BACKGROUND

Down syndrome or trisomy 21, the most common chromosomal disorder, results from the presence of a third copy of chromosome 21 and manifests as mild to moderate intellectual disability, growth retardation, congenital heart defects, gastrointestinal abnormalities, and characteristic facial features. Several methods have been used to screen for Down syndrome in the prenatal period, such as ultrasound, biomarkers, cell-free DNA testing, and combinations of these tests. A positive result from one or more of these screening tests signals the need for confirmatory karyotyping to clinch the diagnosis. Ultrasound between 11 to 14 weeks of gestation can evaluate nuchal translucency (NT) to screen for Down syndrome. During the second trimester, a triple or quadruple test can also be performed alone or in addition to NT to quantify Down syndrome risk. In limited resource settings however, only the measurement of NT via ultrasound can be performed since biomarker tests are either unavailable or inaccessible. While the diagnostic performance of NT measurement alone has been investigated in several observational studies, there is no consensus on its performance as a sole test to screen for Down syndrome.

To determine the diagnostic performance of NT during prenatal first-trimester ultrasound as a screening test for Down syndrome.

We performed a systematic search on the PubMed, ProQuest, and Cochrane Library databases for recent systematic reviews and meta-analyses that addressed the objective. The existing reviews found were then independently appraised by the two reviewers with the AMSTAR-2 checklist. To update the existing reviews, a systematic search was done in the same databases to identify additional primary diagnostic studies, which were appraised using the QUADAS-2 tool. Random-effects univariate meta-analysis and summary receiving operator curve (HSROC) analysis for the outcomes were performed using Review Manager version 5.4 and R version 4.2.2, respectively. Subgroup analysis was performed by stratifying the baseline risk of mothers for fetal anomaly as low- or high-risk. Highrisk mothers were defined as women with risk factors such as advanced age, positive serum screen, presence of other ultrasound anomalies, and history of previous fetus with anomaly.

We found 22 cohort studies (n=225,846) of women at low-risk for fetal anomaly. The pooled sensitivity was 67.8% (95% CI: 61.4%-73.6%, I2=70.4%) and specificity was 96.3% (95% CI: 95.5%-96.9%, I2=96.7%). For low-risk women, the overall certainty of evidence was low, due to different modes of verification and heterogeneity not completely explained by variability in baseline risk or cut-points. Seven studies (n=9,197) were on high-risk women. The pooled sensitivity was 62.2% (95% CI: 54.1%-69.7%, I2=38.8%) and specificity was 96.5% (95% CI: 93.6%-98.1%, I2=95.5%). For women at high-risk, the evidence was rated as moderate due to differential verification.

Our analysis showed that NT measured through first-trimester ultrasound is specific for Down syndrome but has low sensitivity. Despite this, it is a useful screening test for Down syndrome in low-resource settings where other strategies may not be available or accessible. Furthermore, interpretation of NT results must take into consideration its limited sensitivity as this may lead to missed cases.

BACKGROUND

Down syndrome or trisomy 21, the most common chromosomal disorder, results from the presence of a third copy of chromosome 21 and manifests as mild to moderate intellectual disability, growth retardation, congenital heart defects, gastrointestinal abnormalities, and characteristic facial features. Several methods have been used to screen for Down syndrome in the prenatal period, such as ultrasound, biomarkers, cell-free DNA testing, and combinations of these tests. A positive result from one or more of these screening tests signals the need for confirmatory karyotyping to clinch the diagnosis. Ultrasound between 11 to 14 weeks of gestation can evaluate nuchal translucency (NT) to screen for Down syndrome. During the second trimester, a triple or quadruple test can also be performed alone or in addition to NT to quantify Down syndrome risk. In limited resource settings however, only the measurement of NT via ultrasound can be performed since biomarker tests are either unavailable or inaccessible. While the diagnostic performance of NT measurement alone has been investigated in several observational studies, there is no consensus on its performance as a sole test to screen for Down syndrome.

To determine the diagnostic performance of NT during prenatal first-trimester ultrasound as a screening test for Down syndrome.

