The association between macrosomia and glucose, lipids and hormones levels in maternal and cord serum: a case-control study.

BACKGROUND: The formation of macrosomia is associated with excessive nutrition and/or unable to regulate effectively. This case-control study aims to explore the relationship between macrosomia and glucose, lipids and hormones levels in maternal and cord serum. METHODS: In the case-control study, 78 pairs of mothers and newborns were recruited who received care at one hospital of Hebei, China between 2016 and 2019. According to the birth weight (BW) of newborns, participants were divided into macrosomia group (BW ≥ 4000 g, n = 39) and control group (BW between 2500 g and 3999 g, n = 39). Maternal vein blood and cord vein blood were collected and assayed. All data were compared between the two groups. Unconditional logistics regression analysis was used to test the relationship between macrosomia and glucose, lipids and hormones in maternal and cord serum. RESULTS: In maternal and cord serum, the levels of leptin, leptin/adiponectin ratio (LAR), glucose and triglyceride (TG) in macrosomia group were higher than those in control group, and the levels of high-density lipoprotein cholesterol (HDL-C) were lower. The percentage of maternal glucose and lipids transfer to cord blood did not differ between the two groups. High levels of TG in maternal serum were positively correlated with macrosomia, and high levels of LAR, TG and glucose in cord serum were positively correlated with macrosomia. CONCLUSION: In conclusion, the results of the current study, suggest that the nutrients and metabolism-related hormones in maternal and umbilical cord are closely related to macrosomia. During pregnancy, the nutritional status of pregnant women should be paid attention to and to obtain a good birth outcome.

First trimester maternal serum PAPP-A and free ß-hCG levels and risk of SGA or LGA in women with and without GDM.

BACKGROUND: Maternal gestational diabetes (GDM), small (SGA) and large (LGA) for gestational age neonates are associated with increased morbidity in both mother and child. We studied how different levels of first trimester pregnancy associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fß-hCG) were associated with SGA and LGA in GDM pregnancies and controls. METHODS: Altogether 23 482 women with singleton pregnancies participated in first trimester combined screening and delivered between 2014 and 2018 in Northern Finland and were included in this retrospective case-control study. Women with GDM (n = 4697) and controls without GDM (n = 18 492) were divided into groups below 5th and 10th or above 90th and 95th percentile (pc) PAPP-A and fß-hCG MoM levels. SGA was defined as a birthweight more than two standard deviations (SD) below and LGA more than two SDs above the sex-specific and gestational age-specific reference mean. Odds ratios were adjusted (aOR) for maternal age, BMI, ethnicity, IVF/ICSI, parity and smoking. RESULTS: In pregnancies with GDM the proportion of SGA was 2.6% and LGA 4.5%, compared to 3.3% (p = 0.011) and 1.8% (p < 0.001) in the control group, respectively. In ≤ 5th and ≤ 10th pc PAPP-A groups, aORs for SGA were 2.7 (95% CI 1.5-4.7) and 2.2 (95% CI 1.4-3.5) in the GDM group and 3.8 (95% CI 3.0-4.9) and 2.8 (95% CI 2.3-3.5) in the reference group, respectively. When considering LGA, there was no difference in aORs in any high PAPP-A groups. In the low ≤ 5 percentile fß-hCG MoM group, aORs for SGA was 2.3 (95% CI 1.8-3.1) in the control group. In fß-hCG groups with GDM there was no association with SGA and the only significant difference was ≥ 90 percentile group, aOR 1.6 (95% CI 1.1-2.5) for LGA. CONCLUSION: Association with low PAPP-A and SGA seems to be present despite GDM status. High PAPP-A levels are not associated with increased LGA risk in women with or without GDM. Low fß-hCG levels are associated with SGA only in non-GDM pregnancies.

Association of lipid levels at different stages of pregnancy with gestational diabetes mellitus and the incidence of neonatal macrosomia: A retrospective study.

