cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.23787312.v1
title: Risk of adverse pregnancy outcome in isolated single umbilical artery diagnosed at the mid-trimester anomaly scan: a large Danish retrospective cohort study

description: To examine the association of isolated single umbilical artery (iSUA) confirmed at the mid-trimester anomaly scan and adverse pregnancy outcome and congenital malformations with up to 10 years postnatal follow up. This retrospective cohort study included 116,501 singleton pregnancies consecutively enrolled in first trimester screening for aneuploidies and mid-trimester anomaly scan at three University Hospitals in the Capital Region of Copenhagen, Denmark. Data from the Danish Fetal Medicine Database (2008–2017) were verified by manually scrutinizing pre- and postnatal records. The main outcomes of interest were intrauterine fetal demise (IUFD), small for gestational age (SGA), preterm delivery, cesarean section and unrecognized pre- and postnatal congenital malformations. In total, 775 pregnancies with iSUA were identified. Isolated SUA were associated with a significantly increased risk of IUFD (OR 4.16, 95% CI 2.06–8.44), SGA &lt; 3<sup>rd</sup> centile (aOR 2.41, 95% 1.85–3.14) and SGA &lt; 10<sup>th</sup> centile (aOR 1.84, 95% CI 1.53–2.21), but not with preterm delivery or cesarean section. The laterality of the missing artery was not associated with SGA. In total, 4.3% of pregnancies with iSUA had unrecognized congenital malformations. 1.5% with iSUA had congenital cardiovascular malformations, which were considered minor. Isolated SUA is associated with IUFD and SGA, supporting surveillance during third trimester. If, during the mid-trimester scan, the sonographer achieves thorough, extended cardiac views and finds no additional malformation other than SUA, fetal echocardiography seems not to be needed.
DOI: 10.6084/m9.figshare.24145270
title: Impact of increased paternal age on neonatal outcomes in very-low-birth-weight infants

description: Despite the trend of increasing paternal age, its impact on neonatal outcomes, particularly in preterm infants, has not been thoroughly investigated. We aimed to evaluate the perinatal characteristics and neonatal outcomes associated with paternal age. Electronic medical records of very low-birthweight infants admitted to our unit from July 2013 to March 2022 were reviewed. Infants grouped according to paternal age (&lt;35 years, 35–39 years, and ≥40 years) were analyzed for differences in perinatal findings and neonatal outcomes. A total of 637 infants were included (194, 294, and 149 in the &lt;35, 35–39, and ≥40 years groups, respectively). The increase in paternal age paralleled the increase in maternal age. The Z-score of head circumference at birth was significantly different between the groups, showing the lowest median value in the ≥40 years group. Small-for-gestational age (Odds ratio 71.074, <i>p</i> &lt; .001, 95% confidence interval 19.337 − 261.236) and male sex (Odds ratio 3.309, <i>p</i> &lt; .034, 95% confidence interval 1.089 − 8.425), but not paternal or maternal age groups were significant factors associated with head circumference Z-scores less than −2 standard deviation based on the multivariable logistic regression analysis. Infants affected by chromosomal or genetic anomaly were more frequently identified (3.4 vs 0.0 vs 0.5%) in the ≥40 years group than in the other two groups. When infants with anomalies or critical illnesses were excluded, overall neonatal outcomes did not statistically differ according to paternal age. Although increased paternal age ≥40 years may be associated with relatively smaller head circumferences, the impact on fetal head growth does not imply a definite risk for microcephaly. Nonetheless, based on the possible negative impact on chromosomal/genetic anomaly, increased paternal age warrants attention, even though neonatal outcomes concerning prematurity were not significantly affected. A large-scale longitudinal study is needed to further elucidate the impact of advanced paternal age in preterm infants and provide guidelines for appropriate antenatal counseling and surveillance.
DOI: 10.6084/m9.figshare.24145270.v1
title: Impact of increased paternal age on neonatal outcomes in very-low-birth-weight infants

