Maternal overweight and obesity and its association with metabolic changes and fetal overgrowth in the absence of gestational diabetes mellitus: A prospective cohort study.

INTRODUCTION: Previous studies indicated an association between fetal overgrowth and maternal obesity independent of gestational diabetes mellitus (GDM). However, the underlying mechanisms beyond this possible association are not completely understood. This study investigates metabolic changes and their association with fetal and neonatal biometry in overweight and obese mothers who remained normal glucose-tolerant during gestation. MATERIAL AND METHODS: In this prospective cohort study 893 women who did not develop GDM were categorized according to their pregestational body mass index (BMI): 570 were normal weight, 220 overweight and 103 obese. Study participants received a broad metabolic evaluation before 16 weeks and were followed up until delivery to assess glucose levels during the oral glucose tolerance test (OGTT) at mid-gestation as well as fetal biometry in ultrasound and pregnancy outcome data. RESULTS: Increased maternal BMI was associated with an adverse metabolic profile at the beginning of pregnancy, including a lower degree of insulin sensitivity (as assessed by the quantitative insulin sensitivity check index) in overweight (mean difference: -2.4, 95% CI -2.9 to -1.9, p < 0.001) and obese (mean difference: -4.3, 95% CI -5.0 to -3.7, p < 0.001) vs normal weight women. Despite not fulfilling diagnosis criteria for GDM, overweight and obese mothers showed higher glucose levels at fasting and during the OGTT. Finally, we observed increased measures of fetal subcutaneous tissue thickness in ultrasound as well as higher proportions of large-for-gestational-age infants in overweight (18.9%, odds ratio [OR] 1.74, 95% CI 1.08-2.78, p = 0.021) and obese mothers (21.0%, OR 1.99, 95% CI 1.06-3.59, p = 0.027) vs normal weight controls (11.8%). The risk for large for gestational age was further determined by OGTT glucose (60 min: OR 1.11, 95% CI 1.02-1.21, p = 0.013; 120 min: OR 1.13, 95% CI 1.02-1.27, P = 0.025, for the increase of 10 mg/dL) and maternal triglyceride concentrations (OR 1.11, 95% CI 1.01-1.22, p = 0.036, for the increase of 20 mg/dL). CONCLUSIONS: Mothers affected by overweight or obesity but not GDM had a higher risk for fetal overgrowth. An impaired metabolic milieu related to increased maternal BMI as well as higher glucose levels at mid-gestation may impact fetal overgrowth in women still in the range of normal glucose tolerance.

Transition of the genital mollicutes from the second to the third trimester of pregnancy and its association with adverse pregnancy outcomes in GDM women: a prospective, single-center cohort study from China.

BACKGROUND: The association of genital Mollicutes infection transition with adverse pregnancy outcomes was insignificant among general pregnant women, but there remains a paucity of evidence linking this relationship in gestational diabetes mellitus (GDM) women. The aim was to investigate the association between genital Mollicutes infection and transition and adverse pregnancy outcomes in GDM women, and to explore whether this association still exist when Mollicutes load varied. METHODS: We involved pregnant women who attended antenatal care in Chongqing, China. After inclusion and exclusion criteria, we conducted a single-center cohort study of 432 GDM women with pregnancy outcomes from January 1, 2018 to December 31, 2021. The main outcome was adverse pregnancy outcomes, including premature rupture of membrane (PROM), fetal distress, macrosomia and others. The exposure was Mollicutes infection, including Ureaplasma urealyticum (Uu) and Mycoplasma hominis (Mh) collected in both the second and the third trimesters, and testing with polymerase chain reaction method. The logistic regression models were used to estimate the relationship between Mollicutes infection and adverse pregnancy outcomes. RESULTS: Among 432 GDM women, 241 (55.79%) were infected with genital Mollicutes in either the second or third trimester of pregnancy. At the end of the pregnancy follow-up, 158 (36.57%) participants had adverse pregnancy outcomes, in which PROM, fetal distress and macrosomia were the most commonly observed adverse outcomes. Compared with the uninfected group, the Mollicutes (+/-) group showed no statistical significant increase in PROM (OR = 1.05, 95% CI:0.51 ∼ 2.08) and fetal distress (OR = 1.21, 95% CI: 0.31 ∼ 3.91). Among the 77 participants who were both Uu positive in the second and third trimesters, 38 participants presented a declined Uu load and 39 presented an increased Uu load. The Uu increased group had a 2.95 odds ratio (95% CI: 1.10~8.44) for adverse pregnancy outcomes. CONCLUSION: Mollicutes infection and transition during trimesters were not statistically associated with adverse pregnancy outcomes in GDM women. However, among those consistent infections, women with increasing Uu loads showed increased risks of adverse pregnancy outcomes. For GDM women with certain Mollicutes infection and colonization status, quantitative screening for vaginal infection at different weeks of pregnancy was recommended to provide personalized fertility treatment.

Physical activity, gestational weight gain in obese patients with early gestational diabetes and the perinatal outcome - a randomised-controlled trial.

