Exploring potential mid-trimester maternal serum biomarkers for fetal congenital heart disease: a retrospective case-control study
Objective To assess potential associations between maternal serum alpha-fetoprotein (AFP) and free human chorionic gonadotropin beta subunit (free β-hCG) levels during the mid-trimester and the occurrence of fetal congenital heart disease (CHD).Methods A retrospective case-control study was carried...
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Taylor & Francis Group
2025-12-01
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| Series: | The Journal of Maternal-Fetal & Neonatal Medicine |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14767058.2025.2541025 |
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| author | Yuxia Jin Suping Li Jing Li Xiaojun Chai |
| author_facet | Yuxia Jin Suping Li Jing Li Xiaojun Chai |
| author_sort | Yuxia Jin |
| collection | DOAJ |
| description | Objective To assess potential associations between maternal serum alpha-fetoprotein (AFP) and free human chorionic gonadotropin beta subunit (free β-hCG) levels during the mid-trimester and the occurrence of fetal congenital heart disease (CHD).Methods A retrospective case-control study was carried out, analyzing data from 303 pregnant women. Of these, 101 cases were diagnosed with fetal CHD (CHD group), and 202 cases were diagnosed with healthy fetuses (control group). The multiple of median (MoM) of AFP and free β-hCG were measured using time-resolved fluorescence immunoassay during the second trimester, respectively. Binary logistic regression was applied to compare the CHD and control groups, analyze relevant risk factors, and calculate the odds ratio (OR) for each variable. Risk models incorporating AFP, free β-hCG, and other factors, either individually or in combination, were formulated. Receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses were performed to evaluate the diagnostic performance of these models.Results The AFP MoM, hCG MoM, and maternal age in the CHD group were significantly higher than those in the control group. Binary logistic regression analysis revealed that fetal CHD was associated with AFP, β-hCG, and maternal age, with OR values of 4.057 (95% confidence interval (CI): 2.221–7.409, p < .001), 1.978 (95% CI: 1.412–2.772, p < .001), and 1.223 (95% CI: 1.136–1.317, p < .001), respectively. The combining AFP MoM, free β-hCG MoM, maternal age, and gestational days demonstrated a higher diagnostic value compared to single biomarkers, yielding an AUC of 0.794, with a sensitivity of 0.782 and specificity of 0.683 for detecting fetal CHD.Conclusions This study presents an evidence from a domestic Chinese cohort demonstrating that elevated maternal serum AFP and free β-hCG levels during mid-trimester pregnancy are significantly associated with fetal CHD. These biomarkers show promise as potential candidates for noninvasive CHD screening. Further investigation and validation are necessary to confirm these findings. |
| format | Article |
| id | doaj-art-714df751a57944aebd2a3a5a3af7b6e8 |
| institution | DOAJ |
| issn | 1476-7058 1476-4954 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | The Journal of Maternal-Fetal & Neonatal Medicine |
| spelling | doaj-art-714df751a57944aebd2a3a5a3af7b6e82025-08-20T03:22:19ZengTaylor & Francis GroupThe Journal of Maternal-Fetal & Neonatal Medicine1476-70581476-49542025-12-0138110.1080/14767058.2025.2541025Exploring potential mid-trimester maternal serum biomarkers for fetal congenital heart disease: a retrospective case-control studyYuxia Jin0Suping Li1Jing Li2Xiaojun Chai3Department of Prenatal Diagnostic Center, YiWu Maternity and Children Hospital, Jinhua, ChinaDepartment of Fetal Medicine Center, Jiaxing Maternity and Children Health Care Hospital, Jiaxing, ChinaDepartment of Child Healthcare, Jiaxing Maternity and Children Health Care Hospital, Jiaxing, ChinaDepartment of Fetal Medicine Center, Jiaxing Maternity and Children Health Care Hospital, Jiaxing, ChinaObjective To assess potential associations between maternal serum alpha-fetoprotein (AFP) and free human chorionic gonadotropin beta subunit (free β-hCG) levels during the mid-trimester and the occurrence of fetal congenital heart disease (CHD).Methods A retrospective case-control study was carried out, analyzing data from 303 pregnant women. Of these, 101 cases were diagnosed with fetal CHD (CHD group), and 202 cases were diagnosed with healthy fetuses (control group). The multiple of median (MoM) of AFP and free β-hCG were measured using time-resolved fluorescence immunoassay during the second trimester, respectively. Binary logistic regression was applied to compare the CHD and control groups, analyze relevant risk factors, and calculate the odds ratio (OR) for each variable. Risk models incorporating AFP, free β-hCG, and other factors, either individually or in combination, were formulated. Receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses were performed to evaluate the diagnostic performance of these models.Results The AFP MoM, hCG MoM, and maternal age in the CHD group were significantly higher than those in the control group. Binary logistic regression analysis revealed that fetal CHD was associated with AFP, β-hCG, and maternal age, with OR values of 4.057 (95% confidence interval (CI): 2.221–7.409, p < .001), 1.978 (95% CI: 1.412–2.772, p < .001), and 1.223 (95% CI: 1.136–1.317, p < .001), respectively. The combining AFP MoM, free β-hCG MoM, maternal age, and gestational days demonstrated a higher diagnostic value compared to single biomarkers, yielding an AUC of 0.794, with a sensitivity of 0.782 and specificity of 0.683 for detecting fetal CHD.Conclusions This study presents an evidence from a domestic Chinese cohort demonstrating that elevated maternal serum AFP and free β-hCG levels during mid-trimester pregnancy are significantly associated with fetal CHD. These biomarkers show promise as potential candidates for noninvasive CHD screening. Further investigation and validation are necessary to confirm these findings.https://www.tandfonline.com/doi/10.1080/14767058.2025.2541025Congenital heart diseaseserum biomarkermaternal serum prenatal screeningalpha-fetoproteinhuman chorionic gonadotropin |
| spellingShingle | Yuxia Jin Suping Li Jing Li Xiaojun Chai Exploring potential mid-trimester maternal serum biomarkers for fetal congenital heart disease: a retrospective case-control study The Journal of Maternal-Fetal & Neonatal Medicine Congenital heart disease serum biomarker maternal serum prenatal screening alpha-fetoprotein human chorionic gonadotropin |
| title | Exploring potential mid-trimester maternal serum biomarkers for fetal congenital heart disease: a retrospective case-control study |
| title_full | Exploring potential mid-trimester maternal serum biomarkers for fetal congenital heart disease: a retrospective case-control study |
| title_fullStr | Exploring potential mid-trimester maternal serum biomarkers for fetal congenital heart disease: a retrospective case-control study |
| title_full_unstemmed | Exploring potential mid-trimester maternal serum biomarkers for fetal congenital heart disease: a retrospective case-control study |
| title_short | Exploring potential mid-trimester maternal serum biomarkers for fetal congenital heart disease: a retrospective case-control study |
| title_sort | exploring potential mid trimester maternal serum biomarkers for fetal congenital heart disease a retrospective case control study |
| topic | Congenital heart disease serum biomarker maternal serum prenatal screening alpha-fetoprotein human chorionic gonadotropin |
| url | https://www.tandfonline.com/doi/10.1080/14767058.2025.2541025 |
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