Umbilical Cord Biometry and Fetal Abdominal Skinfold Assessment as Potential Biomarkers for Fetal Macrosomia in a Gestational Diabetes Romanian Cohort.

Backgroundand Objectives: Gestational diabetes mellitus (GDM) is a pregnancy-associated pathology commonly resulting in macrosomic fetuses, a known culprit of obstetric complications. We aimed to evaluate the potential of umbilical cord biometry and fetal abdominal skinfold assessment as screening tools for fetal macrosomia in gestational diabetes mellitus pregnant women. Materials and methods: This was a prospective case−control study conducted on pregnant patients presenting at 24−28 weeks of gestation in a tertiary-level maternity hospital in Northern Romania. Fetal biometry, fetal weight estimation, umbilical cord area and circumference, areas of the umbilical vein and arteries, Wharton jelly (WJ) area and abdominal fold thickness measurements were performed. Results: A total of 51 patients were enrolled in the study, 26 patients in the GDM group and 25 patients in the non-GDM group. There was no evidence in favor of umbilical cord area and WJ amount assessments as predictors of fetal macrosomia (p > 0.05). However, there was a statistically significant difference in the abdominal skinfold measurement during the second trimester between macrosomic and normal-weight newborns in the GDM patient group (p = 0.016). The second-trimester abdominal circumference was statistically significantly correlated with fetal macrosomia at term in the GDM patient group with a p value of 0.003, as well as when considering the global prevalence of macrosomia in the studied populations, 0.001, when considering both populations. Conclusions: The measurements of cord and WJ could not be established as predictors of fetal macrosomia in our study populations, nor differentiate between pregnancies with and without GDM. Abdominal skinfold measurement and abdominal circumference measured during the second trimester may be important markers of fetal metabolic status in pregnancies complicated by GDM.

Independent effect of gestational weight gain and prepregnancy obesity on pregnancy outcomes among Saudi women: A sub-cohort analysis from Riyadh mother and baby cohort study (RAHMA).

BACKGROUND: Gestational weight gain (GWG) and prepregnancy obesity are garnering more attention as determining factors of pregnancy outcomes when it comes to the wellbeing of both the mother and her baby. This study was conducted to describe the pattern of GWG among participants of Riyadh Mother and Baby Multicenter Cohort Study (RAHMA) and to investigate the detrimental effects of excessive GWG and prepregnancy obesity on pregnancy outcomes. METHODS: RAHMA is a multicentre cohort study conducted in three hospitals in Riyadh, Saudi Arabia. Participants were categorized according to the Institute of Medicine into inadequate, adequate, and excessive GWG, and stratified by body mass index (BMI) into under/normal weight, overweight, and obese. To examine the independent effect of maternal prepregnancy obesity and GWG, a multivariate regression model was used and adjusted odds ratio (AOR) and 95% Confidence Interval (CI) for each outcome were calculated. RESULTS: A total of 7029 participants were included in this study; 31.8% had adequate GWG, 25.9% had excessive GWG and 42.3% had inadequate GWG, while 29.7% had normal BMI, 33.3% were overweight, 34.8% were obese, and 2.2% were underweight. Excessive GWG was independently associated with increased risk of hypertensive events, (AOR = 1.77, 95% CI 1.20-2.63). Obesity was associated with higher risk of gestational diabetes (AOR 2.11, 95% CI 1.76-2.53), hypertensive events (AOR 2.06, 95% CI 1.48-3.01), and delivery by emergency caesarean section (AOR = 1.63, 95% CI 1.35-1.97). Infants of obese women had increased odds of macrosomia (AOR 3.11, 95% CI 1.94-4.99) and lower odds of low birth weight (AOR = 0.68, 95% CI 0.53-0.88). CONCLUSION: In comparison to excessive GWG, which increases the risk of hypertensive events during pregnancy, prepregnancy obesity is associated with more adverse outcomes including GDM, hypertensive events in pregnancy and emergency CS.

Epidemiology of Macrosomia in Korea: Growth and Development.

