Cannabis exposure during pregnancy and perinatal outcomes: A cohort study.

INTRODUCTION: Cannabis potency and its use during pregnancy have increased in the last decade. The aim of this study was to investigate the impact of antenatal cannabis use on fetal growth, preterm birth and other perinatal outcomes. MATERIAL AND METHODS: A propensity score-matched analysis was performed in women with singleton pregnancies attending a tertiary care site in Barcelona. Women in the cannabis group were selected based on the results of a detection test. Primary outcomes were small for gestational age at birth (SGA), low birthweight and preterm birth. Secondary outcomes were other biometric parameters (neonatal length and head circumference), respiratory distress, admission to the neonatal intensive care unit and breastfeeding at discharge. A second propensity score-matched analysis excluding other confounders (use of other recreational drugs and discontinuation of cannabis use during pregnancy) was performed. RESULTS: Antenatal cannabis was associated with a higher odds ratio of SGA (OR 3.60, 95% CI: 1.68-7.69), low birthweight (OR 3.94, 95% CI: 2.17-7.13), preterm birth at 37 weeks (OR 2.07, 95% CI: 1.12-3.84) and 32 weeks of gestation (OR 4.13, 95% CI: 1.06-16.11), admission to the neonatal intensive care unit (OR 1.95, 95% CI: 1.03-3.71), respiratory distress (OR 2.77, 95% CI: 1.26-6.34), and lower breastfeeding rates at discharge (OR 0.10, 95% CI: 0.05-0.18). When excluding other confounders, no significant association between antenatal cannabis use and SGA was found. CONCLUSIONS: Antenatal cannabis use increases the risk of SGA, low birthweight, preterm birth and other adverse perinatal outcomes. However, when isolating the impact of cannabis use by excluding women who use other recreational drugs and those who discontinue cannabis during pregnancy, no significant association between antenatal cannabis use and SGA birth was found.

Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study.

BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. OBJECTIVE: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile. RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns. CONCLUSION: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

Neonatos con diagnóstico prenatal de hidrops fetal: experiencia durante 10 años en un centro de tercer nivel / Neonates with a prenatal diagnosis of hydrops fetalis: A 10-year experience in a tertiary care center

Introducción: El hidrops fetal (HF) es una condición rara con una alta mortalidad. Este estudio analiza la evolución obstétrica y perinatal de los diagnósticos prenatales de HF, relacionándola con la etiología y el tratamiento intrauterino (TIU) recibido. Pacientes y métodos: Se revisaron 164 gestantes con diagnóstico prenatal de HF entre 2011 y 2021. Se registraron intervenciones prenatales, hallazgos clínicos, etiologías y resultados de los recién nacidos vivos. Resultados: Se realizó un estudio invasivo prenatal en el 79,3% de los pacientes. Las etiologías mayoritarias fueron alteraciones genéticas (31%), infecciones TORCH y por parvovirus B19 (9,7%), y cardiopatías estructurales (9,1%). En el 25,6% se realizó TIU, y entre todas las gestaciones, el 74,4% fueron interrumpidas. Las alteraciones genéticas tuvieron tasas más altas de interrupción legal del embarazo respecto a otras etiologías (p<0,01). Del total, solo nacieron el 25,6% de los fetos, la mayoría pretérmino. Los que recibieron TIU gozaron de mayores tasas de supervivencia perinatal y al año de vida (p<0,001). De entre aquellos nacimientos, las cardiopatías estructurales presentaron las peores tasas de supervivencia, mientras que las causas con mejor pronóstico fueron las taquiarritmias. La supervivencia al año de vida entre aquellos recién nacidos vivos fue del 70%, pero el 58,6% asociaron morbilidad significativa al alta. Conclusiones: A pesar de los avances en el manejo del HF, el mal pronóstico obstétrico, la mortalidad perinatal y la morbilidad de los supervivientes siguen siendo significativos. Estos datos son importantes para asesorar a las familias que reciben un diagnóstico prenatal de HF.(AU)

