Objective: The objective of this study was to evaluate and compare the global cardiac sphericity index (GCSI) of appropriate for gestational age (AGA) fetuses, small for gestational age (SGA) fetuses, and growth-restricted fetuses scanned at term in a government tertiary hospital, maternal high risk (MHR) and to determine the association between the GCSI of these three groups of fetuses and their neonatal outcomes. Methodology: The study prospectively evaluated and compared the GCSI of AGA, SGA, and growth-restricted fetuses. Pregnant women at term seen at the outpatient department and scanned at the MHR clinic then eventually delivered in the same hospital from March to May 2022 were included in this study. Results: GCSIs were measured with 147 fetuses (106 AGA, 38 SGA, and 3 growth‑restricted fetuses). The result indicated that the GCSI of AGA fetuses was higher than that of the SGA and growth‑restricted fetuses. This study found that there is a significantly higher frequency of abnormal GSCI among SGA and growth‑restricted fetuses. This study also found that there is no statistically significant correlation between the GCSI measurements of these three groups of fetuses and their neonatal outcomes. Conclusions Abnormal GCSIs were found in fetuses with an estimated fetal weight <10th percentile (more specifically in growth‑restricted fetuses than in those who are just SGA) as compared with AGA fetuses. However, the correlation between an abnormal GCSI in any of these three groups of fetuses and their neonatal outcomes needs further investigation.
Fetal Growth Retardation

Preeclampsia and intrauterine growth restriction (IUGR) of the fetus are the two most common pregnancy complications worldwide, affecting 5%-10% of pregnant women. Preeclampsia is associated with significantly increased maternal and fetal morbidity and mortality. Hypoxia-induced uteroplacental dysfunction is now recognized as a key pathological factor in preeclampsia and IUGR. Reduced oxygen supply (hypoxia) disrupts mitochondrial and endoplasmic reticulum (ER) function. Hypoxia has been shown to alter mitochondrial reactive oxygen species (ROS) homeostasis and induce ER stress. Hypoxia during pregnancy is associated with excessive production of ROS in the placenta, leading to oxidative stress. Oxidative stress occurs in a number of human diseases, including high blood pressure during pregnancy. Studies have shown that uterine placental tissue/cells in preeclampsia and IUGR show high levels of oxidative stress, which plays an important role in the pathogenesis of both the complications. This review summarizes the role of hypoxia-induced mitochondrial oxidative stress and ER stress in the pathogenesis of preeclampsia/IUGR and discusses the potential therapeutic strategies targeting oxidative stress to treat both the pregnancy complications.
Pregnancy ; Female ; Humans ; Placenta ; Fetal Growth Retardation/etiology* ; Pre-Eclampsia/pathology* ; Reactive Oxygen Species ; Hypoxia/pathology* ; Pregnancy Complications/pathology* ; Endoplasmic Reticulum Stress

OBJECTIVE: To carry out genetic analysis for a fetus with confined placental mosaicism (CPM) for trisomy 2 (T2) in conjunct with fetal uniparental disomy (UPD). METHODS: Amniocentesis and chromosomal karyotyping was carried out for a pregnant woman with a high risk for chromosome 2 anomalies indicated by non-invasive prenatal testing (NIPT). Single nucleotide polymorphism array (SNP-array) and trio-whole exome sequencing (Trio-WES) were carried out. Ultrasonography was used to closely monitor the fetal growth. Multifocal sampling of the placenta was performed after delivery for copy number variation sequencing (CNV-seq). RESULTS: The fetus was found to have a normal chromosomal karyotype. SNP-array has revealed multiple regions with loss of heterozygosity (LOH) on chromosome 2. Trio-WES confirmed the presence of maternal UPD for chromosome 2. Ultrasonography has revealed intrauterine growth restriction and oligohydramnios. Intrauterine fetal demise had occurred at 23⁺⁴ weeks of gestation. Pathological examination had failed to find salient visceral abnormality. The placenta was proved to contain complete T2 by CNV-seq. CONCLUSION T2 CPM can cause false positive result for NIPT and may be complicated with fetal UPD, leading to adverse obstetric outcomes such as intrauterine growth restriction, oligohydramnios and intrauterine fetal demise.
Female ; Humans ; Pregnancy ; Amniocentesis ; Chromosomes, Human, Pair 2/genetics* ; DNA Copy Number Variations ; Fetal Death ; Fetal Growth Retardation/genetics* ; Fetus ; Mosaicism ; Oligohydramnios ; Placenta ; Trisomy/genetics* ; Uniparental Disomy/genetics*

