cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.30781718
title: Elevated serum NLRP3 as an independent risk factor for preeclampsia

description: This study aimed to explore the risk factors for preeclampsia and analyze the clinical significance of serum NOD-like receptor pyrin domain containing 3 (NLRP3) levels in preeclampsia patients, with attention to their association with disease severity. This prospective observational study recruited 113 preeclampsia patients and 100 healthy pregnant women from July 2021 to July 2024. Serum NLRP3 and inflammatory marker levels were measured using enzyme-linked immunosorbent assay (ELISA). Additionally, demographic and clinical data for all participants were collected, and multivariate binary logistic regression analysis was performed to identify risk factors for preeclampsia. Our results showed that serum NLRP3 levels were significantly higher in preeclampsia patients compared to healthy controls, with NLRP3 levels further elevated in patients with severe preeclampsia. Serum NLRP3 levels were positively correlated with serum interleukin (IL)-6, C-reactive protein (CRP), IL-1β levels, and were also positively correlated with BMI. ROC analysis demonstrated that serum NLRP3 had diagnostic value for preeclampsia (AUC = 0.843, sensitivity 75.2%, specificity 76.0%) and for distinguishing severe preeclampsia (AUC = 0.795, sensitivity 83.0%, specificity 63.6%). Furthermore, elevated NLRP3 levels were identified as an independent risk factor for preeclampsia. This study indicated that serum NLRP3 was associated with preeclampsia and its severity. In addition, elevated NLRP3 levels were identified as an independent risk factor for preeclampsia.
DOI: 10.6084/m9.figshare.30781718.v1
title: Elevated serum NLRP3 as an independent risk factor for preeclampsia

description: This study aimed to explore the risk factors for preeclampsia and analyze the clinical significance of serum NOD-like receptor pyrin domain containing 3 (NLRP3) levels in preeclampsia patients, with attention to their association with disease severity. This prospective observational study recruited 113 preeclampsia patients and 100 healthy pregnant women from July 2021 to July 2024. Serum NLRP3 and inflammatory marker levels were measured using enzyme-linked immunosorbent assay (ELISA). Additionally, demographic and clinical data for all participants were collected, and multivariate binary logistic regression analysis was performed to identify risk factors for preeclampsia. Our results showed that serum NLRP3 levels were significantly higher in preeclampsia patients compared to healthy controls, with NLRP3 levels further elevated in patients with severe preeclampsia. Serum NLRP3 levels were positively correlated with serum interleukin (IL)-6, C-reactive protein (CRP), IL-1β levels, and were also positively correlated with BMI. ROC analysis demonstrated that serum NLRP3 had diagnostic value for preeclampsia (AUC = 0.843, sensitivity 75.2%, specificity 76.0%) and for distinguishing severe preeclampsia (AUC = 0.795, sensitivity 83.0%, specificity 63.6%). Furthermore, elevated NLRP3 levels were identified as an independent risk factor for preeclampsia. This study indicated that serum NLRP3 was associated with preeclampsia and its severity. In addition, elevated NLRP3 levels were identified as an independent risk factor for preeclampsia.
DOI: 10.13130/rd_unimi/ui9ecn/0qrbhe
title: Giugno_1880_Pagina_018.jpg

description: Bulletin of 1880/06/05
DOI: 10.13130/rd_unimi/ui9ecn/i5gycb
title: Giugno_1880_Pagina_019.jpg

description: Bulletin of 1880/06/05
DOI: 10.13130/rd_unimi/ui9ecn/sjnstq
title: Giugno_1880_Pagina_020.jpg

description: Bulletin of 1880/06/05
DOI: 10.6084/m9.figshare.28916152
title: What is the role of intrauterine transfusion after single intrauterine death in monochorionic twin pregnancies? Evidence from a systematic review and meta-analysis

