Large For Gestational Age Research Articles

Prevalence of Large for Gestational Age and Polyhydramnios on Late Third-Trimester Ultrasound and Associated Adverse Pregnancy Outcomes [ID 2683531

INTRODUCTION: The objective of this study was to evaluate the prevalence of large for gestational age (LGA) and polyhydramnios found on ultrasound performed between 34 and 38 weeks of gestation and investigate the prevalence of gestational diabetes and delivery outcomes in this population. METHODS: A retrospective cross-sectional study (IRB #4869) was performed including chart review of late third-trimester ultrasounds performed on singleton pregnancies between 34 and 38 weeks of gestation from April 2020 to April 2022 at a hospital-owned private practice. Patients were grouped as no LGA (estimated fetal weight >90%) or polyhydramnios (amniotic fluid index ≥25 or maximum vertical pocket ≥8) or LGA and/or polyhydramnios. Differences in cesarean delivery (CD), gestational diabetes diagnosis, and macrosomia between groups were assessed via χ2 and Fisher's exact tests. RESULTS: Of 1,510 pregnancies, 15.0% (227/1,510) were diagnosed with LGA and/or polyhydramnios on late third-trimester ultrasound. The overall prevalence of CD in the group without LGA and/or polyhydramnios was 25.5%, whereas the rate of CD in patients having LGA and/or polyhydramnios was 44.1% (P<.001). The overall prevalence of macrosomia in the group without LGA and/or polyhydramnios was 8.8%, whereas the rate of macrosomia in patients having LGA and/or polyhydramnios was 17.2% (P<.001). The prevalence of diabetes in pregnancy was not significantly different between groups (without LGA and/or polyhydramnios 12.2% versus having LGA and/or polyhydramnios 16.7%; P=.081). CONCLUSION: Patients with LGA and/or polyhydramnios on late third-trimester ultrasound had significantly higher rates of CD and macrosomia. They were not more likely to have a diagnosis of diabetes during pregnancy. Late third-trimester ultrasound findings of LGA and/or polyhydramnios could be useful in detecting undiagnosed and/or missed diabetes. Future work will evaluate the timing of gestational diabetes screening and subsequent testing for diabetes if findings suggest LGA and/or polyhydramnios.

Per- and polyfluoroalkyl substances (PFAS) and fetal growth: A nation-wide register-based study on PFAS in drinking water

BackgroundThere is inconclusive evidence for an association between per- and polyfluoroalkyl substances (PFAS) and fetal growth. ObjectivesWe conducted a nation-wide register-based cohort study to assess the associations of the estimated maternal exposure to the sum (PFAS4) of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) with birthweight as well as risk of small- (SGA) and large-for-gestational-age (LGA). Materials and methodsWe included all births in Sweden during 2012–2018 of mothers residing ≥ four years prior to partus in localities served by municipal drinking water where PFAS were measured in raw and drinking water. Using a one-compartment toxicokinetic model we estimated cumulative maternal blood levels of PFAS4 during pregnancy by linking residential history, municipal PFAS water concentration and year-specific background serum PFAS concentrations in Sweden. Individual birth outcomes and covariates were obtained via register linkage. Mean values and 95 % confidence intervals (CI) of β coefficients and odds ratios (OR) were estimated by linear and logistic regressions, respectively. Quantile g-computation regression was conducted to assess the impact of PFAS4 mixture. ResultsAmong the 248,804 singleton newborns included, no overall association was observed for PFAS4 and birthweight or SGA. However, an association was seen for LGA, multivariable-adjusted OR 1.08 (95% CI: 1.01–1.16) when comparing the highest PFAS4 quartile to the lowest. These associations remained for mixture effect approach where all PFAS, except for PFOA, contributed with a positive weight. DiscussionsWe observed an association of the sum of PFAS4 – especially PFOS – with increased risk of LGA, but not with SGA or birthweight. The limitations linked to the exposure assessment still require caution in the interpretation.

Breastfeeding, Gestational Diabetes Mellitus, Size at Birth and Overweight/Obesity in Early Childhood.