We performed a systematic search on the PubMed, ProQuest, and Cochrane Library databases for recent systematic reviews and meta-analyses that addressed the objective. The existing reviews found were then independently appraised by the two reviewers with the AMSTAR-2 checklist. To update the existing reviews, a systematic search was done in the same databases to identify additional primary diagnostic studies, which were appraised using the QUADAS-2 tool. Random-effects univariate meta-analysis and summary receiving operator curve (HSROC) analysis for the outcomes were performed using Review Manager version 5.4 and R version 4.2.2, respectively. Subgroup analysis was performed by stratifying the baseline risk of mothers for fetal anomaly as low- or high-risk. Highrisk mothers were defined as women with risk factors such as advanced age, positive serum screen, presence of other ultrasound anomalies, and history of previous fetus with anomaly.

We found 22 cohort studies (n=225,846) of women at low-risk for fetal anomaly. The pooled sensitivity was 67.8% (95% CI: 61.4%-73.6%, I2=70.4%) and specificity was 96.3% (95% CI: 95.5%-96.9%, I2=96.7%). For low-risk women, the overall certainty of evidence was low, due to different modes of verification and heterogeneity not completely explained by variability in baseline risk or cut-points. Seven studies (n=9,197) were on high-risk women. The pooled sensitivity was 62.2% (95% CI: 54.1%-69.7%, I2=38.8%) and specificity was 96.5% (95% CI: 93.6%-98.1%, I2=95.5%). For women at high-risk, the evidence was rated as moderate due to differential verification.

Our analysis showed that NT measured through first-trimester ultrasound is specific for Down syndrome but has low sensitivity. Despite this, it is a useful screening test for Down syndrome in low-resource settings where other strategies may not be available or accessible. Furthermore, interpretation of NT results must take into consideration its limited sensitivity as this may lead to missed cases.

Human ; Mass Screening ; Mothers ; Nuchal Translucency Measurement ; Prenatal Diagnosis

OBJECTIVES: The diagnostic value of ultrasonographic quantitative indicators of umbilical cord coiling, such as the umbilical coiling index (UCI) and pitch value, in identifying hypercoiling and predicting adverse pregnancy outcomes remains controversial. This study aims to evaluate the predictive value of UCI, pitch value, and the cerebroplacental ratio in pregnancies complicated by umbilical cord hypercoiling. METHODS: Pregnant women with densely coiled umbilical cords identified by routine obstetric ultrasound at Changsha Maternal and Child Health Hospital between November 2022 and November 2024 were enrolled. Complete clinical data, including UCI, pitch value, and cerebroplacental ratio (CPR), were collected. Pregnancy outcome scores were calculated, and newborns were categorized into the normal outcome group (n=177) and adverse outcome group (n=85), with the latter further subdivided into mild (n=51), moderate (n=19), and severe (n=15) subgroups. Differences in baseline data, UCI, pitch value, and incidence of CRP<1 were compared between groups and among subgroups. Correlations between UCI, pitch value, and adverse pregnancy outcomes were analyzed. Receiver operating characteristic (ROC) curve were used to assess the predictive performance of UCI, pitch value, CPR<1, and their combinations. RESULTS: Compared with the normal outcome group, the adverse outcome group had higher age, parity, parity, incidence of CPR<1, and UCI, while gestational age at delivery and pitch values were lower (all P<0.05). The incidence of obesity, gestational diabetes mellitus, and hypertensive disorders of pregnancy did not differ significantly between the 2 groups (all P>0.05). The normal outcome group showed lower UCI and higher pitch values than all 3 adverse outcome subgroups (all P<0.05), while differences among the 3 adverse subgroups were not significant (all P>0.05). UCI was positively correlated with adverse pregnancy outcomes (r_s=0.350, P<0.05), whereas pitch value was negatively correlated (r_s=-0.286, P<0.05). ROC curve analysis showed that the area under the curve (AUC) values for predicting adverse outcomes were 0.837 for UCI, 0.886 for pitch value, and 0.610 for CPR<1, with sensitivities of 77.6%, 82.4%, and 27.1% and specificities of 78.5%, 83.6%, and 94.9%, respectively. The combined UCI+CPR<1 and pitch value+CPR<1 models yielded AUCs of 0.841 and 0.886, with sensitivities of 78.8% and 81.2% and specificities of 78.5% and 84.2%, respectively. No significant differences were found between the AUCs of UCI and pitch value (P>0.05), but both outperformed CPR<1 alone (both P<0.001). The combined models showed no significant improvement over UCI or pitch value alone (both P>0.05), though both were superior to CPR<1 alone (both P<0.001). CONCLUSIONS Most umbilical cord hypercoiling cases had favorable outcomes, with UCI, pitch value, CPR<1 and their combinations demonstrating significant predictive value for adverse pregnancy outcomes.
Humans ; Female ; Pregnancy ; Pregnancy Outcome ; Adult ; Ultrasonography, Prenatal/methods* ; Umbilical Cord/diagnostic imaging* ; Hemodynamics ; Predictive Value of Tests ; Infant, Newborn ; ROC Curve

