Large For Gestational Age Group Research Articles

Biomarkers in the prediction of complications in pregnancy after assisted reproductive technology.

To compare the temporal changes in mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) across gestation between assisted reproductive technology (ART) pregnancies complicated with great obstetrical syndromes (GOS) or gestational diabetes (GDM) ± large-for-gestational-age (LGA) fetus, and uncomplicated ART pregnancies. This was a prospective longitudinal study of 143 women with singleton pregnancies who conceived through ART at the Department of Obstetrics and Gynecology, Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong SAR between December 2017 and January 2020. The participants were followed up at 6-6+3, 11-13+6, 20-24+6, 30-34+6, and 35-37+6 weeks for the measurement of MAP, UtA-PI, PlGF, and sFlt-1. A linear mixed-effects analysis was performed to compare the biomarkers in the GOS, GDM ± LGA, and uncomplicated groups across gestation. Thirty-three (23.1%) and fifty-five (31.5%) women were diagnosed with GOS and GDM ± LGA, respectively. The GOS group had higher estimated marginal mean log10 MAP mulitples of the median (MoM) across gestation, compared with the uncomplicated group (0.00771 vs -0.02022; P < 0.001), when adjusting for clinical visits and days of embryo transfer. The absolute mean log10 MAP MoM in the GOS group was found to be significantly higher than that of the uncomplicated group at all clinical visits from 6 weeks onwards. Furthermore, the estimated marginal mean log10 PlGF MoM was significantly lower in the GOS group across gestation, compared with the uncomplicated group (-0.04226 vs 0.05566; P = 0.010). The significant difference in log10 PlGF MoM was observed from 11-13+6 to 30-34+6 week of gestation (P < 0.05). However, no significant differences in the estimated marginal means of log10 UtA-PI MoM and log10 sFlt-1 MoM between GOS and uncomplicated groups were observed. GDM ± LGA group had a lower estimated marginal mean log10 PlGF MoM throughout pregnancy compared with the uncomplicated group (-0.01536 vs 0.05572; P = 0.032). In the individual visit analysis, the significant difference was observed at the 20-24+6 and 35-37+6 weeks visits (P < 0.05). There were no significant differences in estimated marginal mean log10 MoM of MAP, UtA-PI, and sFlt-1 between GDM ± LGA and uncomplicated groups during pregnancy. Our study has revealed that among pregnancies conceived through ART, GOS is associated with higher MAP and lower PlGF from early gestation until late third trimester, while GDM ± LGA is associated with lower PlGF during the second half of pregnancy. The same degree of differences in MAP and PlGF persists from early until late gestation in the GOS group and these findings highlight the importance of early screening during the first trimester to identify women who are at risk for developing GOS following ART procedures. Lastly, the potential of PlGF in predicting the development of GDM from the second trimester of pregnancy requires further investigation.

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.

The relationship between birth weight and obstructive sleep apnea in children

Objective:To study the relationship between children's birth weight and obstructive sleep apnea（OSA）. Methods:The sleep data and birth information of children who underwent polysomnography in the Department of Otorhinolaryngology-Head and Neck Surgery of Henan Children's Hospital from October 2020 to July 2022 were retrospectively analyzed. The data of OSA detection rate, OSA severity, sleep structure and respiratory parameters in different birth weight groups were analyzed. Results:A total of 2 778 children met the inclusion criteria, including 1 833 males and 945 females. According to birth weight, the selected children were divided into three groups: 122 small for gestational age（SGA） group, 2 313 appropriate for gestational age（AGA）, and 343 large for gestational age（LGA） group. There was no significant difference in age between different groups（P=0.061）. In each group, boys are significantly more numerous than girls（P=0.001）. The difference in current body mass index（BMI） between groups was statistically significant: the current BMI was higher in the LGA group（17.51±4.01, P<0.001）. The severity of OSA was different in different birth weight groups（P=0.037）. There was a strong positive correlation between the severity of OSA and birth weight（r=0.992）. Children in the SGA group had shorter rapid eye movement（REM） sleep period（19.00[15.18, 23.33], P=0.012）, higher obstructive apnea-hypopnea index（OAHI） values（1.75[0.60, 5.13], P=0.019）, and had lower central apnea hypopnea index（CAHI） values（0.10[0.00, 0.50], P=0.020）. There were no significant differences in sleep structure and respiratory parameters between the LGA group and the AGA group. Multiple regression analysis of the factors affecting the OAHI index showed that the OAHI index of boys was higher than that of girls（95%CI 1.311-2.096, P<0.001）, and age was negatively correlated with the OAHI index（r=-0.105, 95%CI 0.856-0.946, P<0.001）, current BMI and OAHI index were positively correlated（r=0.037, 95%CI 1.010-1.065, P=0.007）. LGA was positively correlated with OAHI index（r=0.346, 95%CI 1.039-1.921, P=0.027）, and the correlation between LGA and OAHI（r=0.346） was higher than that between SGA and OAHI（r=0.340）. Conclusion:There was no significant difference in the incidence of OSA in children with different birth weight groups, but the OSA severity of LGA group was higher. Gender, age, BMI index and large for gestational age were the influencing factors for the occurrence of OSA in children, which should be paid more attention to in clinical practice.