OBJECTIVES: To study the left heart structure and functional characteristics of term neonates with intrauterine growth restriction (IUGR). METHODS: This study included 86 term neonates with IUGR admitted to the Neonatal Ward of Beijing Friendship Hospital, Capital Medical University from January 2019 to January 2022 as the IUGR group, as well as randomly selected 86 term neonates without IUGR born during the same period as the non-IUGR group. The clinical data and echocardiographic data were compared between the two groups. RESULTS: The analysis of left heart structure and function showed that compared with the non-IUGR group, the IUGR group had significantly lower left ventricular mass, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left atrial diameter, end-diastolic interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic volume, left ventricular end-systolic volume, and stroke volume (P<0.05) and significantly higher ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness, proportion of neonates with a mitral peak E/A ratio of ≥1, and cardiac index (P<0.05). The Spearman correlation analysis suggested that stroke volume was positively correlated with birth weight and body surface area (r_s=0.241 and 0.241 respectively; P<0.05) and that the ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness was negatively correlated with birth weight and body surface area (r_s=-0.229 and -0.225 respectively; P<0.05). CONCLUSIONS The left ventricular systolic function of neonates with IUGR is not significantly different from that of neonates without IUGR. However, the ventricular septum is thicker in neonates with IUGR. This change is negatively correlated with birth weight and body surface area. The left ventricular diastolic function may be impaired in neonates with IUGR.
Humans ; Infant, Newborn ; Birth Weight ; Echocardiography ; Fetal Growth Retardation ; Heart ; Heart Ventricles/diagnostic imaging* ; Ventricular Function, Left

With the increase in the survival rate of very preterm infants, the long-term neurodevelopmental outcomes of such infants have attracted more and more attention. Very preterm infants tend to develop movement disorders and psychological and behavioral problems, including cerebral palsy, developmental coordination disorders, autism spectrum disorders, attention deficit hyperactivity disorders, specific learning disorders, and intellectual developmental disorders. It is of vital importance to improve the long-term prognosis of very preterm infants, and early comprehensive intervention measures can minimize disability and achieve optimal parenting outcomes. This article provides a review of the research progress on the long-term neurodevelopmental outcomes in extremely preterm infants.
Infant ; Female ; Infant, Newborn ; Humans ; Infant, Extremely Premature ; Autism Spectrum Disorder ; Intellectual Disability ; Infant, Very Low Birth Weight ; Attention Deficit Disorder with Hyperactivity ; Fetal Growth Retardation

OBJECTIVE: To explore the clinical and genetic characteristics of a fetus with Melnick-Needles syndrome (MNS). METHODS: A fetus with MNS diagnosed at Ningbo Women and Children's Hospital in November 2020 was selected as the study subject. Clinical data was collected. Pathogenic variant was screened by using trio-whole exome sequencing (trio-WES). Candidate variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasonography of the fetus had shown multiple anomalies including intrauterine growth retardation, bilateral femur curvature, omphalocele, single umbilical artery, and oligohydramnios. Trio-WES revealed that the fetus has harbored hemizygous c.3562G>A (p.A1188T) missense variant of the FLNA gene. Sanger sequencing confirmed that the variant was maternally derived, whilst its father was of a wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+PM2_Supporting+PP3+PP4). CONCLUSION The hemizygous c.3562G>A (p.A1188T) variant of the FLNA gene probably underlay the structural abnormalities in this fetus. Genetic testing can facilitate accurate diagnosis of MNS and provide a basis for genetic counseling for this family.
Child ; Female ; Humans ; Pregnancy ; Abnormalities, Multiple/genetics* ; Fetal Growth Retardation ; Fetus ; Filamins/genetics* ; Genetic Counseling ; Mutation ; Osteochondrodysplasias

