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Fetal cardiac rhabdomyomas susceptible to prenatal treatment with mTOR inhibitors: literature review and proposal of a prenatal management algorithm
(Frontiers Media SA, 2025)
Martinez-Garcia, Alfonso
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Tirado-Aguilar, Omar A.
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Acevedo-Gallegos, Sandra
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Gallardo-Gaona, Juan M.
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Velazquez-Torres, Berenice
Certain types of fetal cardiac rhabdomyomas can lead to severe complications, including intrauterine death, yet no specific criteria have been established for the prenatal use of pharmacological therapies to mitigate the impact of rhabdomyomas. We conducted a narrative review of case reports and case series published between January 1, 2000, and February 28, 2025, identified through PubMed, Scopus, Web of Science, and Google Scholar, describing the prenatal use of mammalian target of rapamycin inhibitors in this context. Thirteen studies reporting on 15 fetuses were included. Five fetuses (33.3%) had a single rhabdomyoma, and 10 (66.6%) had multiple lesions. Prenatal genetic testing for Tuberous Sclerosis Complex was performed in 9 cases (60%): 1 with a TSC1 mutation, 7 with TSC2 mutations, and 1 negative. Sirolimus was the most frequently used inhibitor (86.6%), while everolimus was used in 2 cases (13.3%). The main indication for treatment was progressive tumor growth causing outflow obstruction and/or hemodynamic compromise, including reduced cardiac output, arrhythmias, and fetal hydrops. Therapy was initiated at a median of 30.0 weeks (IQR 26.7–33.1) and completed at 38.0 weeks (IQR 36–39). All reports documented tumor reduction and improved cardiac function, though regrowth occurred in 5 cases (33.3%) after discontinuation. No fetal or neonatal deaths were reported, and none required postnatal cardiac surgery before discharge. Based on these findings, we proposed echocardiographic criteria to identify suitable candidates, including inflow/outflow tract obstruction, severe atrioventricular valve insufficiency, tachyarrhythmia, impaired cardiac function, or hydrops, and developed a structured prenatal management algorithm. Prenatal therapy with mTOR inhibitors, therefore, appears to improve fetal cardiac function by reducing tumor burden and may contribute to better perinatal outcomes, although validation in future studies is required. TSC1: urn:lsid:hgnc.org: HGNC:12362 TSC2: urn:lsid:hgnc.org: HGNC:12363 Sirolimus: urn:lsid:ebi.ac.uk:chebi:9168 Everolimus: urn:lsid:ebi.ac.uk:chebi:68478. ©The authors ©Frontiers Media SA.
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Maternal, fetal, and neonatal serious adverse events associated with low-dose aspirin during the first trimester of pregnancy: A secondary analysis of the Aspirin Supplmentation for Pregnancy Indicated Risk Reduction In Nulliparas (ASPIRIN) trial
(Elsevier BV, 2025)
Rodriguez-Sibaja, Maria J.
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Gálvez Rubalcava, Natalia
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Hagerman-Sucar, Gonzalo
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Alcocer González-Camarena, Paulina
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Gómez Woodworth, Juan Ramón
Background: Low-dose aspirin (LDA) has been shown to reduce the risk of preterm preeclampsia, particularly when initiated early in pregnancy. However, the safety of starting LDA before 11 0/7 weeks of gestation remains unclear. Objective: To assess whether initiating LDA before 11 0/7 weeks of gestation is associated with increased maternal, fetal, or neonatal serious adverse events compared to later initiation. Study Design: This secondary analysis of the ASPIRIN (Aspirin Supplmentation for Pregnancy Indicated Risk Reduction In Nulliparas) trial included 11,879 nulliparous women with singleton pregnancies randomized to receive LDA (81 mg/d) or placebo between 6 0/7–13 6/7 weeks of gestation. Severe adverse events (ie, maternal death, antepartum hemorrhage, postpartum hemorrhage, anemia, preeclampsia or eclampsia, preterm labor, hypertension admission, fever or infection, fetal loss, neonatal death up to 28 days, miscarriage, abortion, or medical termination of pregnancy, and congenital anomalies) were analyzed based on gestational age at LDA initiation (<11 0/7 vs ≥11 0/7 weeks). Furthermore, congenital anomalies were assessed for therapy initiated during the embryonic (ie, <9 0/7 weeks) or fetal period. Interaction tests were performed via logistic regression models on the ASPIRIN trial safety population (ie, participants who received at least one dose of LDA or placebo) and on the subset of participants who had an adherence to the exposure of ≥90%. Results: Among the 11,879 eligible participants for this secondary analysis, 62% (n=7324) initiated the allocated exposure before 11 0/7 weeks vs 38% (n=4555) that initiated LDA or placebo at a later gestational age. Furthermore, in this population, 84.4% (n=10,030) had an adherence to the intervention of 90% or more. Moreover, the proportion of adherence of ≥90% to LDA or placebo was similar between strata (84.6% [n=6195] for <11 0/7 vs 84.2% [n=3835] ≥11 0/7 weeks, P=.570). No significant differences were observed in the maternal, fetal, or neonatal adverse events described above based on the timing of LDA initiation (P>.05 for all interactions). Likewise, congenital anomalies did not significantly differ between embryonic and fetal exposure periods (interaction P-value = .095). Results remained consistent in participants who had an adherence to the exposure of ≥90%. Conclusions: LDA (81 mg/d) initiated before 11 0/7 weeks of gestation may not increase the risk of maternal, fetal, or neonatal serious adverse events or congenital anomalies. These findings provide reassuring evidence of the safety of LDA exposure during early pregnancy. ©The authors ©American Journal of Obstetrics & Gynecology MFM © Elsevier BV.