Composition of Microbiota in Transient and Mature Human Milk: Significant Changes in Large for Gestational Age Group.

The composition of the human milk (HM) microbiota and, consequently, the microorganisms that are passed on to the infant through breastfeeding, can be influenced by various factors such as the mother's health and diet, gestational age, delivery mode, lactation stage, method of infant feeding, and geographical location. The aim of the Human Milk-Gest Study was to compare the microbiota of transient (postpartum 7-15 days) and mature HM (postpartum 45-90 days) of 44 mothers, and to investigate any potential changes associated with preterm birth, mode of delivery, and birth weight in relation to gestational age. The data were classified into five study groups: normal spontaneous delivery-term (NS-T) newborns, cesarean delivery-term (CS-T) newborns, preterm (PT) newborns (with a gestational age of less than 37 weeks), small for gestational age (SGA) newborns, and large for gestational age (LGA) newborns. An analysis of differential abundance was conducted using ANCOM-BC to compare the microbial genera between transient and mature HM samples as well as between other study groups. A significant difference was detected between HM samples at different sampling times and between the study groups (p < 0.01). In transient HM samples, Ralstonia, Burkholderiaceae_uc, and Pelomonas were significantly dominant in the LGA group compared to the NS-T, CS-T, PT, and SGA groups. In mature HM samples, Burkholderiaceae_uc, Ralstonia, Pelomonas, and Klebsiella were significantly dominant in the LGA group compared to the NS-T, CS-T, and PT groups, while Ralstonia, Burkholderiaceae_uc, and Pelomonas were significantly dominant in the LGA group compared to the SGA group. Differences were also detected between the transient and mature HM samples in the CS-T, PT, SGA, and LGA groups, but no differences occurred in the NS-T groups. In conclusion, we showed that Ralstonia, Burkholderiaceae_uc, and Pelomonas were significantly dominant in the LGA group in transient HM and continued in mature HM. The body mass index (BMI) of the mothers in the LGA group was not >30 at conception, however, the maternal BMI at birth and maternal weight gain during pregnancy were higher than in the other groups. The nutritional composition of HM is specifically designed to meet infant nutritional requirements during early life. Evaluating the effects of HM microbiota on infant microbiota composition and short- and long-term health effects in larger studies would be useful.

Neuropsychological development of large for gestational age infants at the age of 12 months

To investigate the level of neuropsychological development in large for gestational age (LGA) infants at the age of 12 months. The infants, aged 12 to <13 months, who attended the Outpatient Service of Child Care in the First Affiliated Hospital of Shandong First Medical University from December 2021 to June 2023, were enrolled as subjects. According to the gestational age and birth weight, they were divided into preterm appropriate for gestational age (AGA) group, preterm LGA group, early term AGA group, early term LGA group, full-term AGA group, and full-term LGA group. A modified Poisson regression analysis was used to investigate the association between LGA and neuropsychological development outcome at 12 months of age. After adjustment for confounding factors, compared with the full-term AGA group at the age of 12 months, the full-term LGA group had a significant increase in the risk of language deficit (RR=1.364, 95%CI: 1.063-1.750), the early term LGA group had significant increases in the risk of abnormal gross motor, fine motor, language, and the preterm LGA group had significant increases in the risk of abnormal language, social behavior, and total developmental quotient (P<0.05); also, the early term AGA group had higher risks of developmental delay across all five attributes and in total developmental quotient at the age of 12 months (P<0.05); except for the language attribute, the preterm AGA group had higher risks of developmental delay in the other 4 attributes (P<0.05). The neuropsychological development of LGA infants with different gestational ages lags behind that of full-term AGA infants at 12 months of age, and follow-up and early intervention of such infants should be taken seriously in clinical practice.