BACKGROUND: Excessive gestational weight gain, especially among women with gestational diabetes, is associated with several adverse perinatal outcomes. Our study aimed to analyse the impact of the use of pedometers to supervise physical activity on maternal health and the obstetric outcomes of pregnant women with obesity and early gestational diabetes. METHODS: 124 pregnant patients were enrolled in the presented research. INCLUSION CRITERIA: singleton pregnancy, age > 18 years, gestational diabetes diagnosed in the first half of pregnancy (< 20th week of pregnancy), obesity according to the American Endocrine Society criteria. Each patient was advised to take at least 5000 steps daily. Patients were randomly assigned to pedometers (N = 62), and were recommended to monitor daily the number of steps. The group without pedometers (N = 62) was not observed. Visit (V1) was scheduled between the 28th and 32nd gestational week (GW), and visit (V2) occurred between the 37th and 39th GW. Anthropometric measurements and blood samples were collected from all patients at each appointment. Foetal and maternal outcomes were analysed at the end of the study. RESULTS: In the group supervised by pedometers, there were significantly fewer newborns with macrosomia (p = 0,03). Only 45% of patients satisfied the recommended physical activity guidelines. Patients who walked more than 5000 steps per day had significantly higher body weight at baseline (p = 0,005), but weight gain was significantly lower than in the group that did not exceed 5000 steps per day (p < 0,001). The perinatal outcome in the group of patients performing more than 5000 steps did not demonstrate significant differences with when compared to less active group. ROC curve for weight gain above the guidelines indicated a statistically substantial cut-off point for this group at the level of 4210 steps/day (p = 0.00001). CONCLUSIONS: Monitoring the activity of pregnant patients with gestational diabetes and obesity by pedometers did not have a significantly impact on their metabolic control and weight gain. However, it contributed to less macrosomia. Furthermore, physical activity over 5,000 steps per day positively affects weight loss, as well as contributes to improved obstetric and neonatal outcomes.

Same disease - different effect: maternal diabetes impact on birth weight stratified by fetal sex.

BACKGROUND: Male-sex is an independent risk factor for adverse perinatal outcomes. One example is gestational diabetes mellitus (GDM), which is associated with large gestational age neonates. It was previously described that fetal glucose metabolism is affected by fetal sex. PURPOSE: To examine whether the birth weight of neonates is affected differently by GDM according to fetal sex. METHODS: A retrospective normalized cohort analysis, using the open database of 2017 Natality Data from the National Vital Statistics System in the US. We compared the delta in neonatal birth weight, according to fetal sex, between pregnancies with or without GDM. Linear regression was used to take into consideration the effect of multiple confounders. For evaluation whether fetal sex is an independent risk factor for macrosomia (> 4000 and > 4500 g) following pregnancies complicated by GDM we used multivariate logistic regression. RESULTS: A significant relationship was found between the sex of the neonate and the delta in birth weight associated with GDM (P-value < 0.0001). The average weight gain in neonates to GDM pregnancies was 71 g in females, and 56 g in males. The prevalence of macrosomia above 4000 g and 4500 g that was attributed to GDM was higher in female-sex neonates compared to male-sex neonates (P < 0.05). CONCLUSION: According to our study results, female sex is associated with higher fetal weight gain in pregnancies complicated by GDM. Moreover, macrosomia's rate (> 4000 g and > 4500 g) attributed to GDM raised in a more significant manner in female-sex neonates.

Neonatal Birthweight Spectrum: Maternal Risk Factors and Pregnancy Outcomes in Saudi Arabia.

Background and Objectives: Low-birth-weight (LBW) neonates are at increased risk of morbidity and mortality which are inversely proportional to birth weight, while macrosomic babies are at risk of birth injuries and other related complications. Many maternal risk factors were associated with the extremes of birthweight. The objectives of this study are to investigate maternal risk factors for low and high birthweight and to report on the neonatal complications associated with abnormal birth weights. Materials and Methods: We conducted a retrospective analysis of medical records of deliveries ≥ 23 weeks. We classified the included participants according to birth weight into normal birth weight (NBW), LBW, very LBW (VLBW), and macrosomia. The following maternal risk factors were included, mother's age, parity, maternal body mass index (BMI), maternal diabetes, and hypertension. The neonatal outcomes were APGAR scores < 7, admission to neonatal intensive care unit (NICU), respiratory distress (RD), and hyperbilirubinemia. Data were analyzed using SAS Studio, multivariable logistic regression analyses were used to investigate the independent effect of maternal risk factors on birthweight categories and results were reported as an adjusted odds ratio (aOR) and 95% Confidence Interval (CI). Results: A total of 1855 were included in the study. There were 1638 neonates (88.3%) with NBW, 153 (8.2%) with LBW, 27 (1.5%) with VLBW, and 37 (2.0%) with macrosomia. LBW was associated with maternal hypertension (aOR = 3.5, 95% CI = 1.62-7.63), while increasing gestational age was less likely associated with LBW (aOR = 0.51, 95% CI = 0.46-0.57). Macrosomia was associated with maternal diabetes (aOR = 3.75, 95% CI = 1.67-8.41), in addition to maternal obesity (aOR = 3.18, 95% CI = 1.24-8.14). The odds of VLBW were reduced significantly with increasing gestational age (aOR = 0.41, 95% CI = 0.32-0.53). In total, 81.5% of VLBW neonates were admitted to the NICU, compared to 47.7% of LBW and 21.6% of those with macrosomia. RD was diagnosed in 59.3% of VLBW neonates, in 23% of LBW, in 2.7% of macrosomic and in 3% of normal-weight neonates. Hyperbilirubinemia was reported in 37.04%, 34.21%, 22.26%, and 18.92% of VLBW, LBW, NBW, and macrosomic newborns, respectively. Conclusions: Most neonates in this study had normal birthweights. Maternal hypertension and lower gestational age were associated with increased risk of LBW. Additionally, maternal obesity and diabetes increased the risk of macrosomia. Neonatal complications were predominantly concentrated in the LBW and VLBW, with a rising gradient as birthweight decreased. The main complications included respiratory distress and NICU admissions.