Background: Breastfeeding appears to reduce the risk of childhood overweight/obesity. However, it remains unclear whether this protective effect persists among high-risk populations. This study aims to investigate the association of breastfeeding with the risk of overweight/obesity in early childhood and whether this association is altered by gestational diabetes mellitus (GDM) or size at birth. Methods: Feeding practices during the first 12 months of age and weight and length at 12-36 months of age were collected. Full breastfeeding includes exclusive and predominant breastfeeding. Children with body mass index (BMI) values greater than 1 standard deviation from the mean of sex- and age-specific BMI were classified as overweight/obese. Multiple generalized estimating equations models were applied to analyze the associations of full breastfeeding duration with overweight/obesity risk. Results: Among all participants (n = 9329), infants with a longer full-breastfeeding duration had a reduced risk of overweight/obesity in early childhood compared with those breastfed for less than one month. Infants exposed to GDM and those born large for gestational age (LGA) had a higher risk of overweight/obesity in early childhood. Among infants of mothers with GDM (n = 1748), infants with full breastfeeding for greater than 6 months (aOR: 0.58; 95% CI: 0.44, 0.78) showed a decreased risk of overweight/obesity in early childhood compared with those breastfed for less than one month. Among LGA infants (n = 1279), infants with full breastfeeding for 3-5 months (aOR: 0.66; 95% CI: 0.57, 0.76) and greater than 6 months (aOR: 0.70; 95% CI: 0.56, 0.88) showed a decreased risk of overweight/obesity in early childhood. Similar results were observed among LGA infants of mothers with GDM. Conclusions: Initiating and prolonging breastfeeding would reduce the risk of overweight/obesity in early childhood, and LGA infants and infants born to mothers with GDM would experience greater benefits.

Italian neonatal birthweight charts derived from INeS not separated by birth order

BackgroundIdentifying high-risk neonates with abnormal fetal growth is crucial for health risk prediction and early intervention. Small for gestational age (SGA) and large for gestational age (LGA) classifications highlight neonates having a higher risk for postnatal diseases. Accurate diagnosis depends on precise anthropometric measurements and appropriate reference data. In 2010, specific neonatal charts for Italian singletons (INeS charts) were published, tracing separately for first- and later-born neonates due to a 3% birth weight difference. We present INeS charts for birth weight non-separated by first- and later-born babies useful when information on parity is unavailable or unreliable, or for better comparisons with other neonatal charts that are not separated by birth-order.MethodsINeS charts were traced using a parametric function. Starting with the parameters estimates published in a different paper, INeS charts not separated by birth order were traced for the gestational age range of 23 to 42 weeks. In a second step the charts were parametrized as Cole and Green Lambda Mu and Sigma (LMS) model, allowing computation of standard deviation scores.ResultsThe centiles of non-separated INeS charts follow between first- and later-born charts. Distances varied due to changing first-born proportions with gestational age, Max differences of about 100g with later born and 70g with first-born were observed at term. S and L functions have a similar shape for boys and girls. S function shows a pick at about 29 weeks, L function has positive values in all the range of gestational age with a pick at 39 weeks.ConclusionsThe study presents non-separated Birth Weight INeS charts, bridging the gap when parity information is unavailable. Differences with separated charts were generally small, making them reliable for neonatal health assessment. Insights from L and S parameters contribute to standardized birth weight and adjust it by sex and Gestational Age, useful for defining SGA or LGA neonates. The paper enhances neonatal care tools, showcasing INeS chart flexibility in different clinical scenarios and supporting neonatology research.

The impact of gestational weight gain on fetal and neonatal outcomes: the Araraquara Cohort Study

BackgroundGestational weight gain (GWG) is an important indicator for monitoring maternal and fetal health. Objective: To evaluate the effect of GWG outside the recommendations of the Institute of Medicine (IOM) on fetal and neonatal outcomes.Study designA prospective cohort study with 1642 pregnant women selected from 2017 to 2023, with gestational age ≤ 18 weeks and followed until delivery in the city of Araraquara, Southeast Brazil. The relationship between IOM-recommended GWG and fetal outcomes (abdominal subcutaneous tissue thickness, arm and thigh subcutaneous tissue area and intrauterine growth restriction) and neonatal outcomes (percentage of fat mass, fat-free mass, birth weight and length, ponderal index, weight adequateness for gestational age by the Intergrowth curve, prematurity, and Apgar score) were investigated. Generalized Estimating Equations were used.ResultsGWG below the IOM recommendations was associated with increased risks of intrauterine growth restriction (IUGR) (aOR 1.61; 95% CI: 1.14–2.27), low birth weight (aOR 2.44; 95% CI: 1.85–3.21), and prematurity (aOR 2.35; 95% CI: 1.81–3.05), and lower chance of being Large for Gestational Age (LGA) (aOR 0.38; 95% CI: 0.28–0.54), with smaller arm subcutaneous tissue area (AST) (-7.99 g; 95% CI: -8.97 to -7.02), birth length (-0.76 cm; 95% CI: -1.03 to -0.49), and neonatal fat mass percentage (-0.85%; 95% CI: -1.12 to -0.58). Conversely, exceeding GWG guidelines increased the likelihood of LGA (aOR 1.53; 95% CI: 1.20–1.96), with lower 5th-minute Apgar score (aOR 0.42; 95% CI: 0.20–0.87), and increased birth weight (90.14 g; 95% CI: 53.30 to 126.99).ConclusionAdherence to GWG recommendations is crucial, with deviations negatively impacting fetal health. Effective weight control strategies are imperative.