Methylation analysis by targeted bisulfite sequencing in large for gestational age (LGA) newborns: the LARGAN cohort

BackgroundIn 1990, David Barker proposed that prenatal nutrition is directly linked to adult cardiovascular disease. Since then, the relationship between adult cardiovascular risk, metabolic syndrome and birth weight has been widely documented. Here, we used the TruSeq Methyl Capture EPIC platform to compare the methylation patterns in cord blood from large for gestational age (LGA) vs adequate for gestational age (AGA) newborns from the LARGAN cohort.ResultsWe found 1672 differentially methylated CpGs (DMCs) with a nominal p < 0.05 and 48 differentially methylated regions (DMRs) with a corrected p < 0.05 between the LGA and AGA groups. A systems biology approach identified several biological processes significantly enriched with genes in association with DMCs with FDR < 0.05, including regulation of transcription, regulation of epinephrine secretion, norepinephrine biosynthesis, receptor transactivation, forebrain regionalization and several terms related to kidney and cardiovascular development. Gene ontology analysis of the genes in association with the 48 DMRs identified several significantly enriched biological processes related to kidney development, including mesonephric duct development and nephron tubule development. Furthermore, our dataset identified several DNA methylation markers enriched in gene networks involved in biological pathways and rare diseases of the cardiovascular system, kidneys, and metabolism.ConclusionsOur study identified several DMCs/DMRs in association with fetal overgrowth. The use of cord blood as a material for the identification of DNA methylation biomarkers gives us the possibility to perform follow-up studies on the same patients as they grow. These studies will not only help us understand how the methylome responds to continuum postnatal growth but also link early alterations of the DNA methylome with later clinical markers of growth and metabolic fitness.

The relationship between gut microbiota, short-chain fatty acids, and glucolipid metabolism in pregnant women with large for gestational age infants.

To elucidate the association between gut microbiota, short-chain fatty acids (SCFAs), and glucolipid metabolism in women with large for gestational age (LGA) infants. A single-center, observational prospective cohort study was performed at a tertiary hospital in Wenzhou, China. Normal pregnant women were divided into LGA group and appropriate for gestational age (AGA) group according to the neonatal birth weight. Fecal samples were collected from each subject before delivery for the analysis of gut microbiota composition (GMC) and SCFAs. Blood samples were obtained at 24-28 weeks of gestation age to measure fasting blood glucose and fasting insulin levels, as well as just before delivery to assess serum triglycerides, total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein. The GMC exhibited differences at various taxonomic levels. Within the Firmicutes phylum, genus Lactobacillus, genus Clostridium, species Lactobacillus agil, and species Lactobacillus salivarius were enriched in the LGA group. Microbispora at genus level, Microbispora rosea at species level belonging to the Actinobacteria phylum, Neisseriales at order level, Bartonellaceae at family level, Paracoccus aminovorans, and Methylobacterium at genus level from the Proteobacteria phylum were more abundant in the LGA group. In contrast, within the Bacteroidetes phylum, Prevotella at genus level and Parabacteroides distasonis at species level were enriched in the AGA group. Although there were few differences observed in SCFA levels and most glucolipid metabolism indicators between the two groups, the serum HDL level was significantly lower in the LGA group compared to the AGA group. No significant relevance among GMC, SCFAs, and glucolipid metabolism indicators was found in the LGA group or in the AGA group. Multiple different taxa, especially phylum Firmicutes, genus Prevotella, and genus Clostridium, might play an important role in excessive fetal growth, and LGA might be associated with the lower serum HDL level.

The association between umbilical cord blood fat-soluble vitamin concentrations and infant birth weight.

Fat-soluble vitamins, including vitamins A, D and E, play an important role in the regulation of glucose and lipid metabolism, and may affect infant birth weight. Evidence on the association of birthweight with fat-soluble vitamins is controversial. Therefore, this study aims is to determine the associations of birthweight with vitamin A, D, and E concentrations in cord blood. A total of 199 mother-infant pairs were enrolled in the study. According to gestational age and birth weight, the mother-infant pairs were divided into small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). The Vitamin A, D, and E concentrations in serum were measured by high-performance liquid chromatography tandem-mass spectrometry. The concentrations of vitamin A in the SGA group were significantly lower than those in the AGA and LGA groups. The concentrations of vitamin E in the SGA group were significantly higher than those in the AGA and LGA groups. However, no significant differences were observed in vitamin D among the three groups. Being male (β = 0.317, p < 0.001) and birth weight (β = 0.229, p = 0.014) were positively correlated with the levels of vitamin A. Birth weight (β = -0.213, p= 0.026) was correlated with lower levels of vitamin E. No correlation was found between influencing Factors and the levels of vitamin D (p> 0.05). After adjusting for gestational age, sex, mother's age, delivery mode, pre-pregnancy BMI, and weight gain during pregnancy, the levels of cord blood vitamin A were positively correlated with birth weight (p=0.012). The infant's birth weight is associated with the levels of cord blood vitamins A and E. The dysregulation of vitamins A and E in infants may be a risk factor for fetal growth and future metabolic diseases.