Associations of early pregnancy serum uric acid levels with risk of gestational diabetes and birth outcomes: a retrospective cohort study.

BACKGROUND: Previous evidence suggests that higher blood uric acid (UA) levels are associated with adverse cardiovascular outcomes during pregnancy and subsequent birth outcomes. However, it has been relatively unclear whether these associations persist in normotensive pregnant women. METHODS: The study was based on a retrospective analysis of 18,250 mother-infant pairs in a large obstetric center in China. Serum UA concentrations in early pregnancy (median: 17.6, IQR: 16.3, 18.6 gestational weeks) were assessed. Hyperuricemia was defined as ≥ one standard deviation (SD) of the reference value for the corresponding gestational age. Outcomes of gestational diabetes mellitus (GDM), preterm birth (PB), low birth weight (LBW), macrosomia, small for gestational age (SGA) and large for gestational age (LGA) were extracted from the medical records. RESULTS: The mean maternal UA level was 0.22 ± 0.05 mmol/L, and 2,896 (15.9%) subjects had hyperuricemia. After adjustment for several covariates, UA was associated with several adverse outcomes. The ORs (95%CI) per one SD increase in serum UA concentration were 1.250 (1.136, 1.277) for GDM, 1.137 (1.060, 1.221) for PB, 1.134 (1.051, 1.223) for LBW, and 1.077 (1.020, 1.137) for SGA, respectively. Similar adverse associations were found between hyperuricemia and GDM, PB (ORs: 1.394 and 1.385, P < 0.001), but not for LBW, macrosomia, SGA, and LGA. Adverse associations tended to be more pronounced in subjects with higher BMI for outcomes including PB, LBW, and SGA (P interaction = 0.001-0.028). CONCLUSION: Higher UA levels in early pregnancy were associated with higher risk of GDM, PB, LBW, and SGA in normotensive Chinese women.

Infants with macrosomia and infants of diabetic mothers have increased carotid artery intima-media thickness in childhood.

Incidence of diabetes during pregnancy is increasing worldwide, and intrauterine hyperglycemia exposure may have long-term adverse effects on the cardiovascular health of children. We investigated prospectively the risk of atherosclerosis and carotid intima-media thickness (CIMT) in infants born macrosomic and in infants of diabetic mothers (IDM) at the age of 8-9 years in 2021. A total of 49 infants of diabetic mothers (IDM group) and 13 macrosomic infants (macrosomic group) were included in the study. They were compared with 26 age-matched healthy children with birth weight appropriate for gestational age born to non-diabetic mothers (control group). Anthropometric measurements, atherosclerosis risk factors, and CIMT measurements were performed. There was no significant difference between the groups in terms of age, gender, actual anthropometric measurements, blood pressure measurements, laboratory parameters, or atherosclerosis risk factors. Gestational age was lower in the IDM group (p < 0.001), while birth weight was higher in the macrosomic group (p < 0.001). High-density lipoprotein cholesterol level was lower in the IDM group than the other groups. Duration of exclusive and total breastfeeding was lower in IDM group than in the control group (p < 0.001 for both). Body mass index, skinfold thickness, waist-to-hip ratio, and waist-to-height ratio were higher in those breastfed for less than 6 months in the IDM group. The CIMT values were statistically higher in IDM [0.43 ± 0.047 (0.34-0.60)] and macrosomic [0.40 ± 0.055 (0.33-0.50)] groups than control group [0.34 ± 0.047 (0.26-0.45)]. CONCLUSION: CIMT values were higher in IDM and macrosomic groups at 8-9 years old age compared to children born with normal birth weight. This indicates intrauterine exposure in both groups. And also, breastfeeding seems very important for IDMs. WHAT IS KNOWN: • Intrauterine hyperglycemia exposure has long-term adverse effects on the cardiovascular health of children. • Infants of diabetic mothers have higher carotid artery intima-media thickness at birth. WHAT IS NEW: • Both infants of diabetic mothers and infants with macrosomia have increased carotid artery intima-media thickness at the age of 8-9 years. • Duration of breast feeding is important especially in infants of diabetic mothers as body mass index, skinfold thickness, waist to hip and height ratio were higher in those breastfed less than 6 months.

Association between second- and third-trimester maternal lipid profiles and adverse perinatal outcomes among women with GDM and non-GDM: a retrospective cohort study.