Antenatal health and perinatal outcomes of Pacific Islander women in Australia with and without gestational diabetes: A ten-year retrospective cohort study.

Pacific Islander (PI) women in Australia have an increased risk of gestational diabetes (GDM); however, their perinatal outcomes are poorly understood. The aim was to determine the maternal characteristics and perinatal outcomes of PI women with and without GDM compared to Australian/European (AE)-born women. A retrospective analysis of perinatal outcomes of singleton deliveries >20 weeks' gestation between 1 January 2011 and 31 December 2020 was conducted at a tertiary provider (Melbourne, Australia). Antenatal details and birth outcomes were extracted from the Birth Outcome Systems database. t-Tests and χ2, univariate and multivariable logistic regression analyses assessed the relationship between ethnicity and outcomes. Of 52,795 consecutive births, 24,860 AE women (13.3% with GDM) and 1207 PI-born women (20.1% with GDM) were compared. PI women had significantly greater pre-pregnancy body mass index (BMI) and significantly lower rates of smoking and nulliparity. PI women with GDM had higher rates of pre-eclampsia (P < 0.001), large-for-gestational age (LGA) neonates (P = 0.037) and neonatal hypoglycaemia (P = 0.017) but lower rates of small-for-gestational age neonates (P = 0.034). Neonatal intensive care unit (NICU)/special care nursery requirements did not increase. After having adjusted for covariates, PI women's risk of LGA neonates (adjusted odds ratio (aOR): 1.06, 95% confidence interval (CI): 0.86-1.31) was attenuated; however, risk of pre-eclampsia (aOR: 1.49, 95% CI: 1.01-2.21) and neonatal hypoglycaemia (aOR: 1.40, 95% CI: 1.01-1.96) still increased. They were less likely to require a primary caesarean section (aOR: 0.86, 95% CI: 0.73-0.99). PI women have higher BMI and GDM rates, contributing to an increased likelihood of adverse perinatal outcomes. BMI is a modifiable risk factor that could be addressed prenatally.

Mean Glucose and Gestational Weight Gain as Predictors of Large-for-Gestational-Age Infants in Pregnant Women with Type 1 Diabetes Using Continuous Glucose Monitoring.

Aims/hypothesis: To compare glycemic metrics during pregnancy between women with type 1 diabetes (T1D) delivering large-for-gestational-age (LGA) and appropriate-for-gestational-age (AGA) infants, and to identify predictors of LGA infants. Materials and Methods: A cohort study including 111 women with T1D using intermittently scanned continuous glucose monitoring from conception until delivery. Average sensor-derived metrics: mean glucose, time in range in pregnancy (TIRp), time above range in pregnancy, time below range in pregnancy, and coefficient of variation throughout pregnancy and in pregnancy intervals of 0-10, 11-21, 22-33, and 34-37 weeks were compared between women delivering LGA and AGA infants. Predictors of LGA infants were sought for. Infant growth was followed until 3 months postdelivery. Results: In total, 53% (n = 59) delivered LGA infants. Mean glucose decreased during pregnancy in both groups, with women delivering LGA infants having a 0.4 mmol/L higher mean glucose from 11-33 weeks (P = 0.01) compared with women delivering AGA infants. Mean TIRp >70% was obtained from 34 weeks in women delivering LGA infants and from 22-33 weeks in women delivering AGA infants. Independent predictors for delivering LGA infants were mean glucose throughout pregnancy and gestational weight gain. At 3 months postdelivery, infant weight was higher in infants born LGA compared with infants born AGA (6360 g ± 784 and 5988 ± 894, P = 0.04). Conclusions/interpretations: Women with T1D delivering LGA infants achieved glycemic targets later than women delivering AGA infants. Mean glucose and gestational weight gain were independent predictors for delivering LGA infants. Infants born LGA remained larger postdelivery compared with infants born AGA.

