Gestational Age Newborns Research Articles

Factors that influence refractive errors in premature infants

Background The prevalence of refractive errors is reported to be higher in children born preterm. Factors such as gestational age, birth weight, and retinopathy of prematurity status, have a significant impact on the refractive development in preterm infants. Prematurity and low birth weight affect the development of organ systems in infants, including the eyes. In addition to immature retinas, other eye conditions, such as refractive status, are also observed. This study aimed to determine the risk factors of refractive status, specifically refractive errors (spherical equivalent, astigmatism, and anisometropia) in premature infants at a tertiary hospital in Bali. MethodsA cross-sectional study was conducted involving 53 premature infants. This study collected samples from January to August 2023 at the Neonatal Intensive Care Unit of Prof. dr. IGNG Ngoerah General Hospital. Data regarding gender, gestational age, birth weight, retinal condition, spherical equivalent, and refractive disorders were collected. The relationship between risk factors and spherical equivalent, astigmatism, and anisometropia were analyzed using multiple regression analysis with statistical significance set at p<0.05. ResultsHypermetropia is the most common finding in premature infants, followed by myopia and astigmatism. The prevalence of myopia (9.4%) and astigmatism (5.7%) is also more common among newborns of gestational age ≤30 weeks (p=0.024). Chronological age was significantly associated with spherical equivalent (β=0.424; p=0.019). ConclusionIn premature infants, chronological age was the risk factor of spherical equivalent. Other risk factors were not associated with the prevalence of refractive errors among premature infants.

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.

Maternal and long-term offspring outcomes of obesity during pregnancy.

Obesity`s prevalence is rising in women of reproductive age worldwide and has become the most common medical condition at this age group. Besides, its occurrence is also rising during pregnancy. This condition not only increases the risk of noncommunicable diseases on the mother, such as cardiovascular disease and diabetes, but also transfers this risk to the offspring. This is a narrative review based on scientific and review articles on the matter. Obesity is associated with an increased risk of gestational diabetes mellitus, gestational hypertension and preeclampsia, venous thromboembolism, infection, and mental health problems. Furthermore, it has an impact on the progress of labor and induction matters. Regarding offspring outcomes, it is related to higher incidence of congenital anomalies, perinatal mortality, and the occurrence of large for gestational age newborns. Still, it has implications on cardiometabolic risk and neurodevelopment in offspring. It is, therefore, imperative to encourage the adoption of healthy lifestyles, especially in the peri-conception and interpregnancy periods. Likewise, there must be support in the multidisciplinary monitoring of these pregnant women to minimize associated complication rates.

Social determinants of health rather than race impact health-related quality of life in 10-year-old children born extremely preterm.

Reducing healthcare disparities among children is extremely important given the potential impact of these disparities on long-term health-related quality of life (HRQL). Race and parental socioeconomic status (SES) are associated with child HRQL, but these associations have not been studied in infants born extremely preterm (EP), a population at increased risk for physical, cognitive, and psychosocial impairments. Achieving health equity for infants born EP across their life course requires identifying the impact of racism and SES on HRQL. We aimed to evaluate the association between self-reported maternal race, SES factors, and HRQL among 10-year-old children born EP. Participants were identified from an ongoing multicenter prospective longitudinal study of Extremely Low Gestational Age Newborns (ELGAN Study), born between 2002 and 2004, and evaluated at 10 years of age using the Pediatric quality of life (QoL) Inventory completed by their parent or guardian, assessing physical, emotional, social, school, and total (composite) QoL domains. Multivariable regression models were used to evaluate the relationship between QoL scores and self-identified maternal race, adjusting for SES factors (education level, marital status, and public insurance). Of 1,198 study participants who were alive at 10 years of age, 863 (72.0%) were evaluated at 10 years of age. Differences in mean 10-year QoL scores across racial groups were observed and were significant on univariate analysis. However, these associations attenuated when adjusted for the marital status, public insurance status, and education status of mothers. A comparison of children with English as the primary language spoken at home vs. any other language revealed a significant difference only in school QoL, in which non-English language was associated with more favorable school QoL scores. Among 10-year-old children born EP, differences in parent-reported QoL were associated with maternal SES factors but not with race. Our results suggest that interventions designed to improve the SES of mothers may enhance the QoL of children born EP. Furthermore, these results underscore that race is a social construct, rather than a biological variable, as we work toward greater equity in care provision.

