Outperformance of interleukin-6 over placental alpha microglobulin-1 in predicting preterm delivery in symptomatic women.

BACKGROUND: Threatened preterm labor is the major cause of hospital admission during the second half of pregnancy. An early diagnosis is crucial for adopting pharmacologic measures to reduce perinatal mortality and morbidity. Current diagnostic criteria are based on symptoms and short cervical length. However, there is a high false-positive rate when using these criteria, which implies overtreatment, causing unnecessary side effects and an avoidable economic burden. OBJECTIVE: This study aimed to compare the use of placental alpha microglobulin-1 and interleukin-6 as vaginal biomarkers combined with cervical length and other maternal characteristics to improve the prediction of preterm delivery in symptomatic women. STUDY DESIGN: A prospective observational study was conducted in women with singleton pregnancies complicated by threatened preterm labor with intact membranes at 24+0 to 34+6 weeks of gestation. A total of 136 women were included in this study. Vaginal fluid was collected with a swab for placental alpha microglobulin-1 determination using the PartoSure test, interleukin-6 was assessed by electrochemiluminescence immunoassay, cervical length was measured by transvaginal ultrasound, and obstetrical variables and newborn details were retrieved from clinical records. These characteristics were used to fit univariate binary logistic regression models to predict time to delivery <7 days, time to delivery <14 days, gestational age at delivery ≤34 weeks, and gestational age at delivery ≤37 weeks, and multivariate binary logistic regression models were fitted with imbalanced and balanced data. Performance of models was assessed by their F2-scores and other metrics, and the association of their variables with a risk or a protective factor was studied. RESULTS: A total of 136 women were recruited, of whom 8 were lost to follow-up and 7 were excluded. Of the remaining 121 patients, 22 had a time to delivery <7 days and 31 had a time to delivery <14 days, and 30 deliveries occurred with a gestational age at delivery ≤34 weeks and 55 with a gestational age at delivery ≤37 weeks. Univariate binary logistic regression models fitted with the log transformation of interleukin-6 showed the greatest F2-scores in most studies, which outperformed those of models fitted with placental alpha microglobulin-1 (log[interleukin-6] vs placental alpha microglobulin-1 in time to delivery <7 days: 0.38 vs 0.30; time to delivery <14 days: 0.58 vs 0.29; gestational age at delivery ≤34 weeks: 0.56 vs 0.29; gestational age at delivery ≤37 weeks: 0.61 vs 0.16). Multivariate logistic regression models fitted with imbalanced data sets outperformed most univariate models (F2-score in time to delivery <7 days: 0.63; time to delivery <14 days: 0.54; gestational age at delivery ≤34 weeks: 0.62; gestational age at delivery ≤37 weeks: 0.73). The performance of prediction of multivariate models was drastically improved when data sets were balanced, and was maximum for time to delivery <7 days (F2-score: 0.88±0.2; positive predictive value: 0.86±0.02; negative predictive value: 0.89±0.03). CONCLUSION: A multivariate assessment including interleukin-6 may lead to more targeted treatment, thus reducing unnecessary hospitalization and avoiding unnecessary maternal-fetal treatment.

Effect of Adherence to the Mediterranean Diet on Maternal Iron Related Biochemical Parameters during Pregnancy and Gestational Weight Gain.