Introduction: Hydrops fetalis (HF) is a rare condition with a high mortality. This study analysed the obstetric and perinatal outcomes of antenatally diagnosed HF according to its aetiology and the possibility of intrauterine treatment (IUT). Patients and methods: We carried out a retrospective review of the health records of 164 pregnant women with a prenatal diagnosis of HF in a tertiary care centre between 2011 and 2021. We analysed prenatal interventions, clinical findings, aetiologies and obstetric and live-born infant outcomes. Results: An invasive prenatal study had been performed in 79.3% cases. The most common aetiologies were genetic disorders (31%), TORCH and parvovirus B19 infections (9.7%) and structural heart diseases (9.1%). Intrauterine treatment was performed in 25.6%, and 74.4% of pregnancies were terminated. Pregnancies with a prenatal diagnosis of genetic or chromosomal disorders had higher rates of elective termination compared to other aetiologies (P<.01). Among all pregnancies, only 25.6% resulted in live births (LBs), most of them preterm. Perinatal and 1-year survival rates were higher in the group that received IUT (P<.001). Among the LBs, structural heart diseases had the worst survival rates, while the aetiology with the best outcomes was tachyarrhythmia. Survival at 1year of life among those born alive was 70%, but 58.6% of these infants had significant morbidity at discharge. Conclusions: Despite advances in the management of FH, the poor obstetric prognosis, perinatal mortality and morbidity of survivors is still significant. These data are important for the purpose of counselling families when HF is diagnosed antenatally.(AU)

Neonates with a prenatal diagnosis of hydrops fetalis: A 10-year experience in a tertiary care center.

INTRODUCTION: Hydrops fetalis (HF) is a rare condition with a high mortality. This study analysed the obstetric and perinatal outcomes of antenatally diagnosed HF according to its aetiology and the possibility of intrauterine treatment (IUT). PATIENTS AND METHODS: We carried out a retrospective review of the health records of 164 pregnant women with a prenatal diagnosis of HF in a tertiary care centre between 2011-2021. We analysed prenatal interventions, clinical findings, aetiologies and obstetric and live-born infant outcomes. RESULTS: An invasive prenatal study had been performed in 79.3% cases. The most common aetiologies were genetic disorders (31%), TORCH and parvovirus B19 infections (9.7%) and structural heart diseases (9.1%). Intrauterine treatment was performed in 25.6%, and 74.4% of pregnancies were terminated. Pregnancies with a prenatal diagnosis of genetic or chromosomal disorders had higher rates of elective termination compared to other aetiologies (P < .01). Among all pregnancies, only 25.6% resulted in live births (LBs), most of them preterm. Perinatal and 1-year survival rates were higher in the group that received IUT (P < .001). Among the LBs, structural heart diseases had the worst survival rates, while the aetiology with the best outcomes was tachyarrhythmia. Survival at 1 year of life among those born alive was 70%, but 58.6% of these infants had significant morbidity at discharge. CONCLUSIONS: Despite advances in the management of FH, the poor obstetric prognosis, perinatal mortality and morbidity of survivors is still significant. These data are important for the purpose of counselling families when HF is diagnosed antenatally.

Mid-trimester uterine artery Doppler for aspirin discontinuation in pregnancies at high risk for preterm pre-eclampsia: Post-hoc analysis of StopPRE trial.

OBJECTIVE: To assess whether aspirin treatment can be discontinued in pregnancies with normal uterine artery pulsatility index (≤90th percentile) at 24-28 weeks. DESIGN: Post-hoc analysis of a clinical trial. SETTING: Nine maternity hospitals in Spain. POPULATION OR SAMPLE: Pregnant individuals at high risk of pre-eclampsia at 11-13 weeks and normal uterine artery Doppler at 24-28 weeks. METHODS: All participants received treatment with daily aspirin at a dose of 150 mg. Participants were randomly assigned, in a 1:1 ratio, either to continue aspirin treatment until 36 weeks (control group) or to discontinue aspirin treatment (intervention group), between September 2019 and September 2021. In this secondary analysis, women with a UtAPI >90th percentile at 24-28 weeks were excluded. The non-inferiority margin was set at a difference of 1.9% for the incidence of preterm pre-eclampsia. MAIN OUTCOME MEASURES: Incidence of preterm pre-eclampsia. RESULTS: Of the 1611 eligible women, 139 were excluded for UtAPI >90th percentile or if UtAPI was not available. Finally, 804 were included in this post-hoc analysis. Preterm pre-eclampsia occurred in three of 409 (0.7%) women in the aspirin discontinuation group and five of 395 (1.3%) women in the continuation group (-0.53; 95% CI -1.91 to 0.85), indicating non-inferiority of aspirin discontinuation. CONCLUSIONS: Discontinuing aspirin treatment at 24-28 weeks in women with a UtAPI ≤90th percentile was non-inferior to continuing aspirin treatment until 36 weeks for preventing preterm pre-eclampsia.

Real-time ultrasound demonstration of uterine isthmus contractions during pregnancy.

