A Narrative Review on the Pathophysiology of Preeclampsia.

Preeclampsia (PE) is a multifactorial pregnancy disorder characterized by hypertension and proteinuria, posing significant risks to both maternal and fetal health. Despite extensive research, its complex pathophysiology remains incompletely understood. This narrative review aims to elucidate the intricate mechanisms contributing to PE, focusing on abnormal placentation, maternal systemic response, oxidative stress, inflammation, and genetic and epigenetic factors. This review synthesizes findings from recent studies, clinical trials, and meta-analyses, highlighting key molecular and cellular pathways involved in PE. The review integrates data on oxidative stress biomarkers, angiogenic factors, immune interactions, and mitochondrial dysfunction. PE is initiated by poor placentation due to inadequate trophoblast invasion and improper spiral artery remodeling, leading to placental hypoxia. This triggers the release of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), causing widespread endothelial dysfunction and systemic inflammation. Oxidative stress, mitochondrial abnormalities, and immune dysregulation further exacerbate the condition. Genetic and epigenetic modifications, including polymorphisms in the Fms-like tyrosine kinase 1 (FLT1) gene and altered microRNA (miRNA) expression, play critical roles. Emerging therapeutic strategies targeting oxidative stress, inflammation, angiogenesis, and specific molecular pathways like the heme oxygenase-1/carbon monoxide (HO-1/CO) and cystathionine gamma-lyase/hydrogen sulfide (CSE/H2S) pathways show promise in mitigating preeclampsia's effects. PE is a complex disorder with multifactorial origins involving abnormal placentation, endothelial dysfunction, systemic inflammation, and oxidative stress. Despite advances in understanding its pathophysiology, effective prevention and treatment strategies remain limited. Continued research is essential to develop targeted therapies that can improve outcomes for both mothers and their babies.

Uterus transplantation: A scoping review focused on obstetric outcomes.

BACKGROUND: Congenital uterine anomalies include a wide diversity of uterine malformations that can compromise reproductive potential. Uterus transplantation (UTx) proposes an innovative treatment for absolute uterine factor infertility; however, there is a lack of standardized protocols to guide clinical management among this population. OBJECTIVES: To describe recipient and donor characteristics and obstetric outcomes in patients undergoing UTx. SEARCH STRATEGY: We performed a literature search using the PubMed database to retrieve available scientific articles. We analyzed the references of included articles to assess additional articles that could be eligible to be included in the review. Likewise, we identified further studies using other methods, including Google Scholar. SELECTION CRITERIA: Titles and abstracts were screened in duplicate to select original reports with information available for the outcomes of interest. DATA COLLECTION AND ANALYSIS: This review assessed the advantages and disadvantages of the techniques used, patient characteristics, obstetric and non-obstetric complications, functional duration of the organ, and neonatal outcomes. MAIN RESULTS: Among the 36 reports included in this review we found 55 pregnancies and 38 live births following UTx and a higher success rate for in vivo uterine donations. The most common obstetric complications reported included miscarriage, pre-eclampsia, and gestational hypertension. The most common non-obstetric complications reported include episodes of rejection, acute kidney injury, anemia, and cholestasis. Living donors required a comprehensive preoperative workup, decreasing organ rejection, infection, and vascular complications. CONCLUSIONS: More studies are needed to standardize the UTx procedure and improve obstetric, fetal, and neonatal outcomes. Further understanding of which recipient and donor characteristics minimize complications will significantly decrease the risk of adverse outcomes.

Placental pathology lesions: International Society for Ultrasound in Obstetrics and Gynecology vs Society for Maternal-Fetal Medicine fetal growth restriction definitions.

