The sFlt-1/PlGF Ratio at 12, 24, and 32 Weeks Gestation in Twin Pregnancies as a Predictor of Late Preterm Birth and Perinatal Event Secondary to Prematurity.

Background: Preterm birth impacts 60% of twin pregnancies, with the subsequent risk of complications in both newborns secondary to the immaturity of organs. This study aims to assess the utility of the sFlt-1/PlGF ratio throughout pregnancy in predicting late preterm birth and adverse perinatal outcomes related to prematurity in twin pregnancies. Methods: This is a prospective cohort study developed 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, from which 54.3% suffered late preterm birth. Results revealed a significant difference in sFlt-1/PlGF ratio at week 32 between term and preterm groups, with a one-unit increase associated with a 1.11-fold increase in the probability of preterm birth. The sFlt-1/PlGF ratio at week 32 alone presented considerable predictive capacities (sensitivity of 71%, specificity of 72%, a PPV of 75%, and an NPV of 68%. Similarly, at week 24, a one-unit increase in sFlt-1/PlGF ratio was associated with a 1.24-fold increase in the probability of adverse perinatal events due to prematurity. Combining parity, maternal age, conception method, BMI, and chorionicity, the model yielded better predictive capacities (sensitivity of 82%, specificity of 80%, PPV of 58%, NPV of 93%). Conclusions: The potential of the sFlt-1/PlGF ratio as a predictive tool for preterm birth and adverse perinatal outcomes secondary to prematurity in twin pregnancies is underscored.

Cerebroplacental Ratio as a Predictive Factor of Emergency Cesarean Sections for Intrapartum Fetal Compromise: A Systematic Review.

Background: This systematic review aimed to clarify the association between the cerebroplacental ratio (CPR) and emergency cesarean sections (CSs) due to intrapartum fetal compromise (IFC). Methods: Datasets of PubMed, ScienceDirect, CENTRAL, Embase, and Google Scholar were searched for studies published up to January 2024 regarding the relationship between the CPR and the rate of CS for IFC, as well as the predictive value of the CPR. Results: The search identified 582 articles, of which 16 observational studies were finally included, most of them with a prospective design. A total of 14,823 patients were involved. A low CPR was associated with a higher risk of CS for IFC. The predictive value of the CPR was very different among the studies due to substantial heterogeneity regarding the group of patients included and the time interval from CPR evaluation to delivery. Conclusions: A low CPR is associated with a higher risk of CS for IFC, although with a poor predictive value. The CPR could be calculated prior to labor in all patients to stratify the risk of CS due to IFC.

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.

Multicentre randomised trial of screening with sFlt1/PlGF and planned delivery to prevent pre-eclampsia at term: protocol of the PE37 study.

INTRODUCTION: Pre-eclampsia affects ~5%-7% of pregnancies. Although improved obstetric care has significantly diminished its associated maternal mortality, it remains a leading cause of maternal morbidity and mortality in the world. Term pre-eclampsia accounts for 70% of all cases and a large proportion of maternal-fetal morbidity related to this condition. Unlike in preterm pre-eclampsia, the prediction and prevention of term pre-eclampsia remain unsolved. Previously proposed approaches are based on combined third-trimester screening and/or prophylactic drugs, but these policies are unlikely to be widely implementable in many world settings. Recent evidence shows that the soluble fms-like tyrosine kinase-1 (s-Flt-1) to placental growth factor (PlGF) ratio measured at 35-37 weeks' gestation predicts term pre-eclampsia with an 80% detection rate. Likewise, recent studies demonstrate that induction of labour beyond 37 weeks is safe and well accepted by women. We hypothesise that a single-step universal screening for term pre-eclampsia based on sFlt1/PlGF ratio at 35-37 weeks followed by planned delivery beyond 37 weeks reduces the prevalence of term pre-eclampsia without increasing the caesarean section rates or worsening the neonatal outcomes. METHODS AND ANALYSIS: We propose an open-label randomised clinical trial to evaluate the impact of a screening of term pre-eclampsia with the sFlt-1/PlGF ratio followed by planned delivery in asymptomatic nulliparous women at 35-37 weeks. Women will be assigned 1:1 to revealed (sFlt-1/PlGF known to clinicians) versus concealed (unknown) arms. A cut-off of >90th centile is used to define the high risk of subsequent pre-eclampsia and offer planned delivery from 37 weeks. The efficacy variables will be analysed and compared between groups primarily following an intention-to-treat approach, by ORs and their 95% CI. This value will be computed using a Generalised Linear Mixed Model for binary response (study group as fixed effect and the centre as intercept random effect). ETHICS AND DISSEMINATION: The study is conducted under the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 20 November 2020. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT04766866.