BACKGROUND: Macrosomia, as an infant with birth weight over 4 kg, can have several perinatal, and neonatal complications. This study aimed to estimate the incidence of macrosomia in Korea and to identify the growth and developmental outcomes and other neonatal complications. METHODS: In total, 397,203 infants who were born in 2013 with birth weight ≥ 2.5 kg and who underwent infant health check-up between their 1st and 7th visit were included from the National Health Insurance Service database. The information was obtained by the International Classification of Diseases-10 codes or self-reported questionnaires in the National Health Screening Program. RESULTS: The distribution of infants by birth weight was as follows: 384,181 (97%) infants in the 2.5-3.99 kg (reference) group, 12,016 (3%) infants in the 4.0-4.49 kg group, 772 (0.2%) infants in the 4.5-4.99 kg group, and 78 (0.02%) infants in the ≥ 5 kg group. Macrosomia showed significantly higher incidence of sepsis, male sex, and mothers with GDM and birth injury. There was a significant difference in weight, height, and head circumference according to age, birth weight group, and combination of age and birth weight, respectively (P < 0.001). The number of infants with the weight above the 90th percentile in macrosomia at each health check-up showed higher incidence than in reference group. The mean body mass index significantly differed among the groups, as 50.6 in infants with 2.5-3.99 kg of birth weight, 63.5 with 4.0-4.49 kg, 71.0 with 4.5-4.99 kg, and 73.1 with ≥ 5 kg. There was a significant difference in the incidence of poor developmental results between infants with macrosomia and the reference group at 24, 36 and 48 month of age. CONCLUSION: Macrosomia was significantly associated with the risk of sepsis, birth injury, obesity and developmental problem especially in a boy born from mothers with gestational diabetes mellitus. Careful monitoring and proper strategies for monitoring growth and development are needed.

The role of cardiovascular risk factors in maternal cardiovascular disease according to offspring birth characteristics in the HUNT study.

A history of preterm or small (SGA) or large (LGA) for gestational age offspring is associated with smoking and unfavorable levels of BMI, blood pressure, glucose and lipids. Whether and to what extent the excess cardiovascular risk observed in women with these pregnancy complications is explained by conventional cardiovascular risk factors (CVRFs) is not known. We examined the association between a history of SGA, LGA or preterm birth and cardiovascular disease among 23,284 parous women and quantified the contribution of individual CVRFs to the excess cardiovascular risk using an inverse odds weighting approach. The hazard ratios (HR) between SGA and LGA offspring and CVD were 1.30 (95% confidence interval (CI) 1.15, 1.48) and 0.89 (95% CI 0.76, 1.03), respectively. Smoking explained 49% and blood pressure may have explained ≈12% of the excess cardiovascular risk in women with SGA offspring. Women with preterm birth had a 24% increased risk of CVD (HR 1.24, 95% CI 1.06, 1.45), but we found no evidence for CVRFs explaining any of this excess cardiovascular risk. While smoking explains a substantial proportion of excess cardiovascular risk in women with SGA offspring and blood pressure may explain a small proportion in these women, we found no evidence that conventional CVRFs explain any of the excess cardiovascular risk in women with preterm birth.

Observations of the Effects of Maternal Fasting Plasma Glucose Changes in Early Pregnancy on Fetal Growth Profiles and Birth Outcomes.

Introduction: Although the role of maternal hyperglycemia on birth outcomes is clear, literature regarding fetal growth is scarce. We examined the possible associations between maternal fasting plasma glucose (FPG) and fetal growth. Materials and Methods: A total of 35,981 singleton-pregnant women with FPG in the first trimester were included. Fetal growth parameters were measured during pregnancy by ultrasound at mid and late pregnancy. Information on birth characteristics was retrieved from medical records. We used multivariable linear and logistic regression to determine the associations between FPG and z-scores of fetal parameters and risks of birth outcomes and to assess effect modification by maternal characteristics. Results: A per-unit increase in FPG levels was negatively associated with fetal parameters in mid pregnancy but positively correlated with those in late pregnancy and with birth characteristics. The effect estimates in late pregnancy were attenuated by maternal pre-pregnancy body mass index (BMI). A significant relationship between FPG and abdominal circumference (AC), an indicator of fetal adiposity, was sustained in subgroups of women with advanced age, positive family history of diabetes, and multiparity in fully adjusted models. After stratification by BMI, high FPG was associated with accelerated AC only in normal controls (0.044 SD; 95% CI: 0.010, 0.079) and overweight/obese women (0.069 SD; 95% CI: -0.002, 0.140) but not in underweight women. High FPG was an independent risk factor for large-for-gestational age in the whole group and stratified subgroups. Conclusions: Increased FPG in early pregnancy is closely related to fetal growth. Maternal characteristics may modify the associations between FPG and fetal adiposity in late pregnancy.

