1.Yinzhihuang Oral Liquid Alleviates Intrahepatic Cholestasis of Pregnancy: Integrated Bioinformatics and Experimental Mechanistic Insight
Ting LIU ; Xinrun ZHUANG ; Wei GU ; Wei LIU ; Jin ZHANG ; Weijian ZENG
Maternal-Fetal Medicine 2025;07(3):131-144
Objective::To systematically study the mechanisms by which Yinzhihuang (YZH), a traditional Chinese medicine, ameliorates intrahepatic cholestasis of pregnancy (ICP), a liver disorder associated with significant maternal and fetal complications.Methods::This experimental study was conducted from January 2024 to August 2024, utilizing data from public databases (Traditional Chinese Medicine Systems Pharmacology, GeneCards, Online Mendelian Inheritance in Man, DisGeNET, Proteome Xchange) alongside in vitro cell culture experiments. Network pharmacology identified active components of YZH and potential therapeutic targets for ICP. Ultra-performance liquid chromatography–mass spectrometry characterized YZH oral liquid, and its effective doses were evaluated in taurocholic acid (TCA)-induced HTR-8/SVneo cells, an in vitro ICP model. ICP-related targets were gathered from multiple databases, and hub genes were selected through bioinformatics and previously identified differentially expressed proteins. Functional annotation and pathway enrichment analyses were conducted, with validation in TCA-induced cells treated with various YZH concentrations (0.1%–5.0%) compared to controls. Molecular docking confirmed predicted interactions.Results::Using network pharmacology, 104 active compounds and 241 potential targets of YZH were identified. Integration of multiple databases yielded 1897 YZH-related therapeutic targets and 3783 ICP-associated genes. Proteomic analysis identified 227 differentially expressed proteins, from which 10 hub genes were selected; among these, APOA2, COL1A1, and ADIPOQ were significantly upregulated in ICP samples. UPLC-ESI-MS/MS detected 2022 compounds, predominantly flavonoids (25.07%, 507/2022) and phenolic acids (14.44%, 292/2022). Molecular docking demonstrated strong binding affinities between several active compounds and the hub genes. In TCA-induced HTR-8/SVneo cells, 0.5% YZH treatment significantly enhanced cell viability and modulated hub gene expression, supporting a potential multi-target mechanism.Conclusion::This study systematically explored the active components and potential targets of YZH in ICP through network pharmacology, proteomics, and in vitro validation. The findings suggest that YZH may act via the PPAR signaling pathway by modulating genes such as PPARA, PPARG, ADIPOQ, and APOA2.
2.Validation of Risk Scoring Systems in Predicting Adverse Cardiac Outcomes in Pregnant Women With Valvular Heart Disease
Malini SUKAYOGULA ; Tarakeswari SURAPANENI ; Anish KEEPANASSERIL
Maternal-Fetal Medicine 2025;07(3):145-150
Objective::To validate and compare the performance of four risk stratification tools—the DEVI (Adverse Cardiac Events in Valvular Rheumatic Heart Disease in Pregnancy) score, Zwangerschap bij Aangeboren Hartafwijking (ZAHARA) score, Cardiac Disease in Pregnancy II (CARPREG II), and modified WHO (mWHO) classification—in predicting adverse cardiac events during pregnancy in women with valvular heart disease (VHD).Methods::This retrospective cohort study was conducted at Fernandez Hospital, a tertiary care referral center in Hyderabad, India, utilizing clinical data from pregnancies managed between January 2011 and December 2023. The primary outcome was the development of composite adverse cardiac events. Discriminative ability was assessed using the area under the receiver operating characteristic curve (AUC), calibration was evaluated via calibration plots, and clinical utility was determined by decision curve analysis (DCA). Categorical variables were reported as frequencies and percentages and continuous variables were presented as means with standard deviations or medians with interquartile ranges. Individual risk assessment was conducted using both the CARPREG II and DEVI risk stratification models, while the ZAHARA score was calculated by aggregating weighted parameters according to established scoring criteria.Results::The study enrolled 176 women and analyzed 205 pregnancies with adverse cardiac events in 19 pregnancies (9.3%). The DEVI score demonstrated superior discrimination (AUC = 0.846, 95% CI: 0.765-0.927, P < 0.001), followed by mWHO (AUC = 0.826, 95% CI: 0.736–0.917, P < 0.001), CARPREG II (AUC = 0.762, 95% CI: 0.652–0.872, P < 0.001), and ZAHARA (AUC = 0.716, 95% CI: 0.628–0.803, P < 0.001). Calibration plots revealed an overestimation of risk at higher probabilities for DEVI and CARPREG II. DCA indicated net clinical benefit for both tools at 10–30% threshold probabilities. Conclusion::The DEVI score showed the highest discriminative performance, though its calibration and clinical utility were comparable to CARPREG II. These findings support its use for risk stratification in pregnant women with VHD, particularly in resource-limited settings where rheumatic VHD predominates.
