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Abstract
Background Fetal growth restriction (FGR) is a condi- tion that a ects 5–10% of pregnancies and is the second most common cause of perinatal mortality. This review presents the most recent knowledge on FGR and focuses on the etiology, classi cation, prediction, diagnosis, and management of the condition, as well as on its neurological comp...
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Abstract Background Affecting approximately 10% of pregnancies, fetal growth restriction (FGR), is the most important cause of perinatal mortality and morbidity. Impaired placental function and consequent mal-perfusion of the placenta is the leading cause of FGR. Although, screening for placental insufficiency based on uterine artery Doppler measur...
Being born small lays the foundation for short-term and long-term implications for life. Intrauterine or fetal growth restriction describes the pregnancy complication of pathological reduced fetal growth, leading to significant perinatal mortality and morbidity, and subsequent long-term deficits. Placental insufficiency is the principal cause of FG...
Citations
... Fetal growth restriction is influenced by maternal, fetal, and placental factors, and is a significant cause of perinatal morbidity and mortality [85,86]. Between 5-10% of pregnancies are complicated by FGR making it the second leading cause of perinatal mortality in babies without congenital anomalies. ...
... Between 5-10% of pregnancies are complicated by FGR making it the second leading cause of perinatal mortality in babies without congenital anomalies. In addition, FGR is responsible for 30% of stillbirths [85]. Placental insufficiency is considered the main cause of FGR, and a variety of screening models related to placental function have been investigated [87][88][89]. ...
Understanding and preventing the “great obstetrical syndromes” has been the focus of pregnancy research for decades. Pregnancy conditions such as preeclampsia, fetal growth restriction, preterm birth, and stillbirth that can result from placental dysfunction may complicate up to 30 million pregnancies worldwide annually. We have proposed a multimodal integrated management strategy using lifestyle, screening, and medical treatment that has the potential to significantly reduce pregnancy complications, decrease maternal and perinatal morbidity and mortality, limit transgenerational transmission of chronic disease, potentially reduce future maternal cardiometabolic risk, decrease health-care related costs, and improve quality of life. Translation of validated components of this model into clinical practice should be a global health-care priority.
... Inadequate regulation of the placental immune environment is associated with pregnancy-related complications. Intrauterine growth restriction (IUGR) impacts around 5-10% of pregnancies [48]. In this condition, the fetus is unable to attain its prospective growth potential due to the harmful environment during pregnancy. ...
... Studies have shown that even though GDM is a transient state in which glycemic regulation usually returns to normal shortly after delivery, it leads to a 40% increase in the risk of developing type 2 diabetes within 10-15 years [7]. Fetal growth restriction (FGR), a common pregnancy complication, is a condition in which the fetus does not develop according to its expected biological potential in the uterus [8]. FGR, in contrast to a small constitution, is a pathological condition (known as placental insufficiency) in which the placenta undersupply nutrients and oxygen to the developing fetus [9]. ...
BACKGROUND
Gestational diabetes mellitus (GDM) is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism; GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development.
AIM
To investigate the associations of serum D-dimer (D-D) and glycosylated hemoglobin (HbA1c) levels with third-trimester fetal growth restriction (FGR) in GDM patients.
METHODS
The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively. Among these women, 63 whose fetuses had FGR were included in the FGR group, and 101 women whose fetuses had normal body weights were included in the normal body weight group (normal group). Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis. The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis, and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression.
RESULTS
Serum fasting blood glucose, fasting insulin, D-D and HbA1c levels were significantly greater in the FGR group than in the normal group, while the homeostasis model assessment of insulin resistance values were lower (P < 0.05). Regarding the diagnosis of FGR based on serum D-D and HbA1c levels, the areas under the curves (AUCs) were 0.826 and 0.848, the cutoff values were 3.04 mg/L and 5.80%, the sensitivities were 81.0% and 79.4%, and the specificities were 88.1% and 87.1%, respectively. The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928, and the sensitivity and specificity were 84.1% and 91.1%, respectively. High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients (P < 0.05).
CONCLUSION
D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent, and their combination can be used as an important index for the early prediction of FGR.
... There are many potential causes of IUGR, ranging from maternal to fetal and uteroplacental factors, with IUGR frequently resulting from a combination of some or all of these (Gilchrist et al., 2018;Nardozza et al., 2017). Fetal causes of IUGR include chromosomal abnormalities and genetic syndromes (5-20% of IUGR cases), intrauterine infections (especially rubella virus, varicella zoster virus and toxoplasma gondii) and extremely rare, inborn errors of metabolism; maternally driven factors include clinical diseases (for example, hypertensive diseases resulting from reduced uteroplacental perfusion, pre-eclampsia, insulin-dependent diabetes mellitus, severe anaemia), malnutrition and nutritional disorders, drug use (particularly tobacco smoking, alcohol, narcotics and teratogenic substances), as well as ethnicity, depression and stress. ...