Gestation is a crucial life stage for both women and offspring, and outcomes are affected by many environmental factors, including diet. The Mediterranean dietary pattern (MD) is considered a healthy eating pattern that can provide the nutritional requirements of pregnancy. Meanwhile, iron deficiency anemia is one of the most frequent complications related to pregnancy. This study aimed to evaluate how the level of adherence to the MD influences maternal gestational weight gain and specific iron-related maternal biochemical parameters during the pregnancy. Accordingly, an observational, population-based study using data from pregnant women conducted over the entire course of their pregnancy was carried out. Adherence to the MD was assessed once using the MEDAS score questionnaire. Of the 506 women studied, 116 (22.9%) were classified as demonstrating a high adherence, 277 (54.7%) a medium adherence, and 113 (22.3%) a low adherence to the MD. No differences were observed in gestational weight gain among the MD adherence groups but the adequacy of weight gain did vary among the groups, with the proportions of inadequate (insufficient or excessive) weight gain presenting the most notable differences. Total anemia prevalence was 5.3%, 15.6%, and 12.3%, respectively, during the first, second, and third trimesters. For iron-related biochemical parameters, no differences are observed among the adherence groups during pregnancy. With high adherence to the MD as the reference group, the crude odds of iron deficiency diagnosis are significant in the first trimester for both the medium [OR = 2.99 (1.55-5.75)] and low [OR = 4.39 (2.15-8.96)] adherence groups, with deficient adherence to the Mediterranean dietary pattern being responsible for 66.5% (35.5-82.6) and 77.2% (53.5-88.8) of the risk of iron deficiency diagnosis for medium and low adherence, respectively. However, adjusted odds ratios were not significant, possibly due to the small sample size. Our data suggest that MD adherence could be related to gestational weight gain adequacy and that optimal adherence could reduce iron deficiency and/or anemia during pregnancy in the studied population.

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.

Social Support and Mental Health in the Postpartum Period in Times of SARS-CoV-2 Pandemic: Spanish Multicentre Cohort Study.

BACKGROUND: To explore the depression and anxiety symptoms in the postpartum period during the SARS-CoV-2 pandemic and to identify potential risk factors. METHODS: A multicentre observational cohort study including 536 women was performed at three hospitals in Spain. The Edinburgh Postnatal Depression Scale (EPDS), the State-Trait Anxiety Inventory (STAI) Scale, the Medical Outcomes Study Social Support Survey (MOS-SSS), and the Postpartum Bonding Questionnaire (PBQ) were assessed after birth. Depression (EPDS) and anxiety (STAI) symptoms were measured, and the cut-off scores were set at 10 and 13 for EPDS, and at 40 for STAI. RESULTS: Regarding EPDS, 32.3% (95% CI, 28% to 36.5%) of women had a score ≥ 10, and 17.3% (95% CI, 13.9% to 20.7%) had a score ≥ 13. Women with an STAI score ≥ 40 accounted for 46.8% (95% CI, 42.3% to 51.2%). A lower level of social support (MOS-SSS), a fetal malformation diagnosis and a history of depression (p = 0.000, p = 0.019 and p = 0.043) were independent risk factors for postpartum depression. A lower level of social support and a history of mental health disorders (p = 0.000, p = 0.003) were independent risk factors for postpartum anxiety. CONCLUSION: During the SARS-CoV-2 pandemic, an increase in symptoms of anxiety and depression were observed during the postpartum period.

Cerebroplacental Ratio Prediction of Intrapartum Fetal Compromise according to the Interval to Delivery.

INTRODUCTION: A controversy exists about the accuracy of the cerebroplacental ratio (CPR) for the prediction of cesarean section for intrapartum fetal compromise (CS-IFC). Our aim was to evaluate whether the interval to delivery modifies the accuracy of CPR either as a single marker or combined with estimated fetal weight centile (EFWc), type of labor onset (TLO), and other clinical variables. METHODS: This was a multicenter retrospective study of 5,193 women with singleton pregnancies who underwent an ultrasound scan at 35+0-41+0 weeks and gave birth within 1 month of examination, at any of the participating hospitals in Spain, UK, and Italy. CS-IFC was diagnosed in case of an abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH <7.20, requiring urgent cesarean section. The diagnostic ability of CPR in multiples of the median (CPR MoM) was evaluated at different intervals to delivery, alone and combined with EFWc, TLO, and other pregnancy data such as maternal age, maternal body mass index, parity, and fetal sex, for the prediction of CS-IFC by means of ROC curves and logistic regression analysis. RESULTS: The predictive ability of CPR MoM for CS-IFC worsened with the interval to delivery. In general, the best prediction was obtained prior to labor and by adding information related to EFWc and TLO (AUC 0.71 [95% CI: 0.64-0.79], 0.73 [95% CI: 0.66-0.80], and 0.75 [95% CI: 0.69-0.81]; p < 0.0001). Addition of more clinical data did not improve prediction. In addition, results did not vary when only cases with spontaneous onset of labor were studied. CONCLUSION: CPR MoM prediction of CS-IFC at the end of pregnancy worsens with the interval to delivery. Accordingly, it should be done in the short term and considering EFWc and TLO.