3.Genetic Analysis of Prenatal Renal Abnormalities in 17q12 Microdeletion Syndrome
Yongmei SHEN ; Yaqi LI ; Xiaomin ZHAO ; Lei ZHANG ; Liying YAO ; Jiasong CAO ; Qimei LIN ; Hefei WANG ; Maolin NIE ; Rongxin WEI ; Ying CHANG
Maternal-Fetal Medicine 2025;07(3):151-156
Objective::To analyze fetal renal abnormality genetic features and the prenatal characteristics of the 17q12 microdeletion syndrome.Methods::This prospective cohort study examined prenatal ultrasound findings of renal abnormalities in pregnant women who underwent single nucleotide polymorphism (SNP) array or copy number variation sequencing (CNV-seq) testing on amniotic fluid or fetal tissue at Tianjin Central Obstetrics and Gynecology Hospital between January 2016 and August 2022. The study cohort comprised women with advanced maternal age, fetal ultrasound anomalies, high-risk non-invasive prenatal testing results, or suspected 17q12 microdeletion syndrome. Comprehensive clinical data, including maternal age, detailed ultrasound findings, and pregnancy outcomes, were systematically collected. SNP-array analysis was conducted using an Affymetrix CytoScan 750 K Array Chip to identify CNVs and loss of heterozygosity, while CNV-seq was performed on the Illumina HiSeq 2000 platform. Detected variants were classified according to the American College of Medical Genetics and Genomics guidelines. Statistical analyses were performed using SPSS version 27.0.Results::Abnormal renal development was identified in 141 patients, among whom 26 exhibited hyperechogenic kidneys (HCK). Of these, 12 cases were associated with 17q12 microdeletion syndrome, while the remaining 14 were linked to other chromosomal abnormalities. When excluding patients with HCK, those diagnosed with polycystic kidney disease demonstrated a higher prevalence of chromosomal abnormalities compared to those with multicystic dysplastic kidney and renal dysplasia. Although isolated conditions such as horseshoe kidney, hydronephrosis, ectopic kidney, and unilateral kidney typically presented with normal chromosomal findings, the incidence of chromosomal abnormalities increased when these conditions coexisted with other anomalies. A detailed analysis of the correlation between 17q12 microdeletion syndrome and HCK revealed that 12 out of the 14 patients diagnosed with 17q12 microdeletion syndrome exhibited HCK. Genetic testing confirmed the syndrome in seven patients, with five cases attributed to novel mutations and two cases resulting from inherited mutations.Conclusion::Fetal HCK was closely associated with the 17q12 microdeletion syndrome, and polycystic kidney disease showed a higher rate of chromosomal abnormalities. Chromosome test results were mostly normal in patients with other renal abnormalities, such as kidney dysplasia, horseshoe kidneys, hydronephrosis, kidney deficiency, and ectopic kidneys. Prenatal diagnosis is recommended, especially in cases of non-isolated fetal renal abnormalities. This study provides strong evidence supporting a link between fetal renal abnormalities and genetic syndromes.
