Pregnancy Gestational Diabetes Research Articles

Adipokines, insulin resistance in early pregnancy and risk for gestational diabetes

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Does behavioral intervention in pregnancy reduce postpartum weight retention? Twelve-month outcomes of the Fit for Delivery randomized trial

Excessive weight gain during pregnancy is a risk factor for postpartum weight retention and future weight gain and obesity. Whether a behavioral intervention in pregnancy can reduce long-term weight retention is unknown. This randomized trial tested whether a low-intensity behavioral intervention to prevent excessive gestational weight gain could increase the proportion of women who returned to prepregnancy weight by 12 mo postpartum. Women (n = 401, 13.5 wk of gestation, 50% normal weight, 50% overweight/obese) were randomly assigned into an intervention or control group; 79% completed the 12-mo assessment. The telephone-based intervention targeted gestational weight gain, healthy eating, and exercise and was discontinued at delivery. In modified intent-to-treat analyses that excluded women with miscarriages (n = 6), gestational diabetes (n = 32), or subsequent pregnancies (n = 32), the intervention had no significant effect on the odds of achieving prepregnancy weight at 12 mo postpartum (n = 331; 35.4% compared with 28.1%; P = 0.18). Completer analyses suggested that the intervention tended to increase the percentages of women who reached prepregnancy weight (n = 261; 45.3% compared with 35.3%; P = 0.09) and significantly reduced the magnitude of mean ± SD postpartum weight retained (1.4 ± 6.3 compared with 3.0 ± 5.7 kg; P = 0.046) at 12 mo. Women in the intervention group reported higher dietary restraint through 6 mo postpartum (P = 0.023) and more frequent self-monitoring of body weight (P < 0.02 for all) throughout the study. A low-intensity behavioral intervention in pregnancy can reduce 12-mo postpartum weight retention and improve dietary restraint and self-weighing in study completers. Future research is needed to test the long-term effects of more intensive behavioral interventions in pregnancy. This trial was registered at clinicaltrials.gov as NCT01117961.

Timing of delivery in women with diabetes in pregnancy.

The incidence of both gestational and pre-gestational diabetes is increasing worldwide. The main cause of this increase is likely the concomitant increase in the incidence of global obesity, but in the case of gestational diabetes, changes in the diagnostic criteria are also a contributing factor. The adverse outcomes associated with pre-gestational diabetes are well known and have led clinicians to implement various strategies that include increased fetal surveillance and induction of labour at various gestational ages. In many cases these same strategies have been applied in clinical practice also to women with gestational diabetes despite there being differences in the type and magnitude of perinatal complications associated with this diagnosis. Despite the widespread application of these clinical practices, there is a paucity of quality data in the medical literature to guide the clinician in choosing a strategy for fetal surveillance and timing of delivery in both gestational diabetes and pre-gestational diabetes pregnancies. In the following review, we will discuss the rationale and consequences of planned delivery in gestational diabetes and pre-gestational diabetes, the evidence supporting different strategies for delivery and finally highlight future targets for research in this area.

Circulating Docosahexaenoic Acid Levels Are Associated with Fetal Insulin Sensitivity

BackgroundArachidonic acid (AA; C20∶4 n-6) and docosahexaenoic acid (DHA; C22∶6 n-3) are important long-chain polyunsaturated fatty acids (LC-PUFA) in maintaining pancreatic beta-cell structure and function. Newborns of gestational diabetic mothers are more susceptible to the development of type 2 diabetes in adulthood. It is not known whether low circulating AA or DHA is involved in perinatally “programming” this susceptibility. This study aimed to assess whether circulating concentrations of AA, DHA and other fatty acids are associated with fetal insulin sensitivity or beta-cell function, and whether low circulating concentrations of AA or DHA are involved in compromised fetal insulin sensitivity in gestational diabetic pregnancies.Methods and Principal FindingsIn a prospective singleton pregnancy cohort, maternal (32-35 weeks gestation) and cord plasma fatty acids were assessed in relation to surrogate indicators of fetal insulin sensitivity (cord plasma glucose-to-insulin ratio, proinsulin concentration) and beta-cell function (proinsulin-to-insulin ratio) in 108 mother-newborn pairs. Cord plasma DHA levels (in percentage of total fatty acids) were lower comparing newborns of gestational diabetic (n = 24) vs. non-diabetic pregnancies (2.9% vs. 3.5%, P = 0.01). Adjusting for gestational age at blood sampling, lower cord plasma DHA levels were associated with lower fetal insulin sensitivity (lower glucose-to-insulin ratio, r = 0.20, P = 0.036; higher proinsulin concentration, r = −0.37, P <0.0001). The associations remained after adjustment for maternal and newborn characteristics. Cord plasma saturated fatty acids C18∶0 and C20∶0 were negatively correlated with fetal insulin sensitivity, but their levels were not different between gestational diabetic and non-diabetic pregnancies. Cord plasma AA levels were not correlated with fetal insulin sensitivity.ConclusionLow circulating DHA levels are associated with compromised fetal insulin sensitivity, and may be involved in perinatally “programming” the susceptibility to type 2 diabetes in the offspring of gestational diabetic mothers.