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Fetal and Neonatal Outcomes in Fetuses with an Estimated Fetal Weight Percentile of 10–20 in the Early Third Trimester: A Retrospective Cohort Study
(MDPI AG, 2025)
Mendez-Piña, Miguel A.
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Lumbreras-Márquez, Mario Isaac
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Acevedo-Gallegos, Sandra
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Velázquez-Torres, Berenice
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Rodriguez-Sibaja, Maria J.
first_pagesettingsOrder Article Reprints Open AccessArticle Fetal and Neonatal Outcomes in Fetuses with an Estimated Fetal Weight Percentile of 10–20 in the Early Third Trimester: A Retrospective Cohort Study by Miguel A. Mendez-Piña 1ORCID,Mario I. Lumbreras-Marquez 1,2,Sandra Acevedo-Gallegos 1,Berenice Velazquez-Torres 1ORCID,Maria J. Rodriguez-Sibaja 1,Dulce M. Camarena-Cabrera 1 andJuan M. Gallardo-Gaona 1,*ORCID 1 Maternal-Fetal Medicine Department, Instituto Nacional de Perinatologia, Mexico City 11000, Mexico 2 Department of Epidemiology and Public Health, Universidad Panamericana School of Medicine, Mexico City 03920, Mexico * Author to whom correspondence should be addressed. Diagnostics 2025, 15(17), 2251; https://doi.org/10.3390/diagnostics15172251 Submission received: 12 June 2025 / Revised: 1 August 2025 / Accepted: 1 August 2025 / Published: 5 September 2025 (This article belongs to the Special Issue Diagnosis and Management of Contemporary Issues in Maternal-Fetal Medicine) Downloadkeyboard_arrow_down Browse Figures Review Reports Versions Notes Abstract Background: Fetal size is often dichotomized as normal or abnormal using the 10th percentile of estimated fetal weight (EFW) or abdominal circumference as a cutoff. While the risk of adverse perinatal outcomes decreases with increasing fetal weight percentile, no percentile completely eliminates that risk. Objective: The aim of this study was to compare perinatal outcomes between fetuses with an EFW between the 10th and 20th percentiles and those with an EFW between the 20th and 90th percentiles (i.e., >20 and <90) at the beginning of the accelerated growth stage (28.0–30.0 weeks’ gestation). Methods: We conducted a retrospective cohort study of singleton pregnancies managed at a quaternary center in Mexico City (2017–2024). Outcomes were compared based on EFW percentiles at 28.0–30.0 weeks. The primary outcome was adverse neonatal outcome (ANeO), defined as the presence of at least one of the following: umbilical artery pH ≤ 7.1, 5 min Apgar ≤ 7, NICU admission, early neonatal hypoglycemia, non-reassuring fetal status, respiratory distress syndrome, intraventricular hemorrhage, hypoxic–ischemic encephalopathy, or perinatal death. Secondary outcomes included progression to fetal growth restriction (FGR) and low birth weight. Modified Poisson regression was used to estimate adjusted risk ratios (aRRs) with 95% confidence intervals (CIs). Results: Among 650 cases, ANeO occurred in 45.8% of fetuses in the 10th–20th percentile group vs. 29.4% in the 20th–90th percentile group (aRR: 1.51, 95% CI: 1.22–1.86; p < 0.001). FGR and low birth weight were also more frequent in the 10th–20th percentile group (21.1% and 27.6% vs. 6.4% and 5.8%, respectively; p < 0.001). Conclusions: Fetuses between the 10th and 20th percentiles at 28–30 weeks have increased risks of neonatal morbidity, FGR, and low birth weight. ©The authors ©Diagnostics © MDPI AG.
