Placental weight mediates the effects of prenatal factors on fetal growth: the extent differs by preterm status

Objective:

Elevated pre‐pregnancy BMI, excessive gestational weight gain (GWG), and gestational diabetes mellitus (GDM) are known determinants of fetal growth. The role of placental weight is unclear. We aimed to examine the extent to which placental weight mediates the associations of pre‐pregnancy BMI, GWG, and GDM with birth weight‐for‐gestational age, and whether the relationships differ by preterm status.

Design and Methods:

We examined 1,035 mother‐infant pairs at birth from the Boston Birth Cohort. Data were collected by questionnaire and clinical measures. Placentas were weighed without membranes or umbilical cords. We performed sequential models excluding and including placental weight, stratified by preterm status.

Results:

We found that 21% of mothers were obese, 42% had excessive GWG, and 5% had GDM. Forty‐one percent were preterm. Among term births, after adjustment for sex, gestational age, maternal age, race, parity, education, smoking, and stress during pregnancy, birth weight‐for‐gestational age z‐score was 0.55 (0.30, 0.80) units higher for pre‐pregnancy obesity vs. normal weight. It was 0.34 (0.13, 0.55) higher for excessive vs. adequate GWG, 0.67 (0.24, 1.10) for GDM vs. no DM, with additional adjustment for pre‐pregnancy BMI. Adding placental weight to the models attenuated the estimates for pre‐pregnancy obesity by 20%, excessive GWG by 32%, and GDM by 21%. Among preterm infants, GDM was associated with 0.67 (0.34, 1.00) higher birth weight‐for‐gestational age z‐score, but pre‐pregnancy obesity and excessive GWG were not. Attenuation by placental weight was 36% for GDM.

Conclusions:

These results suggest that placental weight partially mediates the effects of pre‐pregnancy obesity, GDM, and excessive GWG on fetal growth among term infants.     

Supplementation with polyunsaturated fatty acids in pregnant rats with mild diabetes normalizes placental PPARγ and mTOR signaling in female offspring developing gestational diabetes

Maternal diabetes impairs fetoplacental development and programs metabolic diseases in the offspring. We have previously reported that female offspring of pregnant rats with mild diabetes develop gestational diabetes mellitus (GDM) when they become pregnant. Here, we studied the effects of supplementation with polyunsaturated fatty acids (PUFAs) in pregnant mild diabetic rats (F0) by feeding a 6% safflower-oil-enriched diet from day 1 to 14 followed by a 6% chia-oil-enriched diet from day 14 of pregnancy to term. We analyzed maternal metabolic parameters and placental signaling at term in pregnant offspring (F1). The offspring of both PUFAs-treated and untreated mild diabetic rats developed GDM. Although gestational hyperglycemia was not prevented by dietary PUFAs treatment in F0, triglyceridemia and cholesterolemia in F1 mothers were normalized by F0 PUFAs dietary treatment. In the placenta of F1 GDM rats, PPARγ levels were reduced and lipoperoxidation was increased, changes that were prevented by the maternal diets enriched in PUFAs in the F0 generation. Moreover, fetal overgrowth and placental activation of mTOR signaling pathways were reduced in F1 GDM rats whose mothers were treated with PUFAs diets. These results suggest that F0 PUFAs dietary treatment in pregnancies with mild diabetes improves maternal dyslipidemia, fetal overgrowth and placental signaling in female offspring when they become pregnant. We speculate that an increased PUFAs intake in pregnancies complicated by diabetes may prove effective to ameliorate metabolic programming in the offspring, thereby improving the health of future generations.     

