The sFlt-1/PlGF Ratio at 12, 24, and 32 Weeks Gestation in Twin Pregnancies as a Predictor of Placental Dysfunction.

Background: This study aims to assess the utility of the sFlt-1/PlGF ratio throughout pregnancy in predicting placental dysfunction and neonatal outcomes in twin pregnancies. Methods: Prospective study at a tertiary hospital. All pregnant women with a twin pregnancy who signed the informed consent were included. The sFlt-1/PlGF ratio was measured at 12, 24, and 32 weeks' gestation. Results: Seventy patients were included, and 30% developed placental dysfunction. Differences were found in the mean sFlt-1/PlGF ratios at week 32 (13.6 vs. 31.8, p = 0.007). Optimal cutoffs at 12, 24, and 32 weeks to identify patients who develop placental dysfunction were 32.5, 8.5, and 30.5, respectively, with ORs of 4.25 (1.13-20.69 95% IC; p = 0.044), 13.5 (3.07-67.90 95% IC; p = 0.001), 14.29 (3.59-66.84 95% IC; p < 0.001). The sFlt-1/PlGF ratio at 32 weeks was associated with gestational age at birth. The sFlt-1/PlGF ratio in weeks 24 and 32 had a statistically significant negative correlation with the birth weight percentile in both twins. Conclusions: The potential of the sFlt-1/PlGF ratio as a predictive tool for placental dysfunction in twin pregnancies is underscored.

Perinatal Outcomes of Monochorionic Twin Pregnancies Conceived Naturally Versus through Assisted Reproductive Techniques.

Objective: It has been reported that monochorionic twin pregnancies conceived through assisted reproductive techniques (ART) display a higher risk of second-trimester miscarriage, cesarean delivery, and neonatal death than those conceived naturally. The aim of this study was to compare the perinatal outcomes of monochorionic diamniotic (MCDA) twin pregnancies conceived naturally and through ART in a tertiary hospital. Methods: This was a retrospective cohort study of all MCDA twin pregnancies that received obstetric care and delivered at La Fe University and Polytechnic Hospital between 2015 and 2021. MCDA pregnancies that were referred to the tertiary hospital for specialized management, follow-up, and delivery were also included. The study was approved by The Health Research Institute Hospital La Fe (IIS La Fe). Results: Among the 184 MCDA pregnancies, 149 (81%) had a natural conception, and 35 (19%) were conceived through ART. Patients with an MCDA pregnancy who conceived through ART had a significantly older maternal age (38.0 [35.5-42.5] vs. 32.0 [29.0-36.0], p < 0.001) and an elevated rate of nulliparity (80.0% vs. 50.3%, p = 0.001). Regarding pregnancy complications, MCDA pregnancies through ART were associated with a significantly higher incidence of gestational diabetes (22.9% vs. 2.7%, p < 0.001), hypertensive disorders during pregnancy (22.9% vs. 9.4%, p = 0.04), and other pregnancy complications such as threatened labor or preterm prelabor rupture of membranes (14.3% vs. 36.2%, p = 0.015), than naturally conceived MCDA pregnancies. No differences were found in the incidence of twin-to-twin transfusion syndrome (20% vs. 33.6%, p = 0.155). MCDA pregnancies through natural conception had a greater rate of vaginal delivery than MCDA through ART (16.8% vs. 2.9%, p = 0.032). When adjusted for confounding factors, MCDA pregnancies through ART were only more likely to develop gestational diabetes than those naturally conceived (aOR 7.86, 95% CI 1.55-39.87). No differences were found regarding neonatal outcomes between groups. Conclusions: Compared with naturally conceived MCDA twin pregnancies, those conceived through ART displayed a significantly higher risk of developing gestational diabetes. No differences regarding other pregnancy complications, mode of delivery, or neonatal outcomes were found between groups.

sFlt-1/PlGF ratio as a predictor of pregnancy outcomes in twin pregnancies: a systematic review.

