Association of Maternal Total Cholesterol With SGA or LGA Birth at Term: the Japan Environment and Children's Study.

CONTEXT: Maternal cholesterol is important for fetal development. Whether maternal serum total cholesterol (maternal TC) levels in midpregnancy are associated with small (SGA) or large (LGA) for gestational age independent of prepregnancy body mass index (BMI) and weight gain during pregnancy is inconclusive. OBJECTIVE: This work aimed to prospectively investigate the association between maternal TC in midpregnancy and SGA or LGA. METHODS: The Japan Environment and Children's Study is a nationwide prospective birth cohort study in Japan. Participants in this study included 37 449 nondiabetic, nonhypertensive mothers with singleton birth at term without congenital abnormalities. Birth weight for gestational age less than the 10th percentile and greater than or equal to the 90th percentile were respectively defined as SGA and LGA by the Japanese neonatal anthropometric charts. RESULTS: The mean gestational age at blood sampling was 22.7 ±â€…4.0 weeks. After adjustment for maternal age, sex of child, parity, weight gain during pregnancy, prepregnancy BMI, smoking, alcohol drinking, blood glucose levels, household income, and study areas, 1-SD decrement of maternal TC was linearly associated with SGA (odds ratio [OR]: 1.20; 95% CI, 1.15-1.25). In contrast, 1-SD increment of maternal TC was linearly associated with LGA (OR: 1.13; 95% CI, 1.09-1.16). Associations did not differ according to prepregnancy BMI and gestational weight gain (P for interaction > .20). CONCLUSION: Maternal TC levels in midpregnancy were associated with SGA or LGA in a Japanese cohort. It may help to predict SGA and LGA. Favorable maternal lipid profiles for fetal development must be explored.

Large-for-Gestational-Age, Leptin, and Adiponectin in Infancy.

CONTEXT: Fetal overgrowth "programs" an elevated risk of obesity and type 2 diabetes in adulthood. Plausibly, adipokines may be involved in programming metabolic health. OBJECTIVE: This work aimed to evaluate whether large-for-gestational-age (LGA), an indicator of fetal overgrowth, is associated with altered circulating leptin and adiponectin levels in infancy, and assess the determinants. METHODS: In the Canadian 3D birth cohort, we studied 70 LGA (birth weight > 90th percentile) and 140 optimal-for-gestational-age (OGA, 25th-75th percentiles) infants matched by maternal ethnicity, smoking, and gestational age at delivery. The primary outcomes were fasting leptin, and total and high-molecular-weight (HMW) adiponectin concentrations at age 2 years. RESULTS: LGA infants had higher body mass index (BMI) than OGA infants. However, there were no significant differences in leptin, and total and HMW adiponectin concentrations. Leptin concentrations were positively associated with female sex, weight (z score) gain 0 to 24 months, current BMI, and the sum of triceps and subscapular skinfold thickness, and negatively associated with maternal age and White ethnicity. Female sex was associated with lower total and HMW adiponectin concentrations. Weight (z score) gain 0 to 24 months and current BMI were positively correlated with total and HMW adiponectin concentrations in LGA infants only. CONCLUSION: This study is the first to demonstrate that LGA does not matter for circulating leptin and adiponectin concentrations in infancy, and there may be LGA-specific positive associations between weight gain or current BMI and adiponectin concentrations in infancy, suggesting dysfunction in establishing the adiposity-adiponectin negative feedback loop in LGA individuals.

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.

Effects of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with gestational diabetes mellitus: A protocol for systematic review and meta analysis.