Gestational Diabetes: Risk Factors, Perinatal Complications and Screening Importance in Niger Delta Region of Nigeria: A Public Health Dilemma

Aim: The study identified the incidence of undiagnosed gestational diabetes and its consequences on maternal/neonatal mortality and highlighted screening importance in an African urban setting in the Niger Delta region in Nigeria. Study Design: Randomised study. Place and Duration of Study: Pregnant women attending antenatal clinics in one tertiary, six primary, six secondary, hospitals, and six maternity homes in the Niger delta area of Nigeria between May 2006 to May 2009. Method: A total of 1920 pregnant women were recruited into the study. While 956 received the oral glucose test and formed the study group, 964 declined from continuing in the study, and formed the control group. Results: Women with gestational diabetes were at increased risk for premature rupture of membranes, preterm birth; breech presentation and high birth weight adjusting for maternal age. Conclusion: The presence of gestational diabetes in pregnancy is predictive of poor pregnancy outcome as it remains undetected in conception resulting in unto wards maternal/neonatal complications.

Womenʼs experience of diabetes and diabetes management in pregnancy: a systematic review of qualitative literature

Review question/objective The objective of this review is to synthesise the best available evidence on the experience of diabetes and diabetes management among pregnant women, and how these experiences relate to their understanding of their condition and adherence to treatment regimes Inclusion Criteria Types of participants This review will consider studies that include pregnant women who have pre-existing diabetes mellitus (Type 1 or Type 2 diabetes) or gestational diabetes mellitus. Phenomena of interest This review will consider studies that explore experience among women with pre-existing or gestational diabetes in pregnancy, and their experiences of adhering (or not) to prescribed treatment regimes.

Maternal Vitamin D Deficiency in Early Pregnancy Is Not Associated with Gestational Diabetes Mellitus Development or Pregnancy Outcomes in Korean Pregnant Women in a Prospective Study

The association between vitamin D deficiency in the first trimester and GDM development remains controversial in various ethnicities. We prospectively assessed whether pregnant women with vitamin D deficiency during early pregnancy had an increased likelihood of GDM development or poor fetal growth or pregnancy outcomes compared to those with sufficient vitamin D levels. Serum 25-OH-D measurements and fetal ultrasonograms were carried out at 12-14, 20-22, and 32-34 wk in 523 pregnant women. Each woman was screened for GDM at 24-28 wk. There were no differences in serum 25-OH-D levels at 12-14 wk or 22-24 wk of pregnancy between GDM and non-GDM women after adjusting for maternal age, BMI at prepregnancy, BMI at first visit, BMI at GDM screening, gestational age at sampling, previous history of GDM, vitamin D intake, and seasonal variation in sampling. The risk of GDM, insulin resistance, and impaired β-cell function had no association with serum 25-OH-D levels in crude or adjusted logistic regression analysis. GDM was not associated with maternal serum 25-OH-D deficiency during the first trimester or fetal growth during the first and second trimesters. Pregnancy outcomes such as miscarriage, Apgar 1, Apgar 5 and birth weight were independent of maternal serum 25-OH-D levels during the first, second and third trimester of pregnancy. In conclusion, neither GDM prevalence nor fetal growth during pregnancy is associated with vitamin D deficiency at the first trimester in Korean women. Pregnancy outcomes are also independent of maternal vitamin D status.