OBJECTIVE: To review the usefulness of the sFlt-1/PlGF ratio to detect adverse pregnancy outcomes related to placental dysfunction in twin pregnancies. METHODS: A systematic review in Pubmed-Medline, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, and National Guideline was performed. Studies were selected if they were published in the last 10 years, included a sample size equal to or greater than 10 twin gestations, determined the sFlt-1/PIGF ratio, and revealed the pregnancy outcome of the included patients. RESULTS: A total of 11 studies were selected. Outcomes related to the association between sFlt-1/PlGF ratio throughout pregnancy and perinatal outcome, particularly related to placental dysfunction (early and late-onset preeclampsia and FGR), were collected. The vast majority of studies showed an increased sFlt-1/PlGF ratio in twin pregnancies complicated with preeclampsia or other adverse perinatal outcomes compared with uneventful pregnancies. The included articles revealed promising results when evaluating the usefulness of the sFlt-1/PlGF ratio to rule out preeclampsia. The scarce available data regarding FGR suggests that the sFlt-1/PlGF ratio is a promising tool for detecting this pregnancy complication. Data concerning other aspects of the sFlt-1/PlGF ratio, such as its evolution during healthy twin pregnancies or variations according to chorionicity, is limited. CONCLUSION: The sFlt-1/PlGF ratio in twin pregnancies is useful to detect, and particularly to rule out adverse pregnancy outcomes related to placental dysfunction, such as preeclampsia or FGR.

Severe COVID-19 Infection during Pregnancy Requiring ECMO: Case Report and Review of the Literature.

BACKGROUND: The risk of developing severe COVID-19 that requires admission to an intensive care unit (ICU) and invasive ventilation is increased in pregnant women. Extracorporeal membrane oxygenation (ECMO) has been successfully used to manage critical pregnant and peripartum patients. CASE REPORT: A 40-year-old patient, unvaccinated for COVID-19, presented to a tertiary hospital in January 2021 at 23 weeks of gestation due to respiratory distress, cough, and fever. The patient had a confirmed diagnosis of SARS-CoV-2 with a PCR test in a private center 48 h before. She required admission into the ICU due to respiratory failure. High-flow nasal oxygen therapy, intermittent noninvasive mechanical ventilation (BiPAP), mechanical ventilation, prone positioning, and nitric oxide therapy were administered. Additionally, hypoxemic respiratory failure was diagnosed. Thus, circulatory assistance using ECMO with venovenous access was performed. After 33 days of ICU admission, the patient was transferred to the internal medicine department. She was discharged 45 days after hospital admission. At 37 weeks of gestation, the patient presented active labor and underwent an uneventful vaginal delivery. CONCLUSIONS: Severe COVID-19 in pregnancy may lead to the requirement for ECMO administration. This therapy should be administered in specialized hospitals using a multidisciplinary approach. COVID-19 vaccination should be strongly recommended to pregnant women to decrease the risk of severe COVID-19.

Comparison of Maternal-Fetal Outcomes among Unvaccinated and Vaccinated Pregnant Women with COVID-19.

Background: This study sought to elucidate whether COVID-19 vaccination, during gestation or before conception, entails a decreased incidence of severe COVID-19 disease during pregnancy. Methods: This retrospective cohort study included all pregnant women that were followed up at a tertiary University Hospital with SARS-CoV-2 infection diagnosed between 1 March 2020 and 30 July 2022. The primary outcome of the study was to compare maternal and perinatal outcomes in unvaccinated and vaccinated pregnant patients with SARS-CoV-2 infection. Results: A total of 487 pregnant women with SARS-CoV-2 infection were included. SARS-CoV-2 infection during the third trimester of pregnancy was associated with an 89% lower probability of positive cord-blood SARS-CoV-2 IgG antibodies (OR 0.112; 95% CI 0.039-0.316), compared with infection during the first or the second trimester. Vaccinated pregnant women (201 (41.27%)) with COVID-19 had an 80% lower risk for developing pneumonia and requiring hospital admission due to COVID-19 than unvaccinated patients (aOR 0.209; 95% CI 0.044-0.985). Noticeably, pregnant patients with SARS-CoV-2 infection with at least two doses of the COVID-19 vaccine did not develop severe COVID-19. Conclusion: Vaccinated women with SARS-CoV-2 infection during pregnancy are associated with decreased hospital admission due to COVID-19 as well as reduced progression to severe COVID-19.

Early Fetal Growth Restriction of Both Twins in a Transgender Man.