BACKGROUND: Lipid metabolism disorder during pregnancy has been reported in women with gestational diabetes mellitus (GDM). However, controversy remains regarding the relationship between maternal changes in lipid profiles and perinatal outcomes. This study investigated the association between maternal lipid levels and adverse perinatal outcomes in women with GDM and non-GDM. METHODS: In total, 1632 pregnant women with GDM and 9067 women with non-GDM who delivered between 2011-2021 were enrolled in this study. Serum samples were assayed for fasting total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels during the second and third trimesters of pregnancy. Adjusted odds ratios (AOR) and 95% confidence intervals (95% CI) were calculated via multivariable logistic regression analysis to determine the association of lipid levels with perinatal outcomes. RESULTS: The serum TC, TG, LDL, and HDL levels in the third trimester were significantly higher than those in the second trimester (p < 0.001). Women with GDM had significantly higher levels of TC and TG in the second and third trimesters than those with non-GDM in the same trimesters, while HDL levels decreased in women with GDM (all p < 0.001). After adjusting for confounding factors by multivariate logistic regression, every mmol/L elevation in TG levels of women with GDM in second and third trimesters was associated with a higher risk of caesarean section (AOR = 1.241, 95% CI: 1.103-1.396, p < 0.001; AOR = 1.716, 95% CI: 1.556-1.921, p < 0.001), large for gestational age infants (LGA) (AOR = 1.419, 95% CI: 1.173-2.453, p = 0.001; AOR = 2.011, 95% CI: 1.673-2.735, p < 0.001), macrosomia (AOR = 1.220, 95% CI: 1.133-1.643, p = 0.005; AOR = 1.891, 95% CI: 1.322-2.519, p < 0.001), and neonatal unit admission (NUD; AOR = 1.781, 95% CI: 1.267-2.143, p < 0.001; AOR = 2.052, 95% CI: 1.811-2.432, p < 0.001) cesarean delivery (AOR = 1.423, 95% CI: 1.215-1.679, p < 0.001; AOR = 1.834, 95% CI: 1.453-2.019, p < 0.001), LGA (AOR = 1.593, 95% CI: 1.235-2.518, p = 0.004; AOR = 2.326, 95% CI: 1.728-2.914, p < 0.001), macrosomia (AOR = 1.346, 95% CI: 1.209-1.735, p = 0.006; AOR = 2.032, 95% CI: 1.503-2.627, p < 0.001), and neonatal unit admission (NUD) (AOR = 1.936, 95% CI: 1.453-2.546, p < 0.001; AOR = 1.993, 95% CI: 1.724-2.517, p < 0.001), which were higher than the relative risk of these perinatal outcomes in women with non-GDM. Additionally, every mmol/L increase in second and third-trimester HDL levels of women with GDM was associated with decreased risk of LGA(AOR = 0.421, 95% CI: 0.353-0.712, p = 0.007; AOR = 0.525, 95% CI: 0.319-0.832, p = 0.017) and NUD (AOR = 0.532, 95% CI: 0.327-0.773, p = 0.011; AOR = 0.319, 95% CI: 0.193-0.508, p < 0.001), and the risk reduction was not strong than that of women with GDM. CONCLUSIONS: Among women with GDM, high maternal TG in the second and third trimesters was independently associated with an increased risk of cesarean section, LGA, macrosomia, and NUD. High maternal HDL during the second and third trimesters was significantly associated with decreased risk of LGA and NUD. These associations were stronger than those in women with non-GDM, suggesting the importance of monitoring second and third-trimester lipid profiles in improving clinical outcomes, especially in GDM pregnancies.

The associations of ferritin, serum lipid and plasma glucose levels across pregnancy in women with gestational diabetes mellitus and newborn birth weight.

BACKGROUND: Women with gestational diabetes mellitus (GDM) are at greater risk of abnormal birth weight. Since the level of biochemical indicators could often affect the intrauterine growth and development of the fetus, it is of great practical significance to understand the changes of biochemical levels across pregnancy in women with GDM and to find out the indicators that play an important role in predicting birth weight. METHODS: The data source of this study was from the Xi'an Longitudinal Mother-Child Cohort study (XAMC), in which women with GDM with normal and high pre-pregnancy body mass index (BMI) and their newborns between January 1st and March 31st in 2018 were included. The data of ferritin, serum lipid profile and fasting plasma glucose (FPG) of mothers in the three trimesters of pregnancy, as well as birth weight of newborns were all collected from medical records. Multiple linear regression and multivariate logistic regression analyses were used to explore the association of the biochemical indexes and birth weight. A P value < 0.05 was considered statistically significant. RESULTS: A total of 782 mother-infant pairs were finally included and divided into normal weight group (NG) (n = 530, 67.8%) and overweight/obesity group (OG) (n = 252, 32.2%) according to maternal pre-pregnancy BMI. The level of ferritin in both NG and OG decreased during pregnancy (P for trend < 0.001 for all), whereas the levels of total cholesterol (TC), high density cholesterol (HDL-C), low density cholesterol (LDL-C) and triglycerides (TG) all showed an upward trend (P for trend < 0.05 for all). The levels of FPG in the two groups remained in a relatively stable during the whole pregnancy even though it was higher in OG during the 2nd and 3rd trimesters, whilst HbAlc levels in NG women increased (P for trend = 0.043) during pregnancy. Meanwhile, the risk of macrosomia and large-for-gestational-age (LGA) increased with the increase of FPG level (P for trend < 0.05). Multivariate logistic regression analyses results showed that only FPG level in the 3rd trimester was correlated with birth weight, with birth weight increased by 44.9 g for each SD increase in FPG level. CONCLUSION: Maternal FPG in the 3rd trimester is an independent predictor of newborn birth weight, and a higher level of that is associated with an increased risk of macrosomia and LGA.

Maternal circulating metabolic biomarkers and their prediction performance for gestational diabetes mellitus related macrosomia.