Associations of Maternal Diabetes During Pregnancy with Overweight in Offspring: Results from the Prospective TEDDY Study

Objective: This study aimed to determine the relationship between different forms of, and potential pathways between, maternal diabetes and childhood obesity at different ages. Methods: Prospective cohort data from The Environmental Determinants of Diabetes in the Young (TEDDY) study, which was composed of 5,324 children examined from 0.25 to 6 years of age, were analyzed. Cross‐sectional and longitudinal analyses taking into account potential confounders and effect modifiers such as maternal prepregnancy BMI and birth weight z scores were performed. Results: Offspring of mothers with gestational diabetes mellitus (GDM) or type 1 diabetes mellitus (T1DM) showed a higher BMI standard deviation score and increased risk for overweight and obesity at 5.5 years of age than offspring of mothers without diabetes. While these associations could be substantially explained by maternal prepregnancy BMI in offspring of mothers with GDM, significant associations disappeared after adjustment for birth weight z scores in offspring of T1DM mothers. Furthermore, overweight risk became stronger with increasing age in offspring of mothers with diabetes compared with offspring of mothers without diabetes. Conclusions: Maternal diabetes is associated with increased risk of offspring overweight, and the association appears to get stronger as children grow older. Indeed, intrauterine exposure to maternal T1DM may predispose children to later obesity through increased birth weight, while maternal BMI is more important in children exposed to GDM.     

Placental mitochondrial dysfunction with metabolic diseases: Therapeutic approaches

Both obesity and gestational diabetes mellitus (GDM) lead to poor maternal and fetal outcomes, including pregnancy complications, fetal growth issues, stillbirth, and developmental programming of adult-onset disease in the offspring. Increased placental oxidative/nitrative stress and reduced placental (trophoblast) mitochondrial respiration occur in association with the altered maternal metabolic milieu of obesity and GDM. The effect is particularly evident when the fetus is male, suggesting a sexually dimorphic influence on the placenta. In addition, obesity and GDM are associated with inflexibility in trophoblast, limiting the ability to switch between usage of glucose, fatty acids, and glutamine as substrates for oxidative phosphorylation, again in a sexually dimorphic manner. Here we review mechanisms underlying placental mitochondrial dysfunction: its relationship to maternal and fetal outcomes and the influence of fetal sex. Prevention of placental oxidative stress and mitochondrial dysfunction may improve pregnancy outcomes. We outline pathways to ameliorate deficient mitochondrial respiration, particularly the benefits and pitfalls of mitochondria-targeted antioxidants.     

Hyperglycemia Differentially Affects Maternal and Fetal DNA Integrity and DNA Damage Response

Objective: Investigate the DNA damage and its cellular response in blood samples from both mother and the umbilical cord of pregnancies complicated by hyperglycemia. Methods: A total of 144 subjects were divided into 4 groups: normoglycemia (ND; 46 cases), mild gestational hyperglycemia (MGH; 30 cases), gestational diabetes mellitus (GDM; 45 cases) and type-2 diabetes mellitus (DM2; 23 cases). Peripheral blood mononuclear cell (PBMC) isolation and/or leukocytes from whole maternal and umbilical cord blood were obtained from all groups at delivery. Nuclear and mitochondrial DNA damage were measured by gene-specific quantitative PCR, and the expression of mRNA and proteins involved in the base excision repair (BER) pathway were assessed by real-time qPCR and Western blot, respectively. Apoptosis was measured in vitro experiments by caspase 3/7 activity and ATP levels. Results: GDM and DM2 groups were characterized by an increase in oxidative stress biomarkers, an increase in nuclear and mitochondrial DNA damage, and decreased expression of mRNA (APE1, POLβ and FEN1) and proteins (hOGG1, APE1) involved in BER. The levels of hyperglycemia were associated with the in vitro apoptosis pathway. Blood levels of DNA damage in umbilical cord were similar among the groups. Newborns of diabetic mothers had increased expression of BER mRNA (APE1, POLβ and FEN1) and proteins (hOGG1, APE1, POLβ and FEN1). A diabetes-like environment was unable to induce apoptosis in the umbilical cord blood cells. Conclusions: Our data show relevant asymmetry between maternal and fetal blood cell susceptibility to DNA damage and apoptosis induction. Maternal cells seem to be more predisposed to changes in an adverse glucose environment. This may be due to differential ability in upregulating multiple genes involved in the activation of DNA repair response, especially the BER mechanism. However if this study shows a more effective adaptive response by the fetal organism, it also calls for further studies to determine the limit of this response that definitely changes the fate of a fetus under these conditions of cellular stress.     