Gender dysphoria affects 0.5% of people worldwide. Transgender men display a divergence between the female genetic sex and the gender male identity. To the best of our knowledge, we describe the first case report with regard to a transgender man with a dichorionic diamniotic twin pregnancy obtained by artificial insemination using donor sperm as a monoparental family, presenting early fetal growth restriction of both twins. The patient is a 35-year-old transgender man who had previously received gender-affirming hormone therapy based on testosterone for five years and had a prior bilateral mastectomy as gender-affirming surgery. Whether assisted reproductive techniques have any influence on obstetrical outcomes among these patients and whether prior long-term intake of gender-affirming hormone therapy has an impact on pregnancy and obstetrical outcomes remain to be elucidated.

Combination of Feature Selection and Resampling Methods to Predict Preterm Birth Based on Electrohysterographic Signals from Imbalance Data.

Due to its high sensitivity, electrohysterography (EHG) has emerged as an alternative technique for predicting preterm labor. The main obstacle in designing preterm labor prediction models is the inherent preterm/term imbalance ratio, which can give rise to relatively low performance. Numerous studies obtained promising preterm labor prediction results using the synthetic minority oversampling technique. However, these studies generally overestimate mathematical models' real generalization capacity by generating synthetic data before splitting the dataset, leaking information between the training and testing partitions and thus reducing the complexity of the classification task. In this work, we analyzed the effect of combining feature selection and resampling methods to overcome the class imbalance problem for predicting preterm labor by EHG. We assessed undersampling, oversampling, and hybrid methods applied to the training and validation dataset during feature selection by genetic algorithm, and analyzed the resampling effect on training data after obtaining the optimized feature subset. The best strategy consisted of undersampling the majority class of the validation dataset to 1:1 during feature selection, without subsequent resampling of the training data, achieving an AUC of 94.5 ± 4.6%, average precision of 84.5 ± 11.7%, maximum F1-score of 79.6 ± 13.8%, and recall of 89.8 ± 12.1%. Our results outperformed the techniques currently used in clinical practice, suggesting the EHG could be used to predict preterm labor in clinics.

sFlt-1/PlGF Ratio at 24 Weeks Gestation in Twin Pregnancies as a Predictor of Preeclampsia or Fetal Growth Restriction.

INTRODUCTION: The objective was to elucidate if the sFlt-1/PlGF ratio at 24 weeks in twin pregnancies could be useful to select patients who subsequently develop diseases related to placental dysfunction, such as preeclampsia or fetal growth restriction (FGR). METHODS: This was a prospective study among all twin pregnancies followed up at a tertiary hospital. The sFlt-1/PlGF ratio was determined at 24 weeks. RESULTS: A total of 108 patients with a twin gestation were included. Pregnant women who developed preeclampsia and/or FGR displayed a significantly higher sFlt-1/PlGF ratio at 24 weeks, compared to those who did not develop these diseases (20.3 vs. 4.3, p = 0.002). The mean sFlt-1/PlGF ratio was not significantly different between patients who subsequently developed preeclampsia compared with those that developed FGR (29.8 vs. 18.45, p = 0.42). A sFlt-1/PlGF ratio ≥17 at 24 weeks is associated with a significant increase in the frequency of preeclampsia (odds ratio, 37.13 [95% confidence interval, 4.78-288.25]; p = 0.002), and FGR (odds ratio, 39.58 [95% confidence interval, 6.31-248.17]; p < 0.001). The addition of maternal characteristics and mean pulsatility index of the uterine arteries to the sFlt-1/PlGF ratio at 24 weeks enhances the identification of patients who develop preeclampsia or FGR. CONCLUSION: The sFlt-1/PlGF ratio at 24 weeks in twin pregnancies, combined with the mean pulsatility index of the uterine arteries and maternal characteristics, could select patients who develop preeclampsia or FGR. These patients might benefit from a close follow-up in order to avoid maternal-fetal adverse outcomes.

Diagnosis of intraamniotic inflammation by measuring vaginal interleukin-6 in patients with cervical insufficiency: could amniocentesis be avoided?