Deprived areas and adverse perinatal outcome: a systematic review.

PURPOSE: This systematic review aimed to assess if women living in deprived areas have worse perinatal outcomes than those residing in high-income areas. METHODS: Datasets of PubMed, ScienceDirect, CENTRAL, Embase, and Google Scholar were searched for studies comparing perinatal outcomes (preterm birth, small-for-gestational age, and stillbirth) in deprived and non-deprive areas. RESULTS: A total of 46 studies were included. The systematic review of the literature revealed a higher risk for adverse perinatal outcomes such as preterm birth, small for gestational age, and stillbirth in deprived areas. CONCLUSION: Deprived areas are associated with adverse perinatal outcomes. More multifactorial studies are needed to assess the weight of each factor that composes the socioeconomic gradient of health in adverse perinatal outcomes.

Management of fetuses with apparent normal growth and abnormal cerebroplacental ratio: A risk-based approach near term.

INTRODUCTION: Cerebroplacental ratio (CPR) has been shown to be an independent predictor of adverse perinatal outcome at term and a marker of failure to reach the growth potential (FRGP) regardless of fetal size, being abnormal in compromised fetuses with birthweight above the 10th centile. The main aim of this study was to propose a risk-based approach for the management of pregnancies with normal estimated fetal weight (EFW) and abnormal CPR near term. MATERIAL AND METHODS: This was a retrospective study of 943 pregnancies, that underwent an ultrasound evaluation of EFW and CPR at or beyond 34 weeks. CPR values were converted into multiples of the median (MoM) and EFW into centiles according to local references. Pregnancies were then divided into four groups: normal fetuses (defined as EFW ≥10th centile and CPR ≥0.6765 MoM), small for gestational age (EFW <10th centile and CPR ≥0.6765 MoM), fetal growth restriction (EFW <10th centile and CPR <0.6765 MoM), and fetuses with apparent normal growth (EFW ≥10th centile) and abnormal CPR (<0.6765 MoM), that present FRGP. Intrapartum fetal compromise (IFC) was defined as an abnormal intrapartum cardiotocogram or pH requiring cesarean delivery. Risk comparisons were performed among the four groups, based on the different frequencies of IFC. The risks of IFC were subsequently extrapolated into a gestational age scale, defining the optimal gestation to plan the birth for each of the four groups. RESULTS: Fetal growth restriction was the group with the highest frequency of IFC followed by FRGP, small for gestational age, and normal groups. The "a priori" risks of the fetal growth restriction and normal groups were used to determine the limits of two scales. One defining the IFC risk and the other defining the appropriate gestational age for delivery. Extrapolation of the risk between both scales placed the optimal gestational age for delivery at 39 weeks of gestation in the case of FRGP and at 40 weeks in the case of small for gestational age. CONCLUSIONS: Fetuses near term may be evaluated according to the CPR and EFW defining four groups that present a progressive risk of IFC. Fetuses in pregnancies complicated by FRGP are likely to benefit from being delivered at 39 weeks of gestation.

Primary prevention with vaginal chlorhexidine before 16 weeks reduces the incidence of preterm birth: results of the Preterm Labor Prevention Using Vaginal Antiseptics study.

