Appropriate For Gestational Age Group Research Articles

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.

Behavior of weight z-score in preterm infants who are small for gestational age.

Introduction: the follow-up of small for gestational age (SGA) preterm infants is critical due to their differentiated postnatal growth pattern. Objective: to investigate the weight z-score behavior in SGA preterm infants during a four-week stay in a Neonatal Intensive Care Unit. Methods: a retrospective longitudinal study with data from nutritional anamneses of 190 preterm infants admitted to a Neonatal Intensive Care Unit between January/2017 and December/2019, classified according to nutritional status at birth as either SGA or appropriate for gestational age (AGA). Linear regression was used to verify association between weight z-score with gestational age, birth weight, initiation of enteral nutrition and relative amount of energy and protein administered. Results: SGA preterm infants accounted for 23 % of the study participants. In SGA, the difference in weight score was observed at week 1 when compared to admission (p < 0.05), while in AGA there was a difference sustained during the whole period (p < 0.05). In SGA, the linear regression analysis showed that the change in z-score was explained by time to start of enteral nutrition (p = 0.033), gestational age (p = 0.003) and birth weight (p = 0.001). In AGA the change was explained by gestational age (p = 0.000) and birth weight (p = 0.000). Conclusion: the weight z-score behavior in preterm infants was downward compared to admission, stable at the end of 4 weeks, and different according to nutritional status at birth. In the AGA group the decline in nutritional status was not recovered throughout hospitalization and in the SGA group the unfavorable nutritional status was maintained.

Characteristics of gut microbiota of term small gestational age infants within 1 week and their relationship with neurodevelopment at 6 months

IntroductionSmall for gestational age (SGA) infants are at a higher risk of neurodevelopmental delay than infants appropriate for gestational age (AGA). Previous studies have confirmed that gut microbiota in early life influences subsequent neurodevelopment. However, few studies have reported corresponding data in SGA populations.ObjectiveWe aimed to evaluate the characteristics of the gut microbiota of term SGA infants and the associations between the gut microbiota in SGA infants and neurodevelopmental outcomes at 6 months of age.MethodsFecal samples were collected on days 1, 3, 5, and 7 from term SGA and AGA infants born between June 2020 and June 2021 at the Peking University First Hospital. 16S ribosomal deoxyribonucleic acid amplicon sequencing was used to analyze the fecal microbiota. We followed up for 6 months and used the Ages and Stages Questionnaires-3 (ASQ-3) to evaluate the neurodevelopmental outcomes among SGA infants.ResultsA total of 162 neonates were enrolled, with 41 SGA infants (25.3%) in the study group and 121 AGA infants (74.7%) in the control group. The gut microbial diversity in the SGA group was lower than that in the AGA group on days 1, 3, 5, and 7. Non-metric multidimensional scaling and analysis of similarities showed significant differences between the two groups. The SGA group had increased relative abundances of Ralstonia (3, 5, and 7 days) and Clostridium (3 and 7 days). The dominant microorganisms of the SGA group were Ralstonia on day 1, Escherichia_Shigella on days 3 and 7, and Clostridia on day 5. We found that the gut microbial diversity of SGA infants with poor communication scores was higher than that of SGA infants with good communication scores on day 3. Fine motor scores were negatively correlated with the relative abundance of Bacteroides_fragilis on day 1. A negative correlation was observed between gross motor scores and relative abundance of Clostridium_saccharobutylicum on day 7. Bacteroidota, Bacteroidia, Bacteroides, and Bacteroides_fragilis were the dominant microorganisms in the good communication score group on day 7. Communication scores were positively correlated with the relative abundance of Bacteroidota, Bacteroides, and Bacteroides_fragilis on day 7.ConclusionThe gut microbial diversity of term SGA infants was significantly lower in the first week of life than that of term AGA infants. Certain pathogenic and conditional pathogenic bacteria, such as Escherichia_Shigella, Ralstonia and Clostridium increased or formed the dominant microbiota in SGA infants. Alpha diversity, Bacteroidota, Bacteroides, Bacteroides_fragilis, and Clostridium_saccharobutylicum found in SGA infants may be associated with neurodevelopmental outcomes at 6 months of age, indicating possible therapeutic targets for clinical intervention.