MicroRNA-132 is overexpressed in fetuses with late-onset fetal growth restriction.

Background and Aims: To evaluate the expression of microRNA 132 (miR-132) in fetuses with normal growth and in fetuses with late-onset growth restriction (FGR). Methods: In a prospective cohort study, 48 fetuses (24 with late-onset FGR and 24 with normal growth) were scanned with Doppler ultrasound after 34 weeks to measure the umbilical artery and middle cerebral artery pulsatility indices and followed until birth. Subsequently, blood samples from the umbilical cord were collected to evaluate the expression of miR-132 by means of Real-time quantitative polymerase chain reaction, determining the existence of normality cut-offs and associations with birth weight (BW) centile, cerebroplacental ratio multiples of the median (CPR MoM), and intrapartum fetal compromise (IFC). Results: In comparison with normal fetuses, late-onset FGR fetuses showed upregulation of miR-132 (33.94 ± 45.04 vs. 2.88 ± 9.32 2-ddC t, p < 0.001). Using 5 as a cut-off we obtained a sensitivity of 50% and a specificity of 96% for the diagnosis of FGR, while for IFC these values were respectively 27% and 73%. Expression of miR-132 was associated with BW centile but not with CPR MoM. Finally, the best detection of IFC was achieved combining miR-132 expression and CPR MoM (AUC = 0.69, p < 0.05). Conclusion: Fetuses with late-onset FGR show upregulation of miR-132. Further studies are needed to investigate the role of miR-132 in the management of late-onset FGR.

Healthy mothers with normal cardiotocograms at term. Is maternal age a true determinant of perinatal outcome?

OBJECTIVE: to study the true determinants of adverse perinatal outcome (APO) in term healthy mothers with normal cardiotocograph (CTG), evaluating the real influence of maternal age. MATERIAL AND METHODS: In a retrospective study, we assessed a group of 529 term healthy mothers with normal CTGs that regardless of maternal age, evolved spontaneously up to 41 ± 2 weeks. The result of the conservative management was evaluated by means of univariable and multivariable logistic regression analysis, determining the association of maternal age and other clinical and ultrasonographical parameters with APO. RESULT: In contrast with low CPR MoM (OR = 0.155, p = .014), induction of labor (OR = 2.273, p = .023) and low parity (OR = 0.494, p = .026), maternal age and birth weight centile did not prove to be true determinants of perinatal outcome. The multivariable model for prediction of APO using clinical parameters presented a sensitivity of 35% and 27% for a false positive rate of 10% and 5%, AUC 0.736 (95% CI 0.655-0.818), p < .0001). CONCLUSIONS: in healthy old mothers with normal CTGs at term, APO is determined by low CPR, the existence of labor induction and low parity, while no real influence was observed for maternal age, fetal smallness, and interval examination-delivery. These results do not support the current consensus on induction at earlier weeks to prevent adverse outcomes in all cases of advanced maternal age, advocating for a more individualized, customized, and less interventional management based on fetal hemodynamics.

Risk of Gestational Diabetes Due to Maternal and Partner Smoking.