OBJECTIVES: To construct an intelligent analysis model for classifying fetal orientation during intrapartum ultrasound videos based on multi-feature fusion. METHODS: The proposed model consists of the Input, Backbone Network and Classification Head modules. The Input module carries out data augmentation to improve the sample quality and generalization ability of the model. The Backbone Network was responsible for feature extraction based on Yolov8 combined with CBAM, ECA, PSA attention mechanism and AIFI feature interaction module. The Classification Head consists of a convolutional layer and a softmax function to output the final probability value of each class. The images of the key structures (the eyes, face, head, thalamus, and spine) were annotated with frames by physicians for model training to improve the classification accuracy of the anterior occipital, posterior occipital, and transverse occipital orientations. RESULTS: The experimental results showed that the proposed model had excellent performance in the tire orientation classification task with the classification accuracy reaching 0.984, an area under the PR curve (average accuracy) of 0.993, and area under the ROC curve of 0.984, and a kappa consistency test score of 0.974. The prediction results by the deep learning model were highly consistent with the actual classification results. CONCLUSIONS The multi-feature fusion model proposed in this study can efficiently and accurately classify fetal orientation in intrapartum ultrasound videos.
Humans ; Female ; Ultrasonography, Prenatal/methods* ; Pregnancy ; Fetus/diagnostic imaging* ; Neural Networks, Computer ; Video Recording

Humans ; Pulmonary Atresia/therapy* ; Pregnancy ; Female ; China ; Consensus ; Fetal Heart ; Ultrasonography, Prenatal ; Heart Defects, Congenital/therapy* ; Ventricular Septum ; Cardiac Surgical Procedures/methods*