OBJECTIVE: To investigate the correlation between lipid levels during gestation and the incidence rate of gestational diabetes mellitus (GDM) and macrosomia. METHOD: Clinical records of 607 pregnant women with GDM (GDM group) who delivered in the Obstetrics Department of Fujian Maternal and Child Health Hospital from May to December 2018 and of 833 women with uncomplicated pregnancies (control group) were retrospectively analyzed. After delivery, the entire cohort was further grouped based on the weight of the neonates: women who delivered newborns with body mass <4 kg comprised the normal group (n = 1367), and pregnancies that resulted in delivery of neonates with body mass >4 kg were classified as the macrosomia group (n = 73). Fasting serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and TG/HDL-C ratio were compared between the groups at the early (10-12 weeks), middle (24-28 weeks), and late (28 weeks-delivery) stages of pregnancy, and the correlation between the lipid indices and the rates of GDM and macrosomia were analyzed. RESULTS: There was a gradual increase in TC, TG, LDL-C, and TG/HDL-C levels with increasing gestational weeks in pregnant women. TG and TG/HDL-C levels were markedly higher, while HDL-C was lower in women with GDM compared with women of the same gestational age with uncomplicated pregnancies (p < 0.05). CONCLUSION: Lipid metabolism disorders exist in pregnant women with GDM at different gestational stages and are closely related to the higher incidence of macrosomia. TG, TG/HDL-C, and HDL-C in early and late pregnancy are independent risk factors for macrosomia in all trimesters, and TG/HDL-C ratio at different gestational stages has a good predictive value for macrosomia.

Predictability of Macrosomic Birth based on Maternal Factors and Fetal Aneuploidy Screening Biochemical Markers in Hyperglycemic Mothers.

Background: Macrosomic birth weight has been implicated as a significant risk factor for developing various adult metabolic diseases such as diabetes mellitus and coronary heart diseases; it has also been associated with higher incidences of complicated births. This study aimed to examine the predictability of macrosomic births in hyperglycemic pregnant women using maternal clinical characteristics and serum biomarkers of aneuploidy screening performed in the first half of pregnancy. Methods: A retrospective observational study was performed on a cohort of 1,668 pregnant women who 1) had positive outcomes after undergoing 50-g oral glucose challenge test (OGCT) at two university-based hospitals and 2) underwent any one of the following maternal biomarker screening tests for fetal aneuploidy: triple test, quadruple test, and integrated test. Logistic regression-based models for predicting macrosomic births using maternal characteristics and serum biomarkers were developed and evaluated for prediction power. A nomogram, which is a graphical display of the best predictable model, was then generated. Results: The study cohort included 157 macrosomic birth cases defined as birth weight ≥3,820 g, which was equivalent to the top 10 percentile of the modeling cohort. Three primary models solely based on serum biomarkers achieved area under curves (AUCs) of 0.55-0.62. Expanded models, including maternal demographic and clinical factors, demonstrated an improved performance by 25% (AUCs, 0.69-0.73). Conclusion: Our prediction models will help to identify pregnancies with an elevated risk of macrosomic births in hyperglycemic mothers using maternal clinical factors and serum markers from routine antenatal screening tests. Prediction of macrosomic birth at mid-pregnancy may allow customized antenatal care to reduce the risk of macrosomic births.

Mediating Effects of Maternal Blood Triglycerides on the Relationship between Prepregnancy Body Mass Index and Fetal Macrosomia.

OBJECTIVE: To examine whether the association of prepregnancy body mass index (BMI) with fetal macrosomia is mediated through maternal circulating lipid concentrations during pregnancy. STUDY DESIGN: In this prospective cohort, 3011 eligible pregnant women were enrolled. Information on demographic characteristics were collected using questionnaires, and anthropometrics and laboratory tests were performed at 24 weeks of gestation and before delivery. Macrosomia was defined as birth weight ≥4000 g. Logistic regression and multivariable linear regression, adjusted for age, fetal sex, education, gestational weight gain, fasting blood glucose, gestational diabetes, gestational hypertension, gestational age at delivery, delivery mode, and parity, were used to assess the mediation path between prepregnancy BMI, maternal serum lipids, and fetal macrosomia. RESULTS: A total of 2454 participants with completed records were included in the final analyses. Among the maternal circulating lipid biomarkers, only triglyceride was significantly associated with both prepregnancy BMI and fetal macrosomia risk, adjusting for potential confounders. Mediation analyses demonstrated that the direct effect of prepregnancy BMI on fetal macrosomia was 0.0085 (95% CI, 0.0003-0.018; P < .05), the indirect effect mediated through maternal serum triglycerides was 0.0016 (95% CI, 0.0007-0.0029; P < .001), and the estimated proportion of mediated effect was 15.7% (P < .05). CONCLUSIONS: Maternal circulating triglycerides mediate the association of prepregnancy BMI with the risk of fetal macrosomia.

Maternal lipids are associated with newborn adiposity, independent of GDM status, obesity and insulin resistance: a prospective observational cohort study.