Perinatal outcomes associated with the diagnosis of gestational diabetes: Systematic review and meta-analysis.

OBJECTIVE: To compare perinatal outcomes in pregnant women diagnosed with gestational diabetes using the one-step and the two-step test. METHODS: Meta-analysis of observational studies pregnancies women with gestational diabetes from January 2014 to February 2019. The outcomes studied were induction of labor and delivery, preterm delivery, fetal macrosomia, neonatal hypoglycemia, hyperbilirubinemia, low birth weight, and admission to the neonatal intensive care unit. RESULTS: Eight studies were included with a population of 108,609 pregnancies. Statistical differences were obtained for fetal macrosomia RR0.9 (95%CI0.85-0.97; I20%) and neonatal hypoglycemia RR1.1 (95%CI1.01-1.40; I248.5%). CONCLUSION: Neonatal macrosomia appears to be less present when the one-step diagnostic test is used and neonatal hypoglycemia was lower with the two-step test. Register PROSPERO CRD42020215062.

Reduced glucose-stimulated insulin secretion following a 1-wk IGF-1 infusion in late gestation fetal sheep is due to an intrinsic islet defect.

Insulin and insulin-like growth factor-1 (IGF-1) are fetal hormones critical to establishing normal fetal growth. Experimentally elevated IGF-1 concentrations during late gestation increase fetal weight but lower fetal plasma insulin concentrations. We therefore hypothesized that infusion of an IGF-1 analog for 1 wk into late gestation fetal sheep would attenuate fetal glucose-stimulated insulin secretion (GSIS) and insulin secretion in islets isolated from these fetuses. Late gestation fetal sheep received infusions with IGF-1 LR3 (IGF-1, n = 8), an analog of IGF-1 with low affinity for the IGF binding proteins and high affinity for the IGF-1 receptor, or vehicle control (CON, n = 9). Fetal GSIS was measured with a hyperglycemic clamp (IGF-1, n = 8; CON, n = 7). Fetal islets were isolated, and insulin secretion was assayed in static incubations (IGF-1, n = 8; CON, n = 7). Plasma insulin and glucose concentrations in IGF-1 fetuses were lower compared with CON (P = 0.0135 and P = 0.0012, respectively). During the GSIS study, IGF-1 fetuses had lower insulin secretion compared with CON (P = 0.0453). In vitro, glucose-stimulated insulin secretion remained lower in islets isolated from IGF-1 fetuses (P = 0.0447). In summary, IGF-1 LR3 infusion for 1 wk into fetal sheep lowers insulin concentrations and reduces fetal GSIS. Impaired insulin secretion persists in isolated fetal islets indicating an intrinsic islet defect in insulin release when exposed to IGF-1 LR3 infusion for 1 wk. We speculate this alteration in the insulin/IGF-1 axis contributes to the long-term reduction in ß-cell function in neonates born with elevated IGF-1 concentrations following pregnancies complicated by diabetes or other conditions associated with fetal overgrowth.NEW & NOTEWORTHY After a 1-wk infusion of IGF-1 LR3, late gestation fetal sheep had lower plasma insulin and glucose concentrations, reduced fetal glucose-stimulated insulin secretion, and decreased fractional insulin secretion from isolated fetal islets without differences in pancreatic insulin content.

The factors affecting the physical development of neonates in pregnant women with or without gestational diabetes mellitus.