BACKGROUND: Research on the definition of fetal growth restriction (FGR) has focused on predicting adverse perinatal outcomes. A significant limitation of this approach is that the individual outcomes of interest could be related to the condition and the treatment. Evaluation of outcomes that reflect the pathophysiology of FGR may overcome this limitation. OBJECTIVE: To compare the diagnostic performance of the FGR definitions established by the International Society for Ultrasound in Obstetrics and Gynecology (ISUOG) and the Society for Maternal-Fetal Medicine (SMFM) to predict placental histopathological findings associated with placental insufficiency and a composite adverse neonatal outcome (ANeO). STUDY DESIGN: In this retrospective cohort study of singleton pregnancies, the ISUOG and the SMFM guidelines were used to identify pregnancies with FGR and a corresponding control group. The primary outcome was the prediction of placental histopathological findings associated with placental insufficiency, defined as lesions associated with maternal vascular malperfusion (MVM). A composite ANeO (ie, umbilical artery pH≤7.1, Apgar score at 5 minutes ≤4, neonatal intensive care unit admission, hypoglycemia, respiratory distress syndrome requiring mechanical ventilation, intrapartum fetal distress requiring expedited delivery, and perinatal death) was investigated as a secondary outcome. Sensitivity, specificity, positive and negative predictive values, and the areas under the receiver-operating-characteristics curves were determined for each FGR definition. Logistic regression models were used to assess the association between each definition and the studied outcomes. A subgroup analysis of the diagnostic performance of both definitions stratifying the population in early and late FGR was also performed. RESULTS: Both societies' definitions showed a similar diagnostic performance as well as a significant association with the primary (ISUOG adjusted odds ratio 3.01 [95% confidence interval 2.42, 3.75]; SMFM adjusted odds ratio 2.85 [95% confidence interval 2.31, 3.51]) and secondary outcomes (ISUOG adjusted odds ratio 1.95 [95% confidence interval 1.56, 2.43]; SMFM adjusted odds ratio 2.12 [95% confidence interval 1.70, 2.65]). Furthermore, both FGR definitions had a limited discriminatory capacity for placental histopathological findings of MVM and the composite ANeO (area under the receiver-operating-characteristics curve ISUOG 0.63 [95% confidence interval 0.61, 0.65], 0.59 [95% confidence interval 0.56, 0.61]; area under the receiver-operating-characteristics SMFM 0.63 [95% confidence interval 0.61, 0.66], 0.60 [95% confidence interval 0.57, 0.62]). CONCLUSION: The ISUOG and the SMFM FGR definitions have limited discriminatory capacity for placental histopathological findings associated with placental insufficiency and a composite ANeO. El resumen está disponible en Español al final del artículo.

Cumulative sum learning curve for cordocentesis among maternal-fetal medicine fellows in a low-cost simulation model.

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). RESULTS: Seven second-year MFM fellows with no previous experience in cordocentesis accepted to participate in the study. A total of 2676 procedures were assessed. On average, residents performed 382 ± 70 procedures. The mean number of procedures to achieve proficiency was 369 ± 70, the overall success rate was 84.16%, and the corresponding failure rate was 15.84%. At the end of the study, all fellows were considered competent in cordocentesis. One fellow required 466 attempts to achieve competency, performing a total of 478 procedures, but the resident with the fewest attempts to reach competency required 219 procedures, completing 232 procedures. Some of the most frequent reasons for failed attempts included not reaching the indicated point for vascular access (20.99%) and being unable to retrieve the sample (69.10%). CONCLUSION: CUSUM analysis to assess learning curves, in addition to using low-cost simulation models, helped to appraise individualized learning, allowing an objective demonstration of competency for cordocentesis among MFM fellows.

Abdominal circumference growth velocity as a predictor of adverse perinatal outcomes in small-for-gestational-age fetuses.

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. RESULTS: A total of 154 pregnancies were included for analysis. The median birthweight for the cohort was 2,437 g (interquartile range [IQR] 2280, 2635). Overall, the primary composite outcome was relatively common (29.2%). In addition, there was a significant association between abnormal ACGV and adverse perinatal outcomes (OR 3.37, 95% CI 1.60, 7.13; adjusted OR 4.30, 95% CI 1.77, 10.49). Likewise, the AUC for the ACGV was marginally higher (0.64) than the estimated fetal weight (0.54) and ACGV + estimated fetal weight (0.54). Still, no significant difference was detected between the curves (p = 0.297). CONCLUSIONS: Our results suggest that an ACGV below the 10th centile is a risk factor for adverse perinatal outcomes among small-for-gestational-age fetuses.