BACKGROUND: Asymptomatic isthmic contractions are a frequent physiological phenomenon in pregnancy, sometimes triggered by bladder voiding. They can interfere with proper cervical length assessment and may lead to false images of placenta previa. However, there is limited research on the prevalence and characteristics of these contractions. OBJECTIVE: This study aimed to determine the prevalence and characteristics of isthmic contractions after bladder voiding in the second trimester of pregnancy, to evaluate their effect on cervical length assessment, and to propose a new method for the objective assessment of the presence and intensity of isthmic contractions. STUDY DESIGN: In this prospective observational study, long videos of the uterine cervix were recorded in 30 singleton pregnancies during the second trimester of pregnancy after bladder voiding. Isthmic length and cervicoisthmic length changes were assessed over time. The isthmic length was measured using a new approach, which involved calculating the distance from the base of the cervix to the internal os, including the isthmus. RESULTS: Isthmic contractions were observed in 43% of pregnant women (95% confidence interval, 26%-62%) after bladder voiding. The median time for complete isthmus relaxation was 19.7 minutes (95% confidence interval, 15.0 to not available). No substantial differences in maternal characteristics were found between individuals with and without contractions. The proposed method for measuring isthmic length provided an objective assessment of the presence and intensity of isthmic contractions. A cutoff of 18 mm in isthmic length allowed for the distinction of pregnant women presenting a contraction. In addition, the study identified a characteristic undulatory pattern in the relaxation of the isthmus in half of the cases with contractions. CONCLUSION: Isthmic contractions are a common occurrence after bladder voiding in the second trimester of pregnancy and may interfere with proper cervical length assessment. We recommend performing cervical assessment at least 20 minutes after bladder voiding to reduce the risk of bias in cervical length measurement and to avoid false images of placenta previa. The new method for measuring isthmic length provides an objective way to assess the presence and intensity of isthmic contractions. Further research is needed to understand the role of isthmic contractions in the physiology of pregnancy and birth.

The Arabin cervical pessary for the prevention of preterm birth in twin-to-twin transfusion syndrome treated by fetoscopic laser coagulation: a multicenter randomized controlled trial.

BACKGROUND: Miscarriage and preterm birth are leading causes of loss and disability in monochorionic twins after laser treatment of twin-twin transfusion syndrome. OBJECTIVE: This study aimed to investigate the use of cervical pessary to reduce preterm birth before 32 weeks of gestation in monochorionic diamniotic twin pregnancies after fetal surgery for twin-twin transfusion syndrome. STUDY DESIGN: In this open-label multicenter randomized trial, pregnant women carrying monochorionic diamniotic twins requiring fetoscopic laser coagulation for twin-twin transfusion syndrome were randomly assigned in a 1:1 ratio to pessary placement or conservative management. The primary outcome was birth before 32 weeks of gestation. The secondary outcomes were birth before 28, 30, 34, or 37 weeks of gestation; preterm premature rupture of membranes; fetal and neonatal survival; and a composite of maternal and neonatal complications. The estimated sample size was 364 patients, with 182 cases in each arm of the study. The analysis was performed according to the intention-to-treat principle. Moreover, 2 interim analyses were planned. RESULTS: The trial was stopped prematurely after the first planned interim analysis for futility. Overall, 137 women were included in the analysis, 67 in the pessary group and 70 in the conservative management group. Preterm birth before 32 weeks of gestation occurred in 27 of 67 women (40.3%) in the pessary group and in 25 of 70 women (35.7%) in the conservative management group (adjusted odds ratio, 1.19; 95% confidence interval, 0.58-2.47; P=.63). No differences between groups was observed in the rate of deliveries before 28, 30, 34, and 37 weeks of gestation. Overall survival to delivery was 91.2% (125/137) for at least 1 twin, and 70.8% (97/137) for both twins, with no difference between groups. Neonatal survival at 30 days was 76.5% (208/272). There was no difference between the groups in maternal or neonatal morbidity. CONCLUSION: In monochorionic diamniotic twin pregnancies requiring fetal therapy for twin-twin transfusion syndrome, routine use of cervical pessary did not reduce the rate of preterm birth before 32 weeks of gestation.

Fetal PR Interval in Pregnancies with Intrahepatic Cholestasis of Pregnancy: A Case-Control Study.