Body Composition and "Catch-Up" Fat Growth in Healthy Small for Gestational Age Preterm Infants and Neurodevelopmental Outcomes.

To examine the growth and body composition of small for gestational age (SGA) and appropriate for gestational age (AGA) very low birth weight infants (VLBW) and their outpatient neurodevelopmental outcomes. From 2006–2012, VLBW infants (n = 57 of 92) admitted to the Neonatal Intensive Care Unit (NICU) had serial air displacement plethysmography (ADP) scans and were followed as outpatients. Serial developmental testing (CAT/CLAMS, Peabody Gross Motor Scales) and anthropometrics were obtained from n = 37 infants (29 AGA and 8 SGA) and analyzed via repeated measures analyses of variances. The percentage of body fat, percentage of lean mass, and weight gain were statistically significant between SGA and AGA groups at the first ADP assessment. There was no difference between the two groups in outpatient neurodevelopmental testing. Weight gain as “catch-up” body fat accrual occurs by 67 weeks of PMA. This catch-up growth is associated with normal SGA preterm neurodevelopment as compared to AGA preterm infants.

Parity-Adjusted Term Neonatal Growth Chart Modifies Neonatal Morbidity and Mortality Risk Stratification.

Objective: To investigate the impact of parity-customized versus population-based birth weight charts on the identification of neonatal risk for adverse outcomes in small (SGA) or large for gestational age (LGA) infants compared to appropriate for gestational age (AGA) infants. Study design: Observational, retrospective, cohort study based on electronic medical birth records at a single center between 2006 and 2017. Neonates were categorized by birth weight (BW) as SGA, LGA, or AGA, with the 10th and 90th centiles as boundaries for AGA in a standard population-based model adjusted for gestational age and gender only (POP) and a customized model adjusted for gestational age, gender, and parity (CUST). Neonates defined as SGA or LGA by one standard and not overlapping the other, are SGA/LGA CUST/POP ONLY. Analyses used a reference group of BW between the 25th and 75th centile for the population. Results: Overall 132,815 singleton, live, term neonates born to mothers with uncomplicated pregnancies were included. The customized model identified 53% more neonates as SGA-CUST ONLY who had significantly higher rates of morbidity and mortality compared to the reference group (OR = 1.33 95% CI [1.16–1.53]; p < 0.0001). Neonates defined as LGA by the customized model (LGA-CUST) and AGA by the population-based model LGA-CUST ONLY had a significantly higher risk for morbidity compared to the reference (OR = 1.36 95% CI [1.09–1.71]; p = 0.007) or the LGA POP group. Neonatal mortality only occurred in the SGA and AGA groups. Conclusions: The application of a parity-customized only birth weight chart in a population of singleton, term neonates is a simple platform to better identify birth weight related neonatal risk for morbidity and mortality.

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.

Exosomal miRNA Profile in Small-for-Gestational-Age Children: A Potential Biomarker for Catch-Up Growth.

Objective: The mechanism underlying postnatal growth failure and catch-up growth in small-for-gestational-age (SGA) children is poorly understood. This study investigated the exosomal miRNA signature associated with catch-up growth in SGA children. Methods: In total, 16 SGA and 10 appropriate-for-gestational-age (AGA) children were included. Serum exosomal miRNA was analyzed using next-generation sequencing (NGS). Exosomal miRNA was profiled for five SGA children with catch-up growth (SGA-CU), six SGA children without CU growth (SGA-nCU), and five AGA children. Results: Exosomal miRNA profiles were clustered into three clear groups. The exosomal miRNA expression profiles of the SGA-nCU group differed from those of the SGA-CU and AGA groups. In all, 22 miRNAs were differentially expressed between SGA-nCU and AGA, 19 between SGA-nCU and SGA-CU, and only 6 between SGA-CU and AGA. In both SGA-nCU and SGA-CU, miR-874-3p was upregulated and miR-6126 was downregulated. Therefore, these two miRNAs could serve as biomarkers for SGA. Compared with SGA-CU and AGA, miR-30c-5p, miR-363-3p, miR-29a-3p, and miR-29c-3p were upregulated in SGA-nCU, while miR-629-5p and miR-23a-5p were downregulated. These six miRNAs could be associated with growth failure in SGA-nCU children. Conclusions: SGA children without CU have a distinct exosomal miRNA expression profile compared with AGA and SGA children with CU. Exosomal miRNAs could serve as novel biomarkers for CU.