description: Despite the trend of increasing paternal age, its impact on neonatal outcomes, particularly in preterm infants, has not been thoroughly investigated. We aimed to evaluate the perinatal characteristics and neonatal outcomes associated with paternal age. Electronic medical records of very low-birthweight infants admitted to our unit from July 2013 to March 2022 were reviewed. Infants grouped according to paternal age (&lt;35 years, 35–39 years, and ≥40 years) were analyzed for differences in perinatal findings and neonatal outcomes. A total of 637 infants were included (194, 294, and 149 in the &lt;35, 35–39, and ≥40 years groups, respectively). The increase in paternal age paralleled the increase in maternal age. The Z-score of head circumference at birth was significantly different between the groups, showing the lowest median value in the ≥40 years group. Small-for-gestational age (Odds ratio 71.074, <i>p</i> &lt; .001, 95% confidence interval 19.337 − 261.236) and male sex (Odds ratio 3.309, <i>p</i> &lt; .034, 95% confidence interval 1.089 − 8.425), but not paternal or maternal age groups were significant factors associated with head circumference Z-scores less than −2 standard deviation based on the multivariable logistic regression analysis. Infants affected by chromosomal or genetic anomaly were more frequently identified (3.4 vs 0.0 vs 0.5%) in the ≥40 years group than in the other two groups. When infants with anomalies or critical illnesses were excluded, overall neonatal outcomes did not statistically differ according to paternal age. Although increased paternal age ≥40 years may be associated with relatively smaller head circumferences, the impact on fetal head growth does not imply a definite risk for microcephaly. Nonetheless, based on the possible negative impact on chromosomal/genetic anomaly, increased paternal age warrants attention, even though neonatal outcomes concerning prematurity were not significantly affected. A large-scale longitudinal study is needed to further elucidate the impact of advanced paternal age in preterm infants and provide guidelines for appropriate antenatal counseling and surveillance.
DOI: 10.6084/m9.figshare.24549785
title: Mesenchymal stem cell secretome ameliorates over-expression of soluble fms-like tyrosine kinase-1 (sFlt-1) and fetal growth restriction (FGR) in animal SLE model

description: In the near future, stem cell research may lead to several major therapeutic innovations in medical practice. Secretome, a “by-product” of stem cell line cultures, has many advantages. Its easiness of storage, usage, and fast direct effect are some of those to consider. Fetal growth restriction (FGR) remains one of the significant challenges in maternal-fetal and neonatal medicine. Placentation failure is one of the most profound causal and is often related to increasing sFlt-1 in early pregnancy. This study aimed to investigate hUC-MSC secretome in ameliorating sFlt-1 and how to improve outcomes in preventing FGR in an animal model. Pristane-induced systemic lupus erythematosus (SLE) in a mouse model was used to represent placentation failure and its consequences. Twenty-one mice were randomized into three groups: (I) normal pregnancy, (II) SLE, and (III) SLE with secretome treatment. Pristane was administered in all Groups four weeks prior mating period. Secretome was derived from human umbilical cord mesenchymal stem cells (hUC-MSC) conditioned medium on the 3rd and 4th passage, around day-21 until day-28 from the start of culturing process. Mesenchymal stem cell was characterized using flow cytometry for CD105+, CD90+, and CD73+ surface antigen markers. Immunohistochemistry anlysis by using Remmele’s Immunoreactive Score (IRS) was used to quantify the placental sFlt-1 expression in each group. Birth weight and length were analyzed as the secondary outcome. The number of fetuses obtained was also calculated for pregnancy loss comparison between Groups. The administration of secretome of hUC-MSC was found to lower the expression of the placental sFlt-1 significantly in the pristane SLE animal model (10.30 ± 1.40 vs. 4.98 ± 2.57; <i>p</i> &lt; 0.001) to a level seen in normal mouse pregnancies in Group I (3.88 ± 0.49; <i>p</i> = 0.159). Secretome also had a significant effect on preventing fetal growth restriction in the pristane SLE mouse model (birth weight: 354.29 <b>±</b> 80.76 mg vs. 550 <b>±</b> 64.03 mg; <i>p</i> &lt; 0.001 and birth length: 14.43 <b>±</b> 1.27 mm vs. 19.00 <b>±</b> 1.41 mm), comparable to the birth weight and length of the normal pregnancy in Group I (540.29 <b>±</b> 75.47 mg and 18.14 <b>±</b> 1.34 mm, <i>p</i> = 0.808 and = 0.719). Secretome administration also showed a potential action to prevent high number of pregnancy loss as the number of fetuses obtained could be similar to those of mice in the normal pregnant Group (7.71 ± 1.11 vs. 7.86 ± 1.06; <i>p</i> = 0.794). Administration of secretome lowers sFlt-1 expression in placenta, improves fetal growth, and prevents pregnancy loss in a mouse SLE model.
DOI: 10.6084/m9.figshare.24549785.v1
title: Mesenchymal stem cell secretome ameliorates over-expression of soluble fms-like tyrosine kinase-1 (sFlt-1) and fetal growth restriction (FGR) in animal SLE model