Pregnant women are among the most vulnerable to environmental exposure to tobacco smoke (EET); which has been linked to problems in the mothers' health; one of the most frequent is gestational diabetes (GD). For this reason, there are specific interventions and prevention strategies designed to reduce this exposure risk. However, currently, they are mostly aimed only at aiding the pregnant women with smoking cessation during pregnancy and do not assess or address the risk from passive exposure due to partner smoking. The aim of this work is to study the exposure to EET of pregnant women considering active and passive smoking and to evaluate its effect on the development of GD. This is an observational case-control study within a retrospective cohort of pregnant women. Information on smoking habits was obtained from both personal interviews and recorded medical history. In total, 16.2% of mothers and 28.3% of partners declared having been active smokers during pregnancy; 36.5% of the women presented EET during pregnancy when both active and passive smoking were considered. After adjustments, the association with the EET and GD of the mother was (aOR 1.10 95% CI: 0.64-1.92); for the EET of the partner, it was (aOR 1.66 95% CI: 1.01-2.77); for both partners, it was (aOR 1.82 95% CI: 1.15-2.89), adjusted by the mother's age and body mass index. There is a lack of education regarding the effects of passive exposure to tobacco smoke. It is essential that pregnant women and their partners are educated on the risks of active and passive smoking; this could improve the effectiveness of other GD prevention strategies.

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.

Predictors of adverse perinatal outcome up to 34 weeks, a multivariable analysis study.

The objective was to evaluate the best predictors of adverse perinatal outcome (APO) in foetuses examined up to 34 weeks and delivered by spontaneous or induced labour. This was a retrospective study of 129 pregnancies that underwent an ultrasound Doppler examination at 23-34 weeks and entered into labour within 30 days. Cerebroplacental ratio (CPR) and mean uterine artery pulsatility index (mUtA PI) were converted into multiples of the median (MoM) and estimated foetal weight (EFW) into centiles to adjust for gestational age (GA). Sonographic and clinical parameters were evaluated using logistic regression analysis.The multivariable model for the prediction of APO presented a notable accuracy: Detection rate (DR) was 39.5% for a false positive rate (FPR) of 5% and 56.8% for a FPR of 10%, AUC 0.82, p < .0001. Significant predictors were GA, EFW centile, and CPR MoM, but not mUtA PI MoM. Moreover, the type of labour onset did not exert any influence on APO. In conclusion, up to 34 weeks, prediction of APO after spontaneous or induced labour may be done measuring CPR and EFW.IMPACT STATEMENTWhat is already known on this subject? Earlier in pregnancy, foetal growth restriction is caused by placental disease causing progressive hemodynamic changes. These changes have been exhaustively described. Conversely, information about the best predictors of adverse outcome is scarce.What do the results of this study add? The findings of this study show that prior to 34 weeks and up to 1 month before labour, labour outcome might be predicted by gestational age, foetal cerebroplacental ratio (CPR) and estimated foetal weight (EFW).What are the implications of these findings for clinical practice and/or further research? If CPR behaves as a good marker of outcome not only at the end of pregnancy but also earlier in gestation, it might be interrogated along with EFW in foetuses attempting vaginal delivery to determine the risk of adverse outcome.

Safety of Nicotine Replacement Therapy during Pregnancy: A Narrative Review.

BACKGROUND: Smoking during pregnancy is a public health problem worldwide and the leading preventable cause of fetal morbidity and mortality and obstetric disease. Although the risk of tobacco-related harm can be substantially reduced if mothers stop smoking in the first trimester, the proportion of women who do so remains modest; therefore, the treatment of smoking in pregnant women will be the first therapeutic measure that health professionals should adopt when providing care to pregnant women. The recommendation of nicotine replacement therapy during pregnancy remains controversial due to the potential effects on the health of the fetus. PURPOSE: The aim of this review was to provide an overview of human studies about the use of nicotine replacement therapy during pregnancy, evaluating the efficacy and safety of the different formulations. METHODS: The electronic databases PubMed and EMBASE were searched from May 2012 to May 2022. A total of 95 articles were identified through database searching using a combination of keywords. Out of 79 screened articles and after the removal of duplicates, 28 full-text articles were assessed for eligibility and 12 articles were finally included for review. RESULTS: Although demonstrated to be effective in adult smokers, evidence in support of NRT in pregnant women is limited. The results of the apparent safety of the use of NRT during pregnancy contradict the FDA classification of the different NRT formulations. Faster-acting formulations seem to be the safest and even most beneficial forms for the offspring. CONCLUSIONS: NRT is not completely harmless for the fetus or for the mother; however, if an adequate assessment of the risk-benefit binomial is made, its use during pregnancy to aid in quitting smoking does seem appropriate. It is necessary to establish individual recommendations on the formulation and dose to be used during pregnancy based on individual nicotinic needs.