SGA-born adults with postnatal catch-up have a persistently unfavourable metabolic health profile and increased adiposity at age 32 years.

Catch-up in weight-for-length in the first year of life results in more insulin resistance, an adverse lipid profile and more fat mass (FM) in 21-year-old adults born small for gestational age (SGA-CU) compared to peers born SGA without catch-up and those born appropriate for gestational age (AGA). The aim of present study was to investigate if the adverse metabolic health profile in the SGA-CU group would worsen or remain stable over the years and to determine the cardiometabolic health at 32 years between the SGA and AGA groups. We longitudinally investigated 287 adults, 170 SGA with catch-up growth (SGA-CU) or persistent short stature (SGA-S) and 117 AGA at ages 21 and 32 years. Insulin sensitivity (Si) and β-cell function were measured by frequently sampled i.v. glucose tolerance test, body composition by dual-energy X-ray absorptiometry (DXA) scan, and abdominal adipose tissue and liver fat fraction by MRI scan. Also, fasting serum lipid levels and blood pressure were measured. At age 32 years, SGA-CU had lower Si than AGA (P = 0.030), while SGA-S had similar Si than AGA. FM and trunk fat were higher in SGA-CU than AGA (P = 0.033, P = 0.024, respectively), while SGA-S had lower lean body mass than SGA-CU and AGA (P = 0.001 and P < 0.001, respectively). SGA-CU had significantly higher levels of adverse lipids than AGA. Beta-cell function, visceral fat, liver fat fraction and blood pressure were similar in all groups. Metabolic health parameters in SGA-CU and SGA-S did not worsen compared to AGA during 11 years of follow-up. Gain in weight SDS from birth to age 32 years was associated with a higher risk of developing metabolic syndrome at age 32 years. At age 32 years, SGA-CU adults had insulin resistance, higher FM with central adiposity and an adverse lipid profile. Postnatal catch-up growth increases the cardiometabolic risk; therefore, accelerated gain in weight should be prevented in SGA-born children.

Perinatal and Neonatal Outcomes in Fetal Growth Restriction and Small for Gestational Age.

Alterations in intrauterine fetal growth increase the risk of adverse perinatal and neonatal outcomes. In this retrospective study, we analyzed data of 906 pregnancies collected in our maternal fetal medicine center, with different patterns of growth: 655 AGA (Appropriate for Gestational Age), 62 SGA (Small for Gestational Age: fetuses born with a weight less than 10° centile, not diagnosed before delivery), 189 FGR (Fetal Growth Restriction, classified in early and late according to gestational week at diagnosis). For each group, we compared maternal characteristics, gestational age at delivery, and perinatal and neonatal outcomes. Risk factors for fetal growth alterations were advanced age, being primiparous, and a lower pregestational BMI. FGR fetuses were born at earlier gestational ages (32 [IQR 29–38] early-FGR and 38 [IQR 36–39] late-FGR), with blood gas values comparable to the AGA group but worse neonatal outcomes related to prematurity. Unexpected SGA fetuses born by vaginal delivery, managed as AGA, were more hyperlactacidemic (4.4 [IQR 2.7–5.5]) and hypoxemic (−5.0 [IQR −7.1–2.8]) at birth than both AGA and FGR. However, neonatal outcomes (accesses and days of hospitalization in NICU) were better than FGR, likely due to gestational age and birthweight similar to AGA.

Association of Parental Factors and Insulin-like Growth Factor 2 Polymorphism with Intrauterine Growth Restriction.