OBJECTIVE: This study had three purposes: first, to explore differences in fetal cardiac function in patients with and without intrahepatic cholestasis of pregnancy (ICP) based on PR interval (the interval between the beginning of the atrial contraction and the beginning of the ventricular contraction). Second, to explore a potential correlation between PR interval and bile acid levels in pregnant women with ICP. Third, to study changes in PR interval of fetuses from pregnant women with ICP after administration of ursodeoxycholic acid (UDCA). STUDY DESIGN: This was a prospective observational case-control study. ICP was defined as palmar plantar pruritus of nocturnal predominance for more than 1 week associated with a total bile acid level >10 µmol/L. Control cases were women with pregnancies scheduled for induction or elective cesarean section at term. RESULTS: One hundred and ten women with ICP and 72 controls were included in the study. Median gestational age at inclusion was 35.9 weeks. Median PR interval was significantly longer in fetuses of women with ICP (122 vs. 102 ms, p < 0.001). There was a significant correlation between bile acid levels and PR interval (rho = 0.723, p < 0.001). In 22 fetuses, the median PR interval decreased significantly following UDCA administration (134 vs. 118 ms, p = 0.004). CONCLUSION: PR interval is longer in fetuses of women with ICP. PR interval was significantly correlated with bile acid levels, and administration of UDCA significantly reduced PR interval. KEY POINTS: · Differences in fetal cardiac function in patients with and without intrahepatic cholestasis.. · PR interval and bile acid levels in pregnant women with intrahepatic cholestasis.. · Changes in PR interval of fetuses from pregnant women with ICP after use of UDCA..

Impact of the trait anxiety during pregnancy on birth weight: an observational cohort study.

To explore the effects of antenatal anxiety on fetal growth an observational cohort study was performed, including a cohort of 204 women with singleton pregnancies during the strict lockdown of the COVID-19 pandemic in 2020. Psychosocial factors, maternal demographics, obstetric outcomes, social support (Medical Outcomes Study Social Support Survey, MOS-SSS), and symptoms of anxiety (State-Trait Anxiety Inventory, STAIs and STAIt) and depression (Edinburgh Postpartum Depression Scale, EPDS) were studied as potential predictors of low birth weight. Main outcome measures were birth weight, head circumference and length. Results showed a negative correlation between STAIt score (trait anxiety) and birth weight percentile (r = -0.228, p = .047). In the univariate linear regression analysis, a lower maternal weight and BMI before pregnancy, parity, increased STAIt score and preterm birth below 37 weeks of gestation (p = .008, p = .015, p = .028, p = .047 and p = .022, respectively) were identified as predictive risk factors for low birth weight, whereas in the multivariate lineal regression analysis only a lower maternal weight before pregnancy and an increased STAIt score were independent predictors for low birth weight (p = .020, p = .049, respectively). To conclude, anxiety during pregnancy impacts birth weight, and specifically the trait anxiety, is a predictor for low birth weight.

Universal screening programme for cytomegalovirus infection in the first trimester of pregnancy: study protocol for an observational multicentre study in the area of Barcelona (CITEMB study).

INTRODUCTION: Congenital cytomegalovirus (cCMV) is the leading cause of non-genetic sensorineural hearing loss and one of the main causes of neurological disability. Despite this, no universal screening programme for cCMV has been implemented in Spain. A recent study has shown that early treatment with valaciclovir, initiated in the first trimester and before the onset of signs in the fetus, reduces the risk of fetal infection. This finding favours the implementation of a universal screening programme for cCMV.The aim of this study is to evaluate the performance of a universal screening programme for cCMV during the first trimester of pregnancy in a primary care setting. METHODS AND ANALYSIS: This is an observational multicentre cohort study. The study will be conducted in four primary care settings from the Northern Metropolitan Barcelona area and three related hospitals and will last 3 years and will consist of a recruitment period of 18 months.In their first pregnancy visit, pregnant women will be offered to add a CMV serology test to the first trimester screening tests. Pregnant women with primary infection will be referred to the reference hospital, where they will continue treatment and follow-up according to the clinical protocol of the referral hospital, which includes treatment with valacyclovir. A CMV-PCR will be performed at birth on newborns of mothers with primary infection, and those who are infected will undergo neonatal follow-up for at least 12 months of life.For the analysis, the acceptance rate, the prevalence of primary CMV infections and the CMV seroprevalence in the first trimester of pregnancy will be studied. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University Institute Foundation for Primary Health Care Research Jordi Gol i Gurina Ethics Committee 22/097-P dated 27 April 2022.

Pregnancy-related aortic complications in women with bicuspid aortic valve.