INTRODUCTION: Gestational diabetes mellitus (GDM), a metabolism-related pregnancy complication, is significantly associated with an increased risk of macrosomia. We hypothesized that maternal circulating metabolic biomarkers differed between women with GDM and macrosomia (GDM-M) and women with GDM and normal neonatal weight (GDM-N), and had good prediction performance for GDM-M. METHODS: Plasma samples from 44 GDM-M and 44 GDM-N were analyzed using Olink Proseek multiplex metabolism assay targeting 92 biomarkers. Combined different clinical characteristics and Olink markers, LASSO regression was used to optimize variable selection, and Logistic regression was applied to build a predictive model. Nomogram was developed based on the selected variables visually. Receiver operating characteristic (ROC) curve, calibration plot, and clinical impact curve were used to validate the model. RESULTS: We found 4 metabolism-related biomarkers differing between groups [CLUL1 (Clusterin-like protein 1), VCAN (Versican core protein), FCRL1 (Fc receptor-like protein 1), RNASE3 (Eosinophil cationic protein), FDR <  0.05]. Based on the different clinical characteristics and Olink markers, a total of nine predictors, namely pre-pregnancy body mass index (BMI), weight gain at 24 gestational weeks (gw), parity, oral glucose tolerance test (OGTT) 2 h glucose at 24 gw, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) at 24 gw, and plasma expression of CLUL1, VCAN and RNASE3 at 24 gw, were identified by LASSO regression. The model constructed using these 9 predictors displayed good prediction performance for GDM-M, with an area under the ROC of 0.970 (sensitivity = 0.955, specificity = 0.886), and was well calibrated (P Hosmer-Lemeshow test = 0.897). CONCLUSION: The Model included pre-pregnancy BMI, weight gain at 24 gw, parity, OGTT 2 h glucose at 24 gw, HDL and LDL at 24 gw, and plasma expression of CLUL1, VCAN and RNASE3 at 24 gw had good prediction performance for predicting macrosomia in women with GDM.

Mediation effect of maternal triglyceride and fasting glucose level on the relationship between maternal overweight/ obesity and fetal growth: a prospective cohort study.

BACKGROUND: Previous studies have suggested that maternal overweight/obesity is asscociated with macrosomia. The present study aimed to investigate the mediation effects of fasting plasma glucose (FPG) and maternal triglyceride (mTG) in the relationship between maternal overweight/obesity and large for gestational age (LGA) among non-diabetes pregnant women. METHODS: This prospective cohort study was conducted in Shenzhen from 2017 to 2021. A total of 19,104 singleton term non-diabetic pregnancies were enrolled form a birth cohort study. FPG and mTG were measured at 24-28 weeks. We analyzed the association of maternal prepregancy overweight/obesity with LGA and mediation effects of FPG and mTG. Multivariable logistic regression analysis and serial multiple mediation analysis were performed. The odds ratio (OR) and 95% confidence intervals (CIs) were calculated. RESULTS: Mothers who were overweight or obese had higher odds of giving birth to LGA after adjusting potential confounders (OR:1.88, 95%CI: 1.60-2.21; OR:2.72, 95%CI: 1.93-3.84, respectively). The serial multiple mediation analysis found prepregnancy overweight can not only have a direct positive effect on LGA (effect = 0.043, 95% CI: 0.028-0.058), but also have an indirect effect on the LGA through two paths: the independent mediating role of FPG (effect = 0.004, 95% CI: 0.002-0.005); the independent mediating role of mTG (effect = 0.003,95% CI: 0.002-0.005). The chain mediating role of FPG and mTG has no indirect effect. The estimated proportions mediated by FPG and mTG were 7.8% and 5.9%. Besides, the prepregnancy obesity also has a direct effect on LGA (effect = 0.076; 95%CI: 0.037-0.118) and an indirect effect on LGA through three paths: the independent mediating role of FPG (effect = 0.006; 95%CI: 0.004-0.009); the independent mediating role of mTG (effect = 0.006; 95%CI: 0.003-0.008), and the chain mediating role of FPG and mTG (effect = 0.001; 95%CI: 0.000-0.001). The estimated proportions were 6.7%, 6.7%, and 1.1%, respectively. CONCLUSION: This study found that in nondiabetic women, maternal overweight/obesity was associated with the occurence of LGA, and this positive association was partly mediated by FPG and mTG, suggesting that FPG and mTG in overweight/obese nondiabetic mothers deserve the attention of clinicians.

Maternal plasma vitamin D levels across pregnancy are not associated with neonatal birthweight: findings from an Australian cohort study of low-risk pregnant women.

BACKGROUND: In utero environments can be highly influential in contributing to the development of offspring obesity. Specifically, vitamin D deficiency during pregnancy is associated with adverse maternal and child health outcomes, however its relationship with offspring obesity remains unclear. We assessed maternal vitamin D status across pregnancy, change in plasma vitamin D concentrations and associations with neonatal birthweight, macrosomia and large for gestational age. METHODS: Women (n = 221) aged 18-40 years with singleton (low-risk) pregnancies, attending antenatal clinics at a tertiary-level maternity hospital were recruited at 10-20 weeks gestation. Medical history, maternal weight and blood samples at three antenatal clinic visits were assessed; early (15 ± 3 weeks), mid (27 ± 2 weeks) and late (36 ± 1 weeks) gestation. Maternal 25(OH)D was analysed from stored plasma samples via liquid chromatography-tandem mass spectrometry (LC/MS/MS). Neonatal growth parameters were collected at birth. Unadjusted and adjusted linear and logistic regression assessed associations of maternal vitamin D with birthweight, macrosomia and large for gestational age. RESULTS: Mean plasma 25(OH)D increased from early (83.8 ± 22.6 nmol/L) to mid (96.5 ± 28.9 nmol/L) and late (100.8 ± 30.8 nmol/L) gestation. Overall 98% of women were taking vitamin D-containing supplements throughout their pregnancy. Prevalence of vitamin D deficiency (25(OH)D < 50 nmol/L) was 6.5%, 6.3% and 6.8% at early, mid and late pregnancy respectively. No statistically significant association was found between 25(OH)D or vitamin D deficiency at any timepoint with neonatal birthweight, macrosomia or large for gestational age. CONCLUSIONS: Prevalence of vitamin D deficiency was low in this cohort of pregnant women and likely related to the high proportion of women taking vitamin D supplements during pregnancy. Maternal 25(OH)D did not impact offspring birth weight or birth size. Future studies in high-risk pregnant populations are needed to further assess maternal vitamin D status and factors in utero which promote early life obesity.