Postnatal Genetic and Neurodevelopmental Assessment in Infants Born at Term With Severely Low Birth Weight of Non-placental Origin

ABSTRACT Small for gestational age (SGA) newborns are generally defined as those with a birth weight below the 10th percentile. Fetuses diagnosed with fetal growth restriction (FGR) are usually evaluated to determine if there is a pathological cause and thus a higher risk for adverse outcomes due to being small. Often when this diagnosis is made early in the third trimester, chromosomal microarray analysis is recommended to detect genetic disease. This study was designed to determine the frequency of monogenic disorders in term infants with severely low birth weight but normal Doppler results, as well as to estimate the frequency of neurodevelopmental impairment when a genetic etiology was ruled out. Inclusion criteria for this study were singleton pregnancy; term delivery; birth weight more than 2.5 SDs below the mean; normal Doppler studies of the umbilical artery, fetal middle cerebral artery, cerebroplacental ratio, and uterine artery; no maternal hypertensive disease; and no prenatal fetal structural or identified genetic anomalies or fetal infection. Exclusion criteria included incomplete data. Exome sequencing was completed using saliva sampling and blood sampling, and standard neurodevelopmental assessment techniques were used for children 2 to 3.5 and 6 to 8 years old. Children aged between 3.5 and 6 years were not included because of lack of standardized neurodevelopmental testing. A total of 63 families were contacted, and 7 (11%) reported that a genetic disorder had been diagnosed after birth. In addition, 18 individuals without a known genetic disorder who met all the criteria underwent exome sequencing and neurodevelopmental testing. Of the 7 who reported a postnatally diagnosed genetic syndrome, 5 were Mendelian monogenetic and 2 were epigenetic, including Cockayne syndrome; short stature, microcephaly, and endocrine dysfunction syndrome; Renpenning syndrome; Noonan syndrome; Russell-Silver syndrome; and Prader-Willi syndrome. Median birth weight among the children with genetic disorders was not different from children without. Exome sequencing was normal in the 18 children who were tested and who had not been previously diagnosed with a genetic syndrome. None of the children showed less than average neurodevelopment on overall assessment in the lower age group. In the higher age group, 2 children were classified as having low IQ, with one borderline and one extremely low, with low scores in all other domains as well. In addition, 6 individuals showed a low score in at least 1 of the 5 domains, with the largest deviations showing in the domains of verbal comprehension and working memory. Clinicians should be aware of the potential outcomes of FGR even when other complications are not present. Counseling about genetic analysis prenatally or within a short postnatal timeframe could save a lot of time and effort in evaluating children later. In addition, children should be carefully assessed in later childhood for neurodevelopmental differences that are treatable or that may require different resources. Future research should focus on further homogenizing the population to get more accurate results, as well as dealing with potential biases in this study.

Small for Gestational Age Newborns in French Guiana: The Importance of Health Insurance for Prevention.

Objectives: Small for gestational age (SGA) newborns have a higher risk of poor outcomes. French Guiana (FG) is a territory in South America with poor living conditions. The objectives of this study were to describe risk factors associated with SGA newborns in FG. Methods: We used the birth cohort that compiles data from all pregnancies that ended in FG from 2013 to 2021. We analysed data of newborns born after 22weeks of gestation and/or weighing more than 500g and their mothers. Results: 67,962 newborns were included. SGA newborns represented 11.7% of all newborns. Lack of health insurance was associated with SGA newborns (p < 0.001) whereas no difference was found between different types of health insurance and the proportion of SGA newborns (p = 0.86). Mothers aged less than 20years (aOR = 1.65 [1.55-1.77]), from Haiti (aOR = 1.24 [1.11-1.39]) or Guyana (aOR = 1.30 [1.01-1.68]) and lack of health insurance (aOR = 1.24 [1.10-1.40]) were associated with SGA newborns. Conclusion: Immigration and precariousness appear to be determinants of SGA newborns in FG. Other studies are needed to refine these results.

Evolution of Fetal Growth in Symptomatic Sars-Cov-2 Pregnancies.