BACKGROUND: Cervical insufficiency is a recurrent, passive, and painless dilation of the cervix in the second trimester. The etiology is unclear, but there may be an association with subclinical intraamniotic infection. Interleukin-6 (IL-6) production in the amniotic cavity is induced by bacterial invasion, it is the major proinflammatory cytokine released in response to infection. Although the gold standard method to measure it is through an amniocentesis, the procedure constitutes an invasive technique with several associated risks. The objective of this study is to determine if there is a correlation between intraamniotic and vaginal IL-6 in patients with cervical insufficiency and bulging membranes during the second trimester of pregnancy, in order to avoid an amniocentesis before the rescue cerclage. METHODS: A cohort study was performed in which all patients with cervical insufficiency and bulging membranes admitted into our tertiary hospital between 2019 and 2020 were included, and a control group of asymptomatic women in the second trimester of gestation where studied at the same time. Patients with bulging membranes underwent an amniocentesis to quantify amniotic IL-6, and a sample of vaginal fluid for vaginal IL-6 determination was obtained from both the study and the control group. RESULTS: A total of 20 women were included in each group. Median gestational age at diagnosis was 22 weeks in patients with bulging membranes, and 21 weeks in the control group. Vaginal IL-6 in control group (10.875 pg/mL) is much lower than the study group one (1308.77 pg/ml). In patients with bulging membranes, vaginal IL-6 expression was lower in the vagina than in the amniotic cavity [average IL-6 in the amniotic cavity 26890.07 pg/mL, vs 1308.77 pg/mL in the vagina (p < .01)]. Through a Spearman coefficient correlation rank [rho = 0.709 (p < .001)], there is a positive correlation between amniotic and vaginal IL-6 values. The best value of this correlation was calculated with the ROC curve, being the area under the curve 0.929 (CI 95% 0.721-0.995), and the cutoff of point less than 61.4 pg/ml (sensitivity 83.33%; specificity 92.86%). Patients with vaginal IL-6 < 61.4 pg/ml associated a longer latency time between diagnosis and delivery, a higher neonatal weight and a lower perinatal mortality. Rescue cerclage in vaginal IL-6 < 61.4 pg/ml was the best predictor of good pregnancy outcome. CONCLUSION: There is a correlation between intraamniotic and vaginal IL-6 in patients with cervical insufficiency and bulging membranes during the second trimester of pregnancy. However, further studies are needed in order to considerate the avoidance of an amniocentesis before an emergency cerclage.

Assessment of Dispersion and Bubble Entropy Measures for Enhancing Preterm Birth Prediction Based on Electrohysterographic Signals.

One of the remaining challenges for the scientific-technical community is predicting preterm births, for which electrohysterography (EHG) has emerged as a highly sensitive prediction technique. Sample and fuzzy entropy have been used to characterize EHG signals, although they require optimizing many internal parameters. Both bubble entropy, which only requires one internal parameter, and dispersion entropy, which can detect any changes in frequency and amplitude, have been proposed to characterize biomedical signals. In this work, we attempted to determine the clinical value of these entropy measures for predicting preterm birth by analyzing their discriminatory capacity as an individual feature and their complementarity to other EHG characteristics by developing six prediction models using obstetrical data, linear and non-linear EHG features, and linear discriminant analysis using a genetic algorithm to select the features. Both dispersion and bubble entropy better discriminated between the preterm and term groups than sample, spectral, and fuzzy entropy. Entropy metrics provided complementary information to linear features, and indeed, the improvement in model performance by including other non-linear features was negligible. The best model performance obtained an F1-score of 90.1 ± 2% for testing the dataset. This model can easily be adapted to real-time applications, thereby contributing to the transferability of the EHG technique to clinical practice.

Optimized Feature Subset Selection Using Genetic Algorithm for Preterm Labor Prediction Based on Electrohysterography.

Electrohysterography (EHG) has emerged as an alternative technique to predict preterm labor, which still remains a challenge for the scientific-technical community. Based on EHG parameters, complex classification algorithms involving non-linear transformation of the input features, which clinicians found difficult to interpret, were generally used to predict preterm labor. We proposed to use genetic algorithm to identify the optimum feature subset to predict preterm labor using simple classification algorithms. A total of 203 parameters from 326 multichannel EHG recordings and obstetric data were used as input features. We designed and validated 3 base classifiers based on k-nearest neighbors, linear discriminant analysis and logistic regression, achieving F1-score of 84.63 ± 2.76%, 89.34 ± 3.5% and 86.87 ± 4.53%, respectively, for incoming new data. The results reveal that temporal, spectral and non-linear EHG parameters computed in different bandwidths from multichannel recordings provide complementary information on preterm labor prediction. We also developed an ensemble classifier that not only outperformed base classifiers but also reduced their variability, achieving an F1-score of 92.04 ± 2.97%, which is comparable with those obtained using complex classifiers. Our results suggest the feasibility of developing a preterm labor prediction system with high generalization capacity using simple easy-to-interpret classification algorithms to assist in transferring the EHG technique to clinical practice.