Lipid peroxidation, antioxidant defence and acid-base status in cord blood at birth: the influence of diabetes.

Pregnancy complicated by poor control of diabetes is associated with a higher risk of embryopathies, spontaneous abortions and perinatal mortality. A number of authors suggest an involvement of reactive oxygen species (ROS) in diabetic pregnancy. Determining lipid peroxidation products (LP), scavenging enzyme activities and the umbilical cord blood's acid-base balance may contribute to an adequate diagnosis of the neonate at birth. Nevertheless, such measurements seem to have limited value in practical clinical routine. The present study evaluates LP, antioxidant defence and acid-base status related to diabetic pregnancy. Twenty-eight women with type 1 diabetes (PGDM), 19 with gestational diabetes (GDM) and 13 control cases were investigated. An additional control group consisted of 15 healthy patients with negative diabetic history; all women underwent vaginal delivery. Immediately after delivery cord blood samples and placental tissue were collected for malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) determination. Additionally, pH, pCO2, pO2 and base excess were measured in both vessels and compared to identify and exclude double venous samples. MDA levels in both cord blood and placental homogenates were significantly higher in both pregestational and gestational diabetic groups, but SOD activity was significantly diminished. Cord blood GSH was markedly elevated in PGDM and GDM. We have also shown significant differences in acid-base parameters in infants of PGDM group. Statistical analysis was performed using the Mann-Whitney U-test.These findings indicate an excessive oxidative stress in pregnancy complicated by diabetes mellitus. Evaluating LP products and scavenging enzyme activities may be valuable, sensitive indexes of fetal/neonatal threat in diabetic pregnancy in humans. Since oxidative stress is an important pathway for fetal injury, we believe that obtaining adequate measurements at the time of birth would contribute to clarifying the fetal/neonatal status in a medical and legal context and might be of value in altering therapy in newborn infants.     

Intergenerational transmission of insulin resistance and type 2 diabetes

Studies in women with type 1 or type 2 diabetes mellitus (DM) and their children suggest that the in utero ‘diabetic’ environment in which the fetus develops can increase the risk of diabetes in the child, in a non-genetic but heritable fashion. Studies in rodents provide strong evidence for maternal transmission of diabetes, but are based primarily on a model type 1 DM and there is no standard animal model of type 2 DM in pregnancy or of gestational diabetes mellitus (GDM), although those reported uniformly show glucose intolerance in the offspring. Rodent models of diet-induced obesity have relevance to current upward trends in maternal obesity and GDM, although maternal glucose homeostasis is not always assessed and elements of the diet may have an independent influence. The mechanisms by which maternal type 2DM evokes a higher risk of the disorder in the offspring are likely to result from epigenetic modification in early life of pathways of pancreatic β cells and of liver and muscle insulin signalling pathways. Also, epigenetic processes associated with hormonal imbalance may lead to irreversible ‘reordering’ of hypothalamic neural networks in fetal/neonatal life, permanently alter energy balance and lead to obesity with associated insulin resistance.     

Predictive parameters of gestational diabetes mellitus

Gestational diabetes mellitus is a carbohydrate intolerance recognized in pregnancy. The objective of this study was to determine the prevalence of gestational diabetes mellitus (GDM) of all deliveries at the University Hospital Rijeka, Croatia (34 997 deliveries over 10-year period) using 2-hour 75 g oral glucose tolerant test and to evaluate the impact of GDM on neonatal outcomes and mother's health. Gestational diabetes was diagnosed in 55 of 128 pregnant women with suspected glucose intolerance. Logistic regression analysis was used to examine the relationship between fasting plasma glucose, age, family history, body mass index, maternal weight gain, neonatal weight, neonatal head diameter and Apgar score in the gestational diabetes group and in the non-diabetes group. The results indicate that fasting plasma glucose greater than 7.0 mmol/L and maternal overweight are strong predictors for GDM and macrosomia. There was no difference in the mode of delivery, and vitality and metabolic complications among the infants of all analyzed mothers. We concluded that to prevent GDM as well as to reduce the rate of macrosomic infants good glycemic control should be initiated as soon as possible. The 2-hour 75 g OGTT is worth enough to evaluate GDM. Women should be counseled and encouraged to lose weight before or at the beginning of the conception period.     

