Large For Gestational Age Research Articles

1193-P: GDM Treatment, Diagnosis Timing, and Glycemic Control—Associations with Newborn Outcomes in the SWIFT Study

Suboptimal glycemic control in GDM increases risk of adverse perinatal outcomes. We evaluated GDM treatment type (glyburide vs diet), timing of diagnosis (<20w gestation: early (E) vs. >20w: standard (S), glycemic control (optimal vs suboptimal), and perinatal outcomes. In a diverse cohort of 902 GDM mother-infant dyads (77% Hispanic, Asian, or Black; 23% White), prenatal glycemic control was measured by self-home glucose monitoring and categorized as optimal (≥80% of tests met target, fasting glucose ≤95 mg/dL and 1h post-prandial ≤140 or 2h ≤120) or suboptimal (<80% of tests met target). Compared to the S diagnosis and diet treatment group, the E diagnosis and glyburide treatment group was older, more likely to have prior GDM, and higher prepregnancy BMI and glucose levels on the 3h 100 g prenatal OGTT. Glyburide treatment was associated with suboptimal control (P<0.001). Multivariable logistic regression estimated odds ratios (OR, 95%CI) of perinatal outcomes associated with GDM treatment type, timing of diagnosis, and glycemic control vs. the referent group with S diagnosis and optimal control on diet treatment alone, adjusted for pre-pregnancy BMI, infant sex and gestational age. Among E and S diagnosis groups with suboptimal control both before and after glyburide treatment, ORs, 95%CI were higher for neonatal length of stay ≥3 days: (E 3.6, 1.6-8.1; S 2.0, 1.1-3.6), neonatal hypoglycemia (E 2.4, 1.0-5.9; S 1.9, 1.0-3.6) and large-for-gestational age (LGA) birthweight (E 4.1, 1.8-9.1; S 2.8, 1.6-4.9). For E diagnosis with suboptimal control before, and optimal control after glyburide, the odds of LGA were elevated (2.8, 1.2-6.6) similar to the S diagnosis with suboptimal control after glyburide. Associations did not affect Cesarean delivery or NICU admission. These findings show that even with post-glyburide optimal glycemic control, odds of LGA development associated with exposure to GDM from early gestation may be only partially ameliorated by glyburide treatment. Disclosure J.L.Josefson: None. B.Sun: None. A.Xiang: None. M.Greenberg: None. L.Greenspan: None. J.C.Lo: None. J.N.Davis: None. E.P.Gunderson: None. Funding National Institutes of Health (R01DK122700)

Detection and Quantification of Neurotrophin-3 (NT-3) and Nerve Growth Factor (NGF) Levels in Early Second Trimester Amniotic Fluid: Investigation into a Possible Correlation with Abnormal Fetal Growth Velocity Patterns.

Abnormal fetal growth is associated with adverse perinatal and long-term outcomes. The pathophysiological mechanisms underlying these conditions are still to be clarified. Nerve growth factor (NGF) and neurotrophin-3 (NT-3) are two neurotrophins that are mainly involved in the neuroprotection process, namely promotion of growth and differentiation, maintenance, and survival of neurons. During pregnancy, they have been correlated with placental development and fetal growth. In this study, we aimed to determine the early 2nd trimester amniotic fluid levels of NGF and NT-3 and to investigate their association with fetal growth. This is a prospective observational study. A total of 51 amniotic fluid samples were collected from women undergoing amniocentesis early in the second trimester and were stored at -80 °C. Pregnancies were followed up until delivery and birth weight was recorded. Based on birth weight, the amniotic fluid samples were divided into three groups: appropriate for gestational age (AGA), small for gestational age (SGA), and large for gestational age (LGA). NGF and NT-3 levels were determined by using Elisa kits. NGF concentrations were similar between the studied groups; median values were 10.15 pg/mL, 10.15 pg/mL, and 9.14 pg/mL in SGA, LGA, and AGA fetuses, respectively. Regarding NT-3, a trend was observed towards increased NT-3 levels as fetal growth velocity decreased; median concentrations were 11.87 pg/mL, 15.9 pg/mL, and 23.5 pg/mL in SGA, AGA, and LGA fetuses, respectively, although the differences among the three groups were not statistically significant. Our findings suggest that fetal growth disturbances do not induce increased or decreased production of NGF and NT-3 in early second trimester amniotic fluid. The trend observed towards increased NT-3 levels as fetal growth velocity decreased shows that there may be a compensatory mechanism in place that operates in conjunction with the brain-sparing effect. Further associations between these two neurotrophins and fetal growth disturbances are discussed.