OBJECTIVES: To explore the factors affecting neonatal physical development in pregnant women with or without gestational diabetes mellitus (GDM). METHODS: The subjects were selected from the pregnant woman giving birth in 2nd Affiliated Hospital of Zhengzhou University, from November 2015 to May 2016. The age, occupation, education level, gestational age, body weight before pregnancy, body weight at delivery, body height, delivery pattern, GDM status of pregnant women and neonatal gender, birth weight (BW), chest circumference (CC), head circumference (HC) and birth length (BL) were collected through medical records and questionnaires. The clinical data were retrospectively analyzed and studied. RESULTS: The significant differences were found between women with GDM and without GDM in following neonatal variables (P<0.05): BW, CC, and HC. GDM status increased the incidence of macrosomia (OR = 2.241, 95% CI: 1.406-3.573), large CC (OR = 2.470, 95% CI: 1.687-3.6153). Gestational weight gain (GWG) above IOM guideline was risk factor for macrosomia (OR = 1.763, 95% CI:1.098-2.833), large HC (OR = 1,584, 95% CI: 1.093-2.296) and large CC (OR = 1.707, 95% CI:1.163-2.506). Underweight was risk factor for short BL (OR = 2.543, 95% CI:1.161-5.571) and small CC (OR = 1.901, 95% CI:1.064-3.394). Female neonate was prone to appear short BL(OR = 2.831, 95% CI: 1.478-5.422) and small HC (OR = 2.750, 95% CI: 1.413-5.350), and not likely to macrosomia (OR = 0.538, 95% CI: 0.343-0.843), longer BL (OR = 0.584, 95% CI: 0.401-0.850), large HC (OR = 0.501, 95% CI: 0.352-0.713), and (OR = 0.640, 95% CI: 0.446-0.917). For women with GDM, gestational age was an risk factor of neonatal BW (low BW: OR = 0.207, 95% CI: 0.085-0.503; macrosomia: OR = 1.637, 95% CI: 1.177-2.276), BL (short BL: OR = 0.376, 95% CI: 0.241-0.585; long BL: OR = 1.422, 95% CI: 1.054-1.919), HC (small HC: OR = 0.343, 95% CI: 0.202-0.583; large HC: OR = 1.399, 95% CI: 1.063-1.842) and CC (small CC: OR = 0.524, 95% CI: 0.374-0.733; large CC: OR = 1.485, 95% CI: 1.138-1.936). CONCLUSIONS: In our study, gestational age, GDM status, neonatal gender, GWG and pre-pregnancy body mass index (BMI) are associated the abnormal physical development of neonates. In women with GDM, gestational age was correlate with neonatal abnormal physical developments.

Perinatal Outcomes in a Longitudinal Birth Cohort of First Nations Mothers With Pregestational Type 2 Diabetes and Their Offspring: The Next Generation Study.

OBJECTIVES: There is emerging evidence that First Nations women with diabetes in pregnancy and their offspring have poorer health outcomes than non-First Nations women. The aim of this study was to describe the perinatal outcomes of pregnancies complicated by type 2 diabetes. METHODS: The Next Generation longitudinal study is a First Nations birth cohort of children born to mothers diagnosed in childhood with type 2 diabetes. Pregnant women were prospectively enrolled in the birth cohort, and a review of medical records (including stored fetal ultrasound images) was performed to determine perinatal outcomes for 112 child-mother pairs between 2005 and 2015. Maternal demographics, antenatal variables, fetal ultrasound findings, obstetric and delivery information and neonatal birth outcomes were collected and analyzed. RESULTS: Mothers in our cohort were young and most were overweight at the start of pregnancy. Most had suboptimal glycemic control in the first trimester (median glycated hemoglobin, 9.3%). The cesarean section rate was high at 41%. Over one-half of newborns had macrosomia at birth, and almost 1 in 5 were born with a structural anomaly, mainly renal. Fetal ultrasound significantly underestimated the proportion of infants born with macrosomia (p<0.05) and missed 3 of 7 cardiac defects in this cohort. CONCLUSIONS: High rates of anomalies, macrosomia and cesarean deliveries provide insight into pregnancy management and disease processes for First Nations women with pregestational type 2 diabetes and their offspring, and highlights opportunities for improvement in prenatal care of these women.

Fetal overgrowth in pregnancies complicated by diabetes: validation of a predictive index in an external cohort.