Polymorphism of insulin-like growth factor 2 (IGF2) is known to play a role in cell development. Only the paternal IGF2 copy is active, while the copy inherited from the mother is inactive. This study aimed to explore whether maternal and paternal factors influence IGF2 polymorphism in newborns with intrauterine growth restriction (IUGR) compared to appropriate for gestational age (AGA). A cross-sectional exploratory study was conducted from June 2014 to November 2015 at the Neonatology, Gynecology 1 Clinic, Cluj-Napoca, Romania. The ApaI IGF2 genotypes and allele frequencies were similar in the IUGR and AGA groups (p-value > 0.10). The IUGR babies with a protective IGF2 genetic profile had significantly younger parents (a difference in the median age of 8 years for mothers and 9 years for fathers; p-value < 0.009). The IUGR babies had parents with lower birth weights than AGA babies (mothers’ medians: 2800 g vs. 3100 g; fathers’ medians: 3000 g vs. 3400 g; p-value < 0.02). In univariable regression analysis, the mother’s and father’s birth weight proved to be associated with IUGR. The father’s birth weight proved to be the only factor significantly associated with IUGR, independent of the mother’s birth weight or the presence of a protective IGF2 genetic profile (odd ratio = 0.998 [0.996 to 1.000], p-value = 0.032).

Pediatric respiratory hospitalizations in small for gestational age neonates born at term.

This study investigates the risk for long-term respiratory hospitalizations of offspring born small for gestational age (SGA) at term. A retrospective population-based cohort analysis was performed to examine the risk of long-term respiratory hospitalizations between SGA compared to appropriate for gestational age (AGA) newborns. The analysis included all term singleton deliveries occurring between 1991 and 2014 at a single tertiary medical center. Fetuses with congenital malformations, multiple gestation, cases of perinatal mortality and large for gestational age (LGA) were excluded. A Kaplan-Meier survival curve was used to compare cumulative morbidity incidence up to the age of 18 years, and a Cox hazards regression model was used to control for confounders. During the study period 216,671 deliveries met the inclusion criteria; of them 4.8% (n = 10,450) were diagnosed as SGA neonates. During the follow-up period, the rate of hospitalization due to respiratory morbidity was significantly higher in the SGA group as compared to the AGA group (5.2% vs. 4.7%, OR = 1.13, 95% confidence interval [CI] = 1.03-1.24, p = 0.011). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of respiratory morbidity in the SGA group (log-rank p = 0.026). In the Cox hazards regression model, controlled for relevant clinical confounders, SGA was found to be an independent risk factor for long-term pediatric respiratory morbidity (adjusted hazard ratio [HR] = 1.1, 95% CI = 1.001-1.19, p = 0.049). Being delivered SGA at term is an independent long-term risk factor for pediatric respiratory hospitalization.

Clinical Features of Neurodevelopmental Outcomes in Children with Preterm Severe Fetal Growth Restriction: A Retrospective Observational Study.

Introduction: Fetal growth restriction (FGR) is a clinical condition wherein a fetus fails to achieve the expected growth potential. Although FGR is the leading cause of perinatal morbidity and mortality, there is a lack of knowledge about the long-term developmental outcomes of children who had FGR in Japan. Here, we sought to clarify the features of neurodevelopmental outcomes in preterm-born children with severe FGR (sFGR) and identify associated clinical factors. Methods: The clinical data of 26 preterm sFGR cases and 26 preterm appropriate for gestational age (AGA) cases with a similar gestational age distribution were reviewed retrospectively. Developmental quotient (DQ) scores assessed during the 1- and 2-year corrected ages using the Kyoto Scale of Psychological Development were analyzed. Results: sFGR was diagnosed at 26 (18-34) weeks of gestation, and the gestational age at delivery was 31 (25-36) weeks. The overall DQ scores of children in the sFGR group were significantly lower than those in the AGA group (80 vs. 90.5, P = 0.0127). Of the three areas that comprise the DQ (Postural-Motor, Cognitive-Adaptive, and Language-Social), the sFGR group only showed significantly lower DQ scores (72.5 vs. 88, P = 0.0255) in the Language-Social area. Both fetal body weight and fetal body weight Z score at birth significantly correlated with the DQ scores (r = 0.4912, P = 0.0108, and r = 0.5621, P = 0.0028), whereas neither the duration of fetal growth arrest nor the gestational age at birth correlated with the DQ scores (r = 0.3598, P = 0.0842, and r = 0.3522, P = 0.0776). Conclusions: Our results indicate that preterm-born children with sFGR have greater neurodevelopmental impairment than preterm-born children without FGR, specifically in terms of the DQ scores for the Language-Social area. It is imperative to encourage continuous long-term follow-up and appropriate interventions after birth.