Integrated care of diabetes during pregnancy: a Qatari nationwide cohort

Diabetes in pregnancy (DIP) is associated with adverse fetal and maternal outcomes. DIP is classified as either pre-existing or new-onset diabetes mellitus (DM), which is classified into gestational DM (GDM) and newly detected type 2 (N-T2D). All pregnant women in Qatar who are not known to have pre-existing DM are offered screening for DIP during the first antenatal care visit and after 24 weeks gestation. The study aims to report the DIP screening rates, the prevalence of DIP, and the impact of the universal screening program on adverse pregnancy outcomes. This retrospective study included all women who gave birth in Hamad Medical Corporation (HMC) hospitals between 2019 and 2022. New-onset DIP was defined using the WHO-2013 criteria. The primary outcomes were the screening rates and the prevalence of DIP in Qatar. The secondary outcomes were the difference in preterm delivery, C-section, macrosomia, large for gestational age (LGA), small for gestational age (SGA), and intra-uterine fetal death (IUFD) between women with or without GDM. We included 94,422 women who gave birth to 96,017 neonates (85.7%) out of 112,080 neonates born nationwide. The number of women with pre-existing diabetes was 2496 women. Of 91,926 eligible women, 77,372 (84.2%) were screened for DIP. The prevalence of GDM is 31.6% (95% CI: 31.3-32.0%); N-T2D is 2.2% (95% CI: 2.1-2.3%), and pre-existing Type 2 DM and Type 1 DM was 2.6% (95% CI: 0.8-3.0%) and 0.2% (0.19-0.25), respectively. Compared to the non-GDM group, women with GDM were older (30.8±5.3 versus 29.7±5.2 years, p<0.001). After adjusting for age, women with GDM had lower risk of IUFD and SGA (0.63 [95% CI 0.50-0.80, p<0.001], 0.88 [95% CI 0.84-0.92, p<0.001] respectively) but higher risk of C-section and LFD (1.07 [95% CI 1.04-1.10, p<0.001], 1.09 [95% CI 1.01-1.15, p=0.01], respectively, compared to women with no-GDM. Of the women eligible for screening, 84.2% were screened by the DIP program in Qatar. The prevalence of DIP in Qatar is 36.9%. Integrated care is critical for the screening and management of diabetes during pregnancy. The authors did not receive any funding for this project.

Body composition and motor function in children born large for gestational age at term.

This cross-sectional study compared body composition and motor function between children who were born large for gestational age (LGA) and those born appropriate for gestational age (AGA) and to investigate the association between gait quality and other variables. Body composition was determined using a bioelectrical impedance analyzer. Motor functions were assessed using one-leg standing time, timed up-and-go test, five times sit-to-stand test, and three-dimensional gait analysis. We compared the results between two groups. We performed multiple regression analysis to evaluate the association between gait deviation index and variables of LGA, fat mass index, and motor functions (adjusted for age and sex). Children aged 6-12 years who were born LGA at term (n = 23) and those who were born AGA at term (n = 147) were enrolled. The LGA group had a higher fat mass index (2.9 vs. 2.2, p = 0.006) and lower gait deviation index (91.4 vs. 95.4, p = 0.011) than the AGA group. On multiple regression analysis, gait deviation index was associated with being LGA and fat mass index. In school-aged children who were born LGA, monitoring increased fat mass index and decreased gait deviation index could lessen the risk of metabolic syndrome and reduced gait function. Children aged 6-12 years who were born large for gestational age (LGA) at term showed a higher fat mass index and lower gait deviation index than those who were born appropriate for gestational age at term. No significant differences in balance function or muscle strength were observed between groups. On multiple regression analysis, gait deviation index was associated with being LGA at birth and fat mass index. In school-aged children who were born LGA, monitoring increased fat mass index and decreased gait deviation index could lessen the risk of metabolic syndrome and reduced gait function.

Associations between gestational weight gain and weight development of the offspring: Differences depending on maternal pre-pregnancy BMI

PurposeObesity rates are rising, and the gestational weight gain (GWG) of most women does not comply with current guidelines. This study assesses the association of pre-pregnancy BMI (ppBMI) and GWG with the child’s weight development and investigates whether associations with GWG differ depending on ppBMI.MethodsData were obtained from the cohort study LIFE Child (Germany), comprising 691 mother–child pairs. Children’s weight was followed until age five. Associations between maternal ppBMI, GWG, and children’s weight were evaluated using regression analyses.ResultsThe association between GWG and birth weight (BW) was significantly positive in normal and underweight (n/u) women (βGWG = 0.05, p < 0.01, 95% confidence interval (CI) 0.03—0.07), but not in women with overweight or obesity (o/o) (βGWG = 0.0002, p = 0.99, 95% CI −0.03 to 0.03). The risk of giving birth to an infant who was large for gestational age (LGA) increased with rising GWG in n/u women (OR = 1.6, p < 0.01, 95% CI 1.23—2.25). Women with o/o were at increased risk for a LGA baby regardless of GWG (OR = 3, p < 0.01, 95% CI 1.34—6.97). This trend persisted in the child’s weight development during the first 5 years of life.ConclusionWomen with o/o might increase their offspring’s risk for higher weight at birth and in early childhood. In n/u women, GWG might be the more influential factor. Women should strive for normal weight before conception and should be more attentive to GWG.