description: To investigate the role of intrauterine transfusion (IUT) in affecting the outcome of the surviving twin showing sign of fetal anemia after a single intrauterine fetal death (IUFD) in monochorionic (MC) twin pregnancies. PubMed, Medline and Embase databases were searched (2010–2024). The inclusion criteria were studies reporting the outcome of fetuses showing signs of fetal anemia, defined as the presence of the peak systolic velocity (PSV) of the middle cerebral artery (MCA) &gt;1.5 MoM, after single IUFD receiving compared to those not receiving IUT. The outcomes observed were preterm birth (PTB) &lt;34 and 28 weeks of gestation, either iatrogenic or spontaneous, co-twin intra-IUFD, co-twin neonatal death (NND), anomalies at pre- or post-natal brain imaging, abnormal neurodevelopmental outcome. Risk of bias of the included studies was assessed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. The GRADE methodology was used to assess the quality of the body of retrieved evidence. Random effect meta-analyses of proportions were used to analyze the data. Six studies (78 twin pregnancies complicated by single IUFD showing signs of fetal anemia) were included in the systematic review. Assessment of risk of bias of observational studies according to the ROBINS-I tool is presented. Only one study reported a non-matched comparison between anemic fetuses undergoing compared to those not undergoing IUT, so we could not calculate the summary odd ratios, and we reported the results as pooled proportions. PTB occurred in 51.25% (95% CI 35.76–66.62) of cases &lt; 34 weeks and in 17.99% (95% CI 5.84–34.91) &lt; 28 weeks of gestation. Co-twin IUFD and NND were reported in 8.02% (95% CI 2.30–16.78) and 15.49% (95% CI 7.89–25.05), while abnormal findings at pre-or post-natal brain imaging in 20.30% (95% CI 11.61–30.69). Abnormal neurodevelopmental outcome was reported in 5.93% (95% CI 2.50–18.30). There is a very low grade of evidence that IUT can affect the outcome of anemic fetuses after single IUFD in MC pregnancies. The findings how this systematic review, in view of the limitations of the included studies, highlighted the need for large multicenter studies sharing objective protocols of prenatal management and post-natal assessment of pregnancies complicated by single IUFD are needed to report whether IUT in the anemic fetus after single IUFD can prevent mortality and neuromorbidity.
DOI: 10.6084/m9.figshare.28916152.v1
title: What is the role of intrauterine transfusion after single intrauterine death in monochorionic twin pregnancies? Evidence from a systematic review and meta-analysis

description: To investigate the role of intrauterine transfusion (IUT) in affecting the outcome of the surviving twin showing sign of fetal anemia after a single intrauterine fetal death (IUFD) in monochorionic (MC) twin pregnancies. PubMed, Medline and Embase databases were searched (2010–2024). The inclusion criteria were studies reporting the outcome of fetuses showing signs of fetal anemia, defined as the presence of the peak systolic velocity (PSV) of the middle cerebral artery (MCA) &gt;1.5 MoM, after single IUFD receiving compared to those not receiving IUT. The outcomes observed were preterm birth (PTB) &lt;34 and 28 weeks of gestation, either iatrogenic or spontaneous, co-twin intra-IUFD, co-twin neonatal death (NND), anomalies at pre- or post-natal brain imaging, abnormal neurodevelopmental outcome. Risk of bias of the included studies was assessed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. The GRADE methodology was used to assess the quality of the body of retrieved evidence. Random effect meta-analyses of proportions were used to analyze the data. Six studies (78 twin pregnancies complicated by single IUFD showing signs of fetal anemia) were included in the systematic review. Assessment of risk of bias of observational studies according to the ROBINS-I tool is presented. Only one study reported a non-matched comparison between anemic fetuses undergoing compared to those not undergoing IUT, so we could not calculate the summary odd ratios, and we reported the results as pooled proportions. PTB occurred in 51.25% (95% CI 35.76–66.62) of cases &lt; 34 weeks and in 17.99% (95% CI 5.84–34.91) &lt; 28 weeks of gestation. Co-twin IUFD and NND were reported in 8.02% (95% CI 2.30–16.78) and 15.49% (95% CI 7.89–25.05), while abnormal findings at pre-or post-natal brain imaging in 20.30% (95% CI 11.61–30.69). Abnormal neurodevelopmental outcome was reported in 5.93% (95% CI 2.50–18.30). There is a very low grade of evidence that IUT can affect the outcome of anemic fetuses after single IUFD in MC pregnancies. The findings how this systematic review, in view of the limitations of the included studies, highlighted the need for large multicenter studies sharing objective protocols of prenatal management and post-natal assessment of pregnancies complicated by single IUFD are needed to report whether IUT in the anemic fetus after single IUFD can prevent mortality and neuromorbidity.
DOI: 10.6084/m9.figshare.29661956
title: Whole-exome sequencing for prenatal diagnosis of fetal anomalies: insights from a Jordanian cohort