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Survival assessment in extremely preterm neonates in a middle-income setting
(Frontiers Media SA, 2025)
Rodriguez-Sibaja, Maria J.
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Herrera-Ortega, Olivo
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Lumbreras-Márquez, Mario Isaac
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Morales-Barquet, Deneb
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Acevedo-Gallegos, Sandra
Introduction: Globally, an estimated 15.1 million preterm neonates are born annually, with 1% classified as extremely preterm (i.e., <28.0 weeks of gestation). The survival and outcomes of this vulnerable population are influenced by multiple factors, particularly gestational age, birth weight, and available medical resources. This study aimed to describe the hospital discharge survival of extremely preterm infants born in a middle-income setting. As a secondary objective, we assessed the neonatal morbidity associated with this group.Material and methods: In this cross-sectional study of singleton pregnancies, neonatal survival following extremely preterm birth was determined using three different denominators and expressed as prevalence (i.e., percentages): (1) the total number of extremely preterm births, including intrapartum fetal deaths; (2) the total number of all live births, including neonatal deaths in the delivery room, and (3) the total number of preterm neonates admitted to the neonatal intensive care unit (NICU). Neonatal morbidity was assessed as a secondary outcome.Results: There were no live births between 22.0 and 23.6 weeks of gestation. Overall mortality decreased with increasing gestational age, from 100% (22/22) at <24.0 weeks of gestation to 87% (14/16), 42% (16/38), and 21% (11/52) at a gestational age of 25, 26, and 27 weeks, respectively. The survival rate to NICU discharge among extremely preterm infants was 49% (65/132), 67% (65/97), and 69% (65/93), depending on whether survival was calculated based on all births, all live births, or NICU admissions, respectively. None of the neonates born before 24.6 weeks of gestation survived to discharge. Notably, 97.0% of NICU survivors were diagnosed with major morbidity.Conclusion: The survival rate at NICU discharge exceeds 50% from 26 weeks onwards in a middle-income setting. Importantly, survival rates varied significantly depending on the denominator used, highlighting the need to carefully select inclusion criteria in neonatal survival analyses. Notably, survival after extremely preterm birth was associated with significant morbidity. ©The authors ©Frontiers in Pediatrics.
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Prediction of preeclampsia before 11th week of gestation: a secondary analysis of the ASPIRIN trial
(Elsevier BV, 2025)
Capdeville, Gabriela
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Godinez-Medina, Andrea
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Copado-Mendoza, Diana Y.
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Acevedo-Gallegos, Sandra
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Rodriguez-Bosch, Mario R.
Background: Early screening for preeclampsia is crucial for preventing adverse maternal and fetal events. Current first-trimester algorithms for predicting preeclampsia are designed to evaluate individual risk between 11.0 and 13.6 weeks of gestation based on various maternal characteristics while integrating biophysical and biochemical features. However, there is limited information regarding risk assessment during earlier stages of pregnancy (i.e., <11.0 weeks gestation). Objective: To develop a prediction model for preeclampsia/eclampsia before 11.0 weeks of gestation as a proof-of-concept in a secondary analysis of the ASPIRIN trial. Study design: This study is a secondary analysis of the ASPIRIN trial, a multinational, randomized, double-blind, placebo-controlled trial. The ASPIRIN trial database, obtained from NICHD DASH, included 11,976 nulliparous pregnant women aged 18–40 with gestational ages of 6.0–13.6 weeks at randomization. Participants were assigned to receive either aspirin (81 mg/day) or placebo until 36.0 weeks or delivery. This secondary analysis included pregnancies delivered at ≥20.0 weeks, excluding those in the aspirin group or with gestational ages ≥11.0 weeks at enrollment. The composite outcome was preeclampsia/eclampsia, as reported in the ASPIRIN trial. Predictor variables available in the dataset included maternal age, education (4 levels), body mass index (BMI kg/m2), gravidity, baseline hemoglobin, baseline systolic blood pressure, and baseline diastolic blood pressure. Logistic regression, with logarithmic transformation for continuous variables, was used to develop the model. The area under the ROC curve with a 95% confidence interval (CI) estimated via bootstrap resampling (1,000 iterations) and the P-value of the Hosmer-Lemeshow statistical test are reported as discrimination and calibration measures. This study used the entire available sample using a complete case approach. Results: A total of 3421 participants met the inclusion criteria, with a cumulative incidence of preeclampsia/eclampsia of 2.9% (99/3,421). Maternal age (21.96 ± 4.13 vs 20.86 ± 3.21, P<.001) and BMI (22.49 ± 4.77 vs 20.79 ± 3.55, P<.001) were significantly higher in the preeclampsia/eclampsia group. Gravidity was lower (P=.023), and hemoglobin levels were slightly elevated (11.88 ± 1.52 g/dL vs 11.50 ± 1.61 g/dL, P=.019) in the preeclampsia/eclampsia group. Educational level (P=.070), systolic blood pressure (P=.720), and diastolic blood pressure (P=.390) showed no significant differences between groups. The logistic regression model yielded an AUC of 0.69 (95% CI 0.63–0.74), and the Hosmer-Lemeshow test P-value was 0.094, indicating acceptable discrimination and calibration. Conclusions: This proof-of-concept logistic regression model using first-trimester maternal characteristics demonstrated acceptable predictive performance for preeclampsia/eclampsia before 11.0 weeks of gestation. During this critical period, several interventions could be proposed to reduce preeclampsia risk, including medication adjustments, lifestyle changes, and appropriate referral if needed. Further studies are required to validate these findings and assess their clinical utility in different settings. © The authors © Elsevier.