Effects of ambient air pollution on the risk of small- and large-for-gestational-age births: an analysis using national birth data in Japan.

Small-for-gestational-age (SGA) and large-for-gestational-age (LGA) births are major adverse birth outcomes related to newborn health. In contrast, the association between ambient air pollution levels and SGA or LGA births has not been investigated in Japan; hence, the purpose of our study is to investigate this association. We used birth data from Vital Statistics in Japan from 2017 to 2021 and municipality-level data on air pollutants, including nitrogen dioxide (NO2), sulfur dioxide (SO2), photochemical oxidants, and particulate matter 2.5 (PM2.5). Ambient air pollution levels throughout the first, second, and third trimesters, as well as the whole pregnancy, were calculated for each birth. The association between SGA/LGA and ambient levels of the air pollutants was investigated using crude and adjusted log-binomial regression models. In addition, a regression model with spline functions was also used to detect the non-linear association. We analyzed data from 2,434,217 births. Adjusted regression analyses revealed statistically significant and positive associations between SGA birth and SO2 level, regardless of the exposure period. Specifically, the risk ratio for average SO2 values throughout the whole pregnancy was 1.014 (95% confidence interval [CI] 1.009, 1.019) per 1ppb increase. In addition, regression analysis with spline functions indicated that an increase in risk ratio for SGA birth depending on SO2 level was linear. Furthermore, statistically significant and negative associations were observed between LGA birth and SO2 except for the third trimester. It was suggested that ambient level of SO2 during the pregnancy term is a risk factor for SGA birth in Japan.

Maternal Dietary Cholesterol and Egg Intake during Pregnancy and Large-for-Gestational-Age Infants: A Prospective Cohort Study

BackgroundCholesterol plays a vital role in fetal growth and development during pregnancy. There remains controversy over whether pregnant females should limit their cholesterol intake. ObjectivesThe objective of this study was to investigate the association between maternal dietary cholesterol intake during pregnancy and infant birth weight in a Chinese prospective cohort study. MethodsA total of 4146 mother-child pairs were included based on the Jiangsu Birth Cohort study. Maternal dietary information was assessed with a semiquantitative food-frequency questionnaire. Birth weight z-scores and large-for-gestational-age (LGA) infants were converted by the INTERGROWTH-21st neonatal weight-for-gestational-age standard. Poisson regression and generalized estimating equations were employed to examine the relationships between LGA and maternal dietary cholesterol across the entire pregnancy and trimester-specific cholesterol intake, respectively. ResultsThe median intake of maternal total dietary cholesterol during the entire pregnancy was 671.06 mg/d, with eggs being the main source. Maternal total dietary cholesterol and egg-sourced cholesterol were associated with an increase in birth weight z-score, with per standard deviation increase in maternal total and egg-sourced dietary cholesterol being associated with an increase of 0.16 [95% confidence interval (CI): 0.07, 0.25] and 0.06 (95% CI: 0.03, 0.09) in birth weight z-score, respectively. Egg-derived cholesterol intake in the first and third trimesters was positively linked to LGA, with an adjusted relative risk of 1.11 (95% CI: 1.04, 1.18) and 1.09 (95% CI: 1.00, 1.18). Compared with mothers consuming ≤7 eggs/wk in the third trimester, the adjusted relative risk for having an LGA newborn was 1.37 (95% CI: 1.09, 1.72) for consuming 8–10 eggs/wk and 1.45 (95% CI: 1.12, 1.86) for consuming >10 eggs/wk (P-trend = 0.015). ConclusionsMaternal total dietary cholesterol intake, as well as consuming over 7 eggs/wk during pregnancy, displayed significant positive relationships with the incidence of LGA, suggesting that mothers should avoid excessive cholesterol intake during pregnancy to prevent adverse birth outcomes.

Association of prepregnancy body mass index and gestational weight gain trajectory with adverse pregnancy outcomes—a prospective cohort study in Shanghai

ObjectivesThe objective was to investigate the associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) trajectories with adverse pregnancy outcomes (APOs).DesignThis was a prospective cohort study.SettingThis...

SARS-CoV-2 infection by trimester of pregnancy and adverse perinatal outcomes: a Mexican retrospective cohort study

ObjectiveConflicting evidence for the association between COVID-19 and adverse perinatal outcomes exists. This study examined the associations between maternal COVID-19 during pregnancy and adverse perinatal outcomes including preterm birth (PTB),...

Birth and postnatal outcomes among infants of immigrant parents of different admission categories and parents born in Canada: a population-based retrospective study.

