabetes was divided retrospectively according to neonatal birthweight into three groups-appropriate, small and large for gestational age- and the maternal variables were analysed in relation to birthweight. The baseline concentration of sE-selectin was significantly higher in the large-for-gestational-age group vs. the small-for-gestational-age group (median: 53.1 vs. 39.0 ng/ml, P<0.05). The concentration of sVCAM-1 at baseline was significantly higher in the small-for-gestational-age vs. the appropriate- and large-for-gestational-age groups (median: 846.2 vs. 576.8 and 524.1 ng/ml, respectively; P<0.01 and P<0.001, respectively). The concentration of sE-selectin at baseline and gestational changes in the concentration of sVCAM-1 were related to birthweight. The baseline concentrations of sE-selectin and sVCAM-1 and the gestational change in sVCAM-1 concentration were predictive factors for large for gestational age (cut-off values: 45.0, 644.6 and 38.4 ng/ml; sensitivity: 67.7, 89.3 and 34.4%; specificity: 65.5, 39.7 and 85.5%, respectively). Our study showed a relationship between maternal endothelial dysfunction and fetal growth disturbances during pregnancy in women with diabetes that was not associated with maternal metabolic control. Higher levels of maternal sE-selectin in early pregnancy were associated with increased risk of the large-for-gestational-age condition. High levels of maternal sVCAM-1 in early pregnancy were characteristic of gestation complicated by the small-for-gestational-age condition. Further studies in larger groups are warranted to determine whether markers of maternal endothelial dysfunction are of use in the prediction of abnormal birthweight (large or small for gestational age) in pregnant women with diabetes.

Are birth weight predictors in diabetic pregnancy the same in boys and girls?

Objectives To study the predictors of abnormal fetal growth in diabetic pregnancy, analyzing the role of fetal sex. Study design Observational retrospective study was carried out in a University hospital. We studied 2833 newborns of diabetic mothers who attended the Diabetes and Pregnancy Clinic and delivered in the center between 1/1/1982 and 31/12/2006 (2370 born to women with gestational diabetes mellitus, 391 to women with type 1 diabetes mellitus (DM), and 72 to women with type 2 DM). Logistic regression analyses were performed with a backward method to predict large for gestational age (LGA), small for gestational age (SGA) and macrosomic newborns using relevant variables and their interaction with fetal sex. We have used as potential predictors of abnormal birth weight: maternal prepregnancy age, weight, height and body mass index, prior pregnancy, prior macrosomia, smoking habit, weight increase during pregnancy, hypertension, gestational age at delivery, twin pregnancy, fetal sex, diabetes type, third trimester HbA1c and interaction of fetal sex with all these variables. Results Variables predictive of LGA, SGA and macrosomia were as formerly described. Moreover, some predictors of abnormal growth displayed an interaction with fetal sex. In LGA prediction, male sex displayed a positive interaction with delivery week, prior gestation, diabetes type and twin pregnancy and a negative one with weight increase. In SGA prediction, male sex displayed a positive interaction with delivery week and diabetes type. In macrosomia prediction, male sex displayed a negative interaction with weight increase. Conclusions In this cohort of diabetic pregnancies, some predictors of abnormal birth weight display interaction with fetal sex. In general, associations were more favorable to female fetuses.

266: Fetal growth in diabetic pregnancy: role of insulin like growth factor 1 and its binding protein IGF BP3

266: Fetal growth in diabetic pregnancy: role of insulin like growth factor 1 and its binding protein IGF BP3

267: Fetal growth in diabetic pregnancy: significant role of placental growth hormone

Placental growth hormone (PGH) is the main growth hormone in pregnancy. It was thought to be only found in maternal serum and to act mainly through its actions on Insulin Like Growth Factor 1 (IGF1). The aim of this study was to investigate the action of PGH in nondiabetic compared to Type 1 Diabetic (T1DM) pregnancies.

649 Can fetal growth in diabetic pregnancy be predicted?

649 Can fetal growth in diabetic pregnancy be predicted?

WS17‐11Amniotic fluid erythropoietin concentration and cerebro‐umbilical Doppler flow ratio in diabetic pregnancies and pregnancies complicated by hypertension, pre‐eclampsia or/and intrauterine growth restriction

Subacute or chronic fetal hypoxia is associated with an increase in fetal erythropoietin (EPO) synthesis irrespective of the etiology of hypoxia. Amniotic fluid (AF) EPO level is often elevated in diabetic pregnancies (especially in macrosomic fetuses), and in pregnancies complicated by hypertension (HT), pre‐eclampsia (PE) or/and intrauterine growth restriction (IUGR). It is shown that cerebro‐umbilical arterial flow ratio (RIC/RIU) is often abnormal (less than 1) in the case of fetal hypoxia. We studied AF EPO levels in 29 diabetic pregnancies, 18 pregnancies with HT, PE or/and IUGR and 19 healthy controls. The samples were obtained during the elective amniocenteses in the case of suspected fetal hypoxia or during caesarean sections. Doppler measurements were performed not more than 24 h before amniocenesis. AF EPO levels were significantly elevated in diabetics with abnormal fetal growth (either macrosomia or IUGR) and nondiabetics with HT, PE or/and IUGR as compared with healthy controls or diabetics with normal fetal growth. AF EPO levels of fetuses with normal fetal growth in diabetic mothers were not different from those of healthy controls. There was no correlation between AF EPO levels and RIC/RIU in any of the diabetic or nondiabetic group. However, 5 fetuses had either absent end‐diastolic or reversed umbilical flow. All had elevated AF EPO levels (range 16–15 800 mU/ml). We conclude that both fetal macrosomia and IUGR in diabetic pregnancies seem to cause chronic fetal hypoxia. Normal fetal growth in diabetic pregnancies is not associated with chronic fetal hypoxia. Single measurement of RIC/RIU is of little value in the diagnosis of chronic fetal hypoxia in abnormal pregnancies.

Early delay in fetal growth in diabetic pregnancies

Early delay in fetal growth in diabetic pregnancies

Fetal growth in diabetic pregnancy.

In summary, fetal macrosomia occurs in almost one third of diabetic pregnancies regardless of class. Abnormal fetal fat stores lead to difficult labor, dystocia, and birth injury as well as postnatal metabolic transition. The abnormal body fat distribution at birth may destine some of these infants to lifelong obesity. Abnormal fetal growth in diabetic pregnancy appears to occur with any elevations in maternal glucose levels, however modest. Detection of macrosomia is therefore a major goal of diabetic pregnancy management.

159 Assessment of Early Fetal Growth in Diabetic Pregnancies by Vaginal Sonography

159 Assessment of Early Fetal Growth in Diabetic Pregnancies by Vaginal Sonography

AMINOCUANIDINE IMPROVES FETAL GROWTH IN STREPTOZOTOCIN-INDUCED MATERNAL DIABETES

When streptozotocin-induced diabetes is produced early in gestation in rats, fetal growth is markedly compromised Cross-linking of proteins is increased in the diabetic, due to formation of advanced non-enzymatic glycosylation products (AGP) Aminoguanidine (A), a nucleophilic hydrazine compound, prevents formation of AGP and cross-linking of arterial proteins in vivo in diabetic rats. We administered aminoguanidine (25 rag/Kg IP) daily to control and diabetic rats from day 5 of gestation to sacrifice on day 21. Aminoguanidine produces increased fetal growth in diabetic pregnancies, while slightly retarding fetal growth in controls. Increased placental size in diabetic pregnancies is unaffected by aminoguanidine. These data suggest that reduced fetal growth in diabetic pregnancies may result from non-enzymatic glycosylation.