description: Congenital anomalies are a heterogeneous disorder that occur during fetal development or infancy. Whole exome sequencing (WES) is a promising diagnostic tool for prenatal diagnosis. This study aimed to evaluate the efficiency of WES in identifying the genetic cause of fetal anomalies among Jordanian families. A total of 46 fetuses prenatally diagnosed with various congenital anomalies were included in this study. These cases were categorized into seven groups based on presented phenotypes. DNA was extracted from either chorionic villus samples or amniotic fluid and subjected to singleton WES to identify causative genetic variants. Clinical features and pregnancy outcomes were also collected and reviewed. Variant validation and segregation analysis were performed using ARMS-PCR or Sanger sequencing. Pathogenic or likely pathogenic variants were identified in 26/46 fetuses (56.5%) and variants of uncertain significance (VUS) were detected in 9/46 fetuses (19.6%). In total, 34 variants in 29 genes were identified including 13 pathogenic, 11 likely pathogenic, and 10 VUS. Twenty-three out of 34 variants have never been published. The identified variants were missense (<i>n</i> = 12, 35%), frameshift (<i>n</i> = 10, 29%), nonsense (<i>n</i> = 7, 21%), splice site (<i>n</i> = 3, 9%), and in-frame deletion (<i>n</i> = 2, 6%). Consanguinity was reported in 42 families (91.3%). This study underscores the value of WES in prenatal diagnosis and further expands the mutation spectrum associated with fetal anomalies. It also suggests that WES has strong potential to be used as a routine diagnostic tool in prenatal care. This method enables more precise genetic counseling and aids families facing a recurrent risk of fetal abnormalities in making informed reproductive decisions. To the best of our knowledge, this is the first study in Jordan to utilize prenatal WES for diagnosing fetal anomalies.
DOI: 10.6084/m9.figshare.29661956.v1
title: Whole-exome sequencing for prenatal diagnosis of fetal anomalies: insights from a Jordanian cohort

description: Congenital anomalies are a heterogeneous disorder that occur during fetal development or infancy. Whole exome sequencing (WES) is a promising diagnostic tool for prenatal diagnosis. This study aimed to evaluate the efficiency of WES in identifying the genetic cause of fetal anomalies among Jordanian families. A total of 46 fetuses prenatally diagnosed with various congenital anomalies were included in this study. These cases were categorized into seven groups based on presented phenotypes. DNA was extracted from either chorionic villus samples or amniotic fluid and subjected to singleton WES to identify causative genetic variants. Clinical features and pregnancy outcomes were also collected and reviewed. Variant validation and segregation analysis were performed using ARMS-PCR or Sanger sequencing. Pathogenic or likely pathogenic variants were identified in 26/46 fetuses (56.5%) and variants of uncertain significance (VUS) were detected in 9/46 fetuses (19.6%). In total, 34 variants in 29 genes were identified including 13 pathogenic, 11 likely pathogenic, and 10 VUS. Twenty-three out of 34 variants have never been published. The identified variants were missense (<i>n</i> = 12, 35%), frameshift (<i>n</i> = 10, 29%), nonsense (<i>n</i> = 7, 21%), splice site (<i>n</i> = 3, 9%), and in-frame deletion (<i>n</i> = 2, 6%). Consanguinity was reported in 42 families (91.3%). This study underscores the value of WES in prenatal diagnosis and further expands the mutation spectrum associated with fetal anomalies. It also suggests that WES has strong potential to be used as a routine diagnostic tool in prenatal care. This method enables more precise genetic counseling and aids families facing a recurrent risk of fetal abnormalities in making informed reproductive decisions. To the best of our knowledge, this is the first study in Jordan to utilize prenatal WES for diagnosing fetal anomalies.
DOI: 10.13130/rd_unimi/ui9ecn/0rs2hy
title: Giugno_1880_Pagina_021.jpg

description: Bulletin of 1880/06/06
DOI: 10.6084/m9.figshare.29146468
title: Labor epidural analgesia and autism spectrum disorder in 3-year-old offspring based on data from the Japan Environment and Children’s Study: a prospective cohort study