... Fetal causes of IUGR include chromosomal abnormalities and genetic syndromes (5-20% of IUGR cases), intrauterine infections (especially rubella virus, varicella zoster virus and toxoplasma gondii) and extremely rare, inborn errors of metabolism; maternally driven factors include clinical diseases (for example, hypertensive diseases resulting from reduced uteroplacental perfusion, pre-eclampsia, insulin-dependent diabetes mellitus, severe anaemia), malnutrition and nutritional disorders, drug use (particularly tobacco smoking, alcohol, narcotics and teratogenic substances), as well as ethnicity, depression and stress. However, nearly a third of IUGR births (25-30%) are driven by uteroplacental vascular insufficiency, a complication of pregnancy whereby the supply of oxygen and nutrients to the developing fetus is significantly compromised due to developmental faults in the placenta or placental blood vessels (Gilchrist et al., 2018;Nardozza et al., 2017). Worldwide, IUGR affects up to 10-15% of pregnancies (Armengaud et al., 2021) and is one of the leading causes of perinatal death and postnatal morbidity (Bernstein et al., 2000;Malhotra, Allison, et al., 2019). ...
Intrauterine growth restriction (IUGR) is a pregnancy complication impairing fetal growth and development. The compromised development is often attributed to disruptions of oxygen and nutrient supply from the placenta, resulting in a number of unfavourable physiological outcomes with impaired brain and organ growth. IUGR is associated with compromised development of both grey and white matter, predisposing the infant to adverse neurodevelopmental outcomes, including long‐lasting cognitive and motor difficulties. Cerebral thyroid hormone (TH) signalling, which plays a crucial role in regulating white and grey matter development, is dysregulated in IUGR, potentially contributing to the neurodevelopmental delays associated with this condition. Notably, one of the major TH transporters, monocarboxylate transporter‐8 (MCT8), is deficient in the fetal IUGR brain. Currently, no effective treatment to prevent or reverse IUGR exists. Management strategies involve close antenatal monitoring, management of maternal risk factors if present and early delivery if IUGR is found to be severe or worsening in utero. The overall goal is to determine the most appropriate time for delivery, balancing the risks of preterm birth with further fetal compromise due to IUGR. Drug candidates have shown either adverse effects or little to no benefits in this vulnerable population, urging further preclinical and clinical investigation to establish effective therapies. In this review, we discuss the major neuropathology of IUGR driven by uteroplacental insufficiency and the concomitant long‐term neurobehavioural impairments in individuals born IUGR. Importantly, we review the existing clinical and preclinical literature on cerebral TH signalling deficits, particularly the impaired expression of MCT8 and their correlation with IUGR. Lastly, we discuss the current evidence on MCT8‐independent TH analogues which mimic the brain actions of THs by being metabolised in a similar manner as promising, albeit underappreciated approaches to promote grey and white matter development and improve the neurobehavioural outcomes following IUGR. image
... Surprisingly, prenatal intrauterine growth restriction (IUGR) with or without short long bones was found in 6 MRXS34 patients (75%) [7], stressing the signi cance of biological measurements for prenatal diagnosis of MRXS34. Moreover, IUGR, which is caused by multiple factors, such as placental and maternal factors, as well as genetic factors, such as aneuploidy, pathogenic copy number variation, and monogenic genetic diseases, is not uncommon in prenatal diagnosis [13]. Moreover, supravalvular stenosis and intrauterine growth restriction are features of 7q11.23 microdeletion syndrome [14]. ...
Background
The NONO gene is located on chromosome Xq13.1 and encodes a nuclear protein involved in RNA synthesis, transcriptional regulation, and DNA repair. Hemizygous loss-of-function variants in NONO reportedly cause X-linked syndromic intellectual developmental disorder-34 (MRXS34) in males. At present, there are few clinical reports related to MRXS34, and the mutation spectrum of NONO-related diseases has not been completely determined.
Methods
We report the case of a fetus with noncompaction cardiomyopathy, a short anteroposterior diameter of the corpus callosum and relative macrocephaly. Genotyping examination, including chromosome microarray analysis (CMA) and trio-medical exon sequencing, was performed.
Results
Medical exon sequencing revealed a de novo hemizygous nonsense mutation (c.214 C > T, p.Gln72Ter) in exon 4 of the NONO gene. A review of previous literature suggested that noncompaction cardiomyopathy, abnormalities of the corpus callosum, and macrocephaly are consistent phenotypes of MRXS34.