Prevalence of gestational diabetes mellitus, maternal obesity and associated perinatal outcomes over 10 years in an Australian tertiary maternity provider

BackgroundThe International Association of Diabetes in Pregnancy Study Groups (IADPSG) gestational diabetes mellitus (GDM) criteria have been heavily scrutinised with concerns that the consequent GDM prevalence increase has not been associated with improved perinatal outcomes. AimsAt a tertiary hospital in Melbourne, Australia we aimed to evaluate prevalence trends for GDM, type 2 diabetes (T2DM), maternal obesity and large-for-gestational age (LGA) and assess changes in perinatal outcomes following IADPSG criteria uptake in 2015. MethodsA retrospective cohort study of singleton births from 20 weeks’ gestation was conducted between 1st January 2011 and 31st December 2020. Maternal characteristics and perinatal outcomes were extracted from medical records. Results52,795 pregnancies were included. GDM prevalence increased 2.7 times from 8.9% in 2011 to 23.7% in 2020 and increased annually by 8.59% (95%CI 7.77, 9.42). The rate of T2DM increased annually by 11.69% (95%CI 7.72, 16.67). Obesity prevalence increased annually by 3.18% (95%CI 2.58, 3.78). Induction of labour (IOL) prevalence increased annually by 8.35% (95%CI 5.69, 11.06). LGA prevalence remained unchanged. Increasing maternal obesity was the major contributing factor for LGA prevalence. ConclusionsFrom 2011 to 2020 GDM, obesity and T2DM prevalence increased significantly, with associated increased IOL, without change in LGA rates. Prospective studies are required to explore interactions between GDM, obesity, LGA and obstetric interventions.

Treatment of women with mild gestational diabetes mellitus decreases the risk of adverse perinatal outcomes

AimsGlycemic thresholds used to diagnose gestational diabetes mellitus (GDM) are a continued subject of debate. Lower glycemic thresholds identify women with milder GDM for whom treatment benefit is unclear. We compared adverse maternal and neonatal outcomes in treated and untreated women with mild hyperglycemia. MethodsWe reviewed 11 553 patient charts from two tertiary care centers and included singleton pregnancies >32-week gestation. GDM was diagnosed using the one- or two-step 75 g oral glucose tolerance test (OGTT) depending on the center. All OGTT results were reviewed. Women with glycemic values falling between the thresholds of the two tests, referred to as intermediate hyperglycemic (IH), defined as FPG 5.1–5.2 mmol/L, 1 h PG 10.0–10.5 mmol/L, or 2 h PG 8.5–8.9 mmol/L at 75 g OGTT, were untreated at center A and treated at center B. ResultsThere were 630 women with IH, 334 were untreated (center A) and 296 who were treated (center B). After adjusting for covariates, untreated IH women had significantly higher rates of gestational hypertension (aOR 6.02, P = 0.002), large for gestational age (LGA) (aOR 3.73, P < 0.001) and birthweights > 4000 g (aOR 3.35, P = 0.001). Our results indicate that treating 11 women with IH would prevent one LGA birth and treating 13 would prevent 1 birthweight > 4000 g. ConclusionThe diagnosis of GDM using the two-step OGTT fails to identify subgroups of women with mild hyperglycemia that would benefit from treatment to lower the risk for adverse maternal and neonatal outcomes. Treatment of women with mild hyperglycemia decreased the risk of LGA and birthweight >4000 g by 3-fold.

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

BackgroundPrevious 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.MethodsThis 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.ResultsMothers 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.ConclusionThis 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 obesity alters the placental transcriptome in a fetal sex-dependent manner.