description: To evaluate the association between labor epidural analgesia (LEA) and autism spectrum disorder (ASD) in 3-year-old offspring in Japan. Prospective cohort study utilizing the Japan Environment and Children’s Study, the largest nationwide birth cohort study. A total of 65,742 live singleton offspring were enrolled between January 2011 and March 2014. Offspring born <i>via</i> cesarean delivery or with confirmed chromosomal abnormalities were excluded. Multivariate logistic regression analyses were conducted to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI), accounting for maternal, paternal, and perinatal covariates. Subgroup analyses were performed based on the sex of the offspring. The primary outcome was the diagnosis of ASD at age 3. Among the 65,742 offspring (33,684 boys [51.2%]; mean maternal age, 31.1 [4.9] years), 1,324 (2.0%) were exposed to LEA. ASD was diagnosed in 14 (1.1%) offspring exposed to LEA and 257 (0.4%) not exposed to LEA by age 3. After adjusting for potential confounders, multivariate logistic regression revealed that LEA was associated with an increased risk of ASD (aOR: 2.23; 95% CI: 1.28–3.87). Subgroup analysis indicated that the association was significant in male offspring (aOR: 2.55; 95% CI: 1.40–4.65), but not in female offspring (aOR: 1.41; 95% CI: 0.34–5.91). This study suggests a mild association between LEA and ASD in 3-year-old male offspring. However, the findings should be cautiously interpreted given the limited number of ASD cases in this study. Causal relationships cannot be established since this was an observational study.
DOI: 10.6084/m9.figshare.29146468.v1
title: Labor epidural analgesia and autism spectrum disorder in 3-year-old offspring based on data from the Japan Environment and Children’s Study: a prospective cohort study

description: To evaluate the association between labor epidural analgesia (LEA) and autism spectrum disorder (ASD) in 3-year-old offspring in Japan. Prospective cohort study utilizing the Japan Environment and Children’s Study, the largest nationwide birth cohort study. A total of 65,742 live singleton offspring were enrolled between January 2011 and March 2014. Offspring born <i>via</i> cesarean delivery or with confirmed chromosomal abnormalities were excluded. Multivariate logistic regression analyses were conducted to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI), accounting for maternal, paternal, and perinatal covariates. Subgroup analyses were performed based on the sex of the offspring. The primary outcome was the diagnosis of ASD at age 3. Among the 65,742 offspring (33,684 boys [51.2%]; mean maternal age, 31.1 [4.9] years), 1,324 (2.0%) were exposed to LEA. ASD was diagnosed in 14 (1.1%) offspring exposed to LEA and 257 (0.4%) not exposed to LEA by age 3. After adjusting for potential confounders, multivariate logistic regression revealed that LEA was associated with an increased risk of ASD (aOR: 2.23; 95% CI: 1.28–3.87). Subgroup analysis indicated that the association was significant in male offspring (aOR: 2.55; 95% CI: 1.40–4.65), but not in female offspring (aOR: 1.41; 95% CI: 0.34–5.91). This study suggests a mild association between LEA and ASD in 3-year-old male offspring. However, the findings should be cautiously interpreted given the limited number of ASD cases in this study. Causal relationships cannot be established since this was an observational study.
DOI: 10.13130/rd_unimi/ui9ecn/q3rg1d
title: Giugno_1880_Pagina_022.jpg

description: Bulletin of 1880/06/06
DOI: 10.13130/rd_unimi/ui9ecn/rrxtk9
title: Giugno_1880_Pagina_023.jpg

description: Bulletin of 1880/06/06
DOI: 10.6084/m9.figshare.28455466
title: Prenatal diagnosis and pregnancy outcomes in fetuses with vertebral abnormalities