SARS-CoV-2 is a viral disease with potentially devastating effects. Observational studies of pregnant women infected with SARS-CoV-2 report an increased risk for FGR. This study utilizes data from a prospective SARS-CoV-2 registry in pregnancy, investigating the progression of fetuses to fetal growth restriction (FGR) at birth following maternal SARS-CoV-2 and evaluating the hypothesis of whether the percentage of SGA at birth is increased after maternal SARS-CoV-2 taking into account the time interval between infection and birth. CRONOS is a prospective German registry enrolling pregnant women with confirmed SARS-CoV-2 infection during their pregnancy. SARS-CoV-2 symptoms, pregnancy- and delivery-specific information were recorded. The data evaluated in this study range from March 2020 until August 2021. Women with SARS-CoV-2 were divided into three groups according to the time of infection/symptoms to delivery: Group I<2 weeks, Group II 2-4 weeks, and Group III>4 weeks. FGR was defined as estimated and/or birth weight<10% ile, appropriate for gestational age (AGA) was within 10 and 90%ile, and large for gestational age (LGA) was defined as fetal or neonatal weight>90%ile. Data for a total of 2,650 SARS-CoV-2-positive pregnant women were available. The analysis was restricted to symptomatic cases that delivered after 24+0 weeks of gestation. Excluding those cases with missing values for estimated fetal weight at time of infection and/or birth weight centile, 900 datasets remained for analyses. Group I consisted of 551 women, Group II of 112 women, and Group III of 237 women. The percentage of changes from AGA to FGR did not differ between groups. However, there was a significantly higher rate of large for gestational age (LGA) newborns at the time of birth compared to the time of SARS-CoV-2 infection in Group III (p=0.0024), respectively. FGR rates did not differ between symptomatic COVID infections occurring within 2 weeks and>4 weeks before birth. On the contrary, it presented a significant increase in LGA pregnancies in Group III. However, in this study population, an increase in the percentage of LGA may be attributed to pandemic measures and a reduction in daily activity.

High protein intake can lead to serious hypophosphatemia and hypokalemia in growth restricted preterm newborns.

High protein parenteral nutrition (HPPN) in the early postnatal period is a recommended strategy for very low birth weight (VLBW) infants. However, limited data is available on electrolyte changes when HPPN strategy is utilized. We investigated the impact of HPPN on the development of hypophosphatemia and hypokalemia in preterm VLBW newborns. A retrospective, single-center study investigated the levels of phosphate and potassium in VLBW infants who received HPPN (amino acids intake up to 3.5 g/kg/day) during the first week of life. Preterm infants were divided into two subgroups: appropriate for gestational age (AGA) and small for gestational age (SGA) newborns. Clinical data were obtained from hospital database and medical records. Overall, 170 VLBW infants were included for the study analysis: 41 SGA (mean birth weight 752 ± 39 g) and 129 AGA infants (mean birth weight 994 ± 23 g). Phosphate and potassium levels were significantly lower in the SGA infants compared to AGA infants (Phosphate: 0.97 ± 0.07 mmol/l vs. 1.44 ± 0.04 mmol/l, p < 0.001; Potassium: 3.0 ± 0.1 mmol/l vs. 3.6 ± 0.1 mmol/l, p < 0.001). Repeated measurement of serum phosphate and potassium is recommended when HPPN strategy is utilized in preterm SGA infants where significant hypophosphatemia and hypokalemia might have serious clinical consequences.

Comparison of Parkin Score and New Ballard Score for Gestational Age Assessment in Newborns with Ultrasound Scan as the Standard Reference

Objective: To compare the assessment of gestational age (GA) in newborns using the Parkin Scoring and the New Ballard Scoring methods with the Ultrasound Scan Method as the Standard Reference, conducted at a peripheral military setup.&#x0D; Methodology: A descriptive, cross-sectional study was conducted at the Pediatrics department of Combined Military Hospital (CMH), Abbottabad from July 2019 to June 2020. A total of 102 newborns were recruited from the CMH Nursery. GA was assessed using ultrasound scan, Parkin Score (PS), and the New Ballard Score (NBS). Pearson correlation coefficient statistics were calculated to evaluate the strength of associations among the three methods. The significance level (p value) was set at 0.05.&#x0D; Results: The study included 47 (46.1%) females and 55 (53.9%) males. The highest GA (days) was calculated by ultrasound scan (268.76 ± 0.83), followed by PS GA (266.65 ± 1.00) and NBS (264.38 ± 1.05). There was no significant difference in GA assessment between PS and the ultrasound scan (2.32 ± 1.37 days; p = 0.208). The GA assessment between NBS and the ultrasound scan was found to be significant (4.38 ± 1.37 days; p = 0.004). However, this difference is not clinically significant. The NBS and PS GA assessment had a strong positive correlation (Pearson Coefficient = 0.80).&#x0D; Conclusions: The PS is a reliable method for assessing GA in newborns and is comparable to the NBS. Further research with a larger sample size should be conducted to validate these findings.