OBJECTIVE: To determine the association between maternal lipaemia and neonatal anthropometrics in Malaysian mother-offspring pairs. DESIGN: Prospective observational cohort study. SETTING: Single tertiary multidisciplinary antenatal clinic in Malaysia. POPULATION: A total of 507 mothers: 145 with gestational diabetes mellitus (GDM); 94 who were obese with normal glucose tolerance (NGT) (pre-gravid body mass index, BMI ≥ 27.5 kg/m2 ), and 268 who were not obese with NGT. METHODS: Maternal demographic, anthropometric, and clinical data were collected during an interview/examination using a structured questionnaire. Blood was drawn for insulin, C-peptide, triglyceride (Tg), and non-esterified fatty acid (NEFA) during the 75-g 2-hour oral glucose tolerance test (OGTT) screening, and again at 36 weeks of gestation. At birth, neonatal anthropometrics were assessed and data such as gestational weight gain (GWG) were extracted from the records. MAIN OUTCOME MEASURES: Macrosomia, large-for-gestational-age (LGA) status, cohort-specific birthweight (BW), neonatal fat mass (NFM), and sum of skinfold thickness (SSFT) > 90th centile. RESULTS: Fasting Tg > 95th centile (3.6 mmol/L) at screening for OGTT was independently associated with LGA (adjusted odds ratio, aOR 10.82, 95% CI 1.26-93.37) after adjustment for maternal glucose, pre-gravid BMI, and insulin sensitivity. Fasting glucose was independently associated with a birthweight ratio (BWR) of >90th centile (aOR 2.06, 95% CI 1.17-3.64), but not with LGA status, in this well-treated GDM cohort with pre-delivery HbA1c of 5.27%. In all, 45% of mothers had a pre-gravid BMI of <23 kg/m2 and 61% had a pre-gravid BMI of ≤ 25 kg/m2 , yet a GWG of >10 kg was associated with a 4.25-fold risk (95% CI 1.71-10.53) of BWR > 90th centile. CONCLUSION: Maternal lipaemia and GWG at a low threshold (>10 kg) adversely impact neonatal adiposity in Asian offspring, independent of glucose, insulin resistance and pre-gravid BMI. These may therefore be important modifiable metabolic targets in pregnancy. TWEETABLE ABSTRACT: Maternal lipids are associated with adiposity in Asian babies independently of pre-gravid BMI, GDM status, and insulin resistance.

Comparison of factor XII levels in gestational diabetes, fetal macrosomia, and healthy pregnancies.

BACKGROUND: If not detected and treated, gestational diabetes mellitus (GDM) can cause serious pregnancy complications such as macrosomia, preeclampsia, and fetal/neonatal mortality. Many studies have examined underlying contributing factors for GDM, including hypercoagulation. Factor XII (FXII) is a coagulation factor that increases throughout normal pregnancies, and we evaluated the relationship of GDM with FXII, FXIIa (activated FXII), and other coagulation parameter levels. GDM and macrosomia are closely related, but it is not known whether FXII could be an independent causal factor for macrosomia. METHODS: In this prospective study, blood samples were taken from 69 pregnant women at the time of term delivery to determine levels of FXII, FXIIa, and other coagulation parameters. Based on the results, pregnancies fell into GDM, non-diabetic with macrosomia (M), or healthy (C [control]). RESULTS: FXII concentration levels were significantly higher in GDM patients compared with the M and C groups. There were no significant differences when comparing FXIIa, activated partial thromboplastin time, prothrombin time (PT), and international normalized ratio. The GDM group saw a significant negative correlation between FXII concentrations and maternal pregestational body mass index (BMI) and BMI before delivery. In the M group, a positive correlation was observed between FXII concentrations and newborn weight and newborn weight percentile. CONCLUSIONS: An increase in FXII levels was observed in patients with gestational diabetes. Associations between coagulation parameters and GDM should be further analyzed to define the mechanisms of GDM and possible treatment modalities. TRIAL REGISTRATION: Our study has been registered at clinicaltrials.gov ( NCT03583216 ). Registered on July 11, 2018.

Cord blood leptin DNA methylation levels are associated with macrosomia during normal pregnancy.

BACKGROUND: We previously demonstrated an association between placental leptin (LEP) methylation levels and macrosomia without gestational diabetes mellitus (non-GDM). This study further explored the association between LEP methylation in cord blood and non-GDM macrosomia. METHOD: We carried out a case-control study of 61 newborns with macrosomia (birth weight ≥4000 g) and 69 newborns with normal birth weight (2500-3999 g). Methylation in the LEP promoter region was mapped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS: Average cord blood LEP methylation levels were lower in macrosomia newborns than in control newborns (P < 0.001). Eleven CpG sites were associated with macrosomia. Multivariate logistic regression revealed that low LEP methylation levels [adjusted odds ratio (AOR) = 2.84, 95% confidence interval (CI): 1.72-4.17], high pre-pregnancy body mass index (AOR = 7.44, 95% CI: 1.99-27.75), long gestational age (AOR = 3.18, 95% CI: 1.74-5.79), high cord blood LEP concentration (AOR = 2.25, 95% CI: 1.34-3.77), and male newborn gender (AOR = 3.91, 95% CI: 1.31-11.69) significantly increased the risk of macrosomia. CONCLUSIONS: Lower cord blood LEP methylation levels and certain maternal and fetal factors are associated with non-GDM macrosomia.