Phonological productive processes in full-term schoolchildren and small for gestational age: a case-control study.

To characterize the use of phonological productive processes in a group of full-term children and small for gestational age and compare it with children appropriate for gestational age. Observational, analytical, case-control and non-paired study, nested in a cohort with the outcome of phonological disorder. We assessed 36 children according to the predetermined sample calculation, 24 (66.7%) without phonological disorders and 12 (33.3%) with phonological disorders. Of these, 24 (66.7%) children were classified as small for gestational age (SGA) and 12 (33%) as appropriate for gestational age (AGA). Phonological aspects of oral language were assessed by the ABFW children's language test (2004). The results were subjected to descriptive analysis and, in order to assess the existence of an association among categorical variables, we used Fisher's exact test for association. The SGA group revealed a significantly higher number of phonological processes that change the syllable structure when compared to the AGA group. We noted that the phonological processes present and unexpected for age in the SGA population were: fricative plosivation, liquid simplification, palatal posteriorization and frontalization, plosive and fricative deafening, in addition to simplifying the consonant cluster and simplifying the final consonant, which were the most frequent in both groups. Although no association was found between phonological disorders and SGA children, we have noted a greater use of productive phonological processes in this group.

The mediating role of gestational diabetes mellitus in the associations of maternal prepregnancy body mass index with neonatal birth weight.

BackgroundBoth prepregnancy obesity and gestational diabetes mellitus (GDM) have been linked to adverse neonatal birth weight. However, the mediating role of GDM between prepregnancy obesity and neonatal birth weight is unclear.MethodThe cohort study included 17 260 singleton pregnant women and their newborns. Participants' demographic characteristics, disease history, family history of the disease, and the perinatal outcomes were recorded. The association between maternal prepregnancy body mass index (BMI) status and small for gestational age (SGA) or large for gestational age (LGA) neonates was analyzed using logistic regressions, before and after adjusting for covariates and GDM. The potential mediation of GDM on the association between prepregnancy BMI and adverse birth weight was examined.ResultMultivariate logistic regression demonstrated that prepregnancy underweight women were more likely to deliver SGA neonates compared to those who had normal weights, whereas prepregnancy obese pregnant women were more likely to have LGA neonates. The RMediation analyses illustrated that the mediation effect of GDM on the maternal prepregnancy BMI (continuous variable) and the risk of SGA was not significant, whereas the association between prepregnancy BMI and LGA was statistically mediated by GDM (95%CI of a*b: 0.009‐0.051). The Iacobacci (2012) method indicated that the impact of maternal prepregnancy overweight (Zmediation = 2.418, P = .015) and obesity (Zmediation = 2.165, P = .030) on LGA was partially mediated by GDM, with an indirect effect of 16.3% and 13.1%, respectively.ConclusionPrepregnancy BMI was observed to be associated with SGA and LGA. The association of prepregnancy overweight and obesity with LGA was found to be partially mediated by GDM.

The Assessment of Vitamin D Levels in Pregnant Women is not Associated to Fetal Growth Restriction: A Cross Sectional Study.