Fetomaternal adrenomedullin levels in diabetic pregnancy.

We investigated whether maternal and fetoplacental adrenomedullin, a newly discovered hypotensive peptide involved in the insulin regulatory system, is modified in diabetic pregnancy. We studied its correlation with pregnancy complications associated with this disease. Thirty-six pregnant women with diabetes (13 with type I and 23 with gestational diabetes mellitus) and in 40 uncomplicated pregnancies were included. 10 out of 36 diabetic pregnancies were complicated by gestational hypertension. In each woman, adrenomedullin concentration in maternal and fetal plasma and in amniotic fluid was assessed by specific radioimmunoassay. We found that overall mean amniotic fluid adrenomedullin concentration was higher (p < 0.05) in diabetic (14.7 +/- 1.6 fmol/ml) than in uncomplicated pregnancies (10.8 +/- 0.9 fmol/ml), whereas no differences were present in maternal and fetal plasma adrenomedullin levels between diabetic and uncomplicated pregnant women. High levels of amniotic fluid adrenomedullin were found in both type I and gestational diabetes mellitus pregnancies (13.7 +/- 1.4 and 15.6 +/- 2.2 fmol/ml, respectively). Diabetic pregnancies complicated by gestational hypertension showed lower (p < 0.05) amniotic fluid adrenomedullin concentrations than normotensive diabetic patients. These findings suggest that placental adrenomedullin production is upregulated in diabetic pregnancy, and it may be important to prevent excessive vasoconstriction of placental vessels.     

Impact of maternal circulating cholesterol and gestational diabetes mellitus on lipid metabolism in human term placenta

Maternal hypercholesterolemia (HC) during pregnancy and gestational diabetes mellitus (GDM) are associated with disturbance of fetal development which may also modify key features of placental functions. In this study, we evaluated the impact of maternal hypercholesterolemia on placental cholesterol and lipid metabolism in 59 women classified in two groups according to the median concentration of plasma total cholesterol (6.42 mM). The impact of GDM was also evaluated on the metabolism of placentas obtained from 7 insulin-treated GDM and 7 non-GDM women. We showed that high maternal circulating cholesterol is associated with a significant increase in the LDL-cholesterol, ApoB-100 and triglyceride concentrations in the maternal blood. However the level of cholesterol in the venous cord blood and placenta remains unchanged in response to modification in maternal cholesterol profile. The levels of Fatty acid synthase (FAS) and SREBP-2 expressions in placenta are significantly increased in the HC group while expression of both sterol regulatory element-binding proteins-1 (SREBP-1) and HMG-CoA reductase (HMGR) are not modified. GDM is not associated with modification in the maternal lipid profile but it increases the concentration of inflammatory cytokines (IL-1beta and TNF-alpha) in placenta which correlates with a dramatic induction of FAS expression without affecting the expression of mature SREBPs proteins. In conclusion, our study suggests that in placenta, expressions of key proteins involved in de novo lipid synthesis are affected by changes in maternal metabolism (HC and GDM) that may subsequently affect fetal development.     

Association between maternal and child leptin levels 9 years after pregnancy complicated by gestational diabetes.