Levels of Glucagon-like Peptide 1 are Decreased in Macrosomic Neonates from Non-Diabetic Mothers.

Glucagon-like peptide 1 (GLP-1) is a gut-derived peptide with insulin-like effects. Our aim was to analyze cord blood GLP-1 levels of macrosomic and appropriate-gestational-age (AGA) neonates from non-diabetic mothers. A case-control study was conducted with 22 term macrosomic neonates (birth weight≥4000 g) and 22 AGA (birth weight>10th percentile and<4000 g) pregnancies. Cord blood GLP-1 levels of neonates were measured. There were no significant differences in maternal age, gestational age and gravida between the 2 groups. Umbilical cord blood GLP-1 levels were significantly lower in macrosomic neonates (6.9±2.9 pg/mL) compared with control group (10.3±3.7 pg/mL) (p=0.002). Binary logistic regression analysis showed only the maternal BMI to be an independent statistically significant predictor of macrosomia (odds ratio=2.459; 95% CI, 1.170-5.170; P=0.018). The results of our study revealed decreased GLP-1 levels in macrosomic neonates, and maternal BMI was an independent predictor of macrosomia.

Metabolic profiling of umbilical cord blood in macrosomia.

BACKGROUND/OBJECTIVE: The term macrosomia is used to describe neonates with a birth weight of 4000 g or more. Macrosomia is a potential risk factor for obesity and metabolic syndromes in postnatal and adult life, yet little is known about its associations with metabolic difference in the early age. We performed metabolic profiling of umbilical cord blood to discover differential metabolites of macrosomia. METHODS: We conducted a case-control study of full-term singletons with normal maternal glucose tolerance [50 cases (macrosomia, birth weight ⩾4000 g); 50 controls (normal weight, birth weight 2500-3999 g)]. Metabolites in umbilical cord blood were detected using an untargeted metabolomic approach based on gas chromatography/mass spectrometry. We performed logistic regression to evaluate the associations between metabolites and macrosomia. We also performed pathway analysis based on KEGG and MBRole. RESULTS: Compared with controls, the macrosomia cases had a greater male proportion, gestational age, paternal body mass index (BMI) and maternal pre-pregnancy BMI. Forty-two metabolites differed between the cases and controls. After multivariable adjustment, 2-methylfumarate [adjusted odds ratio (AOR)=1.232, 95% confidence interval (CI): 1.102-1.376], uracil (AOR=38.494, 95% CI: 5.635-262.951), elaidic acid (AOR=0.834, 95% CI: 0.761-0.915), ribose (AOR=0.089, 95% CI: 0.021-0.378), lactulose (AOR=0.815, 95% CI: 0.743-0.894) and 4-aminobutyric acid (AOR=0.835, 95% CI: 0.764-0.912) remained significantly associated with macrosomia. Pyrimidine metabolism and pentose and glucuronate interconversions were the two top-ranking pathways enriched with those metabolites (-log P-value=3.49 and 2.47, respectively). CONCLUSION: Levels of 2-methylfumarate, uracil, ribose, elaidic acid, lactulose and 4-aminobutyric acid were associated with the incidence of macrosomia. The alteration of pathways involving those factors might be linked with the incidence of macrosomia and relevant metabolic syndromes later in life, and further studies are needed to confirm it and verify the mechanisms.

Assessment of lactate production as a response to sustained intrapartum hypoxia in large-for-gestational-age newborns.