4.Intergenerational Associations of Hypertensive Disorders of Pregnancy With Offspring Metabolomics: A Systematic Review
Jinrui XIONG ; Ling-Jun LI ; Yongping ZHANG ; Zhihong ZHANG ; Yue YANG ; Huan HU ; Jinhong LIU ; Zimeng CHEN ; Peng HUANG ; Mengjiao LIU
Maternal-Fetal Medicine 2025;07(3):157-165
Objective::To examine the impact of hypertensive disorders of pregnancy (HDP) on offspring metabolomics.Methods::We searched five databases: PubMed, Ovid Embase, MEDLINE, Web of Science, and China National Knowledge Infrastructure, and included studies that reported metabolomics among human offspring born to HDP-complicated pregnancies.Results::Database search yielded 4054 articles, and after full-text screening, ten observational studies met inclusion criteria. Half of the studies had a sample size of less than 100 and were all observational studies in preeclampsia (PE) and gestational hypertension.Neonates were the most focused group in all included studies. Offspring born to HDP-complicated pregnancies exhibited statistically significant variations in blood metabolomics compared to their counterparts, characterized by amino acids, lipids, carnitine, and others (e.g., 1α,25-(OH) 2-D). Most studies reported a significant increase in differential metabolites of offspring born to HDP-complicated pregnancies. Four studies ( n = 1109) measured lipids-related metabolites, and all consistently showed that offspring born to PE-complicated pregnancies had significantly higher concentrations than non-PE exposed offspring. Conclusion::The existing evidence suggests an intergenerational effect of HDP on offspring metabolomics. Long-term follow-up studies are needed to advance the health effects of related adverse health outcomes and inform the prevention of offspring’s health.
5.The Classification, Prenatal Diagnosis and Perinatal Treatment of Fetal Lingual Lesions
Shuangping LIU ; Mingxing ZHANG ; Qiongjie ZHOU ; Yu XIONG
Maternal-Fetal Medicine 2025;07(3):166-171
Fetal lingual lesion is a rare category of embryological anomalies, characterized by distinctive anatomical positioning, which may precipitate mechanical airway obstruction to unfavorable perinatal outcomes. There is a lack of comprehensive prenatal diagnostic strategies and effective treatments. This review has conducted a systematic literature overview of the clinical classification of fetal lingual anomalies, prenatal diagnosis, and perinatal treatment, including prenatal ultrasonography and magnetic resonance imaging, for optimizing perinatal care and obtaining an improved pregnancy outcome. Utilizing a multidisciplinary team framework, individualized peripartum management strategies are developed, contingent upon the presence or absence of airway compromise, with selective application of the ex-utero intrapartum treatment procedure as clinically warranted. By refining diagnostic accuracy and advancing therapeutic protocols, this review aims to elevate clinical management standards for congenital lingual lesions, thereby enhancing both short-term perinatal outcomes and long-term developmental prognoses.
6.Postpartum Hemorrhage
Wang Michelle J. ; Yinka OYELESE
Maternal-Fetal Medicine 2025;07(1):38-48
Obstetric hemorrhage is the leading cause of maternal death in childbirth; it is estimated that one woman dies every four minutes from postpartum hemorrhage (PPH). PPH is the cause of approximately one-quarter of maternal deaths worldwide and is thus a major public health issue of great importance. Despite modern advances in medicine, hemorrhage continues to lead the causes of pregnancy-related death in most countries, with increasing disparity between countries with highly developed and underdeveloped national healthcare systems. Most deaths caused by PPH are preventable. All involved in the care of pregnant women must be aware of the gravity of this problem, ways of identifying women at risk for severe hemorrhage at childbirth, strategies for preventing and ameliorating blood loss at delivery, and finally ways to deal with obstetric hemorrhage when it does occur. This article reviews the impact of obstetric hemorrhage, the controversy regarding definitions, diagnosis, epidemiology, pathophysiology, and management of obstetric hemorrhage.