BACKGROUND: There is limited study that has conducted a review investigating the clinical effects of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with gestational diabetes mellitus (GDM). Therefore, in order to provide new evidence-based medical evidence for clinical treatment, we undertook a systematic review and meta-analysis to assess the effectiveness and safety of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with GDM. METHODS: This protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement guidelines. We will conduct systematic reviews and meta-analyses to identify relevant randomized controlled trials (RCTs) involving vitamin and omega-3 fatty acid co-supplementation on GDM in electronic databases including PubMed, Web of Science, Embase, and the Cochrane Library up to June 2021. Exclusion criteria include observational studies, non-RCTs, review articles, studies with a sample size <50, and studies with insufficient outcome data. The primary outcomes include fasting glucose and insulin. Secondary outcomes are evaluated in a homeostasis model of insulin resistance, total antioxidant capacity, triglycerides, total cholesterol, low-density lipoprotein cholesterol, preterm birth and macrosomia over 4 kg. RESULTS: The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings. REGISTRATION NUMBER: 10.17605/OSF.IO/NSW54.

Predictors of neonatal adiposity and associations by fetal sex in women with gestational diabetes mellitus and normal glucose-tolerant women.

AIMS: To determine predictors of neonatal adiposity and differences in associations by fetal sex in women with gestational diabetes mellitus (GDM), normal-weight and overweight (BMI ≥ 25 kg/m2) normal glucose-tolerant women (NGT). METHODS: Skinfold thickness was measured in 576 newborns, and cord blood leptin, c-peptide and lipids in 327 newborns in a multi-centric prospective cohort study. RESULTS: Compared to neonates of normal-weight NGT women (327), neonates of women with GDM (97) were more often large-for-gestational age (LGA) (16.5% vs 8.6%, p = 0.024) ,but the macrosomia rate (8.2% vs 5.8%, p = 0.388), sum of skinfolds (13.9 mm ± 2.9 vs 13.3 mm ± 2.6, p = 0.067), neonatal fat mass (1333.0 g ± 166.8 vs 1307.3 g ± 160.9, p = 0.356), and cord blood biomarkers were not significantly different. Compared to neonates of normal-weight NGT women, neonates of overweight NGT women (152) had higher rates of macrosomia (12.5% vs 5.8%, p = 0.012), LGA (17.1% vs 8.6%, p = 0.006), higher sum of skinfolds (14.3 mm ± 2.6 vs 13.2 mm ± 2.6, p < 0.001), neonatal fat mass (1386.0 g ± 168.6 vs 1307.3 g ± 160.9, p < 0.001), % neonatal fat mass > 90th percentile (15.2% vs 7.1%, p < 0.001), without significant differences in cord blood biomarkers. Maternal BMI, fasting glycemia, triglycerides, gestational weight gain, cord blood leptin ,and cord blood triglycerides were independent predictors for neonatal adiposity. Gestational weight gain was positively associated with adiposity in boys only. CONCLUSION: Compared to neonates of normal-weight NGT women, neonates of GDM women have higher LGA rates but similar adiposity, while neonates of overweight NGT women have increased adiposity. Limiting gestational weight gain might be especially important in the male fetus to reduce neonatal adiposity.

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.

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.

Fibrin/fibrinogen degradation products in late pregnancy promote macrosomia prediction in normal uncomplicated pregnancy.

OBJECTIVE: The purpose of this study was to explore the association of fibrin/fibrinogen degradation products (FDP) levels with the risk of macrosomia, and determine whether FDP, either alone or combined with traditional factors in late pregnancy, could be used to predict macrosomia at birth in healthy pregnancies. METHODS: A total of 9464 health pregnant women with singleton pregnancy were recruited in this retrospective cohort study. Maternal plasma FDP levels at hospital admission and birth outcomes were obtained from laboratory system and hospital records, respectively. RESULTS: FDP levels in late pregnancy were significant higher in women who delivered macrosomia than those who delivered infants with normal weight [median (interquartile range, IQR): 8.2 (5.8-11.9) vs. 6.6 (4.7-9.6) mg/L; P < 0.001]. Multivariable logistic regression analysis demonstrated that FDP levels were independently associated with macrosomia risk. Pregnant women in the highest quartile of FDP had a 2.99-fold higher risk of delivering macrosomia compared with those in the lowest (adjusted OR: 2.99; 95% CI: 2.27-3.93). In addition, the incorporation of FDP into the crude prediction model significantly improved the area under curve (AUC) for predicting macrosomia (0.774 vs. 0.787; P < 0.001). CONCLUSION: Our findings suggest that maternal plasma FDP levels in late pregnancy are independently and significantly associated with risk of macrosomia. Combination of FDP levels and traditional risk factors could promote the prediction of macrosomia.