MicroRNA-185-5p: a marker of brain-sparing in foetuses with late-onset growth restriction.

To compare the expression of microRNA-185-5p (miR-185-5p) in normal foetuses and in foetuses with late-onset growth restriction (FGR) and to determine the factors influencing this expression. In a prospective study, 40 foetuses (22 of them with late-onset FGR and 18 with normal growth) were scanned with Doppler ultrasound after week 35 and followed until birth. Subsequently, blood samples from umbilical cords were collected after delivery to evaluate the expression of miR-185-5p using real-time qPCR. Finally, multivariable regression analysis was applied to determine the clinical and ultrasonographic factors influencing miR-185-5p expression in both normal and late-onset FGR foetuses. In comparison with normal foetuses, late-onset FGR foetuses expressed upregulation of miR-185-5p (2.26 ± 1.30 versus 1.27 ± 1.03 2^-ddCt, P = 0.011). Multivariable regression analysis confirmed that cerebroplacental ratio (P < 0.05) was the only determinant of this overexpression. FGR foetuses overexpress miR-185-5p in relation to brain-sparing. Future studies will be needed to investigate the role of miR-185 in the management of late-onset FGR.

Congenital knee dislocation, case report and review of the literature.

Congenital dislocation of the knee (CDK) is characterized by hyperextension of the knee with forward displacement of the proximal tibia. It is associated with other joint dislocations and deformities and may occur isolated or as part of different systemic syndromes. Despite its characteristic postnatal morphology, prenatal descriptions are very scarce. We report a case of CDK diagnosed at 20 weeks, discuss its physiopathology, diagnosis and management and review the current literature.

Sirenomelia, case report and review of the literature.

We present a case of sirenomelia diagnosed in the first trimester of pregnancy. The ultrasound examination showed fused lower extremities and an anechoic structure in the lower abdomen that is clue in the early diagnosis. The postmortem study showed the existence of a single umbilical artery (vitelline artery), with an origin in the abdominal aorta. This finding not only explained the presence of a vascular steal with subsequent underdeveloped of pelvic organs, but also differentiated this condition from caudal regression syndrome.

Birth-weight differences at term are explained by placental dysfunction and not by maternal ethnicity. Study in newborns of first generation immigrants.

OBJECTIVE: The aim of the study was to investigate the influence of ethnicity and cerebroplacental ratio (CPR) on the birth weight (BW) of first generation Indo-Pakistan immigrants' newborns. METHODS: This was a retrospective study in a mixed population of 620 term Caucasian and Indo-Pakistan pregnancies, evaluated in two reference hospitals of Spain and Italy. All fetuses underwent a scan and Doppler examination within two weeks of delivery. The influence of fetal gender, ethnicity, GA at delivery, CPR, maternal age, height, weight and parity on BW was evaluated by multivariable regression analysis. RESULTS: Newborns of first generation Indo-Pakistan immigrants were smaller than local Caucasian newborns (mean BW mean= 3048 ± 435 g versus 3269 ± 437 g, p < .001). Multivariable regression analysis demonstrated that all studied parameters, but maternal age and ethnicity, were significantly associated with BW. The most important were GA at delivery (partial R2 = 0.175, p < .001), CPR (partial R2 = 0.032, p < .001), and fetal gender (partial R2 = 0,029, p < .001). CONCLUSIONS: The propensity to a lower BW, explained by placental dysfunction but not by maternal ethnicity is transmitted to newborns of first generation immigrants. Whatever are the factors implied they persist in the new residential setting.

GESTACOVID project: psychological and perinatal effects in Spanish pregnant women subjected to confinement due to the COVID-19 pandemic.