Predictors of Preeclampsia in Women in the Metformin in Gestational Diabetes(Mig) Study

Background: Gestational Diabetes Mellitus (GDM), maternal obesity and pregnancy weight gain are associated with an increased risk of developing Preeclampsia (PE). The aim of this study was to examine the predictors of PE in women commencing pharmacotherapy for GDM in the Metformin in Gestational diabetes trial.Methods: Descriptive and logistic regression analyses examined the relationship between maternal enrolment characteristics and later development of PE.Results: 46 (6.3%) of 703 women developed PE. At enrolment ((30 (SD3.2) weeks gestation), women who later developed PE had higher HbA1c (6.14% (95% CI 5.84, 6.45) vs. 5.73% (95% CI 5.67, 5.78), P = 0.003), fasting triglycerides (2.93 mmol/L (95% CI 2.57, 3.29) vs. 2.55mmol/L (95% CI 2.47, 2.62), P = 0.03) and blood pressure. Their infants were born 9 days earlier (P < 0.001) but were otherwise not different. In univariate analysis, the strongest positive predictors for PE were Polynesian ethnicity (OR 2.75 (95% CI 1.48, 5.09), P= 0.001), personal or family history of PE (OR 2.65 (95% CI 1.36, 5.16), P=0.004), maternal HbA1c (OR 1.96 (95% CI 1.35, 2.89), P< 0.001), triglycerides (OR 1.45 (95% CI 1.07,1.97), P=0.002), and weight gain from early pregnancy (OR 1.09 (95% CI 1.03,1.17), P=0.01). HDL-C was a negative predictor of PE (OR 0.29 (95% CI 0.09, 0.94), P= 0.04).Following adjustment for Polynesian ethnicity and personal or family history of PE, and when further adjusted for HbA1c or early pregnancy BMI, these variables remained significant.Conclusion: Treatment allocation and BMI were not associated with risk of PE. Personal or family history of PE, Polynesian ethnicity, degree of hyperglycemia, maternal triglycerides and weight gain prior to treatment signal increased risk of subsequent PE in women needing pharmacotherapy for GDM.

Fetal weight estimation in gestational diabetic pregnancies: comparison between conventional and three-dimensional fractional thigh volume methods using gestation-adjusted projection

To evaluate the accuracy of gestation-adjusted birth-weight estimation using a three-dimensional (3D) fractional thigh volume (TVol) method in pregnant women with gestational diabetes mellitus (GDM), and to compare it with the conventional two-dimensional method of Hadlock et al. Pregnant women with GDM were referred at 34 to 36 + 6 weeks' gestation for ultrasound examination. Estimated fetal weight (EFW) was obtained using both the Hadlock and the TVol methods. Using a gestation-adjusted projection method, predicted birth weight was compared to actual birth weight at delivery. Based on 125 pregnancies, the TVol method with gestation-adjusted projection had a mean (± SD) percentage error in estimating birth weight of -0.01 ± 5.0 (95% CI, -0.96 to 0.98)% while the method of Hadlock with gestation-adjusted projection had an error of 1.28 ± 9.1 (95% CI, -0.33 to 2.87)%. The mean percentage error of the two methods was significantly different (P = 0.039), while the random error was not (P = 1.0). For the prediction of macrosomia (birth weight ≥ 4000 g, n = 19), sensitivity was 84 and 63% for the TVol and Hadlock methods, respectively (95% CI for difference -2 to 44%, P = 0.22) and specificity was 96 and 89% for the TVol and Hadlock methods, respectively (95% CI for difference 5-9%, P = 0.01). In women with GDM, a new method of estimating birth weight based on 3D-TVol measurements performed at 34 + 0 to 36 + 6 weeks' gestation and gestation-adjusted projection of estimated fetal weight, is more accurate than the standard method based on Hadlock's formula in predicting birth weight. The TVol method has comparable sensitivity but higher specificity than the Hadlock method in predicting neonatal macrosomia.

Analysis of the effects of gestational diabetes mellitus based on abnormal blood glucose on pregnancy outcomes