description: In the near future, stem cell research may lead to several major therapeutic innovations in medical practice. Secretome, a “by-product” of stem cell line cultures, has many advantages. Its easiness of storage, usage, and fast direct effect are some of those to consider. Fetal growth restriction (FGR) remains one of the significant challenges in maternal-fetal and neonatal medicine. Placentation failure is one of the most profound causal and is often related to increasing sFlt-1 in early pregnancy. This study aimed to investigate hUC-MSC secretome in ameliorating sFlt-1 and how to improve outcomes in preventing FGR in an animal model. Pristane-induced systemic lupus erythematosus (SLE) in a mouse model was used to represent placentation failure and its consequences. Twenty-one mice were randomized into three groups: (I) normal pregnancy, (II) SLE, and (III) SLE with secretome treatment. Pristane was administered in all Groups four weeks prior mating period. Secretome was derived from human umbilical cord mesenchymal stem cells (hUC-MSC) conditioned medium on the 3rd and 4th passage, around day-21 until day-28 from the start of culturing process. Mesenchymal stem cell was characterized using flow cytometry for CD105+, CD90+, and CD73+ surface antigen markers. Immunohistochemistry anlysis by using Remmele’s Immunoreactive Score (IRS) was used to quantify the placental sFlt-1 expression in each group. Birth weight and length were analyzed as the secondary outcome. The number of fetuses obtained was also calculated for pregnancy loss comparison between Groups. The administration of secretome of hUC-MSC was found to lower the expression of the placental sFlt-1 significantly in the pristane SLE animal model (10.30 ± 1.40 vs. 4.98 ± 2.57; <i>p</i> &lt; 0.001) to a level seen in normal mouse pregnancies in Group I (3.88 ± 0.49; <i>p</i> = 0.159). Secretome also had a significant effect on preventing fetal growth restriction in the pristane SLE mouse model (birth weight: 354.29 <b>±</b> 80.76 mg vs. 550 <b>±</b> 64.03 mg; <i>p</i> &lt; 0.001 and birth length: 14.43 <b>±</b> 1.27 mm vs. 19.00 <b>±</b> 1.41 mm), comparable to the birth weight and length of the normal pregnancy in Group I (540.29 <b>±</b> 75.47 mg and 18.14 <b>±</b> 1.34 mm, <i>p</i> = 0.808 and = 0.719). Secretome administration also showed a potential action to prevent high number of pregnancy loss as the number of fetuses obtained could be similar to those of mice in the normal pregnant Group (7.71 ± 1.11 vs. 7.86 ± 1.06; <i>p</i> = 0.794). Administration of secretome lowers sFlt-1 expression in placenta, improves fetal growth, and prevents pregnancy loss in a mouse SLE model.
DOI: 10.6084/m9.figshare.23897036
title: Chest CT scan predictors of intensive care unit admission in hospitalized pregnant women with COVID-19: a case–control study

description: To investigate the role of chest computed tomography (CT) scan in the prediction of admission of pregnant women with COVID-19 into intensive care unit (ICU). This was a single-center retrospective case–control study. We included pregnant women diagnosed with COVID-19 by reverse transcriptase polymerase chain reaction between February 2020 and July 2021, requiring hospital admission due to symptoms, who also had a CT chest scan at presentation. Patients admitted to the ICU (case group) were compared with patients who did not require ICU admission (control group). The CT scans were reported by an experienced radiologist, blinded to the patient’s course and outcome, aided by an artificial intelligence software. Total CT scan score, chest CT severity score (CT-SS), total lung volume (TLV), infected lung volume (ILV), and infected-to-total lung volume ratio (ILV/TLV) were calculated. Receiver operating characteristic curves were constructed to test the sensitivity and specificity of each parameter. 8/28 patients (28.6%) required ICU admission. These also had lower TLV, higher ILV, and ILV/TLV. The area under the curve (AUC) for these three parameters was 0.789, 0.775, and 0.763, respectively. TLV, ILV, and ILV/TLV had good sensitivity (62.5%, 87.5%, and 87.5%, respectively) and specificity (84.2%, 70%, and 73.7%, respectively) for predicting ICU admission at the following selected thresholds: 2255 mL, 319 mL, and 14%, respectively. The performance of CT-SS, CT scan score, and ILV/TLV in predicting ICU admission was comparable. TLV, ILV, and ILV/TLV as measured by an artificial intelligence software on chest CT, may predict ICU admission in hospitalized pregnant women, symptomatic for COVID-19.
DOI: 10.6084/m9.figshare.23897036.v1
title: Chest CT scan predictors of intensive care unit admission in hospitalized pregnant women with COVID-19: a case–control study