INTRODUCTION: Lactate concentration in umbilical cord blood is an important measure of intrapartum anaerobic metabolism. The aim of the study was to compare lactate production of large-for-gestational-age (LGA) fetuses against appropriate-for-gestational-age (AGA) fetuses during hypoxia, in diabetic and non-diabetic mothers. MATERIAL AND METHODS: A total of 17 358 validated paired arterial and venous umbilical cord blood samples taken at birth with a full panel of pH, glucose, and lactate were analyzed relative to LGA (n = 2789) and AGA (n = 14 569). Umbilical cord blood acidemia (pH < mean minus 2 SD) was identified in 518 cases. RESULTS: Diabetes, but not acidemia, was more common among LGA (5.4%) than AGA cases (2.9%) (respectively P < .0001 and P < .69). At normal pH, glucose was lower in non-diabetes LGA cases, but not in diabetes LGA compared with corresponding AGA cases (respectively P < .0001 and P < .067). Glucose levels were higher in all groups during acidemia (P ≤ .0005), with lower values in non-diabetes LGA but not in diabetes LGA compared with corresponding AGA cases (respectively P = .005 and P < .58). At normal pH, lactate was lower in non-diabetes LGA but not in diabetes LGA compared with corresponding AGA cases (respectively P < .0001 and P < .98); during acidemia, lactate levels were higher in all groups (P < .0001), resulting in no significant difference between LGA and AGA in diabetes as well as in non-diabetes cases (respectively P = .29 and P < .084). CONCLUSIONS: Considering cord acidemia a proxy for intrapartum hypoxia, LGA fetuses showed no impaired ability to produce lactate during hypoxia. Maternal diabetes did not hamper the ability of LGA fetuses to produce lactate during hypoxia.

Association of maternal serum lipids at late gestation with the risk of neonatal macrosomia in women without diabetes mellitus.

BACKGROUND: Macrosomia is a serious public health problem worldwide due to its increasing prevalence and adverse influences on maternal and neonatal outcomes. Maternal dyslipidemia exerts potential and adverse impacts on pregnant women and newborns. However, the association between maternal serum lipids and the risk of macrosomia has not yet been clearly elucidated. We explored the association between the maternal lipids profile at late gestation and the risk of having macrosomia among women without diabetes mellitus (DM). METHODS: The medical records of 5407 pregnant women giving birth to single live babies at term were retrospectively analyzed. Subjects with DM, hypertension, thyroid disorders and fetal malformation were excluded. Maternal fasting serum lipids were measured during late pregnancy. Logistic regression analysis was used to analyze the variables associated with the risk of macrosomia. RESULTS: Maternal serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels were related to macrosomia; each 1 mmol/L increase in TG resulted in a 27% increase in macrosomia risk, while each 1 mmol/L increase in HDL-C level resulted in a 37% decrease in macrosomia risk, even after adjusting for potential confounders. Notably, the risk of macrosomia increased progressively with increased maternal serum TG levels and decreased HDL-C levels. Compared with women with serum TG levels < 2.5 mmol/L, women with TG levels greater than 3.92 mmol/L had an approximately 2.8-fold increased risk of macrosomia. Compared with women with serum HDL-C levels above 2.23 mmol/L, women with HDL-C levels of less than 1.62 mmol/L had a 1.9-fold increased risk of giving birth to an infan with macrosomia. In addition, a higher risk of macrosomia was observed in women with simultaneous hypertriglyceridemia and low serum HDL-C levels (odds ratio [OR] 2.400, 95% confidence interval [CI]: 1.760-3.274) compared to those with hypertriglyceridemia or low serum HDL-C alone (OR 2.074, 95% CI: 1.609-2.673 and OR 1.363, 95% CI: 1.028-1.809, respectively). CONCLUSIONS: Maternal serum TG levels and HDL-C levels at late gestation are independent predictors of macrosomia in women without DM.

Correlation of adipokines and markers of oxidative stress in women with gestational diabetes mellitus and their newborns.

AIM: We have shown that some markers of oxidative stress were higher in women with gestational diabetes mellitus (GDM). This study examines the relationship between adipokines and oxidative stress and their potential effects in pregnant women. METHODS: Three markers of oxidative stress (malondialdehyde, 8-isoprostane and xanthine oxidase) and three adipokines (leptin, adiponectin and resistin) were measured in maternal plasma, cord plasma and placenta of 208 pregnant women. RESULTS: Among all these women, 105 were diagnosed with GDM while the other 103 were controls. Leptin, resistin, malondialdehyde, xanthine oxidase and 8-isoprostane in maternal plasma, cord plasma and placenta were significantly higher while maternal adiponectin significantly lower in women with GDM (P < 0.05). Adipokines in maternal plasma, cord plasma and placenta were positively correlated with markers of oxidative stress. Both markers of oxidative stress and adipokines were correlated inversely with homeostasis model assessment of insulin resistance whereas positively with quantitative insulin sensitivity check index (P < 0.01). Adiponectin is negatively correlated with leptin and resistin. Placental/cord leptin and cord resistin levels were higher in the macrosomia while maternal adiponectin level was lower (P < 0.05) than normal birthweight newborns. Both markers of oxidative stress and adipokines in maternal and cord plasma are negatively correlated with newborn birthweight (P < 0.05). CONCLUSION: Adipokines interact with markers of oxidative stress, both of which lead to insulin resistance, GDM and macrosomia. It has long been known that placenta involves in the development of GDM. Adipokines might participate in this process and need to be confirmed by further studies.