Circulating microRNAs overexpressed in macrosomia: an experimental and bioinformatic approach.

Low birth weight (LBW) and macrosomia have been associated with later-in-life metabolic alterations. The aim of this study was to elucidate whether the expression levels of circulating microRNAs (c-miRNAs) associated with adult metabolic diseases are also dysregulated in newborns with LBW or macrosomia. The expression levels of five microRNAs (miRNAs) associated with metabolic diseases were quantified in dried blood spots of newborns with adequate birth weight, LBW and macrosomia by stem-loop real-time polymerase chain reaction. miR-29a-5p, miR-126-3p, miR-221-3p, and miR-486-5p were significantly overexpressed in newborns with macrosomia and showed no significant change in the LBW group compared to normal weight controls. miR-320a showed no statistical difference among groups. We predicted the putative target genes and pathways of the overexpressed miRNAs with bioinformatic tools. Bioinformatic analyses of overexpressed miRNAs predicted target genes involved in carbohydrate metabolism, participate in FoxO and PI3K/Akt signaling pathways, and are associated with diabetes, obesity, and cardiovascular diseases. The overexpression of circulating miR-29a-5p, miR-126-3p, miR-221-3p, and miR-486-5p may explain the increased risk of obesity and diabetes associated with macrosomia. The use of dried blood spots from newborn screening cards to quantify miRNAs expression levels could be an early and minimally invasive predictive tool for these metabolic alterations.

Are serum levels of inhibin A in second trimester predictors of adverse pregnancy outcome?

OBJECTIVE: During pregnancy, inhibin A is mainly derived from the placenta and regulates the implantation and differentiation of embryos. Our aim was to assess whether second trimester serum inhibin A was associated with an increased risk of adverse pregnancy outcomes. METHODS: We investigated the serum levels of Inhibin A during the second trimester in pregnancy, and analyzed associations between the Inhibin A and the risk of adverse pregnancy outcome. 12,124 pregnant women were enrolled in this study between January 2017 and July 2019 at the Obstetrics & Gynecology Hospital of Fudan University. Multivariate logistic regression analysis was conducted to estimate the relative risk between Inhibin A and adverse pregnancy outcome. RESULTS: Compared with the group without adverse pregnancy outcome, during the second trimester of pregnancy, age and Inhibin A were risk factors for pre-eclampsia, gestational diabetes mellitus and preterm delivery; Inhibin A was risk factors for low birth weight. Gravidity and Inhibin A were risk factors for macrosomia; while parity was a protective factor against pre-eclampsia, gestational hypertension and low birth weight. CONCLUSION: Elevated Inhibin A levels in pregnancy are significantly associated with pre-eclampsia, GDM, macrosomia, low birth weight and preterm delivery.

Concentrations of fatty acids among macrosomic neonates delivered by healthy women and women with type 1 diabetes mellitus.

OBJECTIVE: To evaluate the concentration and profile of fatty acids (FAs) among macrosomic neonates delivered by healthy pregnant women and pregnant women with type 1 diabetes mellitus (T1DM). METHODS: A prospective study of women who delivered macrosomic neonates at a University Hospital Center, Zagreb, Croatia, 2016-2018. Maternal, umbilical vein, and arterial blood samples were collected immediately on delivery. After lipid extraction, total FAs in maternal, umbilical vein, and arterial serum samples were assessed by gas chromatography. Data were compared between women with T1DM and healthy control women. RESULTS: In total, 50 women were enrolled: 22 with T1DM and 28 control women. Neonates in the T1DM group had a higher ponderal index as compared with the control group (P=0.006). Umbilical vein insulin, insulin resistance, and leptin concentration were higher in the T1DM group than in the control group (all P<0.001). Umbilical vein serum concentrations of total saturated, monounsaturated, n-3 polyunsaturated, and n-6 polyunsaturated FAs were higher in the T1DM group (P=0.004, P<0.001, P=0.015, and P=0.014, respectively). CONCLUSION: Macrosomic neonates delivered by women with T1DM had a higher Ponderal index, and higher concentrations of insulin, leptin, and FAs in the umbilical vein and artery as compared with control group newborns.