OBJECTIVE: To explore the genetic basis for a Chinese pedigree with 6q26q27 microduplication and 15q26.3 microdeletion. METHODS: A fetus with a 6q26q27 microduplication and a 15q26.3 microdeletion diagnosed at the First Affiliated Hospital of Wenzhou Medical University in January 2021 and members of its pedigree were selected as the study subject. Clinical data of the fetus was collected. The fetus and its parents were analyzed by G-banding karyotyping and chromosomal microarray analysis (CMA), and its maternal grandparents were also subjected to G-banding karyotype analysis. RESULTS: Prenatal ultrasound had indicated intrauterine growth retardation of the fetus, though no karyotypic abnormality was found with the amniotic fluid sample and blood samples from its pedigree members. CMA revealed that the fetus has carried a 6.6 Mb microduplication in 6q26q27 and a 1.9 Mb microdeletion in 15q26.3, and his mother also carried a 6.49 duplication and a 1.867 deletion in the same region. No anomaly was found with its father. CONCLUSION The 6q26q27 microduplication and 15q26.3 microdeletion probably underlay the intrauterine growth retardation in this fetus.
Female ; Humans ; Pregnancy ; East Asian People ; Fetal Growth Retardation/genetics* ; Karyotype ; Pedigree ; Prenatal Diagnosis ; Sequence Deletion ; Chromosome Duplication

Objective: To establish the reference values and growth curves of length for weight and head circumference for weight among Chinese newborns in order to provide a reference for the assessment of body proportionality at birth. Methods: A cross-sectional design was applied. A total of 24 375 singleton live birth newborns with gestational ages at birth of 24⁺⁰ to 42⁺⁶ weeks were recruited from June 2015 to November 2018 from 13 cities including Beijing, Harbin, Xi'an, Shanghai, Nanjing, Wuhan, Guangzhou, Fuzhou, Kunming, Tianjin, Shenyang, Changsha, and Shenzhen, excluding those with maternal or newborn conditions that may impact the establishment of the reference values. The generalized additive model for location, scale, and shape was employed to establish reference values in terms of percentile and growth curves of length for weight and head circumference for weight for male and female newborns. The random forest machine learning method was employed to analyze the importance of variables between the established reference values in this study and the previous published weight/length, body mass index (BMI), ponderal index (PI), weight/head circumference, length/head circumference in the assessment of symmetrical and asymmetrical small for gestational age (SGA) newborns. Results: A total of 24 375 newborns with 13 197 male infants (preterm birth 7 042 infants and term birth 6 155 infants) and 11 178 female infants (preterm birth 5 222 infants and term birth 5 956 infants) were included in this study. The reference values in terms of percentile (P₃, P₁₀, P₂₅, P₅₀, P₇₅, P₉₀, P₉₇) and growth curves of length for weight and head circumference for weight were obtained for male and female newborns with gestational ages of 24⁺⁰ to 42⁺⁶ weeks. The median birth lengths corresponding to the birth weights of 1 500, 2 500, 3 000, and 4 000 g were 40.4, 47.0, 49.3 and 52.1 cm for males and 40.4, 47.0, 49.2, and 51.8 cm for females, respectively; the median birth head circumferences were 28.4, 32.0, 33.2 and 35.2 cm for males and 28.4, 32.0, 33.1, and 35.1 cm for females, respectively. The differences of length for weight between males and females were minimum, with the difference range of -0.3 to 0.3 cm at P₅₀; the differences of head circumference for weight between males and females were minimum, with the difference range of 0 to 0.2 cm at P₅₀. Based on the match between birth length and birth weight for classifying symmetrical and asymmetrical SGA, length for weight and PI contributed the most, accounting for 0.32 and 0.25, respectively; based on the match between birth head circumference and birth weight, head circumference for weight and weight/head circumference contributed the most, accounting for 0.55 and 0.12, respectively; based on the match between birth length or head circumference with birth weight, head circumference for weight and length for weight contributed the most, accounting for 0.26 and 0.21, respectively. Conclusion: The establishment of the new standardized growth reference values and growth curves of length for weight and head circumference for weight among Chinese newborns are useful for clinical practice and scientific research.
Female ; Humans ; Infant, Newborn ; Male ; Birth Weight ; Body Height ; China ; Cross-Sectional Studies ; East Asian People ; Fetal Growth Retardation ; Gestational Age ; Premature Birth ; Reference Values