OBJECTIVE: To investigate the association of isolated thyroid peroxidase antibody (TPOAb) positive in the first trimester with fetal growth. METHODS: A total of 16 446 pregnant women were included in the birth cohort study, whose last menstrual period was between May 2016 and April 2019 and with singleton pregnancy. Maternal serum samples were collected when they firstly came for prenatal care in the first trimester. The pregnant women were consecutively seen and followed in the hospital and the information of pregnant women was extracted from the electronic medical information system. The pregnant women were divided into isolated TPOAb positive group (n=1 654) and euthyroid group (n=14 792). Three fetal ultrasound examinations were scheduled during the routine prenatal visits at the hospital and were performed by trained sonographers. All fetal growth indicators were quantified as gestational age- and gender- adjusted standard deviation score (Z-score) using the generalized additive models for location, scale and shape (GAMLSS). Fetal growth indicators included estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL) and head circumference (HC). Fetal growth restriction (FGR) was defined as AC or EFW Z-score＜3rd centile based on clinical consensus. Generalized estimating equation (GEE) analysis was applied to assess the association of maternal isolated TPOAb positive with fetal growth. The generalized linear model was further used to analyze the association between isolated TPOAb positive and fetal growth indicator at different gestational ages when the fetal growth indicator was significantly associated with isolated TPOAb positive in the GEE mo-del. RESULTS: The median gestational age at three ultrasound measurements was 23.6 (23.3, 24.1), 30.3 (29.7, 30.9), 37.3 (37.0, 37.7) weeks, respectively. The BPD Z-score was higher in isolated TPOAb positive women, compared with the euthyroid pregnant women after adjustment (β=0.057, 95%CI: 0.014-0.100, P=0.009). The generalized linear model showed the BPD Z-score was higher in the isolated TPOAb positive women at the end of 21-25 weeks (β=0.052, 95%CI: 0.001-0.103, P=0.044), 29-32 weeks (β=0.055, 95%CI: 0.004-0.107, P=0.035) and 36-40 weeks (β=0.068, 95%CI: 0.011-0.125, P=0.020), compared with the euthyroid pregnant women. There was no difference in other fetal growth indicators (EFW, AC, FL and HC) and FGR between the isolated TPOAb positive and euthyroid pregnant women. CONCLUSION The BPD Z-score was slightly increased in the isolated TPOAb positive pregnant women in the first trimester, while other fetal growth indicators were not changed. The reproducibility and practical significance of this result need to be confirmed.
Pregnancy ; Female ; Humans ; Pregnancy Trimester, First ; Iodide Peroxidase ; Cohort Studies ; Reproducibility of Results ; Fetal Development ; Fetal Weight ; Fetal Growth Retardation ; Ultrasonography, Prenatal

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the diagnosis of fetuses with anomalies of the central nervous system (CNS) and summarize the outcome of the pregnancies and follow-up. METHODS: A total of 636 fetuses from June 2014 to December 2020 who were referred to the Prenatal Diagnosis Center of Nanjing Drum Tower Hospital due to abnormal CNS prompted by ultrasound were selected as the research subjects. Based on the ultrasound findings, the fetuses were divided into ventricular dilatation group (n = 441), choroid plexus cyst group (n = 41), enlarged posterior fossa group (n = 42), holoprosencephaly group (n = 15), corpus callosum hypoplasia group (n = 22), and other anomaly group (n = 75). Meanwhile, they were also divided into isolated (n = 504) and non-isolated (n = 132) groups based on the presence of additional abnormalities. Prenatal samples (amniotic fluid/chorionic villi/umbilical cord blood) or abortus tissue were collected for the extraction of genomic DNA and CMA assay. Outcome of the pregnancies and postnatal follow-up were summarized and subjected to statistical analysis. RESULTS: In total 636 fetuses with CNS anomalies (including 89 abortus tissues) were included, and 547 cases were followed up. The overall detection rate of CMA was 11.48% (73/636). The detection rates for the holoprosencephaly group, ACC group, choroid plexus cyst group, enlarged posterior fossa group, ventricular dilatation group and other anomaly group were 80% (12/15), 31.82% (7/22), 19.51% (8/41), 14.29% (6/42), 7.48% (33/441) and 9.33% (7/75), respectively. Compared with the isolated CNS anomaly group, the detection rate for the non-isolated CNS anomaly group was significantly higher (6.35% vs. 31.06%) (32/504 vs. 41/132) (χ² = 62.867, P < 0.001). Follow up showed that, for 52 fetuses with abnormal CMA results, 51 couples have opted induced labor, whilst 1 was delivered at full term with normal growth and development. Of the 434 fetuses with normal CMA results, 377 were delivered at full term (6 had developmental delay), and 57 couples had opted induced labor. The rate of adverse pregnancy outcome for non-isolated CNS abnormal fetuses was significantly higher than that of isolated CNS abnormal fetuses (26.56% vs. 10.54%) (17/64 vs. 39/370) (χ² = 12.463, P < 0.001). CONCLUSION Fetuses with CNS anomaly should be tested with CMA to determine the genetic cause. Most fetuses with negative CMA result have a good prognosis, but there is still a possibility for a abnormal neurological phenotype. Fetuses with CNS abnormalities in conjunct with other structural abnormalities are at increased risk for adverse pregnancy outcomes.
Female ; Pregnancy ; Humans ; Holoprosencephaly ; Prenatal Diagnosis/methods* ; Central Nervous System ; Fetus/abnormalities* ; Nervous System Malformations/genetics* ; Microarray Analysis ; Central Nervous System Diseases ; Cysts ; Chromosome Aberrations ; Ultrasonography, Prenatal/methods*