BACKGROUND: Preterm labor is one of the leading causes of perinatal death and is currently considered a syndrome with many causes. One of the most important causes of preterm birth is ascending infection from bacterial vaginosis. Chlorhexidine has proven to be effective against bacterial vaginosis and against bacterial biofilms without affecting gestation. OBJECTIVE: We aimed to evaluate the effectiveness of a universal primary prevention strategy for preterm birth using intravaginal chlorhexidine applied before 16 weeks (Preterm Labor Prevention Using Vaginal Antiseptics study). STUDY DESIGN: We performed a prospective observational study with 2 cohorts of pregnant women that were assigned either to prevention of preterm birth by means of intravaginal chlorhexidine (Cum Laude Chlorhexidine, chlorhexidine digluconate 0.2%) before 16 weeks (n=413), or to no treatment following the usual hospital protocol (n=704). Primary outcomes were the incidence of spontaneous preterm birth before 34 and 37 weeks; the incidence of preterm birth before 34 and 37 weeks, including inductions for premature rupture of membranes; and the incidence of preterm birth before 34 and 37 weeks, including any indication for termination of pregnancy. Both cohorts were compared using Mann-Whitney and Fisher tests. Finally, a multivariable analysis, including the odds ratio was performed, adjusting for clinical parameters, to evaluate the importance of the different determinants in the prediction of preterm birth. RESULTS: In pregnancies treated with chlorhexidine, the incidences of spontaneous preterm birth; preterm birth, including induction for premature rupture of membranas; and preterm birth, including any indication for termination of pregnancy were at 34 and 37 weeks: 0% and 0%, 0.24% and 1.69, and 2.90% and 3.15%, respectively; whereas in nontreated pregnancies, these incidences were 9% and 11%, 12% and 23%, and 35% and 43%, respectively. According to the multivariable analysis, the incidence of preterm birth among women treated with chlorhexidine before 16 weeks was halved (Odds ratio, 0.52; P<.05). CONCLUSION: Universal treatment with vaginal chlorhexidine before 16 weeks reduces the incidence of preterm birth, especially before 34 weeks.

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.

COVID-19 Vaccines and Assisted Reproductive Techniques: A Systematic Review.

Objective: To review the current knowledge concerning COVID-19 vaccination and assisted reproductive techniques (ART). Methods: A systematic review in Pubmed-Medline, the Cochrane Database, the Web of Science, and the National Guideline was performed. Studies were selected if they were primary studies, included vaccinated (case) and unvaccinated (control) patients, and described fertility treatment response. Results: A total of 24 studies were selected. Outcomes related to the association between COVID-19 vaccination and ART were collected. The vast majority of studies found no statistical differences concerning oocyte stimulation response, embryo quality, implantation rates, or pregnancy outcome (clinical or biochemical pregnancy rates and losses) when comparing cases and controls. Similarly, no differences were found when comparing different types of vaccines or distinct ART (artificial insemination, in vitro fertilization, and embryo transfer of frozen embryos). Conclusions: Patients receiving ART and health care professionals should be encouraged to complete and recommend COVID-19 vaccination, as the available evidence regarding assisted reproductive outcomes is reassuring.

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.

An Update on COVID-19 Vaccination and Pregnancy.

Pregnant women are more prone to experience severe COVID-19 disease, including intensive care unit (ICU) admission, use of invasive ventilation, extracorporeal membrane oxygenation (ECMO), and mortality compared to non-pregnant individuals. Additionally, research suggests that SARS-CoV-2 infection during pregnancy is linked to adverse pregnancy outcomes, such as preterm birth, preeclampsia, and stillbirth, as well as adverse neonatal outcomes, including hospitalization and admission to the neonatal intensive care unit. This review assessed the available literature from November 2021 to 19 March 2023, concerning the safety and effectiveness of COVID-19 vaccination during pregnancy. COVID-19 vaccination administered during pregnancy is not linked to significant adverse events related to the vaccine or negative obstetric, fetal, or neonatal outcomes. Moreover, the vaccine has the same effectiveness in preventing severe COVID-19 disease in pregnant individuals as in the general population. Additionally, COVID-19 vaccination is the safest and most effective method for pregnant women to protect themselves and their newborns from severe COVID-19 disease, hospitalization, and ICU admission. Thus, vaccination should be recommended for pregnant patients. While the immunogenicity of vaccination in pregnancy appears to be similar to that in the general population, more research is needed to determine the optimal timing of vaccination during pregnancy for the benefit of the neonate.

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.

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.

Critical Care in SARS-CoV-2 Infected Pregnant Women: A Prospective Multicenter Study.