Infants born to obese mothers have an increased risk of developing obesity and metabolic diseases in childhood and adulthood. Although the molecular mechanisms linking maternal obesity during pregnancy to the development of metabolic diseases in offspring are poorly understood, evidence suggests that changes in the placental function may play a role. Using a mouse model of diet-induced obesity with fetal overgrowth, we performed RNA-seq analysis at embryonic day 18.5 to identify genes differentially expressed in the placentas of obese and normal-weight dams (controls). In male placentas, 511 genes were upregulated and 791 genes were downregulated in response to maternal obesity. In female placentas, 722 genes were downregulated and 474 genes were upregulated in response to maternal obesity. The top canonical pathway downregulated in maternal obesity in male placentas was oxidative phosphorylation. In contrast, sirtuin signaling, NF-kB signaling, phosphatidylinositol, and fatty acid degradation were upregulated. In female placentas, the top canonical pathways downregulated in maternal obesity were triacylglycerol biosynthesis, glycerophospholipid metabolism, and endocytosis. In contrast, bone morphogenetic protein, TNF, and MAPK signaling were upregulated in the female placentas of the obese group. In agreement with RNA-seq data, the expression of proteins associated with oxidative phosphorylation was downregulated in male but not female placentas of obese mice. Similarly, sex-specific changes in the protein expression of mitochondrial complexes were found in placentas collected from obese women delivering large-for-gestational-age (LGA) babies. In conclusion, maternal obesity with fetal overgrowth differentially regulates the placental transcriptome in male and female placentas, including genes involved in oxidative phosphorylation.

Neighborhood Food Environment and Birth Weight Outcomes in New York City

Infants born with unhealthy birth weight are at greater risk for long-term health complications, but little is known about how neighborhood characteristics (eg, walkability, food environment) may affect birth weight outcomes. To assess whether neighborhood-level characteristics (poverty rate, food environment, and walkability) are associated with risk of unhealthy birth weight outcomes and to evaluate whether gestational weight gain mediated these associations. The population-based cross-sectional study included births in the 2015 vital statistics records from the New York City Department of Health and Mental Hygiene. Only singleton births and observations with complete birth weight and covariate data were included. Analyses were performed from November 2021 to March 2022. Residential neighborhood-level characteristics, including poverty, food environment (healthy and unhealthy food retail establishments), and walkability (measured by both walkable destinations and a neighborhood walkability index combining walkability measures like street intersection and transit stop density). Neighborhood-level variables categorized into quartiles. The main outcomes were birth certificate birth weight measures including small for gestational age (SGA), large for gestational age (LGA), and sex-specific birth weight for gestational age z-score. Generalized linear mixed-effects models and hierarchical linear models estimated risk ratios for associations between density of neighborhood-level characteristics within a 1-km buffer of residential census block centroid and birth weight outcomes. The study included 106 194 births in New York City. The mean (SD) age of pregnant individuals in the sample was 29.9 (6.1) years. Prevalence of SGA and LGA were 12.9% and 8.4%, respectively. Residence in the highest density quartile of healthy food retail establishments compared with the lowest quartile was associated with lower adjusted risk of SGA (with adjustment for individual covariates including gestational weight gain z-score: risk ratio [RR], 0.89; 95% CI 0.83-0.97). Higher neighborhood density of unhealthy food retail establishments was associated with higher adjusted risk of delivering an infant classified as SGA (fourth vs first quartile: RR, 1.12; 95% CI, 1.01-1.24). The RR for the association between density of unhealthy food retail establishments and risk of LGA was higher after adjustment for all covariates in each quartile compared with quartile 1 (second: RR, 1.12 [95% CI, 1.04-1.20]; third: RR, 1.18 [95% CI, 1.08-1.29]; fourth: RR, 1.16; [95% CI, 1.04-1.29]). There were no associations between neighborhood walkability and birth weight outcomes (SGA for fourth vs first quartile: RR, 1.01 [95% CI, 0.94-1.08]; LGA for fourth vs first quartile: RR, 1.06 [95% CI, 0.98-1.14]). In this population-based cross-sectional study, healthfulness of neighborhood food environments was associated with risk of SGA and LGA. The findings support use of urban design and planning guidelines to improve food environments to support healthy pregnancies and birth weight.

Continuous glucose monitoring-derived glycemic metrics and adverse pregnancy outcomes among women with gestational diabetes: a prospective cohort study