Transitory Fetal Skin Edema in a Pregnant Patient with a Mild SARS-CoV-2 Infection.

BACKGROUND: Vertical transmission of the Coronavirus Disease 2019 (COVID-19) is still controversial. Additionally, the consequences of the infection during pregnancy in the offspring also are unknown. CASE: A transitory fetal skin edema and polyhydramnios have been demonstrated by ultrasound in a pregnant patient with COVID-19 after a negative RT-PCR for SARS-CoV-2. The fetal findings presented a spontaneous resolution in utero, and abnormal findings were not found in the newborn. CONCLUSION: Women who have undergone SARS-CoV-2 infection during pregnancy should receive a subsequent appropriate follow-up in order to clarify the fetal consequences of the novel coronavirus, if any.

Risk factors for vertical transmission of hepatitis C virus: a single center experience with 710 HCV-infected mothers.

OBJECTIVE: The aim of this study was to analyze the risk factors on the perinatal transmission of hepatitis C virus (HCV). STUDY DESIGN: A retrospective cohort study with 711 infants born to 710 HCV-infected mothers was conducted at the Hospital La Fe, in Valencia, Spain, from 1986 to 2011. As potential risk factors for transmission we analyzed: maternal age, mode of acquisition of HCV infection, HIV co-infection, antiretroviral treatment against HIV, CD4 cell count, HIV and HCV viral load, liver enzyme levels during pregnancy, smoking habit, gestational age, intrapartum invasive procedures, length of rupture of membranes, length of labor, mode of delivery, episiotomy, birth weight, newborn gender and type of feeding. RESULTS: Overall perinatal HCV transmission rate was 2.4%. The significant risk factors related with HCV transmission were maternal virus load >615copies/mL (OR 9.3 [95% CI 1.11-78.72]), intrapartum invasive procedures (OR 10.1 [95% CI 2.6-39.02]) and episiotomy (OR 4.2 [95% CI 1.2-14.16]). HIV co-infection and newborn female were near significance (p=0.081 and 0.075, respectively). CONCLUSIONS: Invasive procedures as fetal scalp blood sampling or internal electrode and episiotomy increase vertical transmission of HCV, especially in patients with positive HCV RNA virus load at delivery.

Good prognosis of cerclage in cases of cervical insufficiency when intra-amniotic inflammation/infection is ruled out.

OBJECTIVE: To determine if absence of sub-clinical intra-amniotic inflammation improves the prognosis of rescue cerclage in cases of bulging membranes. METHODS: Cohort study with all women with bulging membranes admitted into our hospital between 2009 and 2013. Patients underwent amniocentesis to quantify amniotic glucose, leukocytes, IL-6 and leukocyte esterase levels and for microbiological culture. All patients without intra-amniotic inflammation or sub-clinical chorioamnionitis were proposed a physical examination-indicated cervical cerclage. Those who did not accept were treated with bed rest. RESULTS: We enrolled 31 women. Median gestational age at diagnosis was 23 + 1 (21­25 + 4) weeks. Median interval until delivery was 12 (3­52.5) d. IL-6 had the highest diagnostic accuracy for good prognosis. Patients with IL6 <2.90 ng/ml were diagnosed later in pregnancy and presented a longer interval until delivery (89 versus 4 d), higher gestational age at delivery (35 + 1 versus 23 + 3 weeks) and a lower rate of prematurity (54.5% versus 100%) and perinatal mortality (0% versus 80%) than those with IL-6 ≥2.90 ng/ml. Rescue cerclage and low Il-6 were the best predictors of good outcome. CONCLUSION: IL-6 levels in amniotic fluid may be of clinical value for individualizing the management of patients with bulging membranes for placement of rescue cerclage.