Evidence suggests that pregnant women are at a higher risk of complications compared to the general population when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the reasons that lead them to need intensive care are not clear. This is a prospective multicenter study of SARS-CoV-2 positive pregnant women, registered by the Spanish Obstetric Emergency Group, with the objective to define the characteristics of the mothers who were admitted to the Intensive Care Unit (ICU) and to investigate the causes and risk factors for ICU admission. A total of 1347 infected pregnant women were registered and analyzed, of whom, 35 (2.6%) were admitted to the ICU. No differences in maternal characteristics or comorbidities were observed between ICU and non-ICU patients, except for in vitro fertilization and multiple pregnancies. The main causes of admission to the ICU were non-obstetric causes (worsening of the maternal condition and respiratory failure due to SARS-CoV-2 pneumonia, 40%) and a combination of coronavirus disease 2019 (COVID-19) symptoms and obstetrical complications (31.4%). The multivariable logistic analysis confirmed a higher risk of ICU admission when pre-eclampsia or hemorrhagic events coexist with pneumonia. The incidence of thromboembolic events and disseminated intravascular coagulation were also significantly higher among patients admitted to the ICU. Therefore, surveillance and rapid intervention should be intensified in SARS-CoV-2 infected pregnant women with the mentioned risk factors and complications. Emphasis should always be placed on anticoagulant therapy in these patients due to the increased thromboembolic risk, C-section surgery and immobilization in the ICU.

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.

COVID-19 Vaccines during Pregnancy and Breastfeeding: A Systematic Review.

Background: Pregnant and breastfeeding women received unclear recommendations regarding COVID-19 vaccination at the beginning of the pandemic, as they were not included in the initial clinical trials. This systematic review aims to provide an update regarding COVID-19 vaccines during pregnancy and breastfeeding. Methods: The systematic review was carried out through a literature search in Medline/Pubmed. Studies were selected if they included information regarding COVID-19 vaccination during pregnancy and breastfeeding. The PRISMA guidelines for systematic reviews were followed. Results: A total of 33 studies were included. The main adverse effect is pain at the injection site, as in the general population. Adverse effects are more frequent after the second dose, being slightly more frequent after the Moderna vaccine. COVID-19 vaccination reduces the risk of severe COVID-19 in pregnant women. Additionally, COVID-19 vaccination induces artificial active immunogenicity in the mother and natural passive immunogenicity in the child. Breastmilk straddles both immediate antibody-mediated and long-lived cellular-mediated immune protection. Regarding neonatal benefits, vaccination is associated with a larger and more stable Immunoglobulin G response, while COVID-19 Infection is associated with a rapid and long-lasting Immunoglobulin A response. Conclusions: COVID-19 vaccines are not only suggested but strongly recommended for pregnant and breastfeeding populations to protect mothers and newborns.

Pregnancy Outcomes and SARS-CoV-2 Infection: The Spanish Obstetric Emergency Group Study.

Pregnant women who are infected with SARS-CoV-2 are at an increased risk of adverse perinatal outcomes. With this study, we aimed to better understand the relationship between maternal infection and perinatal outcomes, especially preterm births, and the underlying medical and interventionist factors. This was a prospective observational study carried out in 78 centers (Spanish Obstetric Emergency Group) with a cohort of 1347 SARS-CoV-2 PCR-positive pregnant women registered consecutively between 26 February and 5 November 2020, and a concurrent sample of PCR-negative mothers. The patients' information was collected from their medical records, and the association of SARS-CoV-2 and perinatal outcomes was evaluated by univariable and multivariate analyses. The data from 1347 SARS-CoV-2-positive pregnancies were compared with those from 1607 SARS-CoV-2-negative pregnancies. Differences were observed between both groups in premature rupture of membranes (15.5% vs. 11.1%, p < 0.001); venous thrombotic events (1.5% vs. 0.2%, p < 0.001); and severe pre-eclampsia incidence (40.6 vs. 15.6%, p = 0.001), which could have been overestimated in the infected cohort due to the shared analytical signs between this hypertensive disorder and COVID-19. In addition, more preterm deliveries were observed in infected patients (11.1% vs. 5.8%, p < 0.001) mainly due to an increase in iatrogenic preterm births. The prematurity in SARS-CoV-2-affected pregnancies results from a predisposition to end the pregnancy because of maternal disease (pneumonia and pre-eclampsia, with or without COVID-19 symptoms).