Continuous glucose monitoring (CGM) has shown potential in improving maternal and neonatal outcomes in individuals with type 1/2 diabetes, but data in gestational diabetes mellitus (GDM) is limited. We aimed to explore the relationship between CGM-derived metrics during pregnancy and pregnancy outcomes among women with GDM. We recruited 1302 pregnant women with GDM at a mean gestational age of 26.0 weeks and followed them until delivery. Participants underwent a 14-day CGM measurement upon recruitment. The primary outcome was any adverse pregnancy outcome, defined as having at least one of the outcomes: preterm birth, large-for-gestational-age (LGA) birth, fetal distress, premature rupture of membranes, and neonatal intensive care unit (NICU) admission. The individual outcomes included in the primary outcome were considered as secondary outcomes. We conducted multivariable logistic regression to evaluate the association of CGM-derived metrics with these outcomes. Per 1-SD difference in time above range (TAR), glucose area under the curve (AUC), nighttime mean blood glucose (MBG), daytime MBG, and daily MBG was associated with higher risk of any adverse pregnancy outcome, with odds ratio: 1.22 (95% CI 1.08-1.36), 1.22 (95% CI 1.09-1.37), 1.18 (95% CI 1.05-1.32), 1.21 (95% CI 1.07-1.35), and 1.22 (95% CI 1.09-1.37), respectively. Time in range, TAR, AUC, nighttime MBG, daytime MBG, daily MBG, and mean amplitude of glucose excursions were positively associated, while time blow range was inversely associated with the risk of LGA. Additionally, higher value for TAR was associated with higher risk of NICU admission. We further summarized the potential thresholds of TAR (2.5%) and daily MBG (4.8mmol/L) to distinguish individuals with and without any adverse pregnancy outcome. The CGM-derived metrics may help identify individuals at higher risk of adverse pregnancy outcomes. These CGM biomarkers could serve as potential new intervention targets to maintain a healthy pregnancy status among women with GDM. National Key R&D Program of China, National Natural Science Foundation of China, and Westlake Laboratory of Life Sciences and Biomedicine.

Maternal body mass index and risk of fetal overgrowth in women with gestational diabetes Mellitus in Southeast China: a retrospective cohort study

BackgroundTo investigate the relationship between body mass index (BMI) changes and large for gestational age (LGA) in women with gestational diabetes mellitus (GDM).MethodsA retrospective cohort study including 10,486 women with GDM was conducted. A dose‒response analysis of BMI changes and the occurrence of LGA was performed. Binary logistic regressions were performed to assess crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Receiver operating characteristic (ROC) curves and areas under the curve (AUCs) were used to assess the ability of BMI changes to predict LGA.ResultsThe probability of LGA increased with increasing BMI. The risk of LGA increased across the BMI change quartiles. The BMI change remained positively associated with the risk of LGAafter stratification analysis. The AUC was 0.570 (95% CI: 0.557 ~ 0.584)in the entire study population, and the best optimal predictive cut-off value was 4.922, with a sensitivity of 0.622 and a specificity of 0.486. The best optimal predictive cut-off value decreased from the underweight group to the overweight and obese group.ConclusionsBMI changes are related to the risk of LGA and may be a useful predictor of the incidence of LGA in singleton pregnant women with GDM.

Association between HbA1c Levels and Fetal Macrosomia and Large for Gestational Age Babies in Women with Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis of 17,711 Women.

Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy. GDM is associated with serious maternal and fetal complications, in particular, fetal macrosomia and large for gestational age (LGA), which predisposes to a higher risk of childhood obesity and type 2 diabetes mellitus later in life. Early prediction and diagnosis of GDM leads to early interventions such as diet and lifestyle, which could mitigate the maternal and fetal complications associated with GDM. Glycated haemoglobin A1c (HbA1c) has been widely used for monitoring, screening for and diagnosing diabetes and prediabetes. Increasing evidence has also showed that HbA1c could indicate fetal glucose supply. Thus, we hypothesise that the HbA1c level at around 24 to 28 weeks may predict the development of fetal macrosomia or an LGA baby in women with GDM, which could be useful for better prevention of fetal macrosomia and LGA. We searched MEDLINE, EMBASE, Cochrane and Google Scholar databases from inception to November 2022 for relevant studies that reported at least one HbA1c level during 24-28 weeks of pregnancy and fetal macrosomia or an LGA baby. We excluded studies that were not published in the English language. No other search filters were applied during the search. Two independent reviewers selected eligible studies for meta-analysis. Two independent reviewers performed data collection and analyses. The PROSPERO registration number is CRD42018086175. A total of 23 studies were included in this systematic review. Of these, 8 papers reported data of 17,711 women with GDM that allowed for inclusion in a meta-analysis. The obtained results demonstrated the prevalence of fetal macrosomia was 7.4% and of LGA, 13.36%. Meta-analyses showed that the estimated pooled risk ratio (RR) for LGA in women with high HbA1c values compared to normal or low values was 1.70 (95% CI: 1.23-2.35), p = 0.001; and the pooled RR for fetal macrosomia was 1.45 (95% CI: 0.80 to 2.63), p = 0.215. Further research is needed to evaluate the utility of HbA1c levels in predicting the delivery of a baby with fetal macrosomia or LGA in pregnant women.