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Cumulative sum learning curve for cordocentesis among maternal‐fetal medicine fellows in a low‐cost simulation model
(Wiley, 2024)
Pérez-Estrada, Bibiana A.
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Acevedo-Gallegos, Sandra
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Lumbreras-Márquez, Mario Isaac
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Gardner, Roxane
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Gallardo, Juan Manuel
Objective: To determine the individual learning curves for cordocentesis in a low-cost simulator for maternal-fetal medicine (MFM) fellows. Methods: This observational, descriptive, educational, and prospective study was performed from July through November 2022. After an introductory course based on a standardized technique for cordocentesis, each second-year MFM fellow who accepted to participate in the study performed this procedure using a low-cost simulation model, and experienced operators supervised the cordocenteses. Learning curves were then created using cumulative sum analysis (CUSUM). Copyright © 1999-2024 John Wiley & Sons.
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Intended delivery mode and neonatal outcomes in pregnancies with fetal growth restriction
(2023)
Rodriguez-Sibaja, Maria J.
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Mendez-Piña, Miguel A.
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Lumbreras-Márquez, Mario Isaac
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Acevedo-Gallegos, Sandra
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Velazquez-Torres, Berenice
Objective: To compare neonatal outcomes in pregnancies with fetal growth restriction (FGR) by intended delivery mode.Methods: This is a retrospective cohort study of singleton pregnancies with FGR that were delivered ≥34.0 weeks gestation. Neonatal outcomes were compared according to the intended delivery mode, which the attending obstetrician determined. Of note, none of the subjects had a contraindication to labor. Crude and adjusted odds ratios (ORs) and corresponding confidence intervals (CIs) were calculated via logistic regression models to assess the potential association between intended delivery mode and neonatal morbidity defined as a composite outcome (i.e. umbilical artery pH ≤7.1, 5-min Apgar score ≤7, admission to the neonatal intensive care unit, hypoglycemia, intrapartum fetal distress requiring expedited delivery, and perinatal death). A sensitivity analysis excluded intrapartum fetal distress requiring emergency cesarean delivery from the composite outcome since only patients with spontaneous labor or labor induction could meet this criterion. Potential confounders in the adjusted effects models included maternal age, body mass index, hypertensive disorders, diabetes, FGR type (i.e. early or late), and oligohydramnios.
Scopus© Citations 1 10 1
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Abdominal circumference growth velocity as a predictor of adverse perinatal outcomes in small-for-gestational-age fetuses
(2023)
Rodriguez-Sibaja, Maria J.
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Villa-Cueva, Alejandra
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Ochoa-Padilla, Maria
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Rodriguez-Montenegro, Maria S.
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Lumbreras-Márquez, Mario Isaac
Objective: To assess the predictive value of abdominal circumference growth velocity (ACGV) between the second and third trimesters to predict adverse perinatal outcomes in a cohort of small-for-gestational-age fetuses without evidence of placental insufficiency (i.e. fetal growth restriction). Material and methods: This is a single-center retrospective cohort study of all singleton pregnancies with small-for-gestational-age fetuses diagnosed and delivered at a quaternary institution. Crude and adjusted odds ratios (ORs) and corresponding confidence intervals (CIs) were calculated via logistic regression models to assess the potential association between abnormal ACGV (i.e. ≤10th centile) and adverse perinatal outcomes defined as a composite outcome (i.e. umbilical artery pH <7.1, 5-min Apgar score <7, admission to the neonatal intensive care unit, hypoglycemia, intrapartum fetal distress requiring expedited delivery, and perinatal death). Furthermore, the area under the receiver-operating characteristic curve (AUC) of three logistic regression models based on estimated fetal weight and ACGV for predicting the composite outcome is also reported.
Scopus© Citations 2 17 1

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