INTRODUCTION: COVID-19 was declared a pandemic and confinement with movement restriction measures were applied in Spain. Postnatal mental disorders are common but frequently undiagnosed, being a risk period to develop anxiety and depression symptoms. The aim of this study is to evaluate the impact of confinement as depressive and anxiety symptoms in pregnant women (PrW) and puerperal women (PuW) mental health, as well as obstetric and perinatal outcomes during this period. MATERIALS AND METHODS: The self-administered survey consists of a total of 28 questions, the first 16 providing contextual information and the following ones corresponding to the GHQ-12 that has been evaluated in a binomial form. A logistic regression model has been used to assess whether the contextual variables acted as a protective or risk factor and its fitting has been represented by a receiver operating curve. RESULTS: Of the 754 PrW interviewed, 58.22% were screened positive. Confinement time for these was 54.93 ± 9.75 days. The risk factors that were identified after the refinement have been to have a worse general state of health, to be sadder and to be more nervous. Among the protectors have been found to have a higher Apgar 10 score and induction of labor. The area under the adjusted regression adjustment curve was 0.8056. CONCLUSIONS: Our results show a high prevalence of depression and anxiety symptoms with strict confinement measures. PrW and PuW must be considered a risk group to develop mental health disorders during disruption circumstances. Using a mental health screening tool could help to identify a group of patients with more risk and to carry out a careful monitoring to allow adequate management.

Association of first trimester fetal heart rate and nuchal translucency with preterm birth.

OBJECTIVE: To evaluate whether first trimester fetal heart rate (FHR) and nuchal translucency (NT) associate with preterm birth (PTB). METHODS: This was a comparative case-control study of 518 normal pregnancies with no history of PTB, of which 272 delivered at term (TB) and 246 progressed to spontaneous PTB prior to 37, 34, 32, and 28 weeks. Fetal heart rate (FHR) and NT values at the first-trimester scan were compared by means of univariable (Mann-Whitney) and multivariable logistic regression analysis considering hourglass membranes (HM) as the most severe PTB subgroup. Finally, severity trends for both parameters were investigated using correlations with gestational age (GA) at delivery and Kruskal-Walls tests. RESULTS: Regardless of GA at delivery, pregnancies affected with PTB showed higher FHR and thicker NT at the first trimester scan. The association was confirmed by the multivariable analysis and the severity trends, which paired the highest FHR and NT values with the most severe cases of PTB (p < .001) (p < .0001). CONCLUSION: Fetuses with subsequent late, early and very early PTB show higher values of NT and FHR at the first-trimester scan.

Which is the best ultrasound parameter for the prediction of adverse perinatal outcome within 1 day of delivery?

OBJECTIVE: To compare the accuracies of several sonographic parameters for the prediction of adverse perinatal outcome (APO) prior to delivery. METHODS: This was a prospective study of fetuses attending the day hospital unit of a tertiary referral hospital that were scanned at 34-41 weeks and gave birth within 24 h of examination. APO was defined as a composite of abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH < 7.20 requiring urgent cesarean section, neonatal umbilical cord pH < 7.10, 5' Apgar score <7 and postpartum admission to neonatal or pediatric intensive care units. The accuracies of the middle cerebral, vertebral and umbilical arteries pulsatility index multiples of the median (MoM), the cerebroplacental and vertebroplacental ratios MoM and the EFW in centiles for the prediction of APO was evaluated by means of ROC curves and logistic regression analysis. RESULTS: A total of 2140 fetuses were prospectively scanned, however only 182 entered into spontaneous or induced labor and were delivered within 24 h of examination. In this group, MCA PI MoM was the best predictor of APO (AUC = 0.76, 95% CI 0.66-0.85, p < .0001) followed by the CPR MoM (AUC = 0.73, 95% CI 0.63-0.84, p < .0001) and the VPR MoM (AUC = 0.71, 95% CI 0.61-0.81, p < .001). Logistic regression analysis indicated that MCA PI MoM was the only independent determinant for the prediction of APO. CONCLUSION: In a high-risk population of third-trimester fetuses delivering within 24 h of examination, the outcome may be moderately anticipated just with the information provided by the cerebral flow.

Disrupted PGR-B and ESR1 signaling underlies defective decidualization linked to severe preeclampsia.