To investigate the relationship of different types of gestational diabetes mellitus (GDM) and pregnancy outcomes. A total of 4090 cases, who received prenatal examination and delivered in Peking University First Hospital and performed a 75 g oral glucose tolerance test (75 g OGTT) at 24-28 gestational weeks, from January. 1(st), 2011 to Jul 31(st), 2012 , were divided into 2 groups. Normal blood glucose group:the result of OGTT (fasting plasma glucose, 1 hour glucose and 2 hour glucose ) was normal; Gestational diabetes mellitus group (GDM group): the result of OGTT was abnormal at any time point. GDM group were separated into A, B and C. GDM A means fasting plasma glucose annormal but others were normal, GDM B:fasting plasma glucose, 1 hour and/or 2 hour glucose abnormal, GDM C:fasting plasma glucose normal. To analyse the effect of different number of abnormal result of OGTT on pregnancy outcomes, GDM group were divided into I, II and III.GDMI means one abnormal blood glucose of OGTT result, GDM II: two abnormal blood glucose and GDM III:three abnormal blood glucose. We analyzed the pregnant outcomes of each group. (1) Among the 4090 cases, 858 cases (21.98%) were diagnosed as GDM (GDM group), and 82 cases (9.6%, 82/858) were treated with insulin.other 3232 cases with normal blood glucose (normal blood glucose group). In GDM group, the rate of cesarean section (51.9%, 445/858), premature delivery (8.4%, 72/858) and LGA (5.9%, 51/858) were respectively significantly higher than those of normal blood glucose group [ (43.5%, 1406/3232), (5.8%, 189/3232) and(4.2%, 137/3232)] (P < 0.05). But, there was no statistically significant differences for the rate of macrosomia (P > 0.05) between the GDM group(6.8%, 58/858) and normal blood glucose group (6.2%, 199/3232) . (2) In the GDM group, GDM A was 317 cases (36.9%), GDM B 239 cases (27.8%), GDM C 302 cases (35.2%). The incidence of Macrosomia and LGA in GDM B was significantly higher than that in GDM C and normal blood glucose group (P < 0.05). Comparing with GDM A , there was no statistically significance in GDM B and GDM C (P > 0.05). (3) In GDM group, GDMIwas 521 cases (60.7%), GDM II203 cases (15.6%), GDM III 134 cases (23.7%). Compared with the normal blood glucose group, GDM III had a significantly higher incidence of macrosomia and LGA and cesarean section(P < 0.01);and GDM IIhad only a significantly higher incidence of cesarean section(P < 0.01). (4) Among the 4090 cases, there were 1118 patients (27.3%) whose fasting blood glucose was below 4.4 mmol/L, of which 55 cases were diagnosed as GDM. There were 4 premature infants and 1 macrosomia. The GDM group with more than FBG ≥ 5.1 mmol/L had a higher incidence of adverse pregnancy outcomes, it suggested that we should pay more attention and take actively intervented; the pregnant woman is not recommended for 75g OGTT detection when fasting blood glucose was below 4.4 mmol/L because of the low rate of GDM and adverse pregnancy outcomes among them.

Screening for pregestational and gestational diabetes in pregnancy: a survey of obstetrical centers in the northern part of Belgium

BackgroundThere is lack of consensus concerning the best screening strategy for gestational diabetes (GDM). The aim of our survey was therefore to investigate attitudes and practices of all obstetrical centers in the northern part of Belgium regarding screening for pregestational diabetes in early pregnancy and screening for GDM. We also aimed to identify the penetrance of the ‘International Association of Diabetes in Pregnancy Study Groups’ (IADPSG) screening strategy for GDM.MethodsThe survey was conducted from May 2012 till January 2013. The survey was distributed to every obstetrical center in the northern part of Belgium by email and/or mail with reminders by phone and personal contact.ResultsFrom the 65 obstetrical centers, 69% responded. Of all centers, 27% had a structured database on the number of women with GDM. Of all centers, 82% screened for pregestational diabetes in early pregnancy and 56% of centers screened for GDM before 24 weeks. Screening before 24 weeks was mostly based on risk factors. Screening for GDM after 24 weeks, was done universally in 87% of centers. The mean estimated prevalence of GDM was 7 ± 5%. The most commonly used screening strategy was a two-step approach with a glucose challenge test (GCT) and 100 g oral glucose tolerance test (OGTT), used by 56% of centers, with 23 centers using the Carpenter & Coustan criteria. The 75 g OGTT with the IADPSG criteria was used by 33% of centers but 4 of these centers still used a GCT before proceeding to the full OGTT.ConclusionsThis survey demonstrates that in the northern part of Belgium, there still is a large variation in screening strategy for pregestational diabetes in early pregnancy and GDM. Only 25% of centers have already implemented the one-step IADPSG screening strategy.