Placental and cord blood brain derived neurotrophic factor levels are decreased in nondiabetic macrosomia.

PURPOSE: To measure levels of placental brain derived neurotrophic factor (BDNF) gene expression and umbilical cord blood BDNF in neonates with nondiabetic macrosomia and determine associations between these levels and macrosomia. METHODS: This case-control study included 58 nondiabetic macrosomic and 59 normal birth weight mother-infant pairs. Data were collected from interviews and our hospital's database. BDNF gene expression was quantified in placental tissues using quantitative real-time polymerase chain reaction (n = 117). Umbilical cord blood BDNF levels were measured by enzyme-linked immunosorbent assay (n = 90). Multivariate logistic regression models were used to evaluate associations between BDNF levels and macrosomia. RESULTS: Placental BDNF gene expression (P = 0.026) and cord blood BDNF (P = 0.008) were lower in neonates with nondiabetic macrosomia than in normal birth weight controls. Cord blood BDNF was significantly lower in vaginally delivered macrosomic neonates than vaginally delivered controls (P = 0.014), but cord BDNF did not differ between vaginal and cesarean section delivery modes in macrosomic neonates. Cord blood BDNF was positively associated with gestational age in control neonates (r = 0.496, P < 0.001), but not in macrosomic neonates. Cord blood BDNF was positively associated with placental BDNF relative expression (r s = 0.245, P = 0.02) in the total group. Higher cord blood BDNF levels were independently associated with protection against nondiabetic macrosomia (adjusted odds ratio 0.992; 95% confidence interval 0.986-0.998). CONCLUSIONS: Both placental BDNF gene expression and cord blood BDNF were downregulated in neonates with nondiabetic macrosomia compared with normal birth weight neonates. Cord BDNF may partly derive from BDNF secreted by the placenta. Higher cord plasma BDNF levels protected against nondiabetic macrosomia.

Measuring glycated haemoglobin in women with gestational diabetes mellitus: How useful is it?

BACKGROUND: Glycated haemoglobin (HbA1c) is an important tool for assessing glycaemic status in patients with diabetes, but its usefulness in gestational diabetes mellitus (GDM), is unclear. AIMS: The aim of this study is to evaluate whether HbA1c in women with GDM is valuable in predicting adverse pregnancy outcomes. MATERIALS AND METHODS: A retrospective review of women with GDM who had HbA1c measured at diagnosis of GDM (GHb-diag) and at 36 weeks gestation (GHb-36 weeks) was conducted. The association between HbA1c and various pregnancy outcomes was assessed RESULTS: Among 1244 women with GDM in our cohort, both GHb-diag and GHb-36 weeks were independent predictors for large-for-gestation (LGA) babies (OR 1.06, P = 0.005 and OR 1.06, P = 0.002, respectively) and neonatal hypoglycaemia (OR 1.10, P < 0.001 and OR 1.09, P < 0.001, respectively). Women with HbA1c ≥ 5.4% (35 mmol/mol) at diagnosis had significantly greater risk for LGA (15.3% vs 8.2%, P < 0.001) and neonatal hypoglycaemia (42.2% vs 23.6%, P < 0.001) than those below this cut-off. The difference between GHb-diag and GHb-36 weeks was small and improvement in HbA1c by 36 weeks was not associated with better pregnancy outcomes. CONCLUSION: We showed that measurement of HbA1c, either at the time of diagnosis of GDM or toward the end of pregnancy, were both associated with adverse pregnancy outcomes. Women with elevated HbA1c (>5.4% or 35 mmol/mol) at diagnosis of GDM should be monitored closely during pregnancy. However, there is not enough evidence to suggest that repeating HbA1c toward the end of pregnancy will provide additional information in predicting adverse pregnancy outcomes.

Free Fatty Acids of Newborns from Women with Gestational Diabetes Mellitus.