Non-efficacy of early intervention strategy for non-obese patients with early-onset gestational diabetes mellitus: solely based on the short-term outcomes

IntroductionTo verify the effectiveness of intervention in early pregnancy for women with early-onset gestational diabetes mellitus (GDM).Research design and methodsThis study included women with a singleton pregnancy who were diagnosed...

The impact of diabetes during pregnancy on neonatal outcomes among the Aboriginal population in Western Australia: a whole-population study.

Aboriginal and Torres Strait Islander (hereafter Aboriginal) women have a high prevalence of diabetes in pregnancy (DIP), which includes pre-gestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM). We aimed to characterize the impact of DIP in babies born to Aboriginal mothers. A retrospective cohort study, using routinely collected linked health data that included all singleton births (N = 510 761) in Western Australia between 1998 and 2015. Stratified by Aboriginal status, generalized linear mixed models quantified the impact of DIP on neonatal outcomes, estimating relative risks (RRs) with 95% CIs. Ratio of RRs (RRRs) examined whether RRs differed between Aboriginal and non-Aboriginal populations. Exposure to DIP increased the risk of adverse outcomes to a greater extent in Aboriginal babies. PGDM heightened the risk of large for gestational age (LGA) (RR: 4.10, 95% CI: 3.56-4.72; RRR: 1.25, 95% CI: 1.09-1.43), macrosomia (RR: 2.03, 95% CI: 1.67-2.48; RRR: 1.39, 95% CI: 1.14-1.69), shoulder dystocia (RR: 4.51, 95% CI: 3.14-6.49; RRR: 2.19, 95% CI: 1.44-3.33) and major congenital anomalies (RR: 2.14, 95% CI: 1.68-2.74; RRR: 1.62, 95% CI: 1.24-2.10). GDM increased the risk of LGA (RR: 2.63, 95% CI: 2.36-2.94; RRR: 2.00, 95% CI: 1.80-2.22), macrosomia (RR: 1.95, 95% CI: 1.72-2.21; RRR: 2.27, 95% CI: 2.01-2.56) and shoulder dystocia (RR: 2.78, 95% CI: 2.12-3.63; RRR: 2.11, 95% CI: 1.61-2.77). Birthweight mediated about half of the DIP effect on shoulder dystocia only in the Aboriginal babies. DIP differentially increased the risks of fetal overgrowth, shoulder dystocia and congenital anomalies in Aboriginal babies. Improving care for Aboriginal women with diabetes and further research on preventing shoulder dystocia among these women can reduce the disparities.

Evaluating the accuracy of sonographic fetal weight estimations using the Hadlock IV formula in a Chinese population.

Despite being the most generalized formula in China, the Hadlock IV formula has never been examined to determine if it is suitable for Chinese newborns, nor have the factors that might affect its performance been investigated. However, previous studies have reported varying results about other formulas in other nationalities. This study sought to evaluate the performance of the Hadlock IV formula in estimating fetal weight (FW) in pregnant Chinese women and use ultrasound to identify the factors affecting the accuracy of estimations of newborn weight; through these means, we aimed to create a reference for predicting neonatal weight for obstetricians. A retrospective observational study comprising data from 976 cases of live-birth singleton pregnancies at the Shanghai General Hospital was conducted. The participants' clinical data were examined and subjected to a logistic regression analysis to identify the multitude of possible factors affecting the estimation of FW. The proportions and correlations between the accurate and inaccurate estimation groups were compared to determine the different prognosis of these 2 groups. The correlations between the accuracy of the sonographic-based fetal weight estimation (SFWE) and newborns with different weight ranges were also analyzed. The overall accuracy rate of the SFWE predicted by the Hadlock IV formula was 79.61%, while that of the inaccurate estimation group was only 20.39%. The incidence of spontaneous vaginal delivery (VD) was lower in the inaccurate estimation group than in the accurate estimation group (40.7% vs. 48.13%; P=0.041). In the inaccurate estimation group, 11.56% (23/199) of the participants underwent a secondary cesarean section (sCS), compared to only 6.44% (50/777) in the accurate estimation group. The low birth weight (LBW) rates and macrosomia rates were lower in the accurate estimation group than in the inaccurate estimation group, with odds ratios (ORs) of 0.483 and 0.459, respectively (P<0.05). The results indicated that the SFWE was more accurate for newborns weighing 2,500-4,000 g than those weight out of this range. In relation to macrosomia, the SFWE was likely to be underestimated, but it was usually overestimated in the LBW group. The overall performance of the Hadlock IV formula in predicting the birth weight of Chinese newborns remains suboptimal. Extra caution should be exercised in cases of suspected large-for-gestational age (LGA) infants, small-for-gestational age (SGA) infants, infants with macrosomia, or LBW fetuses in the Chinese population.