Father's weight could contribute to large babies in overweight and obese mothers with and without gestational diabetes

We evaluated whether there was an association between fathers’ nutritional status and children's birth weight (BW) considering weight-matched mothers with and without gestational diabetes mellitus (GDM). In total, 86 trios of women, infants, and fathers were evaluated. BW was not different between the groups of obese and non-obese parents, frequency of maternal obesity, or GDM. The percentage of infants who were large for gestational age (LGA) was 25% in the obese group and 14% in the non-obese group (p = 0.44). There was a borderline significance for higher body mass index (p = 0.09) of the father in the LGA group compared with the adequate for gestational age group. These results corroborate the hypothesis that the father's weight can also be relevant for the occurrence of LGA.

Development and validation of risk prediction models for large for gestational age infants using logistic regression and two machine learning algorithms.

Large for gestational age (LGA) is one of the adverse outcomes during pregnancy that endangers the life and health of mothers and offspring. We aimed to establish prediction models for LGA at late pregnancy. Data were obtained from an established Chinese pregnant women cohort of 1285 pregnant women. LGA was diagnosed as >90th percentile of birth weight distribution of Chinese corresponding to gestational age of the same-sex newborns. Women with gestational diabetes mellitus (GDM) were classified into three subtypes according to the indexes of insulin sensitivity and insulin secretion. Models were established by logistic regression and decision tree/random forest algorithms, and validated by the data. A total of 139 newborns were diagnosed as LGA after birth. The area under the curve (AUC) for the training set is 0.760 (95% confidence interval [CI] 0.706-0.815), and 0.748 (95% CI 0.659-0.837) for the internal validation set of the logistic regression model, which consisted of eight commonly used clinical indicators (including lipid profile) and GDM subtypes. For the prediction models established by the two machine learning algorithms, which included all the variables, the training set and the internal validation set had AUCs of 0.813 (95% CI 0.786-0.839) and 0.779 (95% CI 0.735-0.824) for the decision tree model, and 0.854 (95% CI 0.831-0.877) and 0.808 (95% CI 0.766-0.850) for the random forest model. We established and validated three LGA risk prediction models to screen out the pregnant women with high risk of LGA at the early stage of the third trimester, which showed good prediction power and could guide early prevention strategies.

Speech-Encoding Deficits in Neonates Born Large-for-Gestational Age as Revealed With the Envelope Frequency-Following Response.

The present envelope frequency-following response (FFR ENV ) study aimed at characterizing the neural encoding of the fundamental frequency of speech sounds in neonates born at the higher end of the birth weight continuum (>90th percentile), known as large-for-gestational age (LGA). Twenty-five LGA newborns were recruited from the maternity unit of Sant Joan de Déu Barcelona Children's Hospital and paired by age and sex with 25 babies born adequate-for-gestational age (AGA), all from healthy mothers and normal pregnancies. FFR ENV s were elicited to the/da/ syllable and recorded while the baby was sleeping in its cradle after a successful universal hearing screening. Neural encoding of the stimulus' envelope of the fundamental frequency (F 0ENV ) was characterized through the FFR ENV spectral amplitude. Relationships between electrophysiological parameters and maternal/neonatal variables that may condition neonatal neurodevelopment were assessed, including pregestational body mass index (BMI), maternal gestational weight gain and neonatal BMI. LGA newborns showed smaller spectral amplitudes at the F 0ENV compared to the AGA group. Significant negative correlations were found between neonatal BMI and the spectral amplitude at the F 0ENV . Our results indicate that in spite of having a healthy pregnancy, LGA neonates' central auditory system is impaired in encoding a fundamental aspect of the speech sounds, namely their fundamental frequency. The negative correlation between the neonates' BMI and FFR ENV indicates that this impaired encoding is independent of the pregnant woman BMI and weight gain during pregnancy, supporting the role of the neonatal BMI. We suggest that the higher adipose tissue observed in the LGA group may impair, via proinflammatory products, the fine-grained central auditory system microstructure required for the neural encoding of the fundamental frequency of speech sounds.

Does detection of a large for gestational age (LGA) fetus in fetal anomaly scan (FAS) require an early oral glucose screening test (OGTT) and can LGA fetus be detected at birth?