Continuous Glucose Monitoring in Pregnancy: Importance of Analyzing Temporal Profiles to Understand Clinical Outcomes.

OBJECTIVE: To determine if temporal glucose profiles differed between 1) women who were randomized to real-time continuous glucose monitoring (RT-CGM) or self-monitored blood glucose (SMBG), 2) women who used insulin pumps or multiple daily insulin injections (MDIs), and 3) women whose infants were born large for gestational age (LGA) or not, by assessing CGM data obtained from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT). RESEARCH DESIGN AND METHODS: Standard summary metrics and functional data analysis (FDA) were applied to CGM data from the CONCEPTT trial (RT-CGM, n = 100; SMBG, n = 100) taken at baseline and at 24- and 34-weeks' gestation. Multivariable regression analysis determined if temporal differences in 24-h glucose profiles occurred between comparators in each of the three groups. RESULTS: FDA revealed that women using RT-CGM had significantly lower glucose (0.4-0.8 mmol/L [7-14 mg/dL]) for 7 h/day (0800 h to 1200 h and 1600 h to 1900 h) compared with those with SMBG. Women using pumps had significantly higher glucose (0.4-0.9 mmol/L [7-16 mg/dL]) for 12 h/day (0300 h to 0600 h, 1300 h to 1800 h, and 2030 h to 0030 h) at 24 weeks with no difference at 34 weeks compared with MDI. Women who had an LGA infant ran a significantly higher glucose by 0.4-0.7 mmol/L (7-13 mg/dL) for 4.5 h/day at baseline, by 0.4-0.9 mmol/L (7-16 mg/dL) for 16 h/day at 24 weeks, and by 0.4-0.7 mmol/L (7-13 mg/dL) for 14 h/day at 34 weeks. CONCLUSIONS: FDA of temporal glucose profiles gives important information about differences in glucose control and its timing, which are undetectable by standard summary metrics. Women using RT-CGM were able to achieve better daytime glucose control, reducing fetal exposure to maternal glucose.

Neonatal Macrosomia is an Interfering Factor for Analytes on the Colorado State Newborn Screen.

PURPOSE: Neonatal macrosomia is a known complication of maternal obesity and gestational diabetes, and it is a risk factor for obesity and diabetes in offspring. Amino acids and acylcarnitines are biomarkers for obesity in children and adults. These analytes, which are also routinely obtained on the newborn screen, have not been well-characterized in macrosomic newborns. The impact of macrosomia on rates of false-positive results in the newborn screen has also not been well-studied. We test the hypothesis that macrosomia is an interfering factor for amino acids and/or acylcarnitines on the newborn screen. METHODS: Newborn screening analytes determined by tandem mass spectroscopy were obtained from the Colorado Department of Public Health and Environment archives (2016-2018). This included metabolite concentrations obtained at 24-72 hours of life from newborns with birth weight 2500 to 3999 g (nonmacrosomic, n = 131 896) versus 4000 to 8000 g (macrosomic, n = 7806). Mother/infant phenotypic data were limited to information provided on the newborn screening dried blood spot card. Data were analyzed using Student t-test and chi-squared analysis. RESULTS: Macrosomic newborns had elevations in C2, C3, dicarboxylic, and long-chain acylcarnitines (specifically C16 and C18 species). C3 and C18:1 were 2 to 3 times more likely to be above predetermined state cutoffs in macrosomic versus nonmacrosomic newborns (both male and female). MAIN CONCLUSIONS: Macrosomia is an interfering factor for the analytes C3 and C18:1, leading to higher risk of false-positive results for methylmalonic/propionic acidemia and carnitine palmitoyl transferase type 2 deficiency, respectively. Analyte patterns found in macrosomic neonates correspond with similar analyte patterns in obese children and adults.