Obesity is a state of relative leptin resistance, and obesity in childhood is associated with an increased incidence of type 2 diabetes in later life. Offspring of mothers with gestational diabetes mellitus (GDM) are at increased risk of obesity. A cohort consisting of 64 mothers, 33 GDM and 31 controls screened for diabetes during the index pregnancy together with their 9-year-old offspring were studied. Our hypotheses were: 1) an elevated child leptin is associated with elevated maternal leptin in GDM mothers 9 years post delivery; and 2) child leptin at 9 years serves as a marker for incipient insulin resistance. By univariate analyses, child leptins were only significantly correlated with maternal leptins among the offspring of GDMs (OGDM) (r = 0.59; p = 0.001). By multivariate analyses, child leptin for the total study group was significantly associated with child body mass index (BMI) (R(2) = 0.65; p < 0.0001), child fasting insulin (R(2) = 0.08; p = 0.03), and female gender (R(2) = 0.28; p = 0.001). In addition, among OGDM child leptin was associated with maternal leptin (R(2) = 0.14; p = 0.005). Our results suggest that there is an association between maternal and child leptin levels 9 years after a pregnancy complicated by gestational diabetes.     

Reduced Fetal Telomere Length in Gestational Diabetes

Gestational diabetes mellitus (GDM) is an important complication of pregnancy that poses significant threats to women and their offspring. Telomere length shortens as cellular damage increases and is associated with metabolic diseases. Telomere length in fetal leucocytes was determined in 82 infants of women with GDM (N = 82) and 65 normal pregnant women (N = 65). Women with preeclampsia (N = 45) and gestational hypertension (N = 23) were also studied. In the GDM group, telomere length was significantly shorter than normal pregnancy (P = 0.028), but there were no significant differences in fetal telomere length between preeclampsia and normal pregnancy (P = 0.841) and between gestational hypertension and normal pregnancy (P = 0.561). Regression analysis revealed that fetal telomere length was significantly associated with intrauterine exposure to GDM (P = 0.027 after adjustment for maternal age, gestational age at delivery, birth weight and fetal gender). Shortened telomere length may increase the risk of metabolic diseases in adulthood of GDM offspring.     

Correlation between maternal inflammatory markers and fetomaternal adiposity

Outside pregnancy, both obesity and diabetes mellitus are associated with changes in inflammatory cytokines. Obesity in pregnancy may be complicated by gestational diabetes mellitus (GDM) and/or fetal macrosomia. The objective of this study was to determine the correlation between maternal cytokines and fetomaternal adiposity in the third trimester in women where the important confounding variable GDM had been excluded. Healthy women with a singleton pregnancy and a normal glucose tolerance test at 28weeks gestation were enrolled at their convenience. Maternal cytokines were measured at 28 and 37weeks gestation. Maternal adiposity was assessed indirectly by calculating the Body Mass Index (BMI), and directly by bioelectrical impedance analysis. Fetal adiposity was assessed by ultrasound measurement of fetal soft tissue markers and by birthweight at delivery. Of the 71 women studied, the mean maternal age and BMI were 29.1years and 29.2kg/m(2) respectively. Of the women studied 32 (45%) were obese. Of the cytokines, only maternal IL-6 and IL-8 correlated with maternal adiposity. Maternal TNF-α, IL-β, IL-6 and IL-8 levels did not correlate with either fetal body adiposity or birthweight. In this well characterised cohort of pregnant non-diabetic women in the third trimester of pregnancy we found that circulating maternal cytokines are associated with maternal adiposity but not with fetal adiposity.     

1,5-Anhydroglucitol and Neonatal Complications in Pregnancy Complicated by Diabetes