PURPOSE: To assess validity of a fetal overgrowth index in an external cohort of women with diabetes in pregnancy METHODS: We performed a retrospective analysis of data derived from women with singleton gestations complicated by diabetes who delivered January 2015-June 2018. The following index variables were used to calculate risk of fetal overgrowth as defined by a customized birthweight ≥ 90th centile: age, history of fetal overgrowth in a prior pregnancy, gestational weight gain, fetal abdominal circumference measurement and fasting glucose between 24 and 30 weeks. RESULTS: In our validation cohort, 21% of 477 pregnancies were complicated by fetal overgrowth. The predictive index had a bias-corrected bootstrapped area under receiver operating characteristic curve of 0.90 (95% CI 0.86-0.93). 55% of the cohort had a low-risk index (≤ 3) which had a negative predictive value of 97% (95% CI 94-98%), while 18% had a high-risk index (≥ 8) that had a positive predictive value of 74% (95% CI 66-81%). CONCLUSION: The fetal overgrowth index incorporates five factors that are widely available in daily clinical practice prior to the period of maximum fetal growth velocity in the third trimester. Despite substantial differences between our cohort and the one studied for model development, we found the performance of the index was strong. This finding lends support for the general use of this tool that may aid counseling and allow for targeted allocation of healthcare resources among women with pregnancies complicated by diabetes.

Heterozygous recurrent HNF4A variant p.Arg85Trp causes Fanconi renotubular syndrome 4 with maturity onset diabetes of the young, an autosomal dominant phenocopy of Fanconi Bickel syndrome with colobomas.

Heterozygous pathogenic variants in HNF4A cause hyperinsulinism, maturity onset diabetes of the young type 1, and more rarely Fanconi renotubular syndrome. Specifically, the recurrent missense pathogenic variant c.253C>T (p.Arg85Trp) has been associated with a syndromic form of hyperinsulinism with additional features of macrosomia, renal tubular nephropathy, hypophosphatemic rickets, and liver involvement. We present an affected mother, who had been previously diagnosed clinically with the autosomal recessive Fanconi Bickel Syndrome, and her affected son. The son's presentation expands the clinical phenotype to include multiple congenital anomalies, including penile chordee with hypospadias and coloboma. This specific pathogenic variant should be considered in the differential diagnosis of Fanconi Bickel Syndrome when genetics are negative or the family history is suggestive of autosomal dominant inheritance. The inclusion of hyperinsulinism and maturity onset of the diabetes of the young changes the management of this syndrome and the recurrence risk is distinct. Additionally, this family also emphasizes the importance of genetic confirmation of clinical diagnoses, especially in adults who grew up in the premolecular era that are now coming to childbearing age. Finally, the expansion of the phenotype to include multiple congenital anomalies suggests that the full spectrum of HNF4A is likely unknown.

The effect of vascular complications of diabetes mellitus on human umbilical cord tissue and the number of Wharton Jelly's mesenchymal stem cells.

The current study investigated the change in umbilical cord tissue and the number of markers of Wharton's jelly mesenchymal stem cells (WJ-MSC) in pregnant women with gestational diabetes (GDM), with chronic diabetes who developed nephropathy as vascular complication (VC-PGDM), and healthy pregnant women as the control. The umbilical cords (UC) were investigated by the histomorphological method and the number of WJ-MSC were detected by flow-cytometry using the CD90, CD44, CD105, and CD73 markers in Wharton's jelly (WJ) isolated from fresh umbilical cords. The number of positive cells for CD 90, CD44, CD105, and CD73 were found to be elevated in the GDM group, whereas it was significantly diminished in the VC-PGDM group (p = 0.001, p = 0.001, p = 0.001, and p = 0.001). The only histopathological sign in the GDM group were an increased number of pores in the Wharton jelly. Artery wall thickness/cord diamater ratio was increased, which indicates an increase of the artery wall thickness in the VC- PGDM group (p = 0.039 and p = 0.048). The increase in umbilical cord diameter and number of Wharton jelly mesenchymal stem cells in babies of gestational diabetic mothers was considered as an effect of macrosomia seen in babies of mothers with gestational diabetes. Vasculopathy, a long-term complication of diabetes, is known to affect all tissues by causing marked lower perfusion and hypoxia, as well as a decrease in the MSC number in our study.

The triad macrosomia, obesity, and hypertriglyceridemia in gestational diabetes.