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) and trio-whole exome sequencing (trio-WES) for fetuses with increased nuchal translucency (NT) thickness. METHODS: Sixty two pregnant women who had visited Urumqi Maternal and Child Care Health Hospital between June 2018 and June 2020 for NT ≥ 3.0 mm at 11 ~ 13⁺⁶ gestational weeks were selected as study subjects. Relevant clinical data were collected. The patients were divided into 3.0 ~ ＜3.5 mm (n = 33) and ≥3.5 mm groups (n = 29). Chromosome karyotyping analysis and chromosomal microarray analysis were carried out. And trio-WES analysis was performed on 15 samples with NT thickening but negative CMA results. The distribution and incidence of chromosomal abnormalities in the two groups were compared by using chi-square test. RESULTS: The median age of the pregnant women was 29 years old (22 ~ 41 years old), the median thickness of NT was 3.4 mm (3.0 ~ 9.1 mm), and the median gestational age at the detection was 13⁺⁴ weeks (11⁺⁵ ~ 13⁺⁶ weeks). Chromosome karyotyping analysis has detected 12 cases of aneuploidies and 1 case of derivative chromosome. The detection rate was 20.97% (13/62). CMA has detected 12 cases of aneuploidies, 1 case of pathogenic CNV and 5 cases of variant of uncertain significance (VUS), with a detection rate of 29.03% (18/62). The aneuploidy rate for the NT ≥ 3.5 mm group was higher than that for the 3.0 ≤ NT < 3.5 mm group [3.03% (1/33) vs. 41.38% (12/29), χ² = 13.698, P < 0.001]. There was no statistically significant difference between the two groups in the detection rate of fetal pathogenic CNV and VUS (χ² = 0.028, P > 0.05). Trio-WES analysis of 15 samples with negative CMA result and no structural abnormality has identified 6 heterozygous variants, including SOS1: c.3542C>T (p.A1181V) and c.3817C>G (p.L1273V), COL2A1: c.436C>T (p.P146S) and c.3700G>A (p.D1234N), LZTR1: c.1496T>C (p.V499A), and BRAF: c.64G>A (p.D22N), respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were rated as VUS. CONCLUSION NT thickening can indicate chromosome abnormality, and CMA and trio-WES may be used for the prenatal diagnosis.
Pregnancy ; Humans ; Female ; Adult ; Infant ; Nuchal Translucency Measurement/methods* ; Prenatal Diagnosis/methods* ; Chromosome Aberrations ; Aneuploidy ; Fetus/diagnostic imaging* ; Ultrasonography, Prenatal ; DNA Copy Number Variations ; Transcription Factors

OBJECTIVE: To explore the genetic etiology of 5 cases of monochorionic-diamniotic (MCDA) with genetic discordance. METHODS: 148 cases of MCDA twins who were diagnosed by amniocentesis at the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region from January 2016 to June 2020 were selected as the study subjects. Relevant clinical data of the pregnant women were collected, and amniotic fluid samples of the twins were collected separately. Chromosomal karyotyping analysis and single nucleotide polymorphism array (SNP array) assay were carried out. RESULTS: The results of chromosomal karyotyping analysis showed that 5 of the MCDA twins had inconsistent chromosome karyotypes, with an incidence of 3.4% (5/148). SNP array assay showed that 3 fetuses were mosaics. CONCLUSION Genetic discordance occurs among MCDA twins, and prenatal counseling for such cases should be given by doctors with experience in medical genetics and fetal medicine, and personalized clinical management should be recommended.
Child ; Pregnancy ; Female ; Humans ; China ; Twins/genetics* ; Amniocentesis ; Karyotyping ; Fetus ; Twins, Monozygotic/genetics* ; Ultrasonography, Prenatal ; Retrospective Studies