Objective: To determine the association of 1,5-anhydroglucitol (1,5-AG) with neonatal birth weight (NBW) and neonatal hypoglycemia (+NH) in pregnancies complicated by diabetes.Methods: We assessed a retrospective cohort of 102 females, 17 with gestational diabetes (GDM), 48 with type 1 diabetes mellitus (T1DM), and 37 with type 2 diabetes mellitus (T2DM). 1,5-AG and glycated hemoglobin A1C (A1C) values throughout pregnancy were extracted. Linear regression was used to assess their association with NBWs z-scores adjusting for maternal age, ethnicity and body mass index (BMI). +NH was defined by a note in the infant record, glucose <1.7 mmol/L in the first 24 h, or <2.5 mmol/L in the first 48 h after birth. A t test or Welch's approximate t test was used to compare the mean 1,5-AG and A1C of mothers with +NH versus those without (-NH), adjusted for gestational age and analyzed by diabetes type and across trimesters.Results: Mean 1,5-AG significantly differed across groups: T1DM 3.77 ± 2.82 μg/mL, T2DM 5.73 ± 4.38 μg/mL, GDM 8.89 ± 4.39 μg/mL (P<.0001), suggesting less glucose exposure in GDM relative to T1DM or T2DM. A negative linear association was found between mean 1,5-AG and z-scores (R= -0.28, P = .005. In contrast, the association between mean A1C and z-scores was weaker (R = 0.15, P = .14). The mean 1,5-AG tended to be lower in the +NH cohort versus -NH (P = .08), and this was statistically significant (P = .01) among subjects with GDM.Conclusion: The association of 1,5-AG with complications related to glycemic exposure supports the notion of its utility as an adjunct glycemic biomarker in pregnancies complicated by diabetes and across trimesters.Abbreviations: 1,5-AG = 1,5-anhydroglucitol A1C = glycated hemoglobin A1C BMI = body mass index CGM = continuous glucose monitoring GDM = gestational diabetes mellitus LGA = large for gestational age MICC = maternal and infant care unit NBW = neonatal birth weight NH = neonatal hypoglycemia PPH = postprandial hyperglycemia SMBG = self-monitoring of blood glucose T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus     

The role of oral glucose intolerance test in reducing pregnancy complications

The influence of glucose monitoring during pregnancy on newborn body weight, and complications during pregnancy and labor was assessed. We performed a retrospective analysis of macrosomal children, fetal growth, caesarean sections, malformations, still-births and the number of oral glucose tolerance test (OGTT) carried out in a five-year period. The proportion of women participating in OGTT tests increased from 20% to 40% (p<0.05) between 2000 and 2004. Gestation diabetes mellitus (GDM) proportions among pregnant women seen at the Department of Obstetrics and Gynecology at Slavonski Brod General Hospital, Croatia increased from 1% to 6.7% (p < 0. 05) during the observed period. Proportion of births identified as macrosomal decreased from 13.3% to 12.2% (p<0.05). Additionally, infant mortality and still-births along with other fetal and maternal complications declined during the same period. These results suggest that regular measurements of glucose tolerance during pregnancy may prevent preterm birth, decrease the proportion of macrosomal newborns, lower mortality and decrease fetal and maternal complication incidence during pregnancy and delivery.     

Differential expression of placental 11β-hydroxysteroid dehydrogenases in pregnant women with diet-treated gestational diabetes mellitus

Fetal exposure to excess glucocorticoid is one of the critical factors for the fetal origins of adult diseases. However, the mechanism of the local regulation of glucocorticoid activity in the human placenta of pregnancies complicated with gestational diabetes mellitus (GDM) has not been fully understood. We investigated placental 11β-hydroxysteroid dehydrogenases (11β-HSDs) expression, and analyzed their relationship with cortisol levels in maternal and umbilical vein. Pregnant women with GDM after diet intervention (n=23) or normal glucose tolerance (NGT, n=22) were studied at the community-based hospital. We collected maternal and umbilical venous cord blood and placental tissues from both groups. Explanted placentas from NGT were cultured with palmitic acid, dexamethasone, insulin or their mixture for 24-h. We examined plasma cortisol, cortisone to cortisol ratio, insulin, the homeostasis model assessment of insulin resistance index (HOMA-IR) and the insulin secretion index. Quantitative real-time PCR, Western blot and immunohistochemical assay were applied for the measurement of 11β-HSD1 and 11β-HSD2 mRNA and protein. GDM had higher maternal cortisol levels, HOMA-IR, insulin secretion index and higher cortisone to cortisol ratio in umbilical vein. No significant change in cortisol levels in umbilical vein and newborn weight was found. GDM placental 11β-HSD1 levels decreased while 11β-HSD2 increased. Treatment of placenta explants from NGT with palmitic acid, dexamethasone, insulin or their combination resulted in a significant drop of 11β-HSD1 and increase in 11β-HSD2. Differential expression of 11β-HSDs in diet-treated GDM placenta provides a protective mechanism for the fetus throughout the adverse environment of pregnancy by limiting excessive exposure of the fetus to glucocorticoid.     