Association between perfluoroalkyl and polyfluoroalkyl substances exposure and fetal overgrowth: A prospective birth cohort study conducted in China

BackgroundPrenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) has been associated with gestational diabetes mellitus, obesity or overweight in childhood, but data on fetal overgrowth outcomes including macrosomia and large for gestational age (LGA) and among gestational age diverse infants remain scarce. ObjectiveTo evaluate the association between maternal PFASs exposure and macrosomia and LGA, with exploration of the interaction between PFASs exposure and gestational age on fetal overgrowth. Methods: A total of 1441 mother–infants pairs from Guangxi Zhuang Birth Cohort of China were analyzed. Nine PFASs were measured in maternal serum using ultra-high liquid performance chromatographytandem mass spectrometry. Multivaraible logistical regression and generalized additive models were performed for individual PFAS exposures, piecewise regression analysis was used to estimate the breakpoint values for the non-linear dose-response relationships. Bayesian Kernel Machine Regression was performed for PFASs mixture. ResultsIn single pollutant models, maternal PFDA and PFOA exposure showed U-shaped relationship with macrosomia and LGA. When PFDA concentration exceeded 0.32 ng/mL was significantly positively associated with risks of LGA and macrosomia (OR=4.66, 95%CI: 1.26, 17.17; OR=14.43, 95%CI: 2.64, 79.02; respectively), while a negatively association was observed when level below 0.32 ng/mL. When PFOA concentration exceeded 1.20 ng/mL was significantly associated with increased risk of macrosomia (OR=7.75, 95%CI: 1.36, 44.06). In mixed exposure models, mixture of PFASs was positively associated with macrosomia, as well as associated with LGA when all the PFASs were at their 30th percentile or below. The maximum risk of LGA was reached when concentrations of PFUnA, PFDA, or PFBS were at the highest concentrations and the gestational age at the minimum of this study. ConclusionsMaternal exposure to PFDA, PFOA and PFASs mixture were non-monotonically associated with macrosomia and LGA, the direction of the associations depends on the level of exposure.

Glucose Levels of the Oral Glucose Tolerance Test (oGTT) Can Predict Adverse Pregnancy Outcomes in Women with Gestational Diabetes (GDM).

Gestational diabetes (GDM) is a common pregnancy complication defined as a glucose intolerance diagnosis during pregnancy. GDM is strongly associated with adverse fetal and maternal outcomes. In Germany, to screen and diagnose GDM we use a 1 h 50 g oGCT (oral glucose challenge test) followed by a 2 h 75 g oGTT if the first was pathological. This analysis examines the correlation of 75 g oGTT glucose levels and fetomaternal outcome. Data from 1664 patients from a gestational diabetes consultation clinic at the Charité University Hospital in Berlin, Germany, were analyzed retrospectively from 2015 to 2022. The 75 g oGTT blood glucose levels were categorized into isolated fasting hyperglycemia (GDM-IFH), isolated post-load hyperglycemia (GDM-IPH) and combined hyperglycemia (GDM-CH), using the levels of the fasting, 1 h and 2 h values, after glucose application. These subtypes were compared based on their baseline characteristics as well as fetal and maternal outcome. GDM-IFH and GDM-CH women displayed higher pre-conceptional BMI and required insulin therapy more frequently (p < 0.001). The GDM-IFH group was at higher risk of having a primary cesarean section (p = 0.047), while GDM-IPH women were significantly more likely to have an emergent cesarean section (p = 0.013). The offspring of GDM-IFH and GDM-CH women were born with a significantly higher mean birthweight (p < 0.001) and birth weight percentiles (p < 0.001) and were at increased risk of being large for gestational age (LGA) (p = 0.004). Women from the GDM-IPH group delivered significantly more neonates who were small for gestational age (p = 0.027) or with low fetal weight <30th percentile (p = 0.003). This analysis shows a strong association between the glucose response pattern in the 75 g oGTT and adverse perinatal fetomaternal outcome. The differences among the subgroups, specifically concerning insulin therapy, mode of delivery and fetal growth, suggest an individualized approach to prenatal care after a GDM diagnosis.