Most studies of disparities in birth and postnatal outcomes by parental birthplace combine all immigrants into a single group. We sought to evaluate heterogeneity among immigrants in Canada by comparing birth and postnatal outcomes across different immigration categories. We conducted a population-based retrospective study using Statistics Canada data on live births and stillbirths (1993-2017) and infant deaths (1993-2018), linked to parental immigration data (1960-2017). We classified birthing parents as born in Canada, economic-class immigrants, family-class immigrants, or refugees, and evaluated differences in preterm births, small-for-gestational-age (SGA) and large-for-gestational-age (LGA) births, stillbirths, and infant deaths among singleton births by group. Among 7 980 650 births, 1 715 050 (21.5%) were to immigrants, including 632 760 (36.9%) in the economic class, 853 540 (49.8%) in the family class, and 228 740 (13.4%) refugees. Compared with infants of Canadian-born birthing parents, infants of each of the 3 immigrant groups had higher risk of preterm birth, SGA birth, and stillbirth, but lower risk of LGA birth and neonatal death. Compared with infants of economic-class immigrants, infants of refugees had higher risk of early preterm birth (0.9% v. 0.8%, adjusted risk ratio [RR] 1.08, 95% confidence interval [CI] 1.01-1.15) and LGA birth (9.2% v. 7.5%, adjusted RR 1.12, 95% CI 1.10-1.15), but lower risk of SGA birth (10.2% v. 11.0%, adjusted RR 0.92, 95% CI 0.90-0.94), while infants of family-class immigrants had higher risk of SGA birth (12.2% v. 11.0%, adjusted RR 1.01, 95% CI 1.00-1.02). Risk of stillbirth, neonatal death, and overall infant death did not differ significantly among immigrant groups. Heterogeneity exists in outcomes of infants born to immigrants to Canada across immigration categories. These results highlight the importance of disaggregating immigrant populations in studies of health disparities.

ERRγ1 and Aromatase Expression in Human Placental Tissues from Term Deliveries of Large for Gestational Age Newborns

Plain Language SummaryEvents during fetal development are associated with susceptibility to chronic disease in adulthood. Extreme birth weight, for newborns of small for gestational age or large for gestational age (LGA), has been associated with an increased risk of developing metabolic syndrome in adulthood. Even though some intrauterine events during fetal development have been described, there is still a long way for identifying all the factors that are involved in fetal programming. The placenta has an important role in intrauterine programming because it controls the intrauterine environment by supplying oxygen, nutrients, and specific hormones involved in fetal development. Estrogens and androgens in maternal and fetal circulations play an important role in determining a physiological placental phenotype. ERRγ1 expression in placental tissues is involved in aromatase activity regulation and hence in intrauterine estrogen-androgen balance. In this study, we propose that the dysregulation of ERRγ1 in placental tissue might modify the estrogen-androgen balance in the intrauterine environment, representing one of the key factors in the regulation of fetal programming in LGA newborns.

Association between abnormal oral glucose tolerance test patterns in the second trimester and large for gestational age newborns

Objective: To investigate the impact of abnormal patterns of 75 g oral glucose tolerance test (OGTT) in the second trimester on the risk of large for gestational age (LGA) newborn deliveries. Methods: General clinical data and OGTT results of 66 290 pregnant women who received regular prenatal care and delivered in Guangdong Maternal and Child Health Hospital from December 24, 2016 to July 26, 2022 were collected. According to the results of OGTT, the pregnant women were divided into 8 groups: normal blood glucose group (normal fasting blood glucose, 1-hour and 2-hour after oral glucose, 54 518 cases), gestational diabetes mellitus (GDM) 0 group (only abnormal fasting blood glucose, 1 430 cases), GDM 1 group (only abnormal blood glucose at 1-hour after oral glucose, 2 150 cases), GDM 2 group (only abnormal blood glucose at 2-hour after oral glucose, 3 736 cases), GDM 0+1 group (both fasting blood glucose and 1-hour after oral glucose were abnormal, 371 cases), GDM 0+2 group (both fasting blood glucose and 2-hour after oral glucose were abnormal, 280 cases), GDM 1+2 group (abnormal blood glucose at 1-hour and 2-hour after oral glucose, 2 981 cases) and GDM 0+1+2 group (abnormal fasting blood glucose, 1-hour and 2-hour after oral glucose, 824 cases). Multivariate logistic regression was used to analyze the effects of different abnormal OGTT patterns on LGA. In addition, the blood glucose measurements at the three time points of OGTT were combined and used as continuous variables in the receiver operating characteristic (ROC) curve to evaluate the predictive value of each blood glucose measurement mode for LGA and the area under the curve (AUC) was compared. Results: (1) Multivariate logistic regression analysis showed that the risks of LGA were significantly increased in GDM 0 group (OR=1.76, 95%CI: 1.50-2.08; P<0.001), GDM 0+1 group (OR=2.29, 95%CI: 1.72-3.04; P<0.001), and GDM 0+1+2 group (OR=1.98, 95%CI: 1.61-2.43; P<0.001). (2) ROC curve analysis showed that fasting blood glucose, 1-hour after oral glucose, 2-hour after oral glucose, fasting+1-hour after oral glucose, fasting+2-hour after oral glucose, 1-hour+2-hour after oral glucose, and fasting+1-hour+2-hour after oral glucose had certain predictive value for LGA (all P<0.001). The AUC of fasting blood glucose measurement was higher than that of 2-hour blood glucose measurement in predicting LGA, and the difference was statistically significant (P<0.05). There was no significant difference in the AUC between fasting blood glucose and other blood glucose measurement modes for predicting LGA (all P>0.05). Conclusions: In the abnormal OGTT patterns, pregnant women with abnormal fasting blood glucose, abnormal fasting+1-hour after oral glucose, and abnormal fasting+1-hour+2-hour after oral glucose have an increased risk of LGA. Fasting blood glucose measurement is of great significance for the prediction of LGA, and could be used as an optimal indicator to evaluate the risk of LGA in clinical practice.