OBJECTIVES: To describe the aortic-related risks associated with pregnancy in women with bicuspid aortic valve (BAV) and to evaluate changes in aortic diameter in pregnancy. METHODS: Prospective observational study of patients with BAV from a single-site registry of pregnant women with structural heart disease between 2013 and 2020. Cardiac, obstetric and neonatal outcomes were studied. An assessment of aortic dimensions was performed during pregnancy by two-dimensional echocardiography. Aortic diameters were measured at the annulus, root, sinotubular junction and maximum ascending aorta diameter, and the largest diameter was used. Measurements of the aorta were made using the end-diastolic leading edge-to-leading edge convention. RESULTS: Forty-three women (32.9 years, IQR 29.6-35.3) with BAV were included: 9 (20.9%) had repaired aortic coarctation; 23 (53.5%) had moderate or severe aortic valve disease; 5 (11.6%) had a bioprosthetic aortic valve; and 2 (4.7%) had a mechanical prosthetic aortic valve. Twenty (47.0%) were nulliparous. The mean aortic diameter in the first trimester was 38.5 (SD 4.9) mm, and that in the third trimester was 38.4 (SD 4.8) mm. Forty (93.0%) women had an aortic diameter of <45 mm; 3 (7.0%) had 45-50 mm; and none had >50 mm. Three women (6.9%) with BAV presented cardiovascular complications during pregnancy or the postpartum period (two prosthetic thrombosis and one heart failure). No aortic complications were reported. There was a small but significant increase in aortic diameter during pregnancy (third trimester vs first trimester, 0.52 (SD 1.08) mm; p=0.03). Obstetric complications appeared in seven (16.3%) of pregnancies, and there were no maternal deaths. Vaginal non-instrumental delivery was performed in 21 (51.2%) out of 41 cases. There were no neonatal deaths, and the mean newborn weight was 3130 g (95% CI 2652 to 3380). CONCLUSIONS: Pregnancy in BAV women had a low rate of cardiac complications with no aortic complications observed in a small study group. Neither aortic dissection nor need for aortic surgery was reported. A low but significant aortic growth was observed during pregnancy. Although requiring follow-up, the risk of aortic complications in pregnant women with BAV and aortic diameters of <45 mm at baseline is low.

Fetal abdominal cysts: Predicting adverse outcomes.

INTRODUCTION: The primary aim of the study was to identify risk factors associated with fetal or neonatal loss, neonatal morbidity, and the need for surgery in fetuses diagnosed with an abdominal cyst. The secondary aim was to compare the characteristics of the cyst according to trimester at diagnosis. MATERIAL AND METHODS: This was an observational retrospective study performed at Vall d'Hebron University Hospital. The study included pregnant women aged 18 years or older with diagnosis of a fetal abdominal cyst from 2008 to 2021. RESULTS: A total of 82 women with a median gestational age of 31+1 weeks (12+0-39+4) were included in the analysis. Seven (8.5%) cases were diagnosed in the first trimester, 28 (34.1%) in the second trimester, and 47 (57.3%) in the third trimester. Fetal or neonatal loss occurred in 10 (12.2%) cases; significant predictors were diagnosis in the first trimester (OR 36.67, 95% CI: 4.89-274.79), male gender (OR 4.75, 95% CI: 1.13-19.9), and associated abnormalities (OR 15.2, 95% CI: 2.92-79.19). A total of 10 of 75 (13.3%) neonates showed at least one neonatal complication, and the only predictor was occurrence of associated abnormalities (OR 7.36, 95% CI: 1.78-30.51). A total of 16 of 75 (21.3%) neonates required postnatal surgery, and the predictors were second-trimester diagnosis (OR 3.92, 95% CI: 1.23-12.51), associated abnormalities (OR 3.81, 95% CI: 1.15-12.64), and bowel location (OR 10.0, 95% CI: 1.48-67.55). CONCLUSIONS: Factors associated with adverse outcomes in fetuses diagnosed with abdominal cysts are first-trimester diagnosis and associated abnormalities. Cysts detected in the second trimester and those of intestinal origin are more likely to require surgery.

Reference values for interleukin-6 in the amniotic fluid of asymptomatic pregnant women.