Abnormal birth weights for gestational age in relation to maternal characteristics in Sweden: a five year cross-sectional study

BackgroundAbnormal birth weight – small for gestational age (SGA) and large for gestational age (LGA) – are important indicators for newborn health. Due to changes in lifestyle in recent decades, it is essential to keep up-to-date with the latest information on maternal factors linked to abnormal birth weight. The aim of this study is to investigate SGA and LGA in relation to maternal individual, lifestyle and socioeconomic characteristics. .MethodsThis is a register-based cross-sectional study. Self-reported data from Sweden’s Salut Programme maternal questionnaires (2010–2014) were linked with records in the Swedish Medical Birth Register (MBR). The analytical sample comprised 5089 singleton live births. A Swedish standard method using ultrasound-based sex-specific reference curves defines the abnormality of birth weight in MBR. Univariable and multivariable logistic regressions were used to examine crude and adjusted associations between abnormal birth weights and maternal individual, lifestyle and socioeconomic characteristics. A sensitivity analysis, using alternative definitions of SGA and LGA under the percentile method, was undertaken.ResultsIn multivariable logistic regression, maternal age and parity were associated with LGA (aOR = 1.05, CI = 1.00, 1.09) and (aOR = 1.31, CI = 1.09, 1.58). Maternal overweight and obesity were strongly associated with LGA (aOR = 2.28, CI = 1.47, 3.54) and (aOR = 4.55, CI = 2.85, 7.26), respectively. As parity increased, the odds of delivering SGA babies decreased (aOR = 0.59, CI = 0.42, 0.81) and preterm deliveries were associated with SGA (aOR = 9.46, CI = 5.67, 15.79). The well-known maternal determinants of abnormal birthweight, such as unhealthy lifestyles and poor socioeconomic factors, were not statistically significant in this Swedish setting.ConclusionsThe main findings suggest that multiparity, maternal pre-pregnancy overweight and obesity are strong determinants for LGA babies. Public health interventions should address modifiable risk factors, especially maternal overweight and obesity. These findings suggest that overweight and obesity is an emerging public health threat for newborn health. This might also result in the intergenerational transfer of overweight and obesity. These are important messages for public health policy and decision making.

Factors associated with higher risk of small-for-gestational-age infants in women treated for gestational diabetes.

Previously, management of gestational diabetes (GDM) has focused largely on glycaemic control, with a view to reduce the occurrence of large-for-gestational-age (LGA) infants. However, tight glycaemic control in GDM is associated with a higher incidence of small-for-gestational-age (SGA) infants, which has been linked to higher rates of adverse outcomes. The aim was to characterise risk factors associated with having an SGA infant in women being treated for GDM. This was a retrospective observational cohort study of 308 women with GDM. Women were split into groups based on their infant's size at delivery (SGA, appropriate-for-gestational-age (AGA) or LGA). Literature review and expert opinion helped to determine several predictors of women with GDM delivering an SGA infant, and statistical analysis was used to produce odds ratios (OR) for these predictors. The sample included primiparous women with a mean pre-pregnancy body mass index (BMI) of 25.72 (standard deviation: 5.75). Metabolic risk factors associated with delivering an SGA infant included a lower pre-pregnancy BMI (adjusted OR 1.13, P = 0.04, 95% confidence interval (CI): 1.01-1.26), a lower fasting blood glucose level (BGL) (adjusted OR: 3.21, P = 0.01, 95% CI: 1.30-7.93) and growth that was high risk for SGA at baseline ultrasound scan (USS) (adjusted OR: 7.43, P < 0.001, 95% CI: 2.93-18.79). The combined clinical picture of lower pre-pregnancy BMI, fasting BGL and baseline USS growth measurements may indicate a need for less aggressive glucose management in women with GDM to prevent SGA infants.

Continuous glucose monitoring parameters in pregnancy-related complications in patients with type 1 diabetes: a retrospective cohort study.