The incidence of perinatal disease and perinatal mortality in small for gestational age infants increased significantly. This group of people is prone to a variety of long-term metabolic diseases and cardiovascular diseases, and is also prone to growth retardation and neurodevelopmental delay, which will seriously affect the long-term quality of life of children. The article studies the neurodevelopmental outcomes of small-for-gestational-age infants. By reviewing and sorting out previous literature, the neurodevelopmental disorders of small-for-gestational-age infants are analyzed according to five aspects: intellectual development, motor development, language development, sensory development, and mental illness. The classification and summary were carried out, and the influencing factors of neurodevelopmental disorders of SGA were also evaluated, so as to provide reference for promoting the improvement of neurodevelopmental outcomes of small-for-gestational-age infants.
Infant, Newborn ; Pregnancy ; Female ; Child ; Infant ; Humans ; Gestational Age ; Quality of Life ; Infant, Small for Gestational Age ; Fetal Growth Retardation/epidemiology*

Objective: To retrospectively analyze the clinical data of different types of selective intrauterine growth restriction (sIUGR) pregnant women under expectant management, including the natural evolution, typing conversion and perinatal outcomes. Methods: The clinical data of 153 pregnant women with sIUGR under expected treatment in Women's Hospital, Zhejiang University School of Medicine from January 2014 to December 2018 were collected. Maternal characteristics including maternal age, gravidity, parity, method of conception, pregnancy complication, gestational age at delivery, indication for delivery, birth weight, the rate of intrauterine and neonatal death and neonatal outcomes were recorded. Pregnant women with sIUGR were divided into three types according to end-diastolic umbilical artery flow Doppler ultrasonography, and the differences of typing conversion and perinatal outcomes of sIUGR pregnant women based on the first diagnosis were compared. Results: (1) Clinical characteristics and pregnancy outcomes: among 153 pregnant women with sIUGR, 100 cases (65.3%) were diagnosed with type Ⅰ, 35 cases (22.9%) with type Ⅱ, and 18 cases (11.8%) with type Ⅲ. There were no significant differences in age, conception mode, pregnancy complications, first diagnosis gestational age, characteristics of umbilical cord insertion, delivery indications, fetal intrauterine mortality and neonatal mortality among three types of sIUGR pregnant women (all P>0.05). The average gestational age at delivery of type Ⅰ sIUGR was (33.5±1.9) weeks, which was significantly later than those of type Ⅱ and Ⅲ [(31.3±1.8), (31.2±1.1) weeks, P<0.001]. The percentage disordance in estimated fetal weight (EFW) of type Ⅰ sIUGR was significantly lower than those of type Ⅱ and type Ⅲ (P<0.001). The incidence rate of neonatal intensive care unit (NICU) admission, cerebral leukomalacia and respiratory complications of both fetus and necrotizing enterocolitis of large fetus in type Ⅰ were significantly lower than those in type Ⅱ and type Ⅲ (all P<0.05). (2) Typing conversion: in 100 cases of type Ⅰ sIUGR, 18 cases progressed to type Ⅱ and 10 cases progressed to type Ⅲ. Compared with 72 stable type Ⅰ sIUGR, those with progressed type Ⅰ sIUGR had higher incidence of NICU admission and lung disease in both fetuses, and cerebral leukomalacia and necrotizing enterocolitis in large fetus (all P<0.05). The proportion of inconsistent cord insertion was significantly higher in those type Ⅰ progressed to type Ⅲ (6/10) than in those with stable type Ⅰ (19.4%, 14/72) and type Ⅰ progressed to type Ⅱ sIUGR [0 (0/18), P=0.001]. Four cases of type Ⅱ sIUGR reversed to type Ⅰ and 6 cases reversed to type Ⅲ. Compared with type Ⅱ reversed to type Ⅰ sIUGR, those stable type Ⅱ and type Ⅱ reversed to type Ⅲ sIUGR had a higher incidence of NICU admission in large fetus (P<0.05). Two cases of type Ⅲ sIUGR reversed to type Ⅰ and 6 cases progressed to type Ⅱ. There were no significant differences in fetal serious complications in type Ⅲ sIUGR with or without doppler changes (all P>0.05). Conclusions: The different types of sIUGR could convert to each other. The frequency of ultrasound examinations should be increased for patients with the type Ⅰ sIUGR, especially when the percentage discordance in EFW is substantial or with discordant cord insersion.
Pregnancy ; Female ; Infant, Newborn ; Humans ; Fetal Growth Retardation/epidemiology* ; Pregnancy Outcome ; Retrospective Studies ; Enterocolitis, Necrotizing ; Twins, Monozygotic ; Umbilical Arteries/diagnostic imaging* ; Gestational Age ; Ultrasonography, Prenatal/methods* ; Pregnancy, Twin