AIMS: Offspring of women with gestational diabetes (GD) have more macrosomia than newborns of normal mothers. We studied macrosomia frequency, possible pathogenesis, and main predictors of its appearance at different gestational ages. MATERIALS AND METHODS: A total of 1870 pregnant women with GD were recruited in primary care centres and maternity hospitals in the Argentine provinces of Corrientes, Chaco, Buenos Aires, and in Buenos Aires City; 1088 completed gestation and delivered an infant. We collected clinical and metabolic data, personal and obstetric history, and gestational and delivery characteristics. Presence of macrosomia was analysed in the whole population, the entire pregnancy, and in each trimester of gestation. Data were statistically analysed and values were expressed as mean ± SD and percentages. The study protocol was approved by the Ethics Committee and all participants signed informed consent. RESULTS: Macrosomia was found in 12.9% of newborns and obesity in all mothers with no significant differences between mothers with/without macrosomic offspring. In early pregnancy, the main significant indicators of macrosomia were: history of dyslipidaemia (5.6% vs 1.2%, respectively) and macrosomia in previous pregnancies (27% vs 13%, respectively). However, the third trimester showed a significant combination of higher BMI, FBG, and triglycerides. CONCLUSIONS: Offspring of women with GD presented macrosomia in 12.9% of cases, maternal history of dyslipidaemia and macrosomia in previous pregnancies being early predictors. The combination of maternal obesity, FBG, and hypertriglyceridemia became significant during the last trimester of pregnancy.

Associations of maternal glycemia and prepregnancy BMI with early childhood growth: a prospective cohort study.

The prevalence of maternal and child overweight/obesity and gestational hyperglycemia has increased greatly in China in recent years. However, studies examining the relationship between maternal hyperglycemia, maternal prepregnancy body mass index (ppBMI), and offspring obesity in China are limited. Here, we conducted a prospective study of 6684 mother-child pairs in Wuhan, China in 2012-2015. Maternal glucose concentrations were measured at approximately 24-28 weeks of gestation; children's weight and length were measured at birth and at 6, 12, and 24 months of age; and BMI-for-age Z-scores (BMIZ) were calculated for different time points. We found that maternal fasting plasma glucose (FPG) concentrations were positively associated with offspring ponderal index and the risk of macrosomia at birth, but not with BMIZ or the risk of overweight/obesity at 6, 12, and 24 months of age. By contrast, maternal ppBMI was positively associated with both an increased risk of macrosomia at birth and overweight/obesity at 6, 12, and 24 months of age. Here, we observed an interaction effect of the association of FPG and ppBMI on offspring macrosomia and a mediating effect of gestational diabetes mellitus on the pathway between ppBMI and macrosomia. Our findings suggest that maternal ppBMI is a more pronounced predictor than gestational FPG concentrations in both the relation to BMIZ and the risk of overweight/obesity in early childhood.

Infant Death Following Home Birth: A Case Report of Fatal Neonatal Hypoglycemia.

Infants born to diabetic mothers are at increased risk for symptomatic hypoglycemia and death after birth. A 36-year-old G4P3 mother with a history of gestational diabetes and newly diagnosed type II insulin-dependent diabetes gave birth at home, in the care of a midwife, to a macrosomic infant girl (10 lbs.). Several hours after birth, the infant became lethargic and was found to be hypoglycemic (blood sugar: 28 mg/dL). Glucose and sugar water were administered by the midwife; however, the infant continued to decompensate. Emergency medical services were called, and the infant was transported to the hospital where, despite resuscitative efforts, she died. An autopsy and review of the literature was performed. At autopsy, characteristic features of maternal-fetal glucose dysregulation were identified, including fetal macrosomia, cardiomegaly, hepatomegaly, and severe pancreatic islet cell hypertrophy/hyperplasia. Developmental abnormalities and other potential causes of death were not identified. Although deaths due to hypoglycemia cannot be reliably diagnosed postmortem using vitreous glucose levels, a clinical history of maternal glucose dysregulation in combination with certain gross and histologic findings should prompt a pathologist to consider maternal-fetal glucose dysregulation as a diagnosis of exclusion and cause of death.

Gestational diabetes: weight gain during pregnancy and its relationship to pregnancy outcomes.