Gestational diabetes mellitus (GDM) complications increase with late diagnosis and late treatment, so early diagnosis and treatment is one of the most important factors in preventing complications. We tried to find an answer to the question of whether the detection of large for gestational age (LGA) fetus in fetal anomaly scan (FAS) requires earlier oral glucose screening test (OGTT) and predicts LGA fetus at birth. Pregnant women who underwent fetal anomaly scan and gestational diabetes screening at the Department of Obstetrics and Gynecology, University of Health Sciences, Tepecik Training and Research Hospital between 2018 and 2020 were included in this large retrospective cohort study. FAS was routinely performed between 18-22 weeks in our hospital. 75 grams of OGTT was used for gestational diabetes screening and it was performed between 24-28 weeks. This large retrospective cohort study was performed on 3,180 fetuses, 2,904 appropriate for gestational age (AGA) and 276 LGA, in the second trimester. The prevalence of GDM was significantly higher in the LGA group (OR 2.44, 95% CI 1.66-3.58; p < 0.001). Insulin requirement for blood glucose regulation was significantly higher in the LGA group (OR 3.6, 95% CI 1.68-7.7; p = 0.001). Fasting and 1st hour OGTT values were similar between the groups, but 2nd hour OGTT values were significantly higher in the second trimester LGA group (p = 0.041). The prevalence of LGA newborns at birth was higher in second trimester LGA fetuses than in fetuses with AGA (21.1% vs. 7.1%, p < 0.001). The fact that the estimated fetal weight (EFW) measured in the second trimester FAS is LGA may be related to GDM in the future and LGA fetus at birth. A more detailed GDM risk questioning should be performed to these mothers and OGTT should be considered when additional risk factors are detected. In addition to all these, glucose regulation may not be possible with diet alone in mothers who have LGA in the second trimester ultrasound and who may have GDM in the future. These mothers should be monitored more closely and more carefully.

The correlation between blood-lipid ratio in the first trimester and large-for-gestational-age infants

BackgroundTo investigate the correlation between maternal glucose and lipid metabolism indexes and blood-lipid ratio in the first trimester and large-for- gestational-age (LGA) infants.MethodsWomen in the first trimester of pregnancy who underwent regular obstetric examination in the obstetric outpatient department of the Affiliated Hospital of Chengde Medical College from June 2018 to March 2019 were included according to the standard. Basic information were collected based on questionnaires at the first visit of pregnant women, including early fasting blood glucose (FBG), fasting insulin (FINS), glycated hemoglobin (HbA1c), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC), apolipoprotein A1 (APO-A1), apolipoprotein B (APO-B), lipoprotein a (LP(a)), LDL/HDL, TG/HDL, TC/HDL, APO-B/APO-A1 ratio, birth weight of newborns, gestational age at delivery etc.ResultsA total of 418 cases were included for analysis. The incidence rate of LGA infants was 13.88%, and that of small-for-gestational-age (SGA) infants was 4.78%. Univariate analysis revealed that the age, pre-pregnancy body mass index (BMI), weight gain during pregnancy, APO-B/APO-A1 between LGA group and appropriate-for-gestational-age (AGA) group were significantly different (P < 0.05); multivariate stepwise logistic regression analysis indicated that the correlation between maternal age, pre-pregnancy BMI, weight gain during pregnancy, APO-B/APO-A1 level and LGA were statistically significant (P < 0.05); compared with the reference range of APO-B/APO-A1 of 0.46–0.65, values < 0.46 and > 0.65 were protective factor of LGA (P < 0.05). The receiver operating curve(ROC) indicated that the area under the curve (AUC)s for predicting LGA using maternal age, pre-pregnancy BMI, weight gain during pregnancy, and early pregnancy APO-B/APO-A1 were 0.585, 0.606, 0.637, 0.531, respectively. The AUC for a combined prediction model was 0.742, showing greater predictive value than any other factors individually.ConclusionMaternal age, pre-pregnancy BMI, weight gain during pregnancy, and APO-B/APO-A1 levels in first trimester are significant factors influencing the occurrence of LGA infants, and the combination of the four factors would have certain predictive value for LGA.

