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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. doi:10.1097/FM9.0000000000000292

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.

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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. doi:10.1097/FM9.0000000000000291

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.

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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. doi:10.1097/FM9.0000000000000287

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.

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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. doi:10.1097/FM9.0000000000000276

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.

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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. doi:10.1097/FM9.0000000000000296

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.

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Sensitivity of miRNA-181a, miRNA-23b and miRNA-16 in the Late-Onset Neonatal Sepsis: A Diagnostic Study

Divya KATTA ; Sridharan Kopula SATYAMOORTHY ; Balakrishnan Uma MAHESWARI ; Prakash AMBOIRAM ; Kennedy KUMAR

Maternal-Fetal Medicine.2024;06(4):243-248. doi:10.1097/FM9.0000000000000227

Objective::To evaluate the expression and diagnostic value of levels of the microRNAs (miRNAs), miRNA-181a, miRNA-23b, and miRNA-16, in late-onset neonatal sepsis (LOS) and compare them with the diagnostic utility of C-reactive protein (CRP) levels.Methods::This was a prospective diagnostic study conducted between January 2021 and March 2023 at a tertiary care center (Sri Ramachandra Hospital) in India. Quantitative real-time polymerase chain reaction was performed to determine miRNA-181a, miRNA-23b, and miRNA-16 expression levels, and CRP was measured by nephelometry. The diagnostic value of miRNA and CRP levels were analyzed using receiver operating characteristic (ROC) curves. ROC curves were utilized to determine optimal cutoff points, and Mann–Whitney tests were performed using SPSS to ascertain P values, with statistical significance defined as <0.05.Results::This study included 100 samples, with 50 cases of culture-proven LOS (27 females, 23 males) and 50 healthy controls (31 females, 19 males). In LOS, miRNA-181a and miRNA-23b expression levels were significantly downregulated ( P < 0.001), with area under the curve (AUC) values of 0.83 and 0.92, respectively, whereas those of miRNA-16 were significantly upregulated ( P < 0.001; AUC = 0.97). In comparison, CRP levels had an AUC value of 0.831 ( P < 0.001). Further, miRNA-23b showed the highest sensitivity (98%) of markers tested, whereas miRNA-16 exhibited the highest specificity (96%). Conclusion::MiRNA, especially miRNA-16, shows diagnostic potential for neonatal sepsis compared with traditional biomarkers like CRP and procalcitonin, suggesting its use as an early marker for LOS. However, further cohort studies are needed before practical application.

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Successful Delivery After Myomectomy for Spontaneous Ruptured Pyomyoma: A Case Report and Literature Review

Qian ZHOU ; Yi YU ; Juntao LIU ; Jinsong GAO ; Yijun SONG ; Yin SUN ; Qi GUO

Maternal-Fetal Medicine.2024;06(4):249-252. doi:10.1097/FM9.0000000000000239

In this article, we report a case of spontaneous ruptured pyomyoma during pregnancy with successful delivery after myomectomy. A 35-year-old pregnant female (27 weeks of gestation) presented with lower abdominal pain. The patient had a history of uterine fibroids. Ultrasound, computed tomography, and magnetic resonance imaging confirmed a spontaneous ruptured pyomyoma (maximum diameter: 12.6 cm). Myomectomy was performed, and her abdominal distension and pain were significantly improved within 1 day; the condition of the fetus was normal. One month after surgery, severe tenderness was detected in the lower right side of the uterus. Considering the higher risk of uterine rupture and associated complications, a cesarean section was performed. The mother and neonate were discharged 3 and 42 days after delivery, respectively, in good condition. Myomectomy for spontaneous ruptured pyomyoma during pregnancy may be feasible and extend gestational age to improve outcomes for the mother and neonate.

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When Giant Lymphangioma Meets Hydrops Fetalis: An Uncommon Case Report of Lower Extremity Involvement

Martin Ariana MARIE ; Sanchez-Cantu Andrea PAOLA ; Andrea CANTU-RODRIGUEZ ; Raul MARTINEZ-SALINAS ; Valdez-Bocanegra Jesus DAMIAN

Maternal-Fetal Medicine.2024;06(4):253-256. doi:10.1097/FM9.0000000000000249

Approximately 75% of lymphangiomas manifest in the head and neck region, with limb and bone involvement observed in only 2% of cases. This case report presents a rare instance of fetal lymphangioma associated with hydrops fetalis, affecting the left lower extremity and abdomen. A 22-year-old secundigravida woman was referred to the gynecology department at 31.2 weeks of gestation. Initial fetal ultrasound revealed a live fetus with a large lymphangioma involving the left lower extremity, gluteal region, and abdomen. Additional ultrasound findings included subcutaneous edema, pericardial effusion, ascites, placentomegaly, and tricuspid regurgitation. Postnatal clinical examination confirmed the diagnosis of lymphatic malformation. Notably, only one other similar case has been reported in the English-language PubMed database. This report adds to the medical literature as a rare instance of prenatally diagnosed lymphangioma-associated hydrops fetalis.