7.Recognition and Management of Postpartum Hemorrhage
Maternal-Fetal Medicine 2025;07(1):29-37
Postpartum hemorrhage (PPH) is an obstetric emergency and refers to excessive blood loss after birth. Loss of blood volume and oxygen-carrying capacity may lead to maternal hypovolemia and hypotension resulting in tissue hypoxia, the onset of anaerobic metabolism, and multiorgan failure. If timely and appropriate action is not taken, cardiac arrest and maternal death may occur. If the amount of blood loss exceeds 500 mL following a vaginal birth or 1000 mL during or following a cesarean section, it is termed PPH. Similar to any other surgical hemorrhage, PPH is classified into primary PPH (occurs within 24 hours of birth) or secondary PPH (between 24 hours and 12 weeks postpartum). PPH is a major contributor to maternal deaths worldwide, and it is estimated that a person dies because of PPH approximately every 5 minutes. Therefore, measures should be directed at prevention and early detection of PPH with prompt management. The prevalence of PPH varies globally and is influenced by location, socioeconomic factors, and the availability and quality of health care. The World Health Organization reported that PPH accounts for a quarter of global maternal deaths. The Mothers and Babies Reducing Risks through Audits and Confidential Enquiries report from the United Kingdom (2023) highlighted that despite rare mortality due to hemorrhage, the number of people dying of obstetric hemorrhage is not decreasing, particularly among people with abnormally invasive placentation. Additionally, substandard care was found to be responsible for more than 50% of deaths due to PPH in the United Kingdom. Therefore, it is vital that adequate healthcare infrastructure, trained and competent healthcare professionals, and immediate access to resources, interventions, and multidisciplinary teams are essential both in well-resourced and resource-restrained healthcare systems. Healthcare professionals must identify the potential risk factors for PPH and initiate preventive measures whenever possible. Additionally, they must respond swiftly if PPH occurs and ensure a multidisciplinary, multilayered approach for a synchronized response to optimize outcomes. This review article emphasizes the etiopathogenesis, diagnosis, and management of PPH based on current scientific evidence as well as international best practice recommendations.
8.Quantitative Validation of Hematocrit Percentage Drop Cutoff Points in Postpartum Hemorrhage: An Automated Gravimetric Approach
Kway Venance BASIL ; Moreno Ursula MEDINA ; Larraga Karla KREBS ; Moscoso Antonio GORDILLO
Maternal-Fetal Medicine 2025;07(1):3-8
Objective::To validate the hematocrit percentage drop cutoff points for blood loss in patients with postpartum hemorrhage (PPH) using the automated gravimetric method.Methods::A prospective cohort study was conducted from January 2023 to July 2023, in which 107 patients 18 years of age and above were scheduled for elective cesarean with obstetrical indications. We excluded cases with difficulty quantifying blood loss, those with incomplete data, and those of patients who did not consent to participate. Blood loss was measured by an automated gravimetric system integrated into a suction blood collector and surgical gauze weighing systems to automatically sum up blood loss immediately after hysterectomy and fetal delivery. The percentage drop in hematocrit was determined by subtracting the 8-hour postsurgical from presurgical hematocrit, divided by presurgical hematocrit. We performed the Pearson correlation test, and the receiver operating characteristic curve was used to determine cutoff points, their sensitivity, and their specificity. The κ index was used to determine the diagnostic agreement between the two methods.Results::A positive correlation was observed between the volume of blood loss and the percentage drop in hematocrit, with a Pearson correlation index of 0.70 and P < 0.0001. A 14% decrease in hematocrit had an 81.7% agreement rate, with a good κ index of 0.602, a sensitivity of 82.5%, and a specificity of 80.0%. A 10% drop in hemoglobin was sensitive (93.0%) but not very specific (56.0%) for blood loss greater than 1000 mL. Conclusion::The automated gravimetric method strongly correlates with hematocrit changes, providing an accurate real-time diagnosis of PPH. Additionally, a hematocrit percentage drop can retrospectively indicate significant blood loss, aiding in managing patients at risk for long-term PPH complications.