To assess maternal serum levels of vitamin D in fetuses appropriate for gestational age (AGA), small for gestational age (SGA), and with fetal growth restriction (FGR) according to estimated fetal weight (EFW). This cross-sectional study included 87 pregnant women between 26 and 36 weeks of gestation: 38 in the AGA group, 24 in the SGA group, and 25 in the FGR group. Maternal serum vitamin D levels were assessed using the chemiluminescence method. The Fisher exact test was used to compare the results between the groups. The mean ± standard deviation (SD) of maternal age (years) and body mass index (kg/m2) in the AGA, SGA, and FGR groups were 25.26 ± 8.40 / 26.57 ± 4.37; 25.04 ± 8.44 / 26.09 ± 3.94; and 25.48 ± 7.52 / 26.24 ± 4.66, respectively (p > 0.05). The maternal serum vitamin D levels (mean ± SD) of the AGA, SGA, and FGR groups were 22.47 ± 8.35 ng/mL, 24.80 ± 10.76 ng/mL, and 23.61 ± 9.98 ng/mL, respectively, but without significant differences between the groups (p = 0.672). Maternal serum vitamin D levels did not present significant differences among pregnant women with AGA, SGA, or FGR fetuses between 26 and 36 weeks of gestation according to EFW.

Umbilical Cord Blood Adiponectin, Leptin, Insulin, and Ghrelin in Premature Infants and Their Association With Birth Outcomes.

BackgroundPremature/low-birth-weight infants are at significant risk of metabolic diseases in adulthood, which may be related to the levels of fetal adipokine. Here, we investigated the differences in the levels of umbilical cord blood adiponectin, leptin, insulin, and ghrelin in preterm and term infants and sought to elucidate the link between these hormones and fetal growth. We also evaluated the interrelationship among these metabolic hormones in both groups of newborns.MethodsA total of 149 mother–infant pairs (100 in the preterm group and 49 in the term group) were enrolled in the study. The preterm group was further subdivided according to birth weight (≤1,500, 1,501–2,000, 2,001–2,500, and >2,500 g), gestational age (<34 vs. ≥34 weeks), and appropriate for gestational age (AGA) vs. small for gestational age (SGA). The general condition of the mothers and the growth parameters of the newborns at birth were recorded.ResultsThe levels of adiponectin, leptin, and ghrelin were lower in the preterm group than those in the term group (p < 0.05). In the preterm group, the leptin levels of infants with gestational age ≥34 weeks were significantly higher than those of infants with gestational age <34 weeks (mean ln leptin = 0.63 vs. 0.36 ng/ml, p = 0.009). The levels of adiponectin were lower in the SGA group than those in the AGA group (mean ln adiponectin = 2.26 vs. 2.84 µg/ml, p = 0.001), whereas those of ghrelin displayed the opposite trend (mean ln ghrelin = 6.29 vs. 5.71 pg/ml, p < 0.001). Leptin was significantly correlated with insulin both in preterm infants with birth weight (BW) >2,000 g and in term infants. Umbilical cord blood leptin was positively correlated with the BW, birth length, and head circumference of newborns (r = 0.460, 0.311, and 0.310, respectively, all p < 0.05), whereas ghrelin was negatively correlated with the same parameters (r = −0.372, −0.415, and −0.373, respectively, all p > 0.05).ConclusionsThe lack of maturation of adipose tissue and the gastrointestinal tract by the fetus due to prematurity is associated with changes in the levels of cord blood adiponectin, leptin, and ghrelin. The dysregulation of these hormones in preterm infants may be a risk factor for fetal growth and future metabolic diseases.

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.

Small for Gestational Age Preterm Neonates Exhibit Defective GH/IGF1 Signaling Pathway.

Objective: To investigate the impact of fetal growth restriction (FGR) on hormonal regulation of post-natal growth and glucose metabolism [via insulin and growth hormone (GH)/Insulin-like Growth factor 1 (IGF1) axis pathways] in small for gestational age (SGA) neonates.Methods: We conducted a monocentric observational prospective comparative study on 73 singleton babies born with a weight inferior to 2,000 g. We analyzed auxological (weight, height and head circumference), and hormonal (GH, IGF1, and insulin plasma concentrations) data comparing SGA and appropriate for gestational age (AGA) neonates, between day 1 and 60.Results: One third (23/73) of the neonates were SGA. Twenty-five percent (18/73) required insulin for idiopathic hyperglycemia of prematurity and were smaller in weight and head circumference at discharge. In the SGA group compared with the AGA group, GH plasma concentrations were higher at day 3 (70.1 vs. 38.0 mIU/L) and IGF1 plasma concentrations were higher at day 10 (29.0 vs. 18.7 ng/ml).Conclusions: SGA neonates displayed resistance to GH and IGF1, concomitant to insulin resistance. This could partially explain the initial defective catch-up growth and, later in life, the higher prevalence of metabolic syndrome in this population.