description: To investigate the role of chest computed tomography (CT) scan in the prediction of admission of pregnant women with COVID-19 into intensive care unit (ICU). This was a single-center retrospective case–control study. We included pregnant women diagnosed with COVID-19 by reverse transcriptase polymerase chain reaction between February 2020 and July 2021, requiring hospital admission due to symptoms, who also had a CT chest scan at presentation. Patients admitted to the ICU (case group) were compared with patients who did not require ICU admission (control group). The CT scans were reported by an experienced radiologist, blinded to the patient’s course and outcome, aided by an artificial intelligence software. Total CT scan score, chest CT severity score (CT-SS), total lung volume (TLV), infected lung volume (ILV), and infected-to-total lung volume ratio (ILV/TLV) were calculated. Receiver operating characteristic curves were constructed to test the sensitivity and specificity of each parameter. 8/28 patients (28.6%) required ICU admission. These also had lower TLV, higher ILV, and ILV/TLV. The area under the curve (AUC) for these three parameters was 0.789, 0.775, and 0.763, respectively. TLV, ILV, and ILV/TLV had good sensitivity (62.5%, 87.5%, and 87.5%, respectively) and specificity (84.2%, 70%, and 73.7%, respectively) for predicting ICU admission at the following selected thresholds: 2255 mL, 319 mL, and 14%, respectively. The performance of CT-SS, CT scan score, and ILV/TLV in predicting ICU admission was comparable. TLV, ILV, and ILV/TLV as measured by an artificial intelligence software on chest CT, may predict ICU admission in hospitalized pregnant women, symptomatic for COVID-19.
DOI: 10.6084/m9.figshare.23633096
title: Estimated fetal weight standards of the INTERGROWTH-21<sup>st</sup> project for the prediction of adverse outcomes: a systematic review with meta-analysis

description: To systematically review and assess the risk of bias in the literature evaluating the performance of INTERGROWTH-21<sup>st</sup> estimated fetal weight (EFW) standards to predict maternal, fetal and neonatal adverse outcomes. Searches were performed in seven electronic databases (Scopus, Web of Science, Medline, Embase, Lilacs, Scielo and Google Scholar) using citation tools and keywords (intergrowth AND (standard OR reference OR formula OR model OR curve); all from 2014 to the last search on April 16<sup>th</sup>, 2021). We included full-text articles investigating the ability of INTERGROWTH-21<sup>st</sup> EFW standards to predict maternal, fetal or neonatal adverse outcomes in women with a singleton pregnancy who gave birth to infants with no congenital abnormalities. The study was registered on PROSPERO under the number CRD42020115462. Risk of bias was assessed with a customized instrument based on the CHARMS checklist and composed of 9 domains. Meta-analysis was performed using relative risk (RR [95%CI]) and summary ROC curves on outcomes reported by two or more methodologically homogeneous studies. Sixteen studies evaluating fifteen different outcomes were selected. The risk of bias was high (&gt;50% of studies with high risk) for two domains: blindness of assessment (81.3%) and calibration assessment (93.8%). Considering all the outcomes investigated, for 95% of the results, the specificity was above 73.0%, but the sensitivity was below 64.1%. Pooled results demonstrated a higher RR of neonatal small for gestational age (6.71 [5.51–8.17]), Apgar &lt;7 at 5 min (2.17 [1.48–3.18]), and neonatal intensive care unit admission (2.22 [1.76–2.79]) for fetuses classified &lt;10<sup>th</sup> percentile when compared to those classified above this limit. The limitation of the study is the absence of heterogeneity exploration or publication bias investigation, whereas no outcomes were evaluated by more than five studies. The IG-21 EFW standard has low sensitivity and high specificity for adverse events of pregnancy. Classification &lt;10th percentile identifies a high-risk group for developing maternal, fetal and neonatal adverse outcomes, especially neonatal small for gestational age, Apgar &lt;7 at 5 min, and neonatal intensive care unit admission. Future studies should include blind assessment of outcomes, perform calibration analysis with continuous data, and evaluate alternative cutoff points.
DOI: 10.6084/m9.figshare.23633096.v1
title: Estimated fetal weight standards of the INTERGROWTH-21<sup>st</sup> project for the prediction of adverse outcomes: a systematic review with meta-analysis