Conclusion
The mutation (c.214 C > T, p.Gln72Ter) in the NONO gene was present in a fetus with MRXS34. This study expands the mutation spectrum of NONO-related diseases and enlarges noncompaction cardiomyopathy, abnormalities of the corpus callosum and macrocephaly to the phenotype of MRXS34 in fetuses.
... 1,2 FGR is a global problem that affects approximately 10% of pregnancies and is one of the most common complications in obstetrics. 3,4 FGR is a significant contributor to perinatal morbidity and mortality and can also result in long-term metabolic disorders. [5][6][7] The etiology of FGR is multifaceted, encompassing factors associated with the mother, fetus, and placenta. ...
The precise molecular mechanism behind fetal growth restriction (FGR) is still unclear, although there is a strong connection between placental dysfunction, inadequate trophoblast invasion, and its etiology and pathogenesis. As a new type of non‐coding RNA, circRNA has been shown to play a crucial role in the development of FGR. This investigation identified the downregulation of hsa_circ_0034533 (circTHBS1) in FGR placentas through high‐sequencing analysis and confirmed this finding in 25 clinical placenta samples using qRT‐PCR. Subsequent in vitro functional assays demonstrated that silencing circTHBS1 inhibited trophoblast proliferation, migration, invasion, and epithelial mesenchymal transition (EMT) progression and promoted apoptosis. Furthermore, when circTHBS1 was overexpressed, cell function experiments showed the opposite result. Analysis using fluorescence in situ hybridization revealed that circTHBS1 was primarily found in the cytoplasmic region. Through bioinformatics analysis, we anticipated the involvement of miR‐136‐3p and IGF2R in downstream processes, which was subsequently validated through qRT‐PCR and dual‐luciferase assays. Moreover, the inhibition of miR‐136‐3p or the overexpression of IGF2R partially reinstated proliferation, migration, and invasion abilities following the silencing of circTHBS1. In summary, the circTHBS1/miR‐136‐3p/IGF2R axis plays a crucial role in the progression and development of FGR, offering potential avenues for the exploration of biological indicators and treatment targets.
... Placental vascular insufficiency, defined as the inability of the placenta to provide sufficient nutrients and oxygen to the foetus for growth and development, is the most common cause of intrauterine growth retardation and is associated with neonatal morbidity and mortality (6). ...
Background
A diagnosis of Silver–Russell syndrome (SRS), a rare imprinting disorder responsible for foetal growth restriction, is considered for patients presenting at least four criteria of the Netchine-Harbison clinical scoring system (NH-CSS). Certain items of the NH-CSS are not assessable until the age of 2 years. The objective was to determine perinatal characteristics of children with SRS to allow an early diagnosis.
Methods
We retrospectively compared the perinatal characteristics of children with SRS (n = 17) with those of newborns small for gestational age (SGA) due to placental insufficiency (PI) (n = 21).
Results
Children with SRS showed earlier and more severely altered foetal biometry than SGA newborns due to PI. Twenty-three percent of patients with SRS showed uterine artery Doppler anomalies. SRS children were significantly smaller at birth (birth length <-3 SDS in 77% of cases in the SRS group vs. 15% in the PI group, p = 0.0001).
Conclusion
The diagnosis of SRS must be evoked in the neonatal period for SGA newborns with a growth delay present from the second trimester of pregnancy, a birth length <-3 SDS and a relative macrocephaly. Doppler anomalies, classically used to orient the cause of SGA towards PI, did not rule out the diagnosis of SRS.
... The FGR pathogenesis is complex and can be associated with various factors (maternal; placental; fetal), leading to a limited supply of nutrients and oxygen to the fetus [3,[11][12][13][14][15][16][17]. Maternal risk factors such as advanced age, underweight, hypertension, diabetes, genetics, etc., are essential in the formation of FGR [2,18]. ...