Cord Blood Levels of Spexin, Leptin, and Visfatin in Term Infants Born Small, Appropriate, and Large for Gestational Age and Their Association with Newborn Anthropometric Measurements

Children born small for gestational age (SGA) are at risk of future obesity and associated comorbidities. Therefore the identification of risk factors and novel biomarkers which are associated with this risk are needed for early detection and to improve preventive strategies. Spexin (SPX), a novel neuropeptide that is involved in the regulation of obesity and fat metabolism, is a candidate biomarker for predicting obesity and related comorbidities at an early age. The aim of this study was to investigate serum levels of SPX in term infants born small, appropriate, and large for gestational age (LGA) and its association with newborn anthropometric measurements. One hundred and twenty term newborn babies classified as SGA, appropriate for gestational age (AGA), or LGA and their mothers were included. SPX, leptin and visfatin were measured in cord blood and maternal serum by enzyme-linked immunosorbent assay. Fifty-six (46.7%) neonates were girls and 64 (53.3%) were boys. The mean birth weight was 3170.70±663 g, birth length was 48.9±2.79 cm, and head circumference was 34.5±1.67 cm. Birth weights, lengths, and head circumferences of the neonates in the SGA, AGA, and LGA groups were significantly different. Cord blood SPX and leptin levels in the SGA groups were significantly lower than those of both the LGA and AGA groups. Cord blood visfatin levels were significantly lower in the AGA group than the LGA and SGA groups. Maternal SPX levels of SGA babies were significantly lower than those of the mothers in both the LGA and AGA groups, but no significant difference was observed between the SGA and LGA groups. Maternal visfatin levels of the AGA babies were significantly higher than the maternal levels of SGA and LGA groups. There was no difference in terms of maternal leptin levels. Cord blood SPX and leptin levels were positively correlated with birth weight, length and head circumference. Birth weight increased significantly in line with maternal pregestational body mass index. The lowest SPX levels were found in the SGA babies and cord SPX level was significantly correlated with newborn length, weight, and head circumference.

Analysis of physical growth of preterm infants with different intrauterine growth patterns in Haikou

Objective: To analyze the physical growth of preterm infants with different intrauterine growth patterns. Methods: A total of 10 856 preterm infants who were born in various districts of Haikou City from October 1st, 2015 to June 1st, 2021 and received regular health care and management were retrospectively enrolled. The preterm infants were divided into appropriate for gestational age (AGA), small for gestational age (SGA) and large for gestational age (LGA) groups according to different intrauterine growth patterns. The general characteristics of preterm infants in different groups were compared by H test (Kruskal and Wallis) or Chi-squared test. And the developmental curves were plotted by local regression (LOESS) with their physical growth indexes. Results: Of the 10 856 preterm infants, 6 317 were boys and 4 539 were girls. The gestational age at birth was 35 (34, 36) weeks, and the birth weight was 2.5 (2.1, 2.8) kg. There were 754 (6.9%) SGA, 9 301 (85.7%) AGA, and 801 (7.4%) LGA preterm infants. All preterm infants were followed up until 18 months of corrected age. The birth weight of the SGA group was lower than that of the AGA and LGA groups (Z=2 274.93, P<0.001). The proportion of exclusive breastfeeding at the first health care interview was higher in the AGA group (68.6% (6 378/9 301)) than in the SGA group (62.9% (474/754)) (χ2=13.82, P=0.003). The LOESS curving fitting showed that the weight and height of the preterm infants in all the 3 groups increased rapidly during 0-6 months of corrected age. The regression prediction values of weight for age Z-score (WAZ), height for age Z-score (HAZ) and weight for height Z-score (WHZ) were around 0 s, while the regression prediction values of these three indicators in SGA were all below 0 s but greater than -1 s. The rates of low birth weight, growth retardation and wasting during 0-17 months of corrected age were 0.3% (16/4 838)-1.9% (47/2 506), 0.4% (18/4 838) -2.4% (51/2 124), and 2.1% (88/4 135) -4.4% (214/4 838) in AGA groups, and 0 (0/296) -1.0% (2/199), 0 (0/341) -1.6% (3/186) and 1.0% (2/199) -2.6% (9/341) in LGA group, whereas 7.6% (25/330) -16.8% (28/167), 5.2% (17/330)-10.6%(32/303) and 3.9% (3/77) -12.6% (21/167) in SGA group. In addition, the monthly growth of weight and height of preterm infants in all the 3 groups decreased with the increasing age, and the monthly weight gain. The length increment was 4.0 cm/month during corrected 0-2 month of age and 2.4 cm/month during corrected 2-5 month of age in the SGA preterm infants. Conclusions: Most of the preterm infants could have an appropriate catch-up growth, but the growth and development in the SGA preterm infants lags behind that of their AGA and LGA peers. The physical growth of SGA premature infants should be paid more attention to, to timely correct the growth deviations.

