Fetal Macrosomia

Objectives To assess the association between maternal glucose concentrations and adverse perinatal outcomes in women without gestational or existing diabetes and to determine whether clear thresholds for identifying women at risk of perinatal outcomes can be identified.Design Systematic review and meta-analysis of prospective cohort studies and control arms of randomised trials.Data sources Databases including Medline and Embase were searched up to October 2014 and combined with individual participant data from two additional birth cohorts.Eligibility criteria for selecting studies Studies including pregnant women with oral glucose tolerance (OGTT) or challenge (OGCT) test results, with data on at least one adverse perinatal outcome.Appraisal and data extraction Glucose test results were extracted for OGCT (50 g) and OGTT (75 g and 100 g) at fasting and one and two hour post-load timings. Data were extracted on induction of labour; caesarean and instrumental delivery; pregnancy induced hypertension; pre-eclampsia; macrosomia; large for gestational age; preterm birth; birth injury; and neonatal hypoglycaemia. Risk of bias was assessed with a modified version of the critical appraisal skills programme and quality in prognostic studies tools.Results 25 reports from 23 published studies and two individual participant data cohorts were included, with up to 207 172 women (numbers varied by the test and outcome analysed in the meta-analyses). Overall most studies were judged as having a low risk of bias. There were positive linear associations with caesarean section, induction of labour, large for gestational age, macrosomia, and shoulder dystocia for all glucose exposures across the distribution of glucose concentrations. There was no clear evidence of a threshold effect. In general, associations were stronger for fasting concentration than for post-load concentration. For example, the odds ratios for large for gestational age per 1 mmol/L increase of fasting and two hour post-load glucose concentrations (after a 75 g OGTT) were 2.15 (95% confidence interval 1.60 to 2.91) and 1.20 (1.13 to 1.28), respectively. Heterogeneity was low between studies in all analyses.Conclusions This review and meta-analysis identified a large number of studies in various countries. There was a graded linear association between fasting and post-load glucose concentration across the whole glucose distribution and most adverse perinatal outcomes in women without pre-existing or gestational diabetes. The lack of a clear threshold at which risk increases means that decisions regarding thresholds for diagnosing gestational diabetes are somewhat arbitrary. Research should now investigate the clinical and cost-effectiveness of applying different glucose thresholds for diagnosis of gestational diabetes on perinatal and longer term outcomes.Systematic review registration PROSPERO CRD42013004608.

ObjectiveTo determine a precise estimate for the contribution of maternal obesity to macrosomia.Data sourcesThe search strategy included database searches in 2011 of PubMed, Medline (In-Process & Other Non-Indexed Citations and Ovid Medline, 1950-2011), and EMBASE Classic + EMBASE. Appropriate search terms were used for each database. Reference lists of retrieved articles and review articles were cross-referenced.Methods of study selectionAll studies that examined the relationship between maternal obesity (BMI ≥30 kg/m(2)) (pregravid or at 1st prenatal visit) and fetal macrosomia (birth weight ≥4000 g, ≥4500 g, or ≥90th percentile) were considered for inclusion.Tabulation, integration, and resultsData regarding the outcomes of interest and study quality were independently extracted by two reviewers. Results from the meta-analysis showed that maternal obesity is associated with fetal overgrowth, defined as birth weight ≥ 4000 g (OR 2.17, 95% CI 1.92, 2.45), birth weight ≥4500 g (OR 2.77,95% CI 2.22, 3.45), and birth weight ≥90% ile for gestational age (OR 2.42, 95% CI 2.16, 2.72).ConclusionMaternal obesity appears to play a significant role in the development of fetal overgrowth. There is a critical need for effective personal and public health initiatives designed to decrease prepregnancy weight and optimize gestational weight gain.

The associations between maternal pre-pregnancy obesity and low birth weight (LBW, 2) vs. normal BMI (18.5-24.9 kg/m2) were calculated using multiple logistic regression. Risk profiles (in the Lowess method) were presented for BMI values (kg/m2) and threshold BMI values were calculated. (1) In the cohort, LBW affected 6.6% of pregnancies, fetal growth restriction (FGR) 2.3%, and macrosomia 10.6%. (2) The adjusted risk of macrosomia was more than three-fold higher for obesity compared to normal BMI in the whole cohort (AOR = 3.21 (1.69-6.1), p p = 0.022), but only in the normal GWG subgroup. The FGR risk profile was U-shaped: in the entire cohort, the risk was more than three times higher for obesity (AOR = 3.12 (1.02-9.54), p = 0.045) and underweight (AOR = 3.84 (1.13-13.0), p = 0.031). (3) The risk profiles showed that the highest BMI values were found to be associated with a higher risk of these three newborn outcomes and the threshold BMI was 23.7 kg/m2 for macrosomia, 26.2 kg/m2 for LBW, and 31.8 kg/m2 for FGR. These results confirm the multidirectional effects of obesity on fetal growth (low birth weight, fetal growth restriction, and macrosomia). The results for LBW were heavily masked by the effects of abnormal gestational weight gain.

Gestational diabetes mellitus (GDM) is a growing global health concern, driving the need for novel diagnostic and prognostic approaches. The aim of this study was to analyze the amino acid profile in the mother-fetus system (maternal venous blood, umbilical cord blood, and amniotic fluid) and to identify specific biological markers of GDM and macrosomia. Using HPLC-MS/MS, we analyzed serum from maternal venous and umbilical cord blood, along with amniotic fluid, across 94 mother-fetus pairs (53 GDM, 41 controls). Machine learning and metabolic pathway analysis revealed significant alterations in 19 amino acids. In GDM, maternal serum showed elevated 5-OH-lysine and homocitrulline, while cord blood had higher isoleucine, serine, and threonine. Amniotic fluid exhibited increased leucine, isoleucine, threonine, serine, arginine, and ornithine. Conversely, histidine, glutamine, alanine, asparagine, β-/γ-aminobutyric acids, phenylalanine, ornithine, and citrulline were reduced. Histidine, glutamine, and asparagine inversely correlated with blood glucose (r = -0.26, r = -0.33, r = -0.30) and were lower in GDM. These findings highlight three key metabolic loci in GDM pathogenesis, with glutamine, histidine, and asparagine emerging as potential maternal blood biomarkers for early macrosomia prediction. However, given confounding factors in metabolomic studies, further large-scale validation is essential.