Associations of maternal pre-pregnancy BMI and gestational weight gain with the risks of adverse pregnancy outcomes in Chinese women with gestational diabetes mellitus.

BACKGROUND: Give the high background risk of adverse pregnancy outcomes (APOs), it is important to understand the associations of maternal pre-pregnancy body mass index (ppBMI), gestational weight gain (GWG) with APOs in women with gestational diabetes mellitus (GDM). We addressed the independent and joint associations of maternal ppBMI and GWG with APOs in Chinese women with GDM. METHODS: 764 GDM women with singleton delivery were studied and they were stratified into three weight groups by ppBMI (underweight, normal weight and overweight/obesity) following classification standards for Chinese adults and three GWG groups (inadequate, adequate, excessive GWG) by the 2009 Institute of Medicine guidelines, respectively. Univariate and multivariate logistic regression analyses were performed to estimate the odds ratios of APOs. RESULTS: Maternal overweight/obesity was associated with increased odds of pregnancy-induced hypertension [PIH, adjusted odds ratio (aOR): 2.828, 95% confidence interval (CI) 1.382-5.787], cesarean delivery (CS) (aOR 2.466, 95%CI 1.694-3.590), preterm delivery (aOR 2.466, 95%CI 1.233-4.854), LGA (aOR 1.664, 95%CI 1.120-2.472), macrosomia (aOR 2.682, 95%CI 1.511-4.760) and any pregnancy complication (aOR 2.766, 95%CI 1.840-4.158) compared with healthy weight. Inadequate GWG was less likely to develop PIH (aOR 0.215, 95%CI 0.055-0.835), CS (aOR 0.612, 95%CI 0.421-0.889) and any pregnancy complication (aOR 0.628, 95%CI 0.435-0.907), but had higher risk of preterm birth (aOR 2.261, 95%CI 1.089-4.692), while excessive GWG was more vulnerable to LGA (aOR 1.929, 95%CI 1.272-2.923), macrosomia (aOR 2.753, 95%CI 1.519-4.989) and any pregnancy complication (aOR 1.548, 95%CI 1.006-2.382) as compared to adequate GWG. Furthermore, compared to normal weight mothers with adequate GWG, obese mothers with excessive GWG had the highest risk of any pregnancy complication (aOR 3.064, 95%CI 1.636-5.739). CONCLUSIONS: Maternal overweight/obesity and GWG were associated with APOs in the already high-risk settings of GDM. Obese mothers with excessive GWG may confer the greatest risk of adverse outcomes. It was very helpful to reduce the burden of APOs and benefit GDM women by promoting a healthy pre-pregnancy BMI and GWG.

Glycemic Variability and Its Correlation with Large for Gestation-age Babies in Gestational Diabetic Pregnancies.

BACKGROUND: Although glycemic variability (GV) has been shown to be associated with endothelial dysfunction in diabetes mellitus (DM), there is a dearth of literature on its correlation in gestational diabetic pregnancies. AIM: To compare GV and 24-hour ambulatory glucose profile (AGP) in gestational diabetic pregnancies with and without large for gestation-age (LGA) babies. MATERIALS AND METHODS: It was a cross-sectional observational study. A total of 40 pregnant females between 19 and 35 years with gestational DM (GDM) controlled on pharmacotherapy fulfilling inclusion criteria were recruited. A flash glucose monitor (FGM) was used to record AGP between 32 and 36 weeks of gestation in these women. A total of 400 patient days with 38,400 glucose values in the study group were analyzed. Various glucose measures were compared between the GDM pregnancies with or without LGA babies. RESULTS: The incidence of LGA was 15% in these pregnant women who were on pharmacotherapy and apparently controlled as evidenced by self-monitoring of blood sugar values. All the parameters of 24-hour AGP except dinner values were significantly high in the LGA group when compared with the non-LGA group [mean amplitude of glycemic excursion (MAGE) LGA vs non-LGA 74.58 ± 16.83 vs 49.86 ± 12.83 mg/dL, p = 0.002; standard deviation (SD) LGA vs non-LGA 30.19 ± 9.69 vs 20.10 ± 5.97 mg/dL, p = 0.001]. Variables of GV: MAGE and SD were significantly high in the LGA group (p < 0.001). Time below range (TBR) and time above range (TAR) were also significantly altered in the LGA group (p < 0.001). CONCLUSION: High GV and time in the range are the important parameters that can be well correlated with LGA babies in gestational diabetic pregnancies on pharmacotherapy. An FGM is a good monitoring device to measure this parameter and can be used as an adjunct to modify measures to control the glucose values within range in these pregnancies.