Background: Decidualization of the uterine mucosa drives the maternal adaptation to invasion by the placenta. Appropriate depth of placental invasion is needed to support a healthy pregnancy; shallow invasion is associated with the development of severe preeclampsia (sPE). Maternal contribution to sPE through failed decidualization is an important determinant of placental phenotype. However, the molecular mechanism underlying the in vivo defect linking decidualization to sPE is unknown. Methods: Global RNA sequencing was applied to obtain the transcriptomic profile of endometrial biopsies collected from nonpregnant women who suffer sPE in a previous pregnancy and women who did not develop this condition. Samples were randomized in two cohorts, the training and the test set, to identify the fingerprinting encoding defective decidualization in sPE and its subsequent validation. Gene Ontology enrichment and an interaction network were performed to deepen in pathways impaired by genetic dysregulation in sPE. Finally, the main modulators of decidualization, estrogen receptor 1 (ESR1) and progesterone receptor B (PGR-B), were assessed at the level of gene expression and protein abundance. Results: Here, we discover the footprint encoding this decidualization defect comprising 120 genes-using global gene expression profiling in decidua from women who developed sPE in a previous pregnancy. This signature allowed us to effectively segregate samples into sPE and control groups. ESR1 and PGR were highly interconnected with the dynamic network of the defective decidualization fingerprint. ESR1 and PGR-B gene expression and protein abundance were remarkably disrupted in sPE. Conclusions: Thus, the transcriptomic signature of impaired decidualization implicates dysregulated hormonal signaling in the decidual endometria in women who developed sPE. These findings reveal a potential footprint that could be leveraged for a preconception or early prenatal screening of sPE risk, thus improving prevention and early treatments. Funding: This work has been supported by the grant PI19/01659 (MCIU/AEI/FEDER, UE) from the Spanish Carlos III Institute awarded to TGG. NCM was supported by the PhD program FDGENT/2019/008 from the Spanish Generalitat Valenciana. IMB was supported by the PhD program PRE2019-090770 and funding was provided by the grant RTI2018-094946-B-100 (MCIU/AEI/FEDER, UE) from the Spanish Ministry of Science and Innovation with CS as principal investigator. This research was funded partially by Igenomix S.L.

The Diagnostic Ability of the Cerebroplacental Ratio for the Prediction of Adverse Perinatal Outcome and Intrapartum Fetal Compromise within One Day of Delivery.

OBJECTIVES: The objectives of this study were to evaluate the diagnostic abilities of the cerebroplacental ratio (CPR) for the prediction of adverse perinatal outcome (APO) and cesarean section for intrapartum fetal compromise (CS-IFC) within 1 day of delivery. DESIGN: Retrospective observational case-control study. METHODS: This was a study of 254 high-risk fetuses attending the day hospital unit of a tertiary referral hospital that underwent an ultrasound examination at 32-41 weeks and gave birth within 1 day of examination. APO was defined as a composite of abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH <7.20 requiring urgent cesarean section, neonatal umbilical cord pH <7.10, 5-min Apgar score <7, and postpartum admission to neonatal or pediatric intensive care units. CS-IFC was defined in case of abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH <7.20 requiring urgent cesarean section. The diagnostic ability of CPR for the prediction of APO and CS-IFC was calculated alone and in combination with estimated fetal weight and gestational clinical parameters, including the type of labor onset, using ROC curves and logistic regression analysis. RESULTS: CPR in multiples of the median (MoM) was a moderate predictor of APO (area under the curve [AUC] = 0.77, p < 0.0001) and CS-IFC (AUC = 0.82, p < 0.0001). The predictive abilities of the multivariable model for APO (AUC = 0.81, p < 0.0001) and CS-IFC (AUC = 0.82, p < 0.0001) did not differ from those of CPR alone . LIMITATIONS: The small number of cases and the scarcity of information concerning labor induction. CONCLUSION: In high-risk pregnancies, CPR MoM is a moderate predictor of APO and CS-IFC when performed within 24 h of delivery.