INTRODUCTION: Nowadays, proinflammatory factors are considered to play an important role in the pathophysiology of threatened preterm labor or chorioamnionitis. The aim of this study was to establish the normal reference range for interleukin-6 (IL-6) levels in the amniotic fluid and to identify factors which may alter this value. MATERIAL AND METHODS: Prospective study in a tertiary-level center including asymptomatic pregnant women undergoing amniocentesis for genetic studies from October 2016 to September 2019. IL-6 measurements in amniotic fluid were performed using a fluorescence immunoassay with microfluidic technology (ELLA Proteinsimple, Bio Techne). Maternal history and pregnancy data were also recorded. RESULTS: This study included 140 pregnant women. Of those, women who underwent termination of pregnancy were excluded. Therefore, a total of 98 pregnancies were included in the final statistical analysis. The mean gestational age was 21.86 weeks (range: 15-38.7) at the time of amniocentesis, and 38.6 weeks (range: 30.9-41.4) at delivery. No cases of chorioamnionitis were reported. The log10 IL-6 values follow a normal distribution (W = 0.990, p = 0.692). The median, and the 5th, 10th, 90th, and 95th percentiles for IL-6 levels were 573, 105, 130, 1645, and 2260 pg/mL, respectively. The log10 IL-6 values were not affected by gestational age (p = 0.395), maternal age (p = 0.376), body mass index (p = 0.551), ethnicity (p = 0.467), smoking status (p = 0.933), parity (p = 0.557), method of conception (p = 0.322), or diabetes mellitus (p = 0.381). CONCLUSIONS: The log10 IL-6 values follow a normal distribution. IL-6 values are independent of gestational age, maternal age, body mass index, ethnicity, smoking status, parity and method of conception. Our study provides a normal reference range for IL-6 levels in the amniotic fluid that can be used in future studies. We also observed that normal IL-6 values were higher in the amniotic fluid than in serum.

Aspirin Discontinuation at 24 to 28 Weeks' Gestation in Pregnancies at High Risk of Preterm Preeclampsia: A Randomized Clinical Trial.

Importance: Aspirin reduces the incidence of preterm preeclampsia by 62% in pregnant individuals at high risk of preeclampsia. However, aspirin might be associated with an increased risk of peripartum bleeding, which could be mitigated by discontinuing aspirin before term (37 weeks of gestation) and by an accurate selection of individuals at higher risk of preeclampsia in the first trimester of pregnancy. Objective: To determine whether aspirin discontinuation in pregnant individuals with normal soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1:PlGF) ratio between 24 and 28 weeks of gestation was noninferior to aspirin continuation to prevent preterm preeclampsia. Design, Setting, and Participants: Multicenter, open-label, randomized, phase 3, noninferiority trial conducted in 9 maternity hospitals across Spain. Pregnant individuals (n = 968) at high risk of preeclampsia during the first-trimester screening and an sFlt-1:PlGF ratio of 38 or less at 24 to 28 weeks of gestation were recruited between August 20, 2019, and September 15, 2021; of those, 936 were analyzed (intervention: n = 473; control: n = 463). Follow-up was until delivery for all participants. Interventions: Enrolled patients were randomly assigned in a 1:1 ratio to aspirin discontinuation (intervention group) or aspirin continuation until 36 weeks of gestation (control group). Main Outcomes and Measures: Noninferiority was met if the higher 95% CI for the difference in preterm preeclampsia incidences between groups was less than 1.9%. Results: Among the 936 participants, the mean (SD) age was 32.4 (5.8) years; 3.4% were Black and 93% were White. The incidence of preterm preeclampsia was 1.48% (7/473) in the intervention group and 1.73% (8/463) in the control group (absolute difference, -0.25% [95% CI, -1.86% to 1.36%]), indicating noninferiority. Conclusions and Relevance: Aspirin discontinuation at 24 to 28 weeks of gestation was noninferior to aspirin continuation for preventing preterm preeclampsia in pregnant individuals at high risk of preeclampsia and a normal sFlt-1:PlGF ratio. Trial Registration: ClinicalTrials.gov Identifier: NCT03741179 and ClinicalTrialsRegister.eu Identifier: 2018-000811-26.

Pregnancy outcomes and vaccine effectiveness during the period of omicron as the variant of concern, INTERCOVID-2022: a multinational, observational study.