Plasma Glycated CD59 Predicts Early Gestational Diabetes and Large for Gestational Age Newborns.

CONTEXT: Gestational diabetes mellitus (GDM) diagnosed in early pregnancy is a health care challenge because it increases the risk of adverse outcomes. Plasma-glycated CD59 (pGCD59) is an emerging biomarker for diabetes and GDM. The aim of this study was to assess the performance of pGCD59 as a biomarker of early GDM and its association with delivering a large for gestational age (LGA) infant. OBJECTIVES: To assess the performance of pGCD59 to identify women with GDM in early pregnancy (GDM < 20) and assess the association of pGCD59 with LGA and potentially others adverse neonatal outcomes linked to GDM. METHODS: Blood levels of pGCD59 were measured in samples from 693 obese women (body mass index > 29) undergoing a 75-g, 2-hour oral glucose tolerance test (OGTT) at <20 weeks' gestation in the Vitamin D and Lifestyle Intervention study: the main analyses included 486 subjects who had normal glucose tolerance throughout the pregnancy, 207 who met criteria for GDM at <20 weeks, and 77 diagnosed with GDM at pregnancy weeks 24 through 28. Reference tests were 75-g, 2-hour OGTT adjudicated based on International Association of Diabetes and Pregnancy Study Group criteria. The index test was a pGCD59 ELISA. RESULTS: Mean pGCD59 levels were significantly higher (P < 0.001) in women with GDM < 20 (3.9 ±â€…1.1 standard peptide units [SPU]) than in those without (2.7 ±â€…0.7 SPU). pGCD59 accurately identified GDM in early pregnancy with an area under the curve receiver operating characteristic curves of 0.86 (95% confidence interval [CI], 0.83-0.90). One-unit increase in maternal pGCD59 level was associated with 36% increased odds of delivering an LGA infant (odds ratio for LGA vs non-LGA infant: 1.4; 95% CI, 1.1-1.8; P = 0.016). CONCLUSION: Our results indicate that pGCD59 is a simple and accurate biomarker for detection of GDM in early pregnancy and risk assessment of LGA.

First-trimester fasting glycemia as a predictor of gestational diabetes (GDM) and adverse pregnancy outcomes.

AIMS: Studies to prevent gestational diabetes (GDM) have shown the best results when lifestyle measures have been applied early in pregnancy. We aimed to investigate whether first-trimester fasting plasma glucose (FPG) could predict GDM risk and adverse pregnancy outcomes. METHODS: A retrospective analysis of prospectively collected data from singleton pregnancies who were attended at our hospital between 2008 and 2018 (n = 27,198) was performed. We included patients with a recorded first-trimester FPG and complete pregnancy data (n = 6845). Patients under 18, with pregestational diabetes or reproductive techniques, were excluded. First-trimester FPG was evaluated as a continuous variable and divided into quartiles. GDM was diagnosed by NDDG criteria. The relationship between first- and second-trimester glucose > 92 mg/dL was also investigated. The relationship between FPG and pregnancy outcomes was assessed in 6150 patients who did not have GDM. RESULTS: Maternal age was 34.2 ± 3.9 years, BMI 23.1 ± 3.7 kg/m2 and mean FPG 83.0 ± 7.3 mg/dL. Glucose quartiles were: ≤ 78, 79-83, 84-87 and ≥ 88 mg/dL. First-trimester FPG predicted the risk of GDM (7%, 8%, 10.2% and 16% in each quartile, p < 0.001) and the risk of second-trimester glucose > 92 mg/dL (2.6%, 3.8%, 6.3% and 11.4% in each quartile, p < 0.001). FPG was significantly associated with LGA (8.2%, 9.3%, 10% and 11.7% in each quartile, p = 0.011) but not with other obstetrical outcomes. In a multivariate analysis including age, BMI, tobacco use, number of pregnancies and weight gained during pregnancy, first-trimester FPG was an independent predictor of LGA. CONCLUSIONS: First-trimester FPG is an early marker of GDM and LGA.