Intended delivery mode and neonatal outcomes in pregnancies with fetal growth restriction.

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.Results: Seventy-two (34%) patients had an elective cesarean delivery, 73 (34%) had spontaneous labor and were expected to deliver vaginally, and 67 (32%) underwent labor induction. The composite outcome was observed in 65.3%, 89%, and 88.1% of the groups mentioned above, respectively (p < 0.001). Among patients with spontaneous labor and those scheduled for labor induction, 63% and 47.8% required an emergency cesarean delivery for intrapartum fetal distress. Compared to elective cesarean delivery, spontaneous labor (OR 4.32 [95% CI 1.79, 10.42], p = 0.001; aOR 4.85 [95% CI 1.85, 12.66], p = 0.001), and labor induction (OR 3.92 [95% CI 1.62, 9.49] p = 0.002; aOR 5.29 [95% CI 2.01, 13.87], p = 0.001) had higher odds of adverse neonatal outcomes.Conclusion: In this cohort of FGR, delivering at ≥34 weeks of gestation, pregnancies with spontaneous labor, and those that underwent labor induction had higher odds of neonatal morbidity than elective cesarean delivery.

Effects of maternal characteristics and medical history on first trimester biomarkers for preeclampsia.

Objective: To identify and quantify the effects of maternal characteristics and medical history on the distribution of Placental Growth Factor (PlGF), mean arterial pressure (MAP), and Uterine Artery Mean Pulsatility Index (UtA-PI); and to standardize the expected values for these biomarkers in the first trimester to create unique multiples of the median (MoMs) for Latin-American population. Methods: This is a prospective cohort built exclusively for research purposes of consecutive pregnant women attending their first-trimester screening ultrasound at a primary care center for the general population in Mexico City between April 2019 and October 2021. We excluded fetuses with chromosomal abnormalities, major fetal malformations, and women delivering in another care center. Linear regression was used on log-transformed biomarkers to assess the influence of maternal characteristics on non-preeclamptic women to create MoM. Results: Of a total of 2,820 pregnant women included in the final analysis, 118 (4.18%) developed PE, of which 22 (0.78%) delivered before 34 weeks of gestation, 74 (2.62%) before 37 weeks, and 44 (1.56%) from 37 weeks gestation. Characteristics that significantly influenced PLGF were fetal crown rump length (CRL), maternal age, nulliparity, body mass index (BMI), chronic hypertension, Lupus, spontaneous pregnancy, polycystic ovary syndrome (PCOS), hypothyroidism, preeclampsia (PE) in a previous pregnancy, and mother with PE. MAP had significant influence from CRL, maternal age, PE in a previous pregnancy, induction of ovulation, a mother with PE, chronic hypertension, BMI, and hypothyroidism. UtA-PI was influenced by CRL, maternal age, a mother with PE, chronic hypertension, and gestational diabetes mellitus (GDM) in a previous pregnancy. Conclusion: Population-specific multiples of the median (MoMs) for PlGF, MAP, and UtA-PI in the first trimester adequately discriminate among women developing preeclampsia later in pregnancy.

Anomalías congénitas disruptivas asociadas con misoprostol. Reporte de un caso / Disruptive congenital anomalies associated with misoprostol. Case report