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.

Maternal Serum Polyols and Its Link to Gestational Diabetes Mellitus: A Population-Based Nested Case-Control Study.

Sugar alcohols (also called polyols) are regarded as a "healthy" sugar substitute. One of the possible reasons for their safe use in pregnant women is their natural origin and the presence of polyols in maternal and fetal samples during normal human gestation. But little is known about the association between circulating sugar alcohols levels and maternal metabolic disorders during pregnancy. We aimed to detect the concentration of the polyols in participants with and without gestational diabetes mellitus (GDM), and to investigate the association between maternal serum levels of polyols and GDM, as well as newborn outcomes. A nested population-based case-control study was conducted in 109 women with and without GDM. Maternal concentrations of serum erythritol, sorbitol, and xylitol in the fasting state were quantified using a time of flight mass spectrometry system. In women with GDM, serum concentrations of erythritol and sorbitol were higher, but serum concentrations of xylitol were lower than those in women without GDM. Per 1-SD increment of Box-Cox-transformed concentrations of erythritol and sorbitol were associated with the increased odds of GDM by 43% and 155% (95% CI 1.07-1.92 and 95% CI 1.77-3.69), while decreased odds were found for xylitol by 25% (95% CI 0.57-1.00). Additionally, per 1-SD increase of Box-Cox-transformed concentrations of serum sorbitol was associated with a 52% increased odds of large for gestational age newborns controlling for possible confounders (95% CI 1.00-2.30). Maternal circulating sugar alcohols levels during pregnancy were significantly associated with GDM. These findings provide the potential roles of polyols on maternal metabolic health during pregnancy.

Cord Blood Vitamin D Status and Its Anthropometric Correlation in Term, Appropriate-for-Gestational-Age Newborns: A Cross-sectional Study

Introduction: Hypovitaminosis D is highly prevalent worldwide, including in India. Vitamin D deficiency during pregnancy can also lead to deficiency in the foetus. This deficiency can have a negative impact on foetal growth, as vitamin D is essential for calcium and bone homeostasis, as well as skeletal growth. Aim: To determine the cord blood vitamin D status and evaluate the correlation between cord blood vitamin D levels and neonatal anthropometric measurements in term, appropriate- for-gestational-age newborns at birth. Materials and Methods: A cross-sectional study was conducted at a tertiary care centre. Two hundred term, appropriate-for- gestational-age newborns were included in the study. Cord blood 25(OH)D levels and anthropometric measurements were taken at birth. The data were analysed statistically, and significance was determined using the Analysis of Variance (ANOVA) test. Results: Vitamin D levels were deficient (&lt;12 ng/dL) in 80 (40%) samples, insufficient (&lt;20 ng/dL) in 93 (46.5%) samples, and sufficient in 27 (13.5%) samples of cord blood. No significant relationship was found between cord blood vitamin D concentrations and neonatal weight, length, and head circumference at birth (p&gt;0.05). Conclusion: A very high level of vitamin D deficiency or insufficiency was observed in cord blood samples. There was no association between maternal vitamin D concentrations and neonatal anthropometric measurements in the infants.

Avaliação do Eletroencefalograma de Amplitude Integrada em recém-nascidos maiores que 35 semanas de idade gestacional expostos ao crack e/ou cocaína no pré-natal

OBJECTIVE: To evaluate the findings of video aEEG/EEG brain monitoring in newborns of mothers who used cocaine and/or crack during pregnancy and to describe the epidemiological profile of these mothers and infants. METHODS: Descriptive prospective study carried out from August 2019 to February 2020. We included newborns with a gestational age = 35 weeks and a history of maternal use of crack or cocaine during pregnancy. Newborns underwent video aEEG/EEG monitoring for 24 hours in the first 48 hours of life. The assessment of neonatal abstinence syndrome was performed using the Finnegan Score. Demographic and clinical data were analyzed. The Intergrowth-21 curve was used to classify the anthropometric measurements described. Capurro and New-Ballard methods were standardized for determining gestational age in newborns. RESULTS: 12 newborns met the criteria; all scored from 0 to 7 according to the Finnigan score in the first 6 hours of life. In the 30th hour of life, 10 (91%) scored between 0 and 7 and 1 neonate between 8 and 11, considered altered with the need for treatment. At 72 hours of life, the 12 newborns evaluated had scores between 0 and 7. The background electroencephalographic activity pattern in the first 48 hours of life was continuous, with the presence of a sleep-wake cycle in all cases. CONCLUSIONS: Newborns of drug-using mothers may have an early maturation pattern on electroencephalographic assessment. More studies are needed to assess this relationship better.