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OBJECTIVES: To compare perinatal outcomes and the incidence of pregnancy complications between fresh embryo transfer and frozen embryo transfer in singleton pregnant women. METHODS: The clinical data of 3161 in vitro fertilization-embryo transfer cycles conducted in Center for Reproductive Medicine of the Third Affiliated Hospital of Sun Yat-sen University from October 2015 to May 2021 were retrospectively analyzed, among which 1009 cases were fresh embryo transfer (fresh embryo group) and 2152 cases were frozen embryo transfer (frozen embryo group). The baseline characteristics were compared between two groups, and logistic regression was used to analyze the effect of fresh embryo transfer and frozen embryo transfer on pregnancy outcome and complications. RESULTS: Compared with the fresh embryo group, the frozen embryo group had an increased gestational age (P<0.01), increased birth weight (P<0.01), higher cesarean section rate (65.1% vs. 50.7%, AOR=1.791, 95%CI: 1.421-2.256, P<0.01), higher risk of large for gestational age infant (12.7% vs. 9.4%, AOR=1.487, 95%CI: 1.072-2.064, P<0.05) and macrosomia (5.4% vs. 3.2%, AOR=2.126, 95%CI: 1.262-3.582, P<0.01). The incidences of early abortion (18.5% vs. 16.2%, AOR=1.377, 95%CI: 1.099-1.725, P<0.01) and gestational hypertension (3.1% vs. 1.9%, AOR=1.862, 95%CI: 1.055-3.285, P<0.05) in the frozen embryo group were significantly higher than those in the fresh embryo group. Stratified analyses by stage of embryo transfer showed that during blastocyst transfer, the gestational weeks of delivery, birth weight and risk of cesarean section in frozen embryo group were significantly higher than those in fresh embryo group. During cleavage stage embryo transfer, frozen embryo transfer was associated with a higher risk of cesarean section, macrosomia, miscarriage and early miscarriage, and the birth weight of newborns was also significantly increased. CONCLUSIONS: Compared with fresh embryo transfer, frozen embryo transfer is associated with a higher risk of abortion, early abortion, large for gestational age infant, macrosomia, cesarean section, and pregnancy induced hypertension. The birth weight of newborns after frozen embryo transfer is also significantly increased.

Risk of large for gestational age births at early, full and late term in relation to pre-pregnancy body mass index: Mediation by gestational diabetes status.

BACKGROUND: Maternal pre-pregnancy body mass index (BMI) is strongly associated with infant birthweight and the risk differs in pregnancies complicated by gestational diabetes (GDM). OBJECTIVES: To examine the risk of large for gestational age (LGA) (≥97th percentile) singleton births at early term, full term and late term in relation to maternal pre-pregnancy BMI status mediated through GDM. METHODS: We analysed data from the 2018 U.S. National Vital Statistics Natality File restricted to singleton term births (N = 3,229,783). In counterfactual models for causal inference, we estimated the total effect (TE), natural direct effect (NDE) and natural indirect effect (NIE) for the association of pre-pregnancy BMI with subcategories of LGA births at early, full and late term mediated through GDM, using log-binomial regression and adjusting for race/ethnicity, age, education, parity and infant sex. Proportion mediated was calculated on the risk difference scale and potential unmeasured confounders were assessed using the E-value. RESULTS: Overall, 6.4% of women had GDM, and there were 3.6% LGA singleton term births. The highest prevalence of GDM was among pre-gestational overweight/obesity that also had the highest rates of LGA births at term. The TE estimates for the risk of LGA births were the strongest across women with higher pre-pregnancy BMI compared to women with normal pre-pregnancy BMI. The NDE estimates were higher than the NIE estimates for overweight/obese BMI status. The proportion mediated, which answers the causal question to what extent the total effect of the association between pre-pregnancy BMI and LGA births is accounted for through GDM, was the highest (up to 16%) for early term births. CONCLUSIONS: Term singleton births make up the largest proportion in a cohort of newborns. While the percentage mediated through GDM was relatively small, health risks arising from pre-pregnancy overweight, and obesity can be substantial to both mothers and their offspring.

Risk of hypoglycemia by anthropometric measurements in neonates of mothers with diabetes.

Macrosomia in neonates of diabetic women is a risk factor for neonatal hypoglycemia, with an over-risk for asymmetric macrosomia. This study aimed to study the association between anthropometric measurements and hypoglycemia in neonates of mothers treated for gestational diabetes. This is a secondary analysis of the INDAO trial study conducted between May 2012 and November 2016 in 13 French tertiary care university hospitals in 890 pregnant women with gestational diabetes treated with either insulin or glyburide. Neonatal anthropometric measurements were birthweight and weight-length ratio (WLR, defined as birth weight/length). Neonatal hypoglycemia was defined as capillary blood glucose below 36 mg/dL (2 mmol/L) or below 45 mg/dL (2.5 mmol/L) associated with clinical signs after 2 h of life. Their relationships were modeled with logistic regressions using fractional polynomials. Extreme categories of birthweight or WLR adjusted for gestational age at birth and sex were defined as Z-score < -1.28 or > 1.28. These categories were compared to Z-score between -1.28 and 1.28 by estimating odds ratios and confidence intervals for neonatal hypoglycemia. Neonatal hypoglycemia occurred in 9.1% of cases. The relationship between birthweight and WLR Z-scores and neonatal risk of hypoglycemia adjusted for maternal treatment was a U-shaped curve. Adjusted odds ratios for the risk of hypoglycemia were 9.6 (95% CI 3.5, 26.8) and 2.3 (95% CI 1.1, 4.9) for WLR Z-score below -1.28 and above 1.28, respectively, compared with WLR Z-score between -1.28 and 1.28.    Conclusion: Birthweight Z-score was associated with the risk of neonatal hypoglycemia in neonates from mothers treated for gestational diabetes. The risk of neonatal hypoglycemia was increased for both extreme birthweight Z-scores, regardless of maternal treatment. Small for gestational age neonates of diabetic mothers require special attention for the risk of neonatal hypoglycemia. What is Known: • Macrosomia in neonates of diabetic women is a risk factor for neonatal hypoglycemia, with an over-risk for asymmetric macrosomia. Few retrospective studies have assessed the risk for neonatal hypoglycemia among small for gestational age neonates born to diabetic mothers. What is New: • The risk of neonatal hypoglycemia among neonates of diabetic mothers increased for both low and high weight-length ratio, regardless of maternal medicinal treatment, gestational age at birth, and sex of the newborn.