BACKGROUND: Weight gain during pregnancy reflects the mother's nutritional status. However, it may be affected by nutritional therapy and exercise interventions used to control blood sugar in gestational diabetes mellitus (GDM). This study aimed to evaluate weight gain during gestation and pregnancy outcomes among women with GDM. METHODS: A retrospective study involving 1523 women with GDM was conducted between July 2013 and July 2016. Demographic data, gestational weight gain (GWG), blood glucose, glycated-hemoglobin level, and maternal and fetal outcomes were extracted from medical records. Relationships between GWG and pregnancy outcomes were investigated using multivariate logistic regression. RESULTS: In total, 451 (29.6%) women showed insufficient GWG and 484 (31.8%) showed excessive GWG. Excessive GWG was independently associated with macrosomia (adjusted odds ratio [aOR] 2.20, 95% confidence interval [CI] 1.50-3.52, P < 0.001), large for gestational age (aOR 2.06, 95% CI 1.44-2.93, P < 0.001), small for gestational age (aOR 0.49, 95% CI 0.25-0.97, P = 0.040), neonatal hypoglycemia (aOR 3.80, 95% CI 1.20-12.00, P = 0.023), preterm birth (aOR 0.45, 95% CI 0.21-0.96, P = 0.040), and cesarean delivery (aOR 1.45, 95% CI 1.13-1.87, P = 0.004). Insufficient GWG increased the incidence of preterm birth (aOR 3.53, 95% CI 1.96-6.37, P < 0.001). CONCLUSIONS: Both excessive and insufficient weight gain require attention in women with GDM. Nutritional therapy and exercise interventions to control blood glucose should also be used to control reasonable weight gain during pregnancy to decrease adverse pregnancy outcomes.

Comparison of placental three-dimensional power Doppler indices and volume in the first and the second trimesters of pregnancy complicated by gestational diabetes mellitus.

Objective: To compare the changes of placental three-dimensional power Doppler indices and volume in the first and the second trimesters of pregnancy with gestational diabetes mellitus (GDM). Methods: This was a prospective case-control study of singleton pregnancies with risk factors for GDM. Data on placental vascular indices including vascularization index (VI), flow index (FI), and vascularization flow index (VFI), as well as placental volume were obtained and analyzed during the first and the second trimesters between pregnant women with and without GDM. Results: Of the 155 pregnant women enrolled, 31 developed GDM and 124 did not. VI and VFI were significantly lower in the GDM group during the first and second trimesters (VI: p = .023, and VFI: p = .014 in the first trimester; VI: p = .049, and VFI: p = .031 in the second trimester). However, the placental volume was similar in both the groups during the first trimester, while it was significantly increased in the GDM group during the second trimester (p = .022). There were no significant differences in FI and uterine artery pulsatility index between the two groups. After adjustments in multivariate logistic regression analysis, significant differences were observed in the first trimester VFI (adjusted odds ratio (OR) 0.76, 95% confidence interval (CI) 0.61-0.93), second trimester VFI (adjusted or 0.83, 95%CI 0.71-0.96), and second trimester placental volume (adjusted or 1.03, 95%CI 1.01-1.05). Conclusions: Placental vascular indices can provide an insight into placental vascularization in GDM during early pregnancy. VFI rather than placental volume may be a sensitive sonographic marker in the first trimester of GDM placentas.

Attenuation of maternal weight gain impacts infant birthweight: systematic review and meta-analysis.