description: To investigate the genetic risk and pregnancy outcomes of fetuses who had the sonographic diagnosis of vertebral abnormalities (VA). Fifty-two fetuses with sonographically detected VA (excluding neural tube defects) were included in the study. Data on prenatal ultrasound scan, prenatal genetic testing by amniocentesis, and pregnancy outcomes were collected and reviewed. Four types of VA were identified among 52 fetuses: butterfly vertebrae (26.9%, 14/52), hemivertebrae (59.6%, 31/52), hemivertebrae combined with butterfly vertebrae (9.6%, 5/52), and block vertebrae (3.9%, 2/52). Of the 52 fetuses, 33 presented VA as the sole sonographic anomaly, while the remaining 19 had associated anomalies. The positive rate of prenatal diagnosis for fetuses with VA was 19.2% (10/52). Chromosomal analysis, including karyotyping and chromosomal microarray analysis (CMA), detected one case of mosaic trisomy 9 and six cases of (likely) pathogenic copy number variants (CNVs). Whole exome sequencing (WES) identified four likely pathogenic variants in three cases with negative CMA results, specifically c.5110-1G &gt; A in FLNB, c.8366G &gt; A in KMT2D, and c.1275_1283dup as well as c.870 + 2T &gt; C in DLL3. Among the 10 cases with diagnostic genetic testing results, seven fetuses exhibited isolated VA. There was no significant difference in the diagnostic rates between the isolated VA group (21.2%, 7/33) and the non-isolated VA group (15.8%, 3/19) (odds ratio [OR] 0.696, 95% confidence interval [CI] 0.157-3.087, <i>p</i> = 0.910). However, the live birth rate was significantly higher in the isolated VA group (71.9%, 23/32) compared to the non-isolated VA group (38.9%, 7/18) (OR 4.016, 95% CI 1.184-13.622, <i>p</i> = 0.022). Among the 30 live birth cases, two underwent spinal surgery and another two were identified with additional abnormalities. Following appropriate interventions, no apparent abnormalities were observed in the growth and development of 30 live birth cases. Invasive prenatal diagnosis is recommended for all fetuses diagnosed with VA, regardless of whether associated anomalies are present. WES can enhance the diagnostic yield for fetuses with negative CMA results. Fetuses with isolated VA can have favorable pregnancy outcomes when genetic testing results are negative. However, long-term follow-up remains necessary for the assessment of the prognosis of these fetuses.
DOI: 10.6084/m9.figshare.28455466.v1
title: Prenatal diagnosis and pregnancy outcomes in fetuses with vertebral abnormalities

description: To investigate the genetic risk and pregnancy outcomes of fetuses who had the sonographic diagnosis of vertebral abnormalities (VA). Fifty-two fetuses with sonographically detected VA (excluding neural tube defects) were included in the study. Data on prenatal ultrasound scan, prenatal genetic testing by amniocentesis, and pregnancy outcomes were collected and reviewed. Four types of VA were identified among 52 fetuses: butterfly vertebrae (26.9%, 14/52), hemivertebrae (59.6%, 31/52), hemivertebrae combined with butterfly vertebrae (9.6%, 5/52), and block vertebrae (3.9%, 2/52). Of the 52 fetuses, 33 presented VA as the sole sonographic anomaly, while the remaining 19 had associated anomalies. The positive rate of prenatal diagnosis for fetuses with VA was 19.2% (10/52). Chromosomal analysis, including karyotyping and chromosomal microarray analysis (CMA), detected one case of mosaic trisomy 9 and six cases of (likely) pathogenic copy number variants (CNVs). Whole exome sequencing (WES) identified four likely pathogenic variants in three cases with negative CMA results, specifically c.5110-1G &gt; A in FLNB, c.8366G &gt; A in KMT2D, and c.1275_1283dup as well as c.870 + 2T &gt; C in DLL3. Among the 10 cases with diagnostic genetic testing results, seven fetuses exhibited isolated VA. There was no significant difference in the diagnostic rates between the isolated VA group (21.2%, 7/33) and the non-isolated VA group (15.8%, 3/19) (odds ratio [OR] 0.696, 95% confidence interval [CI] 0.157-3.087, <i>p</i> = 0.910). However, the live birth rate was significantly higher in the isolated VA group (71.9%, 23/32) compared to the non-isolated VA group (38.9%, 7/18) (OR 4.016, 95% CI 1.184-13.622, <i>p</i> = 0.022). Among the 30 live birth cases, two underwent spinal surgery and another two were identified with additional abnormalities. Following appropriate interventions, no apparent abnormalities were observed in the growth and development of 30 live birth cases. Invasive prenatal diagnosis is recommended for all fetuses diagnosed with VA, regardless of whether associated anomalies are present. WES can enhance the diagnostic yield for fetuses with negative CMA results. Fetuses with isolated VA can have favorable pregnancy outcomes when genetic testing results are negative. However, long-term follow-up remains necessary for the assessment of the prognosis of these fetuses.