Maternal Serum Ferritin Level in Prediction of Mothers with Appropriate-For-Gestational-Age (AGA), Small-For-Gestational Age (SGA), and Intrauterine Growth Restriction (IUGR)

Background Fetal growth restriction is one of the main causes of perinatal mortality that can be predicted by ferritin. We aimed to evaluate the role of ferritin in prediction of mothers with Appropriate-for-gestational-age (AGA), Small-for-gestational age (SGA) and intrauterine growth restriction (IUGR). Materials and Methods: In this cohort study, we screened 73 mothers with gestational ages of 32-34 weeks. If amniotic fluid index (AFI) was normal and there was no circulation defect, the fetuses were classified in SGA group and in case of presence of oligohydramnios or circulation defect; they were classified in IUGR group. Also, fetuses with normal growth were classified in AGA group. We evaluated the serum ferritin, hemoglobin, and iron of the mothers. Moreover, we evaluated the levels of placenta ferritin, Hb, and hematocrit in the delivery room. Results: In this study, 28 patients were categorized in AGA group, 15 patients in SGA group and 30 patients in IUGR group. Mean weight of all infants was 2210.60 ± 932.77 grams. Also, the mean AFI of all infants was 9.81 ± 3.59. The mean ferritin level of all mothers was 30.29 ± 10.80 and IUGR group had the highest and AGA group had the lowest ferritin levels (P=0.015). Maternal ferritin (µg/l) (Sen: 67.9%, Sp: 61.9%), maternal hematocrit (%) (Sen: 70%; Sp: 62.8%,) and maternal Hb (Sen: 70%, Sp: 65.1%,) could predict IUGR. Conclusion Increased (>34 µg/l) and decreased (

Diagnostic performance of cerebroplacental and umbilicocerebral ratio in appropriate for gestational age and late growth restricted fetuses attempting vaginal delivery: a multicenter, retrospective study

Background Cerebroplacental Doppler studies have been advocated to predict the risk of adverse perinatal outcome (APO) irrespective of fetal weight. Objective To report the diagnostic performance of cerebroplacental (CPR) and umbilicocerebral (UCR) ratios in predicting APO in appropriate for gestational age (AGA) fetuses and in those affected by late fetal growth restriction (FGR) attempting vaginal delivery. Study design Multicenter, retrospective, nested case-control study between 1 January 2017 and January 2020 involving five referral centers in Italy and Spain. Singleton gestations with a scan between 36 and 40 weeks and within two weeks of attempting vaginal delivery were included. Fetal arterial Doppler and biometry were collected. The AGA group was defined as fetuses with an estimated fetal weight and abdominal circumference >10th and <90th percentile, while the late FGR group was defined by Delphi consensus criteria. The primary outcome was the prediction of a composite of perinatal adverse outcomes including either intrauterine death, Apgar score at 5 min <7, abnormal acid-base status (umbilical artery pH < 7.1 or base excess of more than −11) and neonatal intensive care unit (NICU) admission. Area under the curve (AUC) analysis was performed. Results 646 pregnancies (317 in the AGA group and 329 in the late FGR group) were included. APO were present in 12.6% AGA and 24.3% late FGR pregnancies, with an odds ratio of 2.22 (95% CI 1.46–3.37). The performance of CPR and UCR for predicting APO was poor in both AGA [AUC: 0.44 (0.39–0.51)] and late FGR fetuses [AUC: 0.56 (0.49–0.61)]. Conclusions CPR and UCR on their own are poor prognostic predictors of APO irrespective of fetal weight.