Maternal serum uric acid levels in pregnancy and fetal growth.

Objective: Studies of maternal serum uric acid (UA) in pregnancy focus primarily on high levels of UA, however, both low and high UA levels can be markers of oxidative stress, a biological state potentially linked to fetal growth. We therefore aimed to test whether low and high maternal serum UA levels during pregnancy are associated with atypical fetal growth (unusually small or large) measured as birthweight (BW) for gestational age.Methods: The Pregnancy Outcomes and Community Health Study enrolled 3019 pregnant women between their 16th-27th week of pregnancy from 52 clinics in five Michigan communities (1998-2004). Maternal UA levels were measured in blood collected at enrollment among a subcohort of 1291 participants. Infant BW and gestational age were used to calculate gestational age-specific BW Z-score. Infants were grouped as small (SGA = BW < 10th percentile), appropriate (AGA = BW 10th-90th percentile), or large (LGA) = BW > 90th percentile) for their gestational age. Analyses considered multiple potential confounders. Linear spline or multiple linear regression models were applied to evaluate the relationship between maternal UA levels and BW Z-score overall and within SGA, AGA, and LGA groups. Model robustness was tested through bootstrap, sensitivity analysis, and cross-validation techniques.Results: The relation between maternal UA levels and BW Z-score varied by infant group. Among SGA infants, the relation was nonlinear (J-shape): both extremes of UA had lower BW Z-score with a breakpoint of 0.267 mmol/L UA (adjusted regression coefficient ß = 2.32, p = .01 for lower UA; adjusted ß = -37.38, p < .01 for higher UA). Among AGA infants, there was no significant association, and among LGA infants, the relation was linear (adjusted ß = 2.86, p = .03).Conclusions: Future research on maternal UA levels in pregnancy may benefit from considering both very low and high levels, and identifying in utero conditions associated with the two extremes.

Abdominal circumference profiles of macrosomic infants born to mothers with or without hyperglycemia in China.

Objectives: Serial measurements of sonographic fetal abdominal circumference (AC) are useful for monitoring fetal growth during pregnancy and are essential for predicting macrosomia. The study was aiming to compare the AC profiles of infants born to mothers with or without hyperglycemia in Chinese population.Subjects and methods: The "GDM Prevalence Study (GPS)" was a large study conducted in 22 hospitals in three large cities in China, which included 34,085 NGT (normal glucose tolerant) women, 8272 GDM (gestational diabetes mellitus) women and 729 DM (diabetes mellitus) women. A total of 116,740 scans and 103,377 valid AC measurements were performed for the NGT, GDM and DM groups at different gestational age. AC profiles and fetal growth rates at different stages of pregnancy were compared between different groups.Results: The overall AC growth rate (ß) was higher in the macrosomia group than in the no macrosomia group in NGT (ß =10.250 versus 9.541, p < .001), GDM (ß = 10.572 versus 9.705, p < .001) and DM (ß = 11.363 versus 9.924, p < .001) pregnancies. Significant differences were observed between NGT-macrosomia, GDM-macrosomia and DM-macrosomia. Significant differences were also noted between NGT-no macrosomia, GDM-no macrosomia and DM-no macrosomia women. Participants in NGT-macrosomia group exhibited larger AC values than NGT-no macrosomia group beginning at 21 gestational weeks, and GDM-macrosomia group exhibited larger AC values than GDM-no macrosomia group beginning at 22 gestational weeks. AC growth rate was higher in NGT-macrosomia and GDM-macrosomia groups than in the corresponding no macrosomia groups between 22 and 30 gestational weeks.Conclusions: The overall AC growth rates are higher in macrosomia group compared to the no macrosomia group in NGT, GDM as well as DM participants. The significant difference of AC growth rates in NGT-macrosomia and GDM-macrosomia indicate the possible differential underlying mechanisms in developing macrosomia with or without hyperglycemia exposure. Our study demonstrate that larger fetal AC measurements around 21-22 weeks are associated with subsequent diagnosis of macrosomia, suggesting that macrosomia management should be initiated much earlier than we thought.