High level of γH2AX phosphorylation in the cord-blood cells of large-for-gestational-age (LGA) newborns

Newborns can experience adverse effects as a consequence of maternal or in utero exposure, altered growth of the fetus, or placental dysfunctions. Accurate characterization of gestational age allows monitoring of fetal growth, identification of deviations from the normal growth trajectory, and classification of babies as adapted, small, or large for gestational age (AGA, SGA, or LGA). The aim of this work was to evaluate nuclear and oxidative damage in umbilical cord-blood cells of newborns (sampled at birth), by applying the γH2AX assay and the fluorescent probe BODIPY581/591 C11, to detect DNA DSB and cell membrane oxidation, respectively. No statistically significant differences were observed in the proportion of oxidized cord-blood cells among the groups of newborns, although the LGA group showed the highest value. With regard to genome damage, elevated levels of γH2AX foci were detected in the cell nuclei from LGA newborns as compared to AGA or SGA babies, whose values did not differ from each other. Considering that the observed DNA damage, although still repairable, can represent a risk factor for obesity, metabolic diseases, or other pathologies, monitoring genome and cell integrity at birth can provide useful information for prevention of diseases later in life.

Long-Term Health Associated with Small and Large for Gestational Age Births among Young Thai Adults.

We examined the long-term health outcomes associated with being born small for gestational age (SGA) or large for gestational age (LGA). A total of 632 young adults aged ≈20.6 years were recruited from a longitudinal study (Chiang Mai, Thailand) in 2010: 473 born appropriate for gestational age (AGA), 142 SGA, and 17 LGA. The clinical assessments included anthropometry, blood pressure (BP), lipid profile, and an oral glucose tolerance test (OGTT). Young adults born SGA were 1.8 and 3.2 cm shorter than AGA (p = 0.0006) and LGA (p = 0.019) participants, respectively. The incidence of short stature was 8% among SGA compared with 3% in AGA and no cases among LGA participants, with the adjusted relative risk (aRR) of short stature among SGA 2.70 times higher than that of AGA counterparts (p = 0.013). SGA participants also had a 2 h glucose 7% higher than that of the AGA group (105 vs. 99 mg/dL; p = 0.006). Young adults born LGA had a BMI greater by 2.42 kg/m2 (p = 0.025) and 2.11 kg/m2 (p = 0.040) than those of SGA and AGA, respectively. Thus, the rate of overweight/obesity was 35% in the LGA group compared with 14.2% and 16.6% of SGA and AGA groups, respectively, with corresponding aRR of overweight/obesity of 2.95 (p = 0.011) and 2.50 (p = 0.017), respectively. LGA participants had markedly higher rates of BP abnormalities (prehypertension and/or hypertension) with an aRR of systolic BP abnormalities of 2.30 (p = 0.023) and 2.79 (p = 0.003) compared with SGA and AGA groups, respectively. Thai young adults born SGA had an increased risk of short stature and displayed some impairment in glucose metabolism. In contrast, those born LGA were at an increased risk of overweight/obesity and elevated blood pressure. The long-term follow-up of this cohort is important to ascertain whether these early abnormalities accentuate over time, leading to overt cardiometabolic conditions.

Association of maternal serum lipids levels at late gestation with large for gestational age and neonatal macrosomia in nondiabetic women

ObjectivesTo evaluate the relationship between maternal serum lipids at late gestation in nondiabetic women and the risk of large for gestational age (LGA) and neonatal macrosomia.BackgroundLGA is defined as an infant with a birth weight greater than the 90th percentile for the given week of pregnancy. Maternal dyslipidemia can also induce excessive fetal growth by changes in lipid metabolism during pregnancy.Patients and methodsA prospective observational study was conducted on 161 pregnant women aged 20–35 years recruited from the Department of Obstetrics and Gynecology of Menoufia University Hospital and Shebin El-Kom Teaching Hospital from January 2020 till December 2020. The patients included in the study were singleton live pregnancy, pregnant at 37–42 gestational weeks, and naturally conceived. For all patients, detailed history taking, including family history of diabetes mellitus among first-degree relatives, complete clinical examination, and measurements of maternal lipid profile, including total cholesterol, triglyceride (TG), high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol (LDL-C), and fasting blood sugar and 2 h postprandial blood sugar, were done. Obstetric ultrasound was performed to assess fetal growth. Accordingly, patients were classified into three groups as follows: group 1, normal group; group 2, LGA; and group 3, LGA and neonatal macrosomia.ResultsOur results reported that cholesterol level, TG, LDL levels, and fasting blood sugar level were significantly higher in the LGA group when compared with the normal group. These significant higher levels were consistent between the neonatal macrosomic group and the normal group, with the exception of LDL level, which showed a nonsignificant difference. A cutoff level of cholesterol more than 214 has a sensitivity of 93.8%, a specificity of 82.2%, and an accuracy of 85%, whereas a cutoff level of TG more than 244 has a sensitivity of 96.6%, a specificity of 55.3%, and an accuracy of 63%.ConclusionsElevated TG and cholesterol at late gestation are independent predictors for LGA and neonatal macrosomia in nondiabetic pregnant women.