Inversión uterina puerperal: experiencia en nuestro centro / Puerperal uterine inversion: a single-center experience

Objetivo. Evaluar la incidencia, la evolución y el riesgo de recurrencia en casos de inversión uterina puerperal en nuestro centro. Material y métodos. Estudio retrospectivo. Veintidós casos de inversión uterina puerperal entre enero del 1993 y diciembre del 2013. Se analizan los diferentes riesgos. Resultados. Pacientes: edad media: 28 años (18-41); 19 nulíparas (86%); 4 pacientes presentaban cirugía uterina anterior (18%). Trabajo de parto: 6 finalizaron la gestación mediante cesárea (27%), y 16 (73%) vía vaginal. Peso medio de los recién nacidos: 3.111 g (2.130-3.950); 8 casos de retención de placenta (36,4%) y 3 atonías uterinas (13,6%). Tipo inversión: 100% aguda. Complicaciones y manejo: hemorragia severa en 7 pacientes; 20 casos (91%) se resolvieron mediante maniobra de Johnson; 2 histerectomías (9%). No hubo muertes ni recurrencias. Conclusiones. La nuliparidad y la retención de placenta fueron factores de riesgo importantes en nuestro estudio. La precocidad en el diagnóstico y el tratamiento es de vital importancia. La cirugía debe ser la última opción (AU)

Objective. To assess the incidence, outcomes, and risk of recurrence of puerperal uterine inversion in our hospital. Material and methods. A retrospective study was carried out in 22 cases of puerperal uterine inversion from January 1993 to December 2013 in our hospital. We analyzed different risk factors. Results. The mean age of the patients was 28 years (18-41). Nineteen (86%) were nulliparous. Four (18%) had undergone previous uterine surgery. Delivery was through cesarean section in 6 patients (27%) and through the vaginal route in 16 (73%). The mean birthweight was 3111 grams (2130-3950). Retained placenta occurred in 8 patients (36.4%) and uterine atony in 3 (13.6%). Uterine inversion was acute in all patients. Complications and management consisted of severe hemorrhage in 7 patients, 20 cases (91%) were resolved by the Johnson procedure, and 22 hysterectomies (9%) were performed. There were no deaths and no recurrences. Conclusions. In our study, important risk factors were nulliparity and placenta accreta. Early diagnosis and treatment are of the utmost importance. Surgery should be the last option (AU)

Arabin cerclage pessary as a treatment of an acute urinary retention in a pregnant woman with uterine prolapse.

A 35-year-old gravida 7, para 1, and abortus 5 female with hypogastric pain and inability to void urine after 14 + 3 weeks of amenorrhea was examined in the emergency department. One year before, a uterine prolapse had been diagnosed in another hospital. Examination showed a uterine prolapse grade 2 with palpable bladder. The patient was unable to void urine. After a manual reduction of the uterine prolapse, the patient underwent an emergency catheterization for bladder drainage. A Hodge pessary (size 70) was placed, which led to spontaneous micturitions. Due to the persistence of the symptoms the following day, Hodge pessary was replaced by an Arabin cerclage pessary. Although the pessary could be removed from the beginning of the second trimester, due to the uterine prolapse as a predisposing factor in the patient and the uncomplicated progression of pregnancy, it was decided to maintain it in our patient. Therefore, Arabin cerclage pessary allowed a successful pregnancy outcome and was not associated with threatened preterm delivery or vaginal infection.

Linfangioleiomiomatosis pulmonar y gestación / Pulmonary lymphangioleiomyomatosis and pregnancy

La linfangioleiomiomatosis (LAM) es una rara enfermedad pulmonar intersticial de muy baja incidencia, que ocasiona complicaciones importantes durante la gestación por mala adaptación a los cambios cardiorrespiratorios propios del embarazo. Presentamos el caso de una paciente diagnosticada de LAM en la infancia, que presentó 2 cuadros de disnea con buena resolución y evolución de su gestación(AU)

Lymphangioleiomyomatosis (LAM) is a rare interstitial lung disease with a very low incidence, which causes serious complications during pregnancy due to poor cardiorespiratory adaptation to the changes produced by pregnancy. We report a patient diagnosed with LAM in childhood, who experienced two episodes of dyspnea with good resolution and pregnancy outcome(AU)