Comparisons of the Rates of Large-for-Gestational-Age Newborns between Women with Diet-Controlled Gestational Diabetes Mellitus and Those with Non-Gestational Diabetes Mellitus.

(1) Objectives: The primary objective is to compare the rate of large-for-gestational-age (LGA) between women with diet-controlled gestational diabetes mellitus (GDM) and those with non-GDM, and to assess whether or not diet-controlled GDM is an independent factor of LGA fetuses. The secondary objectives are to compare the rates of other common adverse pregnancy outcomes, such as preeclampsia, cesarean section rate, preterm birth, and low Apgar score, between pregnancies with diet-controlled GDM and non-GDM pregnancies. (2) Methods: A retrospective cohort study was conducted on singleton pregnancies, diagnosed with GDM and non-GDM between 24 and 28 weeks of gestation, based on a two-step screening test. The prospective database of the obstetric department was accessed to retrieve the records meeting the inclusion criteria, and full medical records were comprehensively reviewed. The patients were categorized into two groups, GDM (study group) and non-GDM (control group). The main outcome was the rate of LGA newborns, and the secondary outcomes included pregnancy-induced hypertension, preterm birth, cesarean rate, low Apgar scores, etc. (3) Results: Of 1364 recruited women, 1342 met the inclusion criteria, including 1177 cases in the non-GDM group and 165 (12.3%) in the GDM group. Maternal age and pre-pregnancy BMI were significantly higher in the GDM group. The rates of LGA newborns, PIH, and cesarean section were significantly higher in the GDM group (15.1% vs. 7.1%, p-value < 0.001; 7.8% vs. 2.6%, p-value = 0.004; and 54.5% vs. 41.5%, p-value = 0.002; respectively). On logistic regression analysis, GDM was not significantly associated with LGA (odds ratio 1.64, 95% CI: 0.97-2.77), while BMI and gender were still significantly associated with LGA. Likewise, GDM was not significantly associated with the rate of PIH (odds ratio: 1.7, 95% CI: 0.825-3.504), while BMI and maternal age were significantly associated with PIH, after controlling confounding factors. (4) Conclusions: The rates of LGA newborns, PIH, and cesarean section are significantly higher in women with diet-controlled GDM than those with non-GDM. Nevertheless, the rates of LGA newborns and PIH are not directly caused by GDM but mainly caused high pre-pregnancy BMI and advanced maternal age, which are more commonly encountered among women with GDM.

Discrete glucose profiles identified using continuous glucose monitoring data and their association with adverse pregnancy outcomes