Placental virtual biopsy: 3D-US hemodynamics of normal pregnancy versus gestational diabetes

Objectives: We used three-dimensional ultrasound with trans-abdominal Power-Doppler (3D-US PD) to determine placental vascular evolution in normal pregnancies (NP) and in insulin-dependent Gestational Diabetes Pregnancies (GDP). Study design: We obtained 473 measurements from 43 NP at 20 weeks -40 weeks gestation and 122 measurements from 70 insulin-dependent GDP at 22 weeks -40 weeks. Standardization was achieved recording three successive placental vascular tree volumes, measuring the spherical volume between the chorionic and basal plates always under or near funicular insertion. Parameters analysed were: mean intensity of blood flow (Flow Index, FI); percentage of volume occupied by vessels (Vascularisation Index, VI); and intensity of blood flow in the volume occupied by vessels (Vascularisation-flow index, VFI). Results: In NP, FI increased throughout early pregnancy and decreased before delivery and correlated with fetal parameters. In contrast, in GDP, FI was high from the onset, better correlated with placental parameters, and had a diagnostic cutoff value of 45, which was only found in 7% of NP at the end of the pregnancy. VI was variable and had a low diagnostic value, being related to placental parameters; VI values were significantly lower in NP ( 17.4 ± 7.4%) than in GDP (21 ± 12%) with a diagnostic cutoff point at 31%. In NP, FI-peak was at 32 weeks, two weeks after the VI-peak, while VFI showed no significant differences. Conclusions: The results showed that placental blood flow (FI) was related to fetal circulation, while the percentage of vessels per volume (VI) was related to maternal circulation. 3D-US PD indicated a diagnosis of GDP for FI > 45 and VI > 30%. We also discuss the values of change in VI that predict changes in fetal FI.

Longitudinal Relationship of Physical Activity With Insulin Sensitivity in Overweight and Obese Pregnant Women

Physical activity (PA) initiated in the second half of pregnancy does not affect (or modify) insulin sensitivity in normal weight women. However, this might be different in obese women with lower insulin sensitivity. To test the hypothesis that in overweight and obese women at risk for gestational diabetes, PA is related to improved maternal glucose and insulin metabolism in pregnancy. A longitudinal study, with measurements at 15, 24, and 32 weeks of gestation, was conducted. Time spent in moderate-to-vigorous PA (MVPA) was measured objectively. In regression models, the relationship between time spent in MVPA at week 15 and changes in MVPA from 15 weeks to 24 or 32 weeks with fasting glucose, glycosylated hemoglobin, fasting insulin, insulin sensitivity, and insulin response at week 24 or 32 was assessed. In a group of 24 women, MVPA in early pregnancy was significantly associated with a reduced first- and second-phase insulin response at week 32. Women with larger decreases in MVPA throughout pregnancy had significantly higher fasting insulin levels, worse insulin sensitivity, increased first- and second-phase insulin response, and higher triglyceride levels in late pregnancy compared to women with smaller decreases in MVPA. Time spent in MVPA was not related to glucose or glycosylated hemoglobin levels. In our group of overweight and obese pregnant women, MVPA was associated with improved insulin sensitivity, insulin response, and decreased triglycerides at 32 weeks of pregnancy. This supports efforts for counseling obese women at risk for gestational diabetes in pregnancy to maintain their MVPA levels.

Fetal cerebral hemodynamic in gestational diabetic versus normal pregnancies: a Doppler velocimetry of middle cerebral and umbilical arteries

Gestational diabetes mellitus (GDM) is one of the most common complications in pregnancies. Evaluating other conditions, including intra uterine growth restriction and pre-eclampsia, some studies have shown significant changes in blood flow velocity of fetal middle cerebral artery (MCA). Our study is one of the few that has aimed to assess the effects of GDM on Doppler parameters of the fetal MCA and umbilical artery (UA) and to compare with normal pregnancies. This cross-sectional study was performed on 66 pregnant women, including 33 women with GDM and the others without it, in Akbar-Abadi University Hospital in Tehran, Iran during 2010-2011. Peak systolic and diastolic velocities, pulsatility index (PI), resistance index (RI) and systolic diastolic ratio (SD) were recorded in UA as well as both right and left fetal MCAs for every recruited pregnant women by means of Doppler ultrasonography. The mean gestational age at the time of examination was 34.45 (SD = 2.62) weeks in GDM group. Although all of the measured Doppler parameters had higher values in GDM pregnancies, the differences were not significant between two groups of study; except for the left fetal MCA-PI, which was significantly higher in GDM group [2.07 (SD = 0.07) vs. 1.85 (SD = 0.74), P = 0.03]. Our results show that gestational diabetes may contribute to an elevated PI in the fetal MCA. Although there is not yet strong proof for the effect of GDM on the fetal brain hemodynamics, the significant higher MCA-PI warrants more attention towards better controlling of the hyperglycemia during pregnancy.