Nomogram-based risk prediction of macrosomia: a case-control study.

BACKGROUND: Macrosomia is closely associated with poor maternal and fetal outcome. But there is short of studies on the risk of macrosomia in early pregnancy. The purpose of this study is to establish a nomogram for predicting macrosomia in the first trimester. METHODS: A case-control study involving 1549 pregnant women was performed. According to the birth weight of newborn, the subjects were divided into macrosomia group and non-macrosomia group. The risk factors for macrosomia in early pregnancy were analyzed by multivariate logistic regression. A nomogram was used to predict the risk of macrosomia. RESULTS: The prevalence of macrosomia was 6.13% (95/1549) in our hospital. Multivariate logistic regression analysis showed that prepregnancy overweight (OR: 2.13 95% CI: 1.18-3.83)/obesity (OR: 3.54, 95% CI: 1.56-8.04), multiparity (OR:1.88, 95% CI: 1.16-3.04), the history of macrosomia (OR: 36.97, 95% CI: 19.90-68.67), the history of GDM/DM (OR: 2.29, 95% CI: 1.31-3.98), the high levels of HbA1c (OR: 1.76, 95% CI: 1.00-3.10) and TC (OR: 1.36, 95% CI: 1.00-1.84) in the first trimester were the risk factors of macrosomia. The area under ROC (the receiver operating characteristic) curve of the nomogram model was 0.807 (95% CI: 0.755-0.859). The sensitivity and specificity of the model were 0.716 and 0.777, respectively. CONCLUSION: The nomogram model provides an effective mothed for clinicians to predict macrosomia in the first trimester.

Determinants of fetal macrosomia among live births in southern Ethiopia: a matched case-control study.

BACKGROUND: Fetal macrosomia defined as birth weight of 4000 g and above regardless of gestational age and associated with adverse maternal and fetal outcomes, especially among women in developing countries like Ethiopia. Despite the observed burden, there is limited evidence on determinants of fetal macrosomia. This study aimed to identify determinants of fetal macrosomia among live births at Wolaita Sodo town Southern Ethiopia. METHODS: A facility-based matched case-control study design involved 360 singletons deliveries attended at hospitals in Wolaita Sodo town, southern Ethiopia, with 120 cases and 240 controls included. Cases and control were matched by maternal age. Cases were neonates with a birth weight of ≥ 4000, while controls were neonates with a birthweight between 2500gm and less than 4000gm. Data were collected by interviews, measuring, and reviewing mothers' medical documents. Conditional logistic regression analysis was carried to identify the independent predictor variables. Statistical significance was set using a p-value < 0.05 and 95% CI for AOR. RESULTS: Male neonates were four times more likely to be macrosomia than female neonates MAOR = 4.0 [95%CI; 2.25-7.11, p < 0.001]. Neonates born at gestational age ≥ 40 weeks were 4.33 times more likely to be macrosomia with MAOR = 4.33 [95%CI; 2.37-7.91, p < 0.001]. Neonates born from physically inactive mothers were 7.76 times more likely to be macrosomia with MAOR = 7.76 [95CI; 3.33-18.08, p < 0.001]. Neonates born from mothers who consumed fruits and dairy products in their diet frequently were 2 and 4.9 times more likely to be macrosomia MAOR = 2.03 [95%CI; 1.11-3.69, p = 0.021] and AOR = 4.91[95%CI; 2.36-10.23, p < 0.001] respectively. CONCLUSION: Mothers' physical exercise and consumption of fruit and dairy products were significant predictor variables for fetal macrosomia. Hence, health care providers may use these factors as a screening tool for the prediction, early diagnosis, and timely intervention of fetal macrosomia and its complications.

A predictive model of macrosomic birth based upon real-world clinical data from pregnant women.

BACKGROUND: Fetal macrosomia is associated with an increased risk of several maternal and newborn complications. Antenatal predication of fetal macrosomia remains challenging. We aimed to develop a nomogram model for the prediction of macrosomia using real-world clinical data to improve the sensitivity and specificity of macrosomia prediction. METHODS: In the present study, we performed a retrospective, observational study based on 13,403 medical records of pregnant women who delivered singleton infants at a tertiary hospital in Shanghai from 1 January 2018 through 31 December 2019. We split the original dataset into a training set (n = 9382) and a validation set (n = 4021) at a 7:3 ratio to generate and validate our model. The candidate variables, including maternal characteristics, laboratory tests, and sonographic parameters were compared between the two groups. A univariate and multivariate logistic regression was carried out to explore the independent risk factors for macrosomia in pregnant women. Thus, the regression model was adopted to establish a nomogram to predict the risk of macrosomia. Nomogram performance was determined by discrimination and calibration metrics. All the statistical analysis was analyzed using R software. RESULTS: We compared the differences between the macrosomic and non-macrosomic groups within the training set and found 16 independent risk factors for macrosomia (P < 0.05), including biparietal diameter (BPD), head circumference (HC), femur length (FL), amniotic fluid index (AFI) at the last prenatal examination, pre-pregnancy body mass index (BMI), and triglycerides (TG). Values for the areas under the curve (AUC) for the nomogram model were 0.917 (95% CI, 0.908-0.927) and 0.910 (95% CI, 0.894-0.927) in the training set and validation set, respectively. The internal and external validation of the nomogram demonstrated favorable calibration as well as discriminatory capability of the model. CONCLUSIONS: Our model has precise discrimination and calibration capabilities, which can help clinical healthcare staff accurately predict macrosomia in pregnant women.