INTRODUCTION: Fetal macrosomia in gestational diabetes mellitus is contributed to by compensatory fetal mechanisms responding to alterations in maternal metabolism. OBJECTIVES: To compare FFA and blood glucose concentrations of newborns derived from healthy and hyperglycemic mothers. METHODS: Prospective study included two equal groups of term newborns (50) from GDM and healthy mothers. Blood was derived from umbilical and cubital vein of mothers immediately after birth. RESULTS: The mean FFA concentration of mothers did not differ whereas in infants of GDM mothers FFA were significantly lower. A significant correlation was found between FFA levels of healthy mothers and their newborns (p < 0.05). No such correlation was found in GDM group (p > 0.05). A significant correlation was found between mother's and newborn's glycemia (p < 0.05) in both groups. CONCLUSION: Suppression of FFA acids in newborn blood of mothers with GDM may represent the lipogenic and antilipolytic activity of the fetus.

The association of early unexplained elevated alanine aminotransferase with large-for-gestational-age birthweight.

BACKGROUND: Nonalcoholic fatty liver disease causes hepatic insulin resistance and is associated with metabolic syndrome. Elevated levels of alanine aminotransferase are associated with nonalcoholic fatty liver disease. The effect of hepatic insulin resistance is not only increased glycogen breakdown but also liberation of free fatty acids due to increased lipolysis. Both of these fuel sources are associated with macrosomia. There is little known about the impact of maternal nonalcoholic fatty liver disease on excessive fetal growth. OBJECTIVE: The purpose of this study was to investigate the association of early elevated alanine aminotransferase with large-for-gestational-age birthweight. STUDY DESIGN: This is a secondary analysis from a nested case-control study of maternal alanine aminotransferase values measured between 8-18 weeks and subsequent gestational diabetes. We included women with singleton gestations with complete delivery information and without known diabetes, liver disease, or moderate self-reported alcohol use during pregnancy. We used inverse probability weighting to standardize the population and minimize selection bias. We calculated population-based birthweight z scores and defined large for gestational age as ≥90th percentile for gestational age. We compared maternal baseline characteristics with analysis of variance, Fisher exact test, or Wilcoxon rank sum. We then performed conditional logistic regression to evaluate the relationship between alanine aminotransferase and large for gestational age adjusting for maternal age, body mass index, parity, gestational diabetes, smoking, and maternal weight gain. RESULTS: We identified 26 cases of large for gestational age out of 323 mother-infant dyads. The mean maternal body mass index was higher in the large-for-gestational-age group compared to controls (33.7 [SD 4.3] vs 28.9 [SD 6.5], P = .002). Large-for-gestational-age babies were less likely to be male (8 [31%] vs 172 [58%], P = .01) and had a higher mean gestational age (39.5 [SD 0.9] vs 38.4 [SD 2.3] weeks, P = .01). Maternal and infant characteristics were otherwise similar. The mean alanine aminotransferase among the large-for-gestational-age cases was 28 (SD 37) U/L compared to 16 (SD 8) U/L for controls. Each unit increase in log-transformed alanine aminotransferase was associated with a 3-fold odds of large for gestational age (adjusted odds ratio, 3.05; 95% confidence interval, 2.27-4.10; P < .0001), and alanine aminotransferase ≥90th percentile (26 U/L) was associated with a 4-fold increased odds of large for gestational age (adjusted odds ratio, 4.03; 95% confidence interval, 2.84-5.70; P < .0001). This association was unchanged when analysis was restricted only to women without gestational diabetes with a glucose loading test <120 mg/dL (log-transformed alanine aminotransferase: adjusted odds ratio, 3.05; 95% confidence interval, 1.04-8.96; P = .04, and alanine aminotransferase ≥90th percentile: adjusted odds ratio, 4.21; 95% confidence interval, 1.20-14.82; P = .03). CONCLUSION: Unexplained elevated alanine aminotransferase in the first trimester was associated with a 4-fold increase in the odds of large-for-gestational-age birthweight even in the absence of clinical glucose intolerance. This may represent the impact of maternal nonalcoholic fatty liver on the fetal developmental milieu.

Calcium plus vitamin D supplementation affects pregnancy outcomes in gestational diabetes: randomized, double-blind, placebo-controlled trial.