Despite many interventions aiming to reduce excessive gestational weight gain (GWG), it is currently unclear the impact on infant anthropometric outcomes. The aim of this review was to evaluate offspring anthropometric outcomes in studies designed to reduce GWG. A systematic search of seven international databases, one clinical trial registry and three Chinese databases was conducted without date limits. Studies were categorised by intervention type: diet, physical activity (PA), lifestyle (diet + PA), other, gestational diabetes mellitus (GDM) (diet, PA, lifestyle, metformin and other). Meta-analyses were reported as weighted mean difference (WMD) for birthweight and birth length, and risk ratio (RR) for small for gestational age (SGA), large for gestational age (LGA), macrosomia and low birth weight (LBW). Collectively, interventions reduced birthweight, risk of macrosomia and LGA by 71 g (WMD: -70.67, 95% CI -101.90 to -39.43, P<0.001), 16% (RR: 0.84, 95% CI 0.73-0.98, P=0.026) and 19% (RR: 0.81, 95% CI 0.69-0.96, P=0.015), respectively. Diet interventions decreased birthweight and LGA by 99 g (WMD -98.80, 95% CI -178.85 to -18.76, P=0.016) and 65% (RR: 0.35, 95% CI 0.17-0.72, P=0.004). PA interventions reduced the risk of macrosomia by 51% (RR: 0.49, 95% CI 0.26-0.92, P=0.036). In women with GDM, diet and lifestyle interventions reduced birthweight by 211 and 296 g, respectively (WMD: -210.93, 95% CI -374.77 to -46.71, P=0.012 and WMD:-295.93, 95% CI -501.76 to -90.10, P=0.005, respectively). Interventions designed to reduce excessive GWG lead to a small reduction in infant birthweight and risk of macrosomia and LGA, without influencing the risk of adverse outcomes including LBW and SGA.

Disadvantages of a weight estimation formula for macrosomic fetuses: the Hart formula from a clinical perspective.

PURPOSE: Sonographic fetal weight (FW) estimation to detect macrosomic fetuses is an essential part of everyday routine work in obstetrics departments. Most of the commonly used weight estimation formulas underestimate FW when the actual birth weight (BW) exceeds 4000 g. One of the best-established weight estimation formulas is the Hadlock formula. In an effort to improve the detection rates of macrosomic infants, Hart et al. published a specially designed formula including maternal weight at booking. The usefulness of the Hart formula was tested. METHODS: Retrospective study of 3304 singleton pregnancies, birth weight ≥ 3500 g. The accuracy of the Hadlock and Hart formula were tested. A subgroup analysis examined the influence of the maternal weight. The Chi-squared test and one-way analysis of variation were carried out. For all analyses, p < 0.05 was considered statistically significant. RESULTS: The overall percentages of births falling within ± 5% and ± 10% of the BW using the Hadlock formula were 27% and 53%, respectively. Using the Hart formula, 24% and 54% were identified within these levels. With the Hart formula, 94% of all weight estimations fall within 4200 g ± 5% and nearly 100% fall within 4200 g ± 10%. CONCLUSIONS: Applying the Hart formula results in an overestimation of fetal weight in neonates with a birth weight < 4000 g and fails to identify high-risk fetuses. We, therefore, do not consider Hart's formula to be of clinical relevance.

Adipose Tissue Inflammation and Adrenomedullin Overexpression Contribute to Lipid Dysregulation in Diabetic Pregnancies.

Context: Impaired maternal lipid metabolism in gestational diabetes mellitus (GDM) has detrimental effects on maternal health and fetal growth. We previously reported the excessive expression of adrenomedullin (ADM) and its receptors in GDM adipose tissues compared with normal glucose-tolerant pregnancies. In the present study, we determined the mechanisms underlying enhanced expression of ADM and its receptors. Design: Omental adipose tissue (OAT) samples were collected from women during cesarian section of term pregnancy with nonoverweight (NOW; n = 9), overweight (OW; n = 8), obese (OBS; n = 10), and GDM (n = 10) status. Results: The expression of ADM and its receptors was greater in OATs from GDM than from women who were NOW, OW, and OBS. The expression of adipokines, leptin, and resistin were significantly increased, but adiponectin was decreased in OATs from patients with GDM compared with those without GDM. Macrophage infiltration and TNF-α expression were greater in OAT from pregnant women with GDM than in pregnant women without GDM. Furthermore, TNF-α dose dependently increased mRNA for ADM and its receptor components calcitonin receptor-like receptor and receptor activity-modifying proteins 2 and 3 in OAT explants from women who were NOW. Human adipocytes treated with ADM significantly increased glycerol release in culture medium, and the increases of glycerol in culture medium of OAT from women with GDM were attenuated by ADM antagonists, ADM22-52. Conclusions: Increased macrophage infiltration and TNF-α expression in adipose tissue from GDM, but not from OBS, tissues stimulate ADM and its receptor overexpression, leading to enhanced lipolysis and hyperlipidemia. This might contribute to fetal macrosomia and adiposity in diabetic pregnancies.