BACKGROUND: In 2021, we showed an increased risk associated with COVID-19 in pregnancy. Since then, the SARS-CoV-2 virus has undergone genetic mutations. We aimed to examine the effects on maternal and perinatal outcomes of COVID-19 during pregnancy, and evaluate vaccine effectiveness, when omicron (B.1.1.529) was the variant of concern. METHODS: INTERCOVID-2022 is a large, prospective, observational study, involving 41 hospitals across 18 countries. Each woman with real-time PCR or rapid test, laboratory-confirmed COVID-19 in pregnancy was compared with two unmatched women without a COVID-19 diagnosis who were recruited concomitantly and consecutively in pregnancy or at delivery. Mother and neonate dyads were followed until hospital discharge. Primary outcomes were maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI). Vaccine effectiveness was estimated, adjusted by maternal risk profile. FINDINGS: We enrolled 4618 pregnant women from Nov 27, 2021 (the day after WHO declared omicron a variant of concern), to June 30, 2022: 1545 (33%) women had a COVID-19 diagnosis (median gestation 36·7 weeks [IQR 29·0-38·9]) and 3073 (67%) women, with similar demographic characteristics, did not have a COVID-19 diagnosis. Overall, women with a diagnosis had an increased risk for MMMI (relative risk [RR] 1·16 [95% CI 1·03-1·31]) and SPMMI (RR 1·21 [95% CI 1·00-1·46]). Women with a diagnosis, compared with those without a diagnosis, also had increased risks of SNMI (RR 1·23 [95% CI 0·88-1·71]), although the lower bounds of the 95% CI crossed unity. Unvaccinated women with a COVID-19 diagnosis had a greater risk of MMMI (RR 1·36 [95% CI 1·12-1·65]). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications (RR 2·51 [95% CI 1·84-3·43]), perinatal complications (RR 1·84 [95% CI 1·02-3·34]), and referral, intensive care unit (ICU) admission, or death (RR 11·83 [95% CI 6·67-20·97]). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 [95% CI 2·02-4·12]) and referral, ICU admission, or death (RR 20·82 [95% CI 10·44-41·54]). 2886 (63%) of 4618 total participants had at least a single dose of any vaccine, and 2476 (54%) of 4618 had either complete or booster doses. Vaccine effectiveness (all vaccines combined) for severe complications of COVID-19 for all women with a complete regimen was 48% (95% CI 22-65) and 76% (47-89) after a booster dose. For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48-87) and 91% (65-98) after a booster dose. INTERPRETATION: COVID-19 in pregnancy, during the first 6 months of omicron as the variant of concern, was associated with increased risk of severe maternal morbidity and mortality, especially among symptomatic and unvaccinated women. Women with complete or boosted vaccine doses had reduced risk for severe symptoms, complications, and death. Vaccination coverage among pregnant women remains a priority. FUNDING: None.

Array study in fetuses with nuchal translucency above the 95th percentile: a 4-year observational single-centre study.

PURPOSE: To evaluate the performance of chromosomal microarray analysis (CMA) in fetuses with nuchal translucency (NT) > 95th percentile. Secondary objectives were to analyze these results according to NT thickness, below or above 3.5 mm, and those without associated anomalies. METHODS: This observational single-cohort study was conducted between 2015 and 2018 in fetuses with NT > 95th percentile. Following an invasive test, quantitative fluorescence-polymerase chain reaction (QF-PCR) was performed, and if normal, CMA was performed. Pathogenic copy number variants (CNVs), non-reported pathogenic CNV, pathogenic autosomal recessive variants and variants of unknown significance (VUS) were analysed. RESULTS: One-hundred and sixty-two fetuses with NT > 95th percentile, normal QF-PCR and CMA were included. Amongst 128 fetuses with NT between the 95th percentile and 3.5 mm, one (0.8%) had a pathogenic CNV, four (3.1%) had non-reported pathogenic CNV, one (0.8%) had pathogenic autosomal recessive variant and 13 (10.2%) had VUS. Amongst 34 fetuses with NT ≥ 3.5 mm, four (11.8%) had pathogenic CNV, one (2.9%) had non-reported pathogenic CNV, one (2.9%) had pathogenic autosomal recessive variant and four (11.8%) had VUS. Four in 162 (2.5%) fetuses had CNVs at the chromosome 16p13.11 region. Amongst 154 fetuses without structural abnormalities and normal QF-PCR, three (1.9%) had a pathogenic CNV, 5 (3.2%) had non-reported pathogenic CNV, one (0.6%) autosomal recessive pathogenic CNV and 16 (10.4%) had VUS. CONCLUSION: Pathogenic CNVs were found in 1% of fetuses with an NT thickness between the 95th percentile and 3.5 mm and in 12% of fetuses with NT ≥ 3.5 mm. CNVs were found at the 16p13.11 region in 2.5% of cases.

Confirmation of preeclampsia-like syndrome induced by severe COVID-19: an observational study.