Continuous glucose monitoring (CGM) improves pregnancy outcomes in patients with type 1 diabetes (T1D). The primary study objective was to analyze associations between numerous novel CGM parameters and neonatal complications, such as large‑for‑gestational‑age (LGA) neonates, hypoglycemia, hyperbilirubinemia, transient breathing disorders, preterm births, as well as pre‑eclampsia. In this single‑center retrospective cohort study, we recruited 102 eligible pregnant women with T1D who were treated with sensor‑augmented pumps with suspend‑before‑low function from the first trimester. The pregnant patients were admitted for at least 1 control hospital visit in each trimester of gestation for anthropometric and laboratory measurements and collection of sensor data. The median (interquartile range) percentage values for glycated hemoglobin (HbA1c) (first trimester, 6.23 [5.91-6.9]; second trimester, 5.49 [5.16-5.9]; third trimester, 5.75 [5.39-6.29]) and for time‑in‑range (first trimester, 72.4 [67.3-80.3]; second trimester, 72.5 [64.7-79.6]; third trimester, 75.9 [67.1-81.4] met the criteria of well‑controlled T1D in each trimester of pregnancy. Nonetheless, we noted 27% of LGA births, 25% of neonatal hypoglycemia, 33% of hyperbilirubinemia, and 13% of preterm births. Worse glycemic control and more glycemic fluctuations in the second and third trimesters were mainly associated with increased risk of LGA at birth, transient breathing disorders, and hyperbilirubinemia. CGM parameters (mean of daily differences, high blood glucose index, glycemic risk assessment in diabetes equation, or continuous overall net glycemic action) in the patients with T1D are significantly associated with the increased risk of LGA at birth and neonatal transient breathing disorders and hyperbilirubinemia. However, we did not find evidence that novel CGM indices could be more effective in predicting those events than the commonly used CGM parameters or HbA1c levels.

A Comparison of the Umbilical Artery Doppler Indices between Pregnancies with Advanced and Normal Maternal Age in the Second Trimester

Objective: To compare the pulsatile index (UA-PI), resistance index (UA-RI), and systolic/diastolic ratio (UA-S/D) of the umbilical artery between pregnant women with advanced maternal age (AMA) and normal maternal age. Materials and Methods: Participants were pregnant women who attended antenatal care at the maternal-fetal medicine unit at Bhumibol Adulyadej Hospital, Royal Thai Air Force, Bangkok, Thailand. The present study was conducted between February and December 2022. Participants who met inclusion criteria were classified as study for the patients aged 35 years and older, and control groups for the patients younger than 35 years old. All participants underwent ultrasonography for umbilical artery Doppler velocimetry measurement including UA-PI, UA-RI, and UA-S/D. Demographic characters of both study and control groups were included for statistical calculation. Results: Five hundred pregnant women with gestational age between 18 and 24 weeks were enrolled. The mean age of the study and the control group were 37.9 and 26.0 years, respectively. Participants in the study group have higher BMI than the control group. The study and the control group had comparable diastolic and systolic blood pressure. The mean (standard deviation) of UA-PI, UA-RI, and S/D ratio of the study/control group were 1.33±0.21/1.27±0.22, 0.77±0.1/0.74±0.09, and 4.24±0.98/3.95±0.97, respectively, with statistical significance. The study group had a significantly higher number of large for gestational age (LGA), pregnancy induced hypertension (PIH), and gestational diabetes mellitus (GDM) than the control group. Conclusion: AMA pregnancy had higher UA-PI, UA-RI, UA-S/D, incidence of PIH, GDM, and LGA than those age less than 35 years. Keywords: Advanced maternal age; Umbilical artery Doppler indices; Second trimester

Association between excessive fetal growth and maternal cancer in Shanghai, China: a large, population-based cohort study

The prevalence of high birth weight or large for gestational age (LGA) infants is increasing, with increasing evidence of pregnancy-related factors that may have long-term impacts on the health of the mother and baby. We aimed to determine the association between excessive fetal growth, specifically LGA and macrosomia, and subsequent maternal cancer by performing a prospective population-based cohort study. The data set was based on the Shanghai Birth Registry and Shanghai Cancer Registry, with medical records from the Shanghai Health Information Network as a supplement. Macrosomia and LGA prevalence was higher in women who developed cancer than in women who did not. Having an LGA child in the first delivery was associated with a subsequently increased risk of maternal cancer (hazard ratio [HR] = 1.08, 95% confidence interval [CI] 1.04–1.11). Additionally, in the last and heaviest deliveries, there were similar associations between LGA births and maternal cancer rates (HR = 1.08, 95% CI 1.04–1.12; HR = 1.08, 95% CI 1.05–1.12, respectively). Furthermore, a substantially increased trend in the risk of maternal cancer was associated with birth weights exceeding 2500 g. Our study supports the association between LGA births and increased risks of maternal cancer, but this risk requires further investigation.