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Blended Phenotypes From a SERPINA 11 Pathogenic Variant Over Underlying Immune Fetal Hydrops: A Rare Case Report and Literature Review

Beck Manisha M. ; Luke Noel D. ; Anand Reena SAKTE ; Preethi NAVANEETHAN ; Rekha ATHIYARATH ; Sumita DANDA

Maternal-Fetal Medicine.2024;06(4):257-261. doi:10.1097/FM9.0000000000000250

Fetal hydrops can stem from immune or nonimmune causes. Immune causes often involve red cell alloimmunization, whereas nonimmune causes encompass structural malformations, aneuploidy, infections, lymphatic system disorders, genetic syndromes, and more. In a rare and complex case, we encountered a fetal hydrops presentation characterized by blended phenotypes, indicating both a genetic and an underlying immune etiology. The mother, Rhesus negative, presented with a history of adverse obstetric events. At 21 weeks, the current fetus was diagnosed with hydrops. Maternal blood tests unveiled Rhesus alloimmunization, featuring a positive indirect Coombs test at a 1:512 dilution and the presence of anti-D, anti-C, and anti-E antibodies. Fetal blood sampling revealed an O-positive blood group with a hemoglobin level of 10 gm/dL. Despite administering intrauterine transfusion to the fetus, there was no improvement; instead, the fetal hydrops worsened, accompanied by the emergence of nuchal and axillary masses. Exome sequencing of fetal DNA revealed the fetus was homozygous for a pathogenic variant in the SERPINA11 gene and compound heterozygous for a pathogenic variant in the PIEZO1 gene. Furthermore, the combination of pathogenic variants in SERPINA11 and PIEZO1 genes has not been described in cases of fetal hydrops before. This case posed significant challenges in management due to the concurrent presence of both immune and nonimmune hydrops. We describe some of the diagnostic challenges faced in clinical management of this case.

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Unique Ultrastructural Alterations in the Placenta Associated With Macrosomia Induced by Gestational Diabetes Mellitus

Junxiang WEI ; Tianyu DONG ; Mingxia CHEN ; Xiao LUO ; Yang MI

Maternal-Fetal Medicine.2024;06(3):164-172. doi:10.1097/FM9.0000000000000240

Objective::To investigate the morphological and ultrastructural alterations in placentas from pregnancies with gestational diabetes mellitus (GDM)-induced macrosomia, term nondiabetic macrosomia, and normal pregnancies.Methods::Sixty full-term placentas were collected, and clinical data along with informed consent were obtained from pregnant women who underwent regular visit checks and delivered their newborns in Northwest Women’s and Children’s Hospital between May and December 2022. Placentas were divided into three equal groups: normal pregnancy (control group), nondiabetic macrosomia group, and macrosomia complicated with GDM (diabetic macrosomia) group. Gross morphological data of placentas were recorded, and placental samples were processed for examination of ultrastructural and stereological changes using transmission electron microscopy. Analysis of variance and chi-squared test were used to examine the differences among the three groups for continuous and categorical variables, respectively.Results::The baseline characteristics of mothers and neonates did not differ across the three groups, except for a significantly higher birth weight in the diabetic macrosomia group (4172.00 ± 151.20 g vs. 3192.00 ± 328.70 g, P < 0.001) and nondiabetic macrosomia group (4138.00 ± 115.20 g vs. 3192.00 ± 328.70 g, P < 0.001) compared with control group. Examination of the placentas revealed that placental weight was also highest in the diabetic macrosomia group compared with control group (810.00 ± 15.81 g vs. 490.00 ± 51.48 g, P < 0.001) and nondiabetic macrosomia group (810.00 ± 15.81 g vs. 684.00 ± 62.69 g, P < 0.001), but the ratio of neonatal birth weight to placental weight (BW/PW) was significantly lower in the diabetic macrosomia group compared with that in the control group (5.15 ± 0.19 vs. 6.54 ± 0.63, P < 0.001) and nondiabetic macrosomia group (5.15 ± 0.19 vs. 6.09 ± 0.52, P < 0.001) group. In contrast, the BW/PW ratio in nondiabetic macrosomia did not differ significantly from that in the control group. Distinct ultrastructural changes in terminal villi and stereological alterations in microvilli were observed in the diabetic macrosomia group, including changes in the appearance of cytoplasmic organelles and the fetal capillary endothelium and thickness of the vasculo-syncytial membrane and basal membrane. Conclusion::Significant ultrastructural and stereological alterations were discovered in the placentas from pregnant women with macrosomia induced by GDM. These alterations may be the response of the placenta to the hyperglycemia condition encountered during pregnancies complicated with GDM.

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