description: To systematically review and assess the risk of bias in the literature evaluating the performance of INTERGROWTH-21<sup>st</sup> estimated fetal weight (EFW) standards to predict maternal, fetal and neonatal adverse outcomes. Searches were performed in seven electronic databases (Scopus, Web of Science, Medline, Embase, Lilacs, Scielo and Google Scholar) using citation tools and keywords (intergrowth AND (standard OR reference OR formula OR model OR curve); all from 2014 to the last search on April 16<sup>th</sup>, 2021). We included full-text articles investigating the ability of INTERGROWTH-21<sup>st</sup> EFW standards to predict maternal, fetal or neonatal adverse outcomes in women with a singleton pregnancy who gave birth to infants with no congenital abnormalities. The study was registered on PROSPERO under the number CRD42020115462. Risk of bias was assessed with a customized instrument based on the CHARMS checklist and composed of 9 domains. Meta-analysis was performed using relative risk (RR [95%CI]) and summary ROC curves on outcomes reported by two or more methodologically homogeneous studies. Sixteen studies evaluating fifteen different outcomes were selected. The risk of bias was high (&gt;50% of studies with high risk) for two domains: blindness of assessment (81.3%) and calibration assessment (93.8%). Considering all the outcomes investigated, for 95% of the results, the specificity was above 73.0%, but the sensitivity was below 64.1%. Pooled results demonstrated a higher RR of neonatal small for gestational age (6.71 [5.51–8.17]), Apgar &lt;7 at 5 min (2.17 [1.48–3.18]), and neonatal intensive care unit admission (2.22 [1.76–2.79]) for fetuses classified &lt;10<sup>th</sup> percentile when compared to those classified above this limit. The limitation of the study is the absence of heterogeneity exploration or publication bias investigation, whereas no outcomes were evaluated by more than five studies. The IG-21 EFW standard has low sensitivity and high specificity for adverse events of pregnancy. Classification &lt;10th percentile identifies a high-risk group for developing maternal, fetal and neonatal adverse outcomes, especially neonatal small for gestational age, Apgar &lt;7 at 5 min, and neonatal intensive care unit admission. Future studies should include blind assessment of outcomes, perform calibration analysis with continuous data, and evaluate alternative cutoff points.
DOI: 10.6084/m9.figshare.23664744
title: A high Z-score might increase the positive predictive value of cell-free noninvasive prenatal testing for singleton-pregnant women

description: To explore the positive predictive value (PPV) in noninvasive prenatal testing (NIPT)-positive cases and analyze the effect of the Z-score intervals on PPV performance. In this retrospective study, 26,667 pregnant women underwent NIPT from November 2014 to August 2022, of which 169 were NIPT-positive cases. NIPT-positive cases were divided into three groups according to the Z-score: 3 ≤ <i>Z</i> &lt; 6, 6 ≤ <i>Z</i> &lt; 10, and <i>Z</i> ≥ 10. The PPVs of NIPT were 91.26% (94/103) for trisomy (T) 21, 80.65% (25/31) for T18, and 36.84% (7/19) for T13. The PPVs for the 3 ≤ <i>Z</i> &lt; 6, 6 ≤ <i>Z</i> &lt; 10, and <i>Z</i> ≥ 10 groups were 50%, 84.62%, and 87.95%, respectively. A higher PPV was found in the NIPT results when the Z-score was larger, with significant differences. The PPVs for T21/T18/T13 were 71.43%/42.86%/25% for 3 ≤ <i>Z</i> &lt; 6, 90.32%/85.71%/57.14% for 6 ≤ <i>Z</i> &lt; 10, and 93.85%/100%/25% for <i>Z</i> ≥ 10. For T21, T18, and T13, the correlations between the Z-score and fetal fraction concentration in true positives were <i>r</i> = 0.85, <i>r</i> = 0.59, and <i>r</i> = 0.71 (all <i>p &lt; .</i>001), respectively. Z-score is associated with the PPV performance of NIPT in fetal T13, T18, and T21. The possibility of false positives caused by placental chimerism should be considered when determining whether high Z-values lead to high PPVs.