Continuous glucose monitoring has facilitated the evaluation of dynamic changes in glucose throughout the day and their effect on fetal growth abnormalities in pregnancy. However, studies of multiple continuous glucose monitoring metrics combined and their association with other adverse pregnancy outcomes are limited. This study aimed to (1) use machine learning techniques to identify discrete glucose profiles based on weekly continuous glucose monitoring metrics in pregnant individuals with pregestational diabetes mellitus and (2) investigate their association with adverse pregnancy outcomes. This study analyzed data from a retrospective cohort study of pregnant patients with type 1 or 2 diabetes mellitus who used Dexcom G6 continuous glucose monitoring and delivered a nonanomalous, singleton pregnancy at a tertiary center between 2019 and 2023. Continuous glucose monitoring data were collapsed into 39 weekly glycemic measures related to centrality, spread, excursions, and circadian cycle patterns. Principal component analysis and k-means clustering were used to identify 4 discrete groups, and patients were assigned to the group that best represented their continuous glucose monitoring patterns during pregnancy. Finally, the association between glucose profile groups and outcomes (preterm birth, cesarean delivery, preeclampsia, large-for-gestational-age neonate, neonatal hypoglycemia, and neonatal intensive care unit admission) was estimated using multivariate logistic regression adjusted for diabetes mellitus type, maternal age, insurance, continuous glucose monitoring use before pregnancy, and parity. Of 177 included patients, 90 (50.8%) had type 1 diabetes mellitus, and 85 (48.3%) had type 2 diabetes mellitus. This study identified 4 glucose profiles: (1) well controlled; (2) suboptimally controlled with high variability, fasting hypoglycemia, and daytime hyperglycemia; (3) suboptimally controlled with minimal circadian variation; and (4) poorly controlled with peak hyperglycemia overnight. Compared with the well-controlled profile, the suboptimally controlled profile with high variability had higher odds of a large-for-gestational-age neonate (adjusted odds ratio, 3.34; 95% confidence interval, 1.15-9.89). The suboptimally controlled with minimal circadian variation profile had higher odds of preterm birth (adjusted odds ratio, 2.59; 95% confidence interval, 1.10-6.24), cesarean delivery (adjusted odds ratio, 2.76; 95% confidence interval, 1.09-7.46), and neonatal intensive care unit admission (adjusted odds ratio, 4.08; 95% confidence interval, 1.58-11.40). The poorly controlled profile with peak hyperglycemia overnight had higher odds of preeclampsia (adjusted odds ratio, 2.54; 95% confidence interval, 1.02-6.52), large-for-gestational-age neonate (adjusted odds ratio, 3.72; 95% confidence interval, 1.37-10.4), neonatal hypoglycemia (adjusted odds ratio, 3.53; 95% confidence interval, 1.37-9.71), and neonatal intensive care unit admission (adjusted odds ratio, 3.15; 95% confidence interval, 1.20-9.09). Discrete glucose profiles of pregnant individuals with pregestational diabetes mellitus were identified through joint consideration of multiple continuous glucose monitoring metrics. Prolonged exposure to maternal hyperglycemia may be associated with a higher risk of adverse pregnancy outcomes than suboptimal glycemic control characterized by high glucose variability and intermittent hyperglycemia.

Association of maternal nutritional status and small for gestational age neonates in peri-urban communities of Karachi, Pakistan: findings from the PRISMA study

BackgroundEarly pregnancy nutritional status can be associated with adverse birth outcomes such as small-for-gestational age (SGA) and low birth weight (LBW). BMI (Body Mass Index) and MUAC (Mid-upper arm circumference) are easy to use assessments and are indicative of the pre-pregnancy nutritional status if obtained in the first trimester. This study primarily assesses the association of maternal nutritional status using BMI and MUAC with SGA in a community-based cohort of Pakistani women. It also aims to determine the predictive ability of MUAC and BMI in predicting SGA. Secondarily, we assessed the association between maternal nutrition and large for gestational age (LGA) and LBW.MethodsThis study is a secondary analysis of an ongoing pregnancy cohort “Pregnancy Risk Infant Surveillance and Measurement Alliance (PRISMA)“in Ibrahim Hyderi and Rehri Goth, Karachi. PRISMA participants who were enrolled between January 2021 to August 2022 were included given they had a gestational age < 14 weeks confirmed via ultrasound, MUAC and BMI measurements were available and birth weight was captured within 72 hours. Multivariable logistic regression was used to determine an association between maternal nutritional status and SGA. The PRISMA study was approved by the Aga Khan University Ethics Review Committee (2021–5920-15,518).ResultsOf 926 women included in the analysis, 26.6% (n = 247) had a low MUAC (< 23 cm) while 18.4% (n = 171) were underweight (BMI < 18.5 kg/m2). Nearly one third of low MUAC and underweight women delivered SGA infants (34.4 and 35.1% respectively). Underweight women and women with low MUAC had a statistically significant association with SGA (Underweight: OR 1.49, 95% CI 1.1,2.4; Low MUAC-OR 1.64, 95% CI 1.2,2.3) as well as LBW (Underweight: OR-1.63, 95% CI 1.1,2.4; Low MUAC-OR-1.63, 95% CI 1.2,2.3). ROC curves showed that MUAC and BMI had modest predictability for SGA (AUC < 0.7).ConclusionMaternal nutritional status as indicated by BMI and MUAC are strongly associated with adverse pregnancy outcomes including SGA, LGA and LBW. Although MUAC and BMI are widely used to determine maternal nutritional status, they have poor predictive ability for newborn size. Further research is needed to identify other tools or a combination of tools to better predict adverse birth outcomes in resource-limited settings and plan interventions.