9.Identification of a Fetal De Novo Splice Variant in ARCN1 Associated With Growth and Skeletal Abnormalities
Wencong HE ; Zejun YANG ; Jianjian CUI ; Ruilin MA ; Hui TAO ; Yanan LI ; Yin ZHAO
Maternal-Fetal Medicine 2025;07(1):9-14
Objective::To report a fetus with ARCN1-related syndrome caused by a novel de novo heterozygous variant, highlighting the importance of early genetic diagnosis in prenatal care. Methods::The clinical and genetic data of a fetus with a complex combination of clinical signs and a novel de novo heterozygous variant were collected and have been summarized in this study. The potential pathogenic variant was identified throughout the whole exome sequencing and the effects of candidate variants were further validated by a minigene splicing assay. Results::Prenatal systematic ultrasound detected fetal growth restriction. Genetic analysis identified a novel de novo heterozygous variant within the ARCN1 gene—c.1241 +5G>A-located in intron 8. In vitro minigene splicing assays demonstrated that the variant led to two abnormal transcripts. The longer transcript retained 189 base pairs of intron 8, resulting in a truncated protein of 414 amino acids (p.Ser415*). The shorter transcript involved exon 8 skippings, producing a truncated protein of 407 amino acids (p.Ile378Serfs*31). Conclusion::A novel de novo heterozygous variant of the ARCN1 gene, namely NM_001655.5: c.1241 +5G>A, was discovered and identified in a fetus with rhizomelic short stature, microretrognathia, and developmental delays.
10.Diagnostic Accuracy of Magnetic Resonance Imaging in the Diagnosis of Placenta Accreta Spectrum: A Systematic Review and Meta-analysis
Suzi ABDELAZIZ ; El-Goly Nour A. ; Maged Ahmed M. ; Nehal BASSIOUNY ; Nihal EL-DEMIRY ; Ahmed SHAMEL
Maternal-Fetal Medicine 2025;07(1):15-21
Objective::To evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) in diagnosing placenta accreta spectrum (PAS).Methods::We conducted a comprehensive literature search from database inception to November 2023 using terms such as placenta creta, increta, percreta, PAS, MRI, and their respective Medical Subject Headings terms. All prospective and retrospective cohort, case-control, and cross-sectional studies involving prenatal magnetic resonance imaging diagnosis of PAS with subsequent pathological confirmation were included.Results::A total of 40 studies encompassing 3664 women met the inclusion criteria, with 1894 cases confirmed pathologically as PAS. The overall sensitivity of MRI was 0.867 (95% confidence interval ( CI): 0.807-0.910), and the specificity was 0.860 (95% CI: 0.799-0.905), with a correlation of 0.693 between sensitivity and specificity. The estimated odds ratio was 28.693 (95% CI: 14.463-56.924), the negative likelihood ratio was 0.178 (95% CI: 0.122-0.258), and the positive likelihood ratio was 4.316 (95% CI: 3.186-5.846). Analysis of individual MRI criteria revealed estimates of sensitivity, specificity, odds ratio, negative likelihood ratio, and positive likelihood ratio for abnormal placental bed vascularization as 0.500, 0.740, 2.788, 0.571, and 1.645 respectively; 0.384, 0.985, 6.270, 0.471, and 2.720 for bladder wall interruption; 0.766, 0.818, 13.638, 0.262, and 3.375 for the presence of dark intraplacental bands; 0.691, 0.913, 10.828, 0.352, and 3.361 for heterogeneous placenta; 0.688, 0.984, 34.886, 0.254, and 7.164 for indistinctive myometrium; 0.757, 0.864, 8.496, 0.362, and 2.778 for loss of retroplacental dark zone; 0.828, 0.593, 5.829, 0.329, and 1.766 for myometrial thinning; and 0.518, 0.916, 9.473, 0.411, and 3.526 for placental bulge, respectively. Conclusion::MRI demonstrates significant utility in diagnosing PAS and its severity. It is recommended for use in all cases with inconclusive ultrasonographic findings.Registration::Registration number CRD42021267501.

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