Serum fructosamine predicts macrosomia in well-controlled hyperglycaemic pregnant women: An observational cross-sectional study.

AIM: While serum fructosamine may be a good marker of glucose control in pregnant women with diabetes, its relationship with macrosomia is still uncertain. METHODS: In 130 hyperglycaemic women with singleton pregnancies (117 gestational diabetes mellitus, 13 pregestational diabetes), serum fructosamine and HbA1c levels were measured at 25±7 weeks of gestation. Levels in mothers of infants with and without macrosomic newborns (birth weight>4000g and/or large-for-gestational-age birth weight>90th percentile) were compared using logistic regression analysis adjusted for macrosomia risk factors. RESULTS: These 130 pregnant women were 33±5 years old; their BMI before pregnancy was 27.7±6.9kg/m2, and they gained 7.5±5.1kg during the first 6 months of gestation. Glucose control was good according to HbA1c levels (5.3±0.3%; 34±2mmol/mol), yet 17/130 (13%) newborns had macrosomia: 3900±227g vs 3057±512g (P<0.001) in the others. These mothers were older and had higher parity, whereas their BMI scores before pregnancy and gestational weight gains did not differ. Fructosamine levels were also higher at 221±40µmol/L vs 192±22µmol/l (P<0.001), respectively, and remained significant even after adjusting for maternal age, BMI, parity, type of diabetes, antecedents of macrosomia and excessive gestational weight gain. By contrast, HbA1c did not differ between the two groups. In fact, nearly two-thirds (64.7%) of the mothers of macrosomic newborns had fructosamine levels>200µmol/l vs 31.9% of mothers with non-macrosomic newborns (P<0.05). CONCLUSION: High fructosamine levels are associated with macrosomia in the newborns of well-controlled hyperglycaemic pregnant women.

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.

Excessive Weight Gain Before and During Gestational Diabetes Mellitus Management: What Is the Impact?

OBJECTIVE: Conventional gestational diabetes mellitus (GDM) management focuses on managing blood glucose in order to prevent adverse outcomes. We hypothesized that excessive weight gain at first presentation with GDM (excessive gestational weight gain [EGWG]) and continued EGWG (cEGWG) after commencing GDM management would increase the risk of adverse outcomes, despite treatment to optimize glycemia. RESEARCH DESIGN AND METHODS: Data collected prospectively from pregnant women with GDM at a single institution were analyzed. GDM was diagnosed on the basis of Australasian Diabetes in Pregnancy Society 1998 guidelines (1992-2015). EGWG means having exceeded the upper limit of the Institute of Medicine-recommended target ranges for the entire pregnancy, by GDM presentation. The relationship between EGWG and antenatal 75-g oral glucose tolerance test (oGTT) values and adverse outcomes was evaluated. Relationships were examined between cEGWG, insulin requirements, and large-for-gestational-age (LGA) infants. RESULTS: Of 3,281 pregnant women, 776 (23.6%) had EGWG. Women with EGWG had higher mean fasting plasma glucose (FPG) on oGTT (5.2 mmol/L [95% CI 5.1-5.3] vs. 5.0 mmol/L [95% CI 4.9-5.0]; P < 0.01), after adjusting for confounders, and more often received insulin therapy (47.0% vs. 33.6%; P < 0.0001), with an adjusted odds ratio (aOR) of 1.4 (95% CI 1.1-1.7; P < 0.01). aORs for each 2-kg increment of cEGWG were a 1.3-fold higher use of insulin therapy (95% CI 1.1-1.5; P < 0.001), an 8-unit increase in final daily insulin dose (95% CI 5.4-11.0; P < 0.0001), and a 1.4-fold increase in the rate of delivery of LGA infants (95% CI 1.2-1.7; P < 0.0001). CONCLUSIONS: The absence of EGWG and restricting cEGWG in GDM have a mitigating effect on oGTT-based FPG, the risk of having an LGA infant, and insulin requirements.