OBJECTIVE: The present study was designed to assess the effects of Ca+vitamin D supplementation on pregnancy outcomes in women with gestational diabetes mellitus (GDM). DESIGN: A randomized, double-blind, placebo-controlled trial was conducted among sixty women with GDM. Participants were divided into two groups to receive Ca+vitamin D supplements or placebo. Individuals in the Ca+vitamin D group (n 30) received 1000 mg Ca/d and two pearls containing 1250 µg (50 000 IU) of cholecalciferol (vitamin D(3)) during the intervention (one at study baseline and another at day 21 of the intervention); those in the placebo group (n 30) received two placebos of vitamin D at the mentioned times and placebos of Ca every day for 6 weeks. Pregnancy outcomes were determined. SETTING: A urban community setting in Arak, Iran. SUBJECTS: Sixty women with GDM and their newborns, living in Arak, Iran were enrolled. RESULTS: Women treated with Ca+vitamin D had a significant decrease in caesarean section rate (23·3 % v. 63·3 %, P=0·002) and maternal hospitalization (0 v. 13·3 %, P=0·03) compared with those receiving placebo. In addition, newborns of GDM women randomized to Ca+vitamin D had no case of macrosomia, while the prevalence of macrosomia among those randomized to placebo was 13·3 % (P=0·03). Lower rates of hyperbilirubinaemia (20·0 % v. 56·7 %, P=0·03) and hospitalization (20·0 % v. 56·7 %, P=0·03) were also seen in the supplemented group of newborns than in the placebo group. CONCLUSIONS: Ca+vitamin D supplementation for 6 weeks among pregnant women with GDM led to decreased caesarean section rate and maternal hospitalization, and decreased macrosomia, hyperbilirubinaemia and hospitalization in newborns.

Troponin T and NT ProBNP Levels in Gestational, Type 1 and Type 2 Diabetic Mothers and Macrosomic Infants.

This study compares NT proBNP and troponin T levels in umbilical cord arterial blood and postnatal echocardiographic findings for infants of gestational and pregestational diabetic mothers and macrosomic infants. Twenty-seven infants of pregestational diabetic mothers, 61 infants of gestational diabetic mothers and 37 macrosomic infants of nondiabetic mothers were prospectively enrolled in this study along with a control group of 58 healthy infants of mothers without any pregestational or gestational disorders as the control group. All enrollees were born after 34 weeks of gestation. For this study, umbilical cord blood was drawn during delivery to determine NT proBNP and troponin T levels. Echocardiography was performed 24-72 h after the delivery. Umbilical cord troponin T and NT proBNP levels were found to be higher in the diabetic and macrosomic groups than in the control group (all of them p < 0.001). NT proBNP levels were positively correlated with interventricular septum thickness in the pregestational and gestational infants of diabetic mothers groups (r = 0.564 and r = 0.560, respectively, p < 0.01). Both pregestational and gestational diabetic mothers were divided into two groups according to HbA1c levels in the third trimester as good (<6.1 %) and suboptimal (>6.1 %) metabolic control. In the good and suboptimal metabolic control diabetic groups, NT proBNP levels were also positively correlated with interventricular septum thickness (r = 0.536 and r = 0.576, respectively, p < 0.01). In the suboptimal metabolic control diabetic group, NT proBNP was only found to be positively correlated with the left ventricular mass index (r = 0.586, p < 0.01). While there was no correlation in the myocardial performance index between infants of diabetic mothers and the control group, the myocardial performance index of macrosomic infants was lower than that of the control group (p = 0.017). Cardiac biomarkers (NT proBNP and troponin T) were elevated in infants of diabetic mothers and macrosomic infants. While there was a positive correlation between NT proBNP levels and cardiac structure in infants of pregestational and gestational diabetic mothers, there was no relationship between NT proBNP levels and cardiac function.

Placental Weight in Pregnant Women with Type 1 Diabetes Mellitus: The Association with Fetal Growth.

Objective To determine the association between placental weight (PW) and large for gestational age (LGA) in women with type 1 diabetes mellitus (T1DM) and whether glycemic control modifies the association. Study Design In a retrospective analysis of a cohort of women with T1DM, poor glycemic control was defined as glycohemoglobin A1(HbA1)≥ 8.5% (≥2 standard deviations [SD] above mean), and LGA as birth weight > 90th percentile, according to gestation, race, and sex. Multivariable logistic regression was used for analysis. Stratified analyses (HbA1 < 8.5% vs. HbA1 ≥ 8.5%) assessed the role of glycemic control on association between PW and LGA. Results PW in 302 pregnancies was positively associated with LGA (first vs. fourth quartile of PW; odds ratio [OR] = 9.56; 95% confidence interval [CI]: 4.14-22.08). Association varied significantly by glycemic control in the first trimester, but not in the second and third trimesters. For women with first trimester HbA1 concentration < 8.5%, there was no statistically significant association; however, with HbA1 ≥ 8.5%, there was a strong association (OR = 13.40, 95% CI: 3.31, 54.27). Conclusion There was a significant positive association between PW and LGA in infants of women with T1DM, particularly evident in pregnancies with poor glycemic control during the first trimester, highlighting the importance of achieving good glycemic control early in gestation.