BACKGROUND: Since the outbreak of the COVID-19 pandemic, some studies have reported an increased preeclampsia incidence in pregnant women with SARS-CoV-2 infection. Several explanations for this association have been proposed, including a preeclampsia-like syndrome induced by severe COVID-19. This syndrome was described in a small case series and has not been confirmed in larger studies, and its effect on perinatal outcomes has not been studied. OBJECTIVE: This study aimed to confirm the preeclampsia-like syndrome because of COVID-19 and to investigate its implications on pregnancy outcomes and prognosis. STUDY DESIGN: This was a prospective, observational study conducted in a tertiary referral hospital. The inclusion criteria were pregnant women admitted to the intensive care unit for severe pneumonia because of COVID-19. They were classified into 3 groups based on clinical and laboratory findings: preeclampsia, preeclampsia-like syndrome, and women without preeclampsia features. The 3 cohorts were analyzed and compared at 3 different times: before, during, and after severe pneumonia. The main outcomes were incidence of adverse perinatal outcomes and signs and symptoms of PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, and increased angiogenic factors (soluble fms-like tyrosine kinase 1-to-placental growth factor ratio). RESULTS: A total of 106 women were admitted to the intensive care unit because of severe pneumonia, and 68 women were included in the study. Of those, 53 (50.0%) did not meet the diagnostic criteria for preeclampsia and remained pregnant after pneumonia (non-preeclampsia); 7 (6.6%) met the diagnostic criteria for preeclampsia, had abnormal (>38) soluble fms-like tyrosine kinase 1-to-placental growth factor ratio (preeclampsia), and delivered during severe pneumonia, and 8 (7.5%) met the diagnostic criteria for preeclampsia, had normal (≤38) soluble fms-like tyrosine kinase 1-to-placental growth factor ratio (preeclampsia like), and did not deliver during pneumonia. Despite not having delivered, most preeclampsia-related features improved after severe pneumonia in women with preeclampsia-like syndrome. Women with preeclampsia had significantly poorer outcomes than women with preeclampsia-like syndrome or without preeclampsia. CONCLUSION: More than 50% of women with severe COVID-19 and diagnostic criteria for preeclampsia may not be preeclampsia but a preeclampsia-like syndrome, which may affect up to 7.5% of women with severe COVID-19. Preeclampsia-like syndrome might have similar perinatal outcomes to those of normotensive women with severe pneumonia because of COVID-19. For these reasons, preeclampsia-like syndrome should be excluded by using soluble fms-like tyrosine kinase 1-to-placental growth factor ratio in future research and before making clinical decisions.

Usefulness of angiogenic factors in prenatal counseling of late-onset fetal growth-restricted and small-for-gestational-age gestations: a prospective observational study.

OBJECTIVES: To create a predictive model including biomarkers and evaluate its ability to predict adverse perinatal outcomes in late-onset small fetuses, ultimately helping to provide individualized counseling at the time of diagnosis. METHODS: This was a prospective observational study, including singleton pregnancies with an estimated fetal weight (EFW) below the 10th percentile, at a gestational age between 32 + 0 and 36 + 6 weeks of gestation (WG). Variables recorded at diagnosis to predict adverse pregnancy outcomes were: soluble fms-like tyrosine-kinase-1 to placental growth factor ratio (sFlt-1/PlGF), fetal Doppler (umbilical artery and middle cerebral artery), uterine artery pulsatility index (UtAPI), EFW percentile, gestational age, and the presence of maternal risk factors for placental insufficiency. Logistic regression models were developed for the prediction of three co-primary outcomes: composite adverse perinatal outcomes (APO), and the need for elective delivery before 35 or 37 WG. RESULTS: Sixty (52.2%) fetal growth restricted (FGR) and 55 (47.8%) small for gestational age (SGA) were enrolled. Thirteen (11.3%) women needed elective delivery before 35 WG and 27 (23.5%) women before 37 WG. At least one APO occurred in 43 (37.4%) pregnancies. The best marker in univariate analyses was the sFlt-1/PlGF ratio [AUC = 0.932 (95% CI, 0.864-0.999)]. The multivariate model including sFlt-1/PlGF showed a better predictive performance for APO than the multivariate model without sFlt-1/PlGF (P < 0.024). CONCLUSIONS: sFlt-1/PlGF is a good predictor of APO at the time of late-onset FGR/SGA diagnosis. Our predictive models may be useful to provide early individualized prenatal counseling in this group of women. Further studies are needed to validate these preliminary findings in a larger cohort.

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.