Resumen ANTECEDENTES: La exposición prenatal al misoprostol puede asociarse con un espectro de defectos congénitos que varían desde anomalías del sistema nervioso central, secuencia de Moebius, defectos en la pared abdominal, defectos transversales en las extremidades hasta alteraciones fetales. Esos defectos se observan más comúnmente con esquemas de solo misoprostol para inducción del aborto. Por esos antecedentes es importante que la historia clínica de toda paciente obstétrica sea exhaustiva para permitir identificar el antecedente de la exposición prenatal luego de un aborto fallido. CASO CLINICO: Paciente de 21 años, con 32 semanas de embarazo, con diagnóstico de feto con ventriculomegalia. En la evaluación ecográfica destacó la ventriculomegalia triventricular severa, simétrica y la angulación de ambas extremidades inferiores en varo. La resonancia magnética reportó: ventriculomegalia no comunicante severa, bilateral, simétrica, por probable estenosis del acueducto de Silvio. Cariotipo 46,XY y perfil TORCH negativo. El embarazo finalizó mediante cesárea, por indicación fetal a las 35 semanas. La evaluación al nacimiento reportó: parálisis facial bilateral, macrocefalia y pie equino varo bilateral. Al volver a interrogar a la paciente refirió haber sido tratada con misoprostol en el primer trimestre del embarazo, con fines abortivos. Al descartar las alteraciones cromosómicas e infecciosas se estableció el diagnóstico de secuencia Moebius. CONCLUSIONES: La exposición prenatal al misoprostol está relacionada con la aparición de defectos vasculares en algunos fetos expuestos. Aún no se ha determinado el espectro preciso ni la estimación potencial de teratogenicidad. La historia clínica es el pilar para la asociación en estos casos.

Abstract BACKGROUND: Prenatal misoprostol exposure can be associated with a spectrum of birth defects, ranging from central nervous system abnormalities, Moebius sequence, abdominal wall defects, as well as transverse limb defects, fetal abnormalities are more commonly seen with the use of the misoprostol-only regimen for induction of abortion, such that a thorough medical history is essential to detect a history of prenatal exposure after a failed abortion. CLINICAL CASE: A 21-year-old patient, with a 32-week pregnancy, who attended the institute with a diagnosis of a fetus with ventriculomegaly, the ultrasound evaluation highlighted severe symmetric triventricular ventriculomegaly and angulation of both lower extremities in varus, magnetic resonance imaging reported severe non-communicating ventriculomegaly Symmetric bilateral, due to probable stenosis of the aqueduct of Silvio, the karyotype reported 46, XY, as well as a negative TORCH profile, however, a cesarean section was performed for fetal indication at 35 weeks, the evaluation at birth showed bilateral facial paralysis, macrocephaly and foot Bilateral equinus varus, upon re-examination the patient referred the use of misoprostol in the first trimester of pregnancy for abortive purposes, so as there were no chromosomal or infectious alterations, a Moebius sequence was suggested. CONCLUSIONS : Prenatal exposure to misoprostol is related to the appearance of vascular disruption defects in some exposed fetuses, the precise spectrum and potential estimation of teratogenicity have not yet been determined, the clinical history is the mainstay for the association in these cases.

Cord Blood SARS-CoV-2 IgG Antibodies and Their Association With Maternal Immunity and Neonatal Outcomes.

Passive transplacental immunity is crucial for neonatal protection from infections. Data on the correlation between neonatal immunity to SARS-CoV-2 and protection from adverse outcomes is scarce. This work aimed to describe neonatal seropositivity in the context of maternal SARS-CoV-2 infection, seropositivity, and neonatal outcomes. This retrospective nested case-control study enrolled high-risk pregnant women with a SARS-CoV-2 RT-PCR positive test who gave birth at the Instituto Nacional de Perinatología in Mexico City and their term neonates. Anti-SARS-CoV-2 IgG antibodies in maternal and cord blood samples were detected using a chemiluminescent assay. In total, 63 mother-neonate dyads (mean gestational age 38.4 weeks) were included. Transplacental transfer of SARS-CoV-2 IgG occurred in 76% of neonates from seropositive mothers. A positive association between maternal IgG levels and Cycle threshold (Ct) values of RT-qPCR test for SARS-CoV-2 with neonatal IgG levels was observed. Regarding neonatal outcomes, most seropositive neonates did not require any mechanical ventilation, and none developed any respiratory morbidity (either in the COVID-19 positive or negative groups) compared to 7 seronegative neonates. Furthermore, the odds of neonatal respiratory morbidity exhibited a tendency to decrease when neonatal IgG levels increase. These results add further evidence suggesting passive IgG transfer importance.