973 Placental gene expression: histologic evidence of maternal vascular malperfusion and small for gestational age newborns

973 Placental gene expression: histologic evidence of maternal vascular malperfusion and small for gestational age newborns

Arterial hypertension and smoking in pregnant women in the Valencian Community: maternal and neonatal outcomes

ObjectiveHypertension and smoking during pregnancy have been linked to various adverse maternal and fetal outcomes. The objective of this work is to study how the smoking influences the development of hypertension, its effects on the pregnant woman, and on the newborn. Materials and methodsAn observational study in two phases was carried out: the descriptive first phase allows characterization of the sample and the analytical second phase is a case–control nested in a retrospective cohort corresponding to pregnancy. ResultsA total of 712 women were included in the study. Of the 672 (94.4%) non-hypertensive women, 533 (79.3%) were non-smoking and 139 (20.7%) smoking. For the 40 (5.6%) hypertensive women, 30 (75.0%) were non-smoking and 10 (25.0%) smoking. The prevalence of hypertension was of 5.6%. Women who quit smoking before pregnancy saw a reduced risk of hypertension. For women who smoke during pregnancy, those of younger ages, with a normal body mass index, who are primiparous, employed and with a low-medium level of education have higher risk of hypertension. The risk of hypertension according to the level of physical activity during leisure time follows a “U” shape, with those who perform light physical activity at the lowest risk of hypertension. Hypertensive women have a higher risk of small for gestational age newborns. Smoking does not pose an additional risk for adverse outcomes once hypertension is diagnosed. ConclusionsFuture studies should aim to determine the role of smoking habit in the appearance of hypertension in pregnancy in order to establish adequate intervention guidelines that may aid in reducing the prevalence of hypertension.

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.

Comprehensive assessment of the genetic characteristics of small for gestational age newborns in NICU: from diagnosis of genetic disorders to prediction of prognosis

BackgroundIn China, ~1,072,100 small for gestational age (SGA) births occur annually. These SGA newborns are a high-risk population of developmental delay. Our study aimed to evaluate the genetic profile of SGA newborns in the newborn intensive care unit (NICU) and establish a prognosis prediction model by combining clinical and genetic factors.MethodsA cohort of 723 SGA and 1317 appropriate for gestational age (AGA) newborns were recruited between June 2018 and June 2020. Clinical exome sequencing was performed for each newborn. The gene-based rare-variant collapsing analyses and the gene burden test were applied to identify the risk genes for SGA and SGA with poor prognosis. The Gradient Boosting Machine framework was used to generate two models to predict the prognosis of SGA. The performance of two models were validated with an independent cohort of 115 SGA newborns without genetic diagnosis from July 2020 to April 2022. All newborns in this study were recruited through the China Neonatal Genomes Project (CNGP) and were hospitalized in NICU, Children’s Hospital of Fudan University, Shanghai, China.ResultsAmong the 723 SGA newborns, 88(12.2%) received genetic diagnosis, including 42(47.7%) with monogenic diseases and 46(52.3%) with chromosomal abnormalities. SGA with genetic diagnosis showed higher rates in severe SGA(54.5% vs. 41.9%, P=0.0025) than SGA without genetic diagnosis. SGA with chromosomal abnormalities showed higher incidences of physical and neurodevelopmental delay compared to those with monogenic diseases (45.7% vs. 19.0%, P=0.012). We filtered out 3 genes (ITGB4, TXNRD2, RRM2B) as potential causative genes for SGA and 1 gene (ADIPOQ) as potential causative gene for SGA with poor prognosis. The model integrating clinical and genetic factors demonstrated a higher area under the receiver operating characteristic curve (AUC) over the model based solely on clinical factors in both the SGA-model generation dataset (AUC=0.9[95% confidence interval 0.84–0.96] vs. AUC=0.74 [0.64–0.84]; P=0.00196) and the independent SGA-validation dataset (AUC=0.76 [0.6–0.93] vs. AUC=0.53[0.29–0.76]; P=0.0117).ConclusionSGA newborns in NICU presented with roughly equal proportions of monogenic and chromosomal abnormalities. Chromosomal disorders were associated with poorer prognosis. The rare-variant collapsing analyses studies have the ability to identify potential causative factors associated with growth and development. The SGA prognosis prediction model integrating genetic and clinical factors outperformed that relying solely on clinical factors. The application of genetic sequencing in hospitalized SGA newborns may improve early genetic diagnosis and prognosis prediction.