Adipocytokines during pregnancy and postpartum in women with gestational diabetes and healthy controls.

This study aims to explore the changes in maternal serum adipocytokines during pregnancy and post partum in normal and complicated with gestational diabetes (GDM) pregnancies and to investigate the relationship between serum adipocytokines and some of major metabolic parameters. 236 pregnant women (127 with GDM and 109 control group) and 50 postpartum women (30 with GDM during pregnancy and 20 controls). Using ELISA and EIA kits, serum levels of adipocytokines were tested during pregnancy and post partum. Maternal adipocytokines levels were correlated with some metabolic parameters. Women with GDM had lower values of adiponectin and higher values of leptin during pregnancy (p<0.001; 0.0001) and post partum (p<0.002; 0.0001). Serum apelin was significantly lower in GDM group (p<0.009). However, we did not find significance for resistin (p<0.317) and apelin (p<0.218). Positive correlation for leptin and negative for adiponectin was found for pre-pregnancy and pregnancy body mass index, glycated hemoglobin and homeostasis model assessment of insulin resistance index. Using cut point of 8.2 μg/ml for adiponectin and 28.7 ng/ml for leptin could exclude GDM with a sensitivity of 83.6%/81.2% and specificity of 56.6%/64.2% (area under the curve 0.702 and 0.827). There are constant differences in adiponectin and leptin levels between GDM and control group during pregnancy and post partum. Apelin was decreased in our GDM group and no differences were found for resistin and visfatin. Further studies are required to verify the mechanism of this alteration and whether the adipocytokines can be predictors for GDM at an early stage of pregnancy.

Obesity in Pregnancy

Obesity has increased dramatically in the United States over the last several decades, with approximately 40% of women now considered overweight or obese. Obesity has been shown to be associated with poor pregnancy outcomes, including increased rates of cesarean delivery, preeclampsia, gestational diabetes, fetal macrosomia, stillbirth, and postterm pregnancy. In this review, we discuss the association of obesity with maternal, fetal, and pregnancy outcomes as well as the recommendations for care of the obese gravida. Obstetricians and gynecologists and family physicians. After completing the CME activity, physicians should be better able to describe the maternal, neonatal, and intrapartum complications associated with obesity in pregnancy and implement additional changes to prenatal care appropriate for the obese gravida.

The multidisciplinary management of type 2 and gestational diabetes in pregnancy

The UK is experiencing a dramatic increase in the prevalence of type 2 diabetes mellitus (T2D). Consequently, there is a corresponding increase in diabetes in pregnancy, with 87.5% of pregnancies in the UK complicated by diabetes due to gestational diabetes mellitus (GDM), and 27% of those with pre-existing diabetes having T2D (National Centre for Health and Clinical Excellence (NICE), 2008a ). Although the risks to mother and baby are similar to type 1 diabetes (T1D), the approach and management often differ. Women with GDM and T2D are more likely to be older, multiparous and live in deprived areas. Certain ethnic groups are more prone to GDM and T2D, and there is a strong association between being overweight or obese and diabetes. Women who develop GDM in pregnancy also have an increased risk of T2D in later life ( Diabetes UK, 2011a ). Some surveys, such as the Confidential Enquiry into Maternal and Child Health ( CEMACH, 2007a ) have shown that women with T2D often receive suboptimum care prior to conception and in early pregnancy. This paper presents an overview of the multidisciplinary management of T2D and GDM in pregnancy and identifies areas where care may be lacking for these women.

Reduced apoptosis in term placentas from gestational diabetic pregnancies.