We aimed to explore the potential link of maternal age at menarche (mAAM) gene polymorphisms with risk of the fetal growth restriction (FGR). This case (FGR)–control (FGR free) study included 904 women (273 FGR and 631 control) in the third trimester of gestation examined/treated in the Departments of Obstetrics. For single nucleotide polymorphism (SNP) multiplex genotyping, 50 candidate loci of mAAM were chosen. The relationship of mAAM SNPs and FGR was appreciated by regression procedures (logistic/model-based multifactor dimensionality reduction [MB-MDR]) with subsequent in silico assessment of the assumed functionality pithy of FGR-related loci. Three mAAM-appertain loci were FGR-linked to genes such as KISS1 (rs7538038) (effect allele G-odds ratio (OR)allelic = 0.63/рperm = 0.0003; ORadditive = 0.61/рperm = 0.001; ORdominant = 0.56/рperm = 0.001), NKX2-1 (rs999460) (effect allele A-ORallelic = 1.37/рperm = 0.003;ORadditive = 1.45/рperm = 0.002; ORrecessive = 2.41/рperm = 0.0002),GPRC5B (rs12444979) (effect allele T-ORallelic = 1.67/рperm = 0.0003; ORdominant = 1.59/рperm = 0.011; ORadditive = 1.56/рperm = 0.009). The haplotype ACA FSHB gene (rs555621*rs11031010*rs1782507) was FRG-correlated (OR = 0.71/рperm = 0.05). Ten FGR-implicated interworking models were founded for 13 SNPs (рperm ≤ 0.001). The rs999460 NKX2-1 and rs12444979 GPRC5B interplays significantly influenced the FGR risk (these SNPs were present in 50% of models). FGR-related mAAM-appertain 15 polymorphic variants and 350 linked SNPs were functionally momentous in relation to 39 genes participating in the regulation of hormone levels, the ovulation cycle process, male gonad development and vitamin D metabolism. Thus, this study showed, for the first time, that the mAAM-appertain genes determine FGR risk.
... Interpretation of our results is further confounded by recognized differences in infant sizes in different national populations [35,36]. SGA only partially overlaps with fetal growth restriction (FGR), a pathologic condition characterized by hypoxia and lack of nutrition [33,37,38], which occurs in 3-10% on newborns in the general population and up to 25% of pregnancies in low-and middle-income countries. The level of detail required to assess FGR was not collected in our study. ...
The management of chronic myeloid leukemia (CML) diagnosed during pregnancy is a rare and challenging situation. We report the treatment and outcome of 87 cases diagnosed in chronic phase from 2001–2022 derived from the largest international observational registry, supported by the European LeukemiaNet (ELN), of 400 pregnancies in 299 CML women. Normal childbirth occurred in 76% without an increased rate of birth abnormalities or life-threatening events, including in patients untreated or treated with interferon-α and/or imatinib in 2nd–3rd trimester. The low birth weight rate of 12% was comparable to that seen in the normal population. Elective and spontaneous abortions occurred in 21% and 3%, respectively. The complete hematologic response rate before labor was 95% with imatinib and 47% with interferon only. No disease progression during pregnancy was observed, 28% of the patients switched their therapy at varying times after delivery. Treatment options balance the efficacy and safety for mother and infant: interferon-α can commence in the 1st trimester and continued throughout in cases of good disease control and tolerability. Because of limited placental crossing, selected tyrosine kinase inhibitors (imatinib and nilotinib) seem to be safe and effective options in 2nd and 3rd trimester while hydroxycarbamide offers few benefits.
... LGA fetuses have a heightened risk of adverse outcomes during labor, such as shoulder dystocia and/or perinatal brachial plexus palsy [10]. Despite the significant progress that has been achieved in the field of fetal monitoring and high-risk pregnancy management, the precise mechanisms and the underlying cause(s) of impaired fetal growth are yet to be fully elucidated [11,12]. ...
... The long-term effects of SGA and FGR on adult life have been extensively investigated [11,[43][44][45]. A recently published study has explored the correlation between FGR, including SGA cases and preterm birth, and kidney size and kidney function by measuring several biochemical markers, such as the renin-angiotensin-aldosterone system (RAAS), in adolescents. ...
Background: Despite the considerable progress made in recent years in fetal assessment, the etiology of fetal growth disturbances is not as yet well understood. In an effort to enhance our knowledge in this area, we investigated the associations of the amniotic fluid angiotensinogen of the renin–angiotensin system with fetal growth abnormalities. Methods: We collected amniotic fluid samples from 70 pregnant women who underwent amniocentesis during their early second trimester. Birth weight was documented upon delivery, after which the embryos corresponding to the respective amniotic fluid samples were categorized into three groups as follows: small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Amniotic fluid angiotensinogen levels were determined by using ELISA kits. Results: Mean angiotensinogen values were 3885 ng/mL (range: 1625–5375 ng/mL), 4885 ng/mL (range: 1580–8460 ng/mL), and 4670 ng/mL (range: 1995–7250 ng/mL) in the SGA, LGA, and AGA fetuses, respectively. The concentrations in the three groups were not statistically significantly different. Although there were wide discrepancies between the mean values of the subgroups, the large confidence intervals in the three groups negatively affected the statistical analysis. However, multiple regression analysis revealed a statistically significant negative correlation between the angiotensinogen levels and gestational age and a statistically significant positive correlation between the birth weight and angiotensinogen levels. Discussion: Our findings suggest that fetal growth abnormalities did not correlate with differences in the amniotic fluid levels of angiotensinogen in early second trimester pregnancies. However, increased angiotensinogen levels were found to be consistent with a smaller gestational age at birth and increased BMI of neonates.