UPLC-MS metabolic profiling of second trimester amniotic fluid and maternal urine and comparison with NMR spectral profiling for the identification of pregnancy disorder biomarkers

We report on the first untargeted UPLC-MS study of 2nd trimester maternal urine and amniotic fluid (AF), to investigate the possible metabolic effects of fetal malformations (FM), gestational diabetes mellitus (GDM) and preterm delivery (PTD). For fetal malformations, considerable metabolite variations were identified in AF and, to a lesser extent, in urine. Using validated PLS-DA models and statistical correlations between UPLC-MS data and previously acquired NMR data, a metabolic picture of fetal hypoxia, enhanced gluconeogenesis, TCA activity and hindered kidney development affecting FM pregnancies was reinforced. Moreover, changes in carnitine, pyroglutamate and polyols were newly noted, respectively, reflecting lipid oxidation, altered placental amino acid transfer and alterations in polyol pathways. Higher excretion of conjugated products in maternal urine was seen suggesting alterations in conjugation reactions. For the pre-diagnostic GDM group, no significant changes were observed, either considering amniotic fluid or maternal urine, whereas, for the pre-PTD group, some newly observed changes were noted, namely, the decrease of particular amino acids and the increase of an hexose (possibly glucose), suggesting alteration in placental amino acid fluxes and a possible tendency for hyperglycemia. This work shows the potential of UPLC-MS for the study of fetal and maternal biofluids, particularly when used in tandem with comparable NMR data. The important roles played by sampling characteristics (e.g. group dimensions) and the specific experimental conditions chosen for MS methods are discussed.     

The Effects of Implementing the International Association of Diabetes and Pregnancy Study Groups Criteria for Diagnosing Gestational Diabetes on Maternal and Neonatal Outcomes

Background

In 2010, the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recommended a new strategy for the screening and diagnosis of gestational diabetes mellitus (GDM). However, no study has indicated that adopting the IADPSG recommendations improves perinatal outcomes. The objective of this study was to evaluate the effects of implementing the IADPSG criteria for diagnosing GDM on maternal and neonatal outcomes.

Methodology/Principal Findings

Previously, we used a two-step approach (a 1-h, 50-g glucose challenge test followed by a 3-h, 100-g glucose tolerance test when indicated) to screen for and diagnose GDM. In July 2011, we adopted the IADPSG recommendations in our routine obstetric care. In this study, we retrospectively compared the rates of various maternal and neonatal outcomes in all women who delivered after 24 weeks of gestation during the periods before (P1, between January 1, 2009 and December 31, 2010) and after (P2, between January 1, 2012 and December 31, 2013) the IADPSG criteria were implemented. Pregnancies complicated by multiple gestations, fetal chromosomal or structural anomalies, and pre-pregnancy diabetes mellitus were excluded. Our results showed that the incidence of GDM increased from 4.6% using the two-step method to 12.4% using the IADPSG criteria. Compared to the women in P1, the women in P2 experienced less weight gain during pregnancy, lower birth weights, shorter labor courses, and lower rates of macrosomia (<4000 g) and large-for-gestational age (LGA) infants. P2 was a significant independent factor against macrosomia (adjusted odds ratio [OR] 0.63, 95% confidence interval [CI] 0.43–0.90) and LGA (adjusted OR 0.74, 95% CI 0.61–0.89) after multivariable logistic regression analysis.

Conclusions/Significance

The adoption of the IADPSG criteria for diagnosis of GDM was associated with significant reductions in maternal weight gain during pregnancy, birth weights, and the rates of macrosomia and LGA.