Gestational diabetic mellitus (GDM) pregnancies have an increased risk of macrosomic infants and large placental mass, though the mechanisms explaining each of these is uncertain. We sought to evaluate the contribution of apoptosis to placental size and the expression of glucose transporters (SLC2A) in GDM pregnancies. Maternal age and pre-pregnancy body weight were documented. Newborn weights were recorded after delivery. Placentas 37-40-week gestation from control patients (no pregnancy complication) (n = 5), or with GDM (n = 5) were weighed immediately after delivery. Villous samples (4 mm diameter) were collected and divided into specimens; one was fixed in 4% paraformaldehyde for immunostaining using terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL) and activated caspase-3. The other specimen was snap frozen in liquid nitrogen and stored at -80°C for active caspase-3, poly(ADP-ribose) polymerase (PARP), SLC2A1 and SLC2A3 gene expression analysis. Our results showed that maternal age and pre-pregnancy body weight were significantly higher in the GDM group when compared with those from the controls (P < 0.05). The mean neonatal birth weight and placenta weight were significantly higher in the GDM group compared with that from the controls (P < 0.05). The apoptotic index of placentas (0.05 ± 0.01 v. 0.17 ± 0.04, P < 0.04), active caspase-3 polypeptide fragments and PARP protein were significantly decreased in GDM placentas as compared with controls. Further, the level of placental SLC2A1 protein expression was ∼3-fold higher in GDM placentas. Our results suggest that reduced apoptosis in GDM placentas may contribute to increased placental tissue, which together with enhanced SLC2A1 expression, could play a role in fetal macrosomia.

Mitochondrial DNA Copy Number and Oxidative DNA Damage in Placental Tissues from Gestational Diabetes and Control Pregnancies: A Pilot Study

Available evidence supports the role of reactive oxygen species in the pathogenesis of placental insufficiency, gestational diabetes mellitus (GDM), and other pregnancy complications. Abnormal placental mitochondrial function resulting from reactive oxygen species may also be an important precedent of adverse perinatal outcomes. We investigated the association of placental oxidative stress with placental mitochondrial DNA (mtDNA) copy number, an indicator of placental mitochondrial density and possible mitochondrial dysfunction, using samples collected from GDM cases and controls. 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, was measured in placentas of 19 GDM cases and 21 controls using a competitive immunoassay. Placental mtDNA copy number was determined using real-time quantitative PCR. Bivariate and multivariable linear regression procedures were used to evaluate associations of these two biomarkers. Placental DNA oxidation was positively associated with mtDNA copy number in both GDM and control placentas. After adjusting for maternal age, pre-pregnancy body mass index and gestational age at delivery, mtDNA copy number increased (beta = 67.0; 95% CI 27.8 - 106.2, p = 0.001) for every 0.1 ng/microg increase of placental 8-OHdG among GDM cases and controls. These cross sectional data suggest an association of placental mtDNA copy number with oxidative stress. The consequences of placental oxidative stress and mitochondrial dysfunction on the course and outcomes of pregnancy remain to be elucidated in larger prospective studies.

Amniotic Fluid Oxidative and Nitrosative Stress Biomarkers Correlate with Fetal Chronic Hypoxia in Diabetic Pregnancies

Background: In spite of improvement in obstetrical care, pregnancy in women with type 1 diabetes mellitus is associated with increased perinatal morbidity and mortality. Hyperglycemia during pregnancy causes excessive fetal growth and chronic fetal hypoxia as reflected in increased erythropoietin (EPO) levels in amniotic fluid (AF). Objectives: We hypothesized that the degree of fetal hypoxia would correlate with fetal oxidative and nitrosative stress as evidenced by the concentration of specific biomarkers in AF. Material and Methods: 19 pregnant women with type 1 or insulin-treated gestational diabetes mellitus were studied. AF samples were collected and processed for EPO, meta-tyrosine, nitro-tyrosine and 8-hydroxy-2-deoxiguanosine by chemiluminescent immunoassay and high-performance liquid chromatography coupled to tandem mass spectrometry methods, respectively. Results: The mean (SD) of the last HbA_1c concentration before delivery was 7.7% (1.1). Median gestational age was 258 days (range 231–268). Birth weight was 3,868 ± 695 g with a z-score >2 SD in 47% of the cases. A significant correlation was found between the concentrations of AF EPO and meta-tyrosine/phenylalanine ratio (p < 0.001), nitro-tyrosine (p < 0.01) and 8-oxo-dG/2dG ratio (p < 0.001). Conclusions: We confirmed that fetuses of type 1 diabetes or insulin-treated gestational diabetes pregnancies experience chronic hypoxia as reflected by increased EPO concentrations in AF near term. Moreover, EPO levels significantly correlated with the concentration of oxidative and nitrosative stress biomarkers in AF. This pro-oxidant status may predispose newborn infants to poor postnatal adaptation and early neonatal complications.