The association of maternal serum uric acid with the risk of small for gestational age newborn: a retrospective cohort study

Problem Prior results on the association between serum uric acid (UA) levels in the early trimester and the risk of small for gestational age (SGA) remain unclear. This study evaluated the association of maternal first-, second-, and third-trimester UA levels with the risk of SGA infants. Method of study A total of 23, 194 singleton mothers from the International Peace Maternity and Child Health Hospital between January 2014 and January 2017 were included. Maternal UA levels were measured at 12.1 ± 1.08th (UA1) and 32.2 ± 1.03th (UA2) gestational weeks. △UA was calculated as the difference between UA2 and UA1. Logistic regression and restricted cubic spline (RCS) were performed to evaluate the association between maternal UA and △UA during pregnancy and SGA. Receiver operating characteristic (ROC) analysis was employed to assess the serum uric acid prediction value. Results Women in the higher quartiles of UA1 had a significantly higher risk of SGA. A clear increased risk for SGA was observed with higher quartiles for UA2 (p for trend <0.05). An approximately “J-shaped” relationship was observed between UA2 and △UA, and the risk of SGA was observed. When compared with those with a lower level of UA in the first trimester, those with a higher level of UA1, the more increase in the later UA levels were associated with a higher risk of SGA [adjusted odds ratio (aOR) = 1.67, 95% CI:1.37–2.05]. The ROC curve areas were 0.525 for UA1, 0.582 for UA2 and 0.576 for △UA. Conclusions The findings suggested that non-preeclamptic and non-hypertensive women who experienced early pregnancy with high UA levels had an elevated risk of SGA. Moreover, a high maternal UA level in the earlier trimester may be an early predictor of SGA.

Results of enzyme immunoassay of vasculoendothelial growth factor (VEGF) in blood serum in premature newborns with perinatal hypoxic damage to the central nervous system

Background. Vasculoendothelial growth factor (VEGF) is responsible for vascular remodeling, influences the formation of post-hypoxic structural changes in the newborn brain and is synergistically closely related to neurotrophic factors, being an inhibitor of apoptosis processes, which are important for lesions of the central nervous system in newborns of various types of gestational age, having suffered both acute asphyxia at birth and chronic intrauterine hypoxia. VEGF has been little studied in premature newborns, which are at high risk for the formation of intraventricular hemorrhage and periventricular leukomalacia.Aim. To study changes in the serum concentration of VEGF, its role in the pathogenesis of severe hypoxic-ischemic lesions of the central nervous system in premature newborns of various gestational ages, as well as to determine its prognostic significance for the formation of severe structural brain lesions.Materials and methods. We observed 120 children with a gestational age from 25 to 36 weeks. The children were divided into 4 groups according to changes to neurosonography data. Determination of protein level was carried out by enzyme immunoassay.Results and conclusion. With the formation of ischemic and combined (intraventricular hemorrhage and periventricular leukomalacia) forms of post-hypoxic changes in the brain in newborns, by 5–7th days of life the concentration of VEGF significantly decreased compared to the test on the 1st day of life, and by the 4th week of life it decreased in 4 times in case of combined lesions. VEGF cannot be used as a marker of damage in the acute period (up to 5 days of life), since its initial levels in the blood serum do not differ significantly from those in the control group. However, a decrease in its concentration by the end of the 1st week of life makes it possible to reliably predict the formation of post-hypoxic changes in the brain. A decrease in the level of VEGF in the blood serum in premature newborns with structural changes according to neurosonography by the 4th week of life coincides with the timing of the formation of gliotic changes, which significantly affects the developmental prognosis of the examined children