Neonatal Birthweight, Infant Feeding, and Childhood Metabolic Markers.

Antenatal and early neonatal nutritional environment may influence later metabolic health. Infants of mothers with gestational diabetes mellitus (GDM) have higher risk for childhood obesity and metabolic syndrome (MetS). Leptin and adiponectin are known biomarkers for MetS and may guide interventions to reduce later obesity. We sought to examine the relationship between birthweight, early infancy feeding practices, and biomarkers for MetS in offspring of women with mild GDM. Secondary analysis of a prospective observational follow-up study on the offspring of women who participated in a multicenter randomized treatment trial on mild GDM. Children were evaluated by research coordinators and biospecimens collected at the age of 5 to 10. Plasma concentrations of leptin and adiponectin were compared between large for gestational age (LGA) and average birthweight (AGA) infants, and according to whether solid foods were introduced early (<6 months of age) or at the recommended age (≥6 months of age). Multivariable analysis adjusted for fetal sex, race/ethnicity, and maternal body mass index. Leptin and adiponectin were measured in 336 plasma samples. In bivariate analysis, compared with AGA children, LGA children had lower leptin (5.0 ng/mL [3.6-6.0] vs. 5.8 ng/mL [4.5 = 6.6], p = 0.01) and similar adiponectin (6.3 µg/mL [5.1-7.9] vs. 6.4 µg/mL [5.3-8.6], p = 0.49) concentrations. Maternal/child characteristics were similar between the early/delayed solid feeding groups. Leptin and adiponectin concentrations were similar in the early fed and delayed feeding groups (5.8 ng/mL [4.6-6.7] vs. 5.6 ng/mL [4.2-6.6], p = 0.50 and 6.4 µg/mL [5.4-8.1] vs. 6.4 µg/mL [5.1-8.8], p = 0.85, respectively). After controlling for covariates, children who were LGA and AGA at birth had similar leptin concentrations. Birthweight and early infancy feeding practice are not associated with alterations in leptin and adiponectin in children of women with mild GDM. · Adipocytokines are markers of metabolic status.. · Children of women with mild GDM may be at risk for MetS.. · Biomarkers similar in LGA and AGA groups.. · Biomarkers similar in early and delayed solid-fed groups.. · Nonhuman milk does not modify effect of feeding practice..

Differences of DNA methylation patterns in the placenta of large for gestational age infant

To investigate the molecular mechanisms of later metabolic health changes in large for gestational age (LGA) newborns by analyzing deoxyribonucleic acid (DNA) methylation patterns in the placenta of LGA and appropriate for gestational age (AGA) newborns.A total of 6 placentas of LGA and 6 placentas of AGA newborns were enrolled as LGA group and AGA group. DNA methylation was analyzed using the Illumina Infinium Human MethylationEPIC BeadChip microarrays and verified via pyrosequencing and reverse transcription-quantitative real-time polymerase chain reaction. Functional enrichment analysis were constructed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis based on the differentially methylated regions between LGA and AGA groups.Clinical investigation showed that LGA newborns had significantly lower hemoglobin and blood glucose compared to AGA newborns. Birth weight was negatively correlated to hemoglobin and blood glucose. Genome-wide DNA methylation analysis identified 17 244 methylation variable positions achieving genome-wide significance (adjusted P < .05). 34% methylation variable positions were located in the gene promoter region. A total of 117 differentially methylated regions were revealed by bump hunting analysis, which mapped to 107 genes. Function analysis showed 13 genes enriched in adhesion and infection process, endocrine and other factor-regulated calcium reabsorption, calcium signaling pathway and transmembrane transport. Four genes linked to type II diabetes mellitus. Among the 13 genes, we selected GNAS and calcium voltage-gated channel subunit alpha1 G for independent verification of pyrosequencing, and the messenger ribonucleic acid levels of guanine nucleotide binding protein, calcium voltage-gated channel subunit alpha1 G, DECR1, and FK506 binding protein 11 were verified by reverse transcription-quantitative real-time polymerase chain reaction.DNA methylation variation and gene expression differences in placental samples were associated with LGA newborns, which linking the effect of intrauterine environment to regulation of the offspring's gene expression. Furthermore, pathway analysis suggested that intrauterine environment affecting fetal growth might had a functional impact on multiple signaling pathways involved in fetal growth, metabolism, and inflammation. Further studies were required to understand the differences of methylation patterns.