Anti-SARS-CoV-2-specific antibodies in human breast milk following SARS-CoV-2 infection during pregnancy: a prospective cohort study.

BACKGROUND: While the presence of SARS-CoV-2 in human breast milk is contentious, anti-SARS-CoV-2 antibodies have been consistently detected in human breast milk. However, it is uncertain when and how long the antibodies are present. METHODS: This was a prospective cohort study including all consecutive pregnant women with confirmed SARS-CoV-2 infection during pregnancy, recruited at six maternity units in Spain and Hong Kong from March 2020 to March 2021. Colostrum (day of birth until day 4 postpartum) and mature milk (day 7 postpartum until 6 weeks postpartum) were prospectively collected, and paired maternal blood samples were also collected. Colostrum samples were tested with rRT-PCR-SARS-CoV-2, and skimmed acellular milk and maternal sera were tested against SARS-CoV-2 specific immunoglobulin M, A, and G reactive to receptor binding domain of SARS-CoV-2 spike protein 1 to determine the presence of immunoglobulins. Then, we examined how each immunoglobulin type in the colostrum was related to the time of infection by logistic regression analysis, the concordance between these immunoglobulins in the colostrum, maternal serum, and mature milk by Cohen's kappa statistic, and the relationship between immunoglobulin levels in mature milk and colostrum with McNemar. RESULTS: One hundred eighty-seven pregnant women with confirmed SARS-CoV-2 infection during pregnancy or childbirth were recruited and donated the milk and blood samples. No SARS-CoV-2 was found in the human breast milk. Immunoglobulin A, G, and M were present in 129/162 (79·6%), 5/163 (3·1%), and 15/76 (19·7%) colostrum samples and in 17/62 (27·42%), 2/62 (3·23%) and 2/62 (3·23%) mature milk samples, respectively. Immunoglobulin A was the predominant immunoglobulin found in breast milk, and its levels were significantly higher in the colostrum than in the mature milk (p-value < 0.001). We did not find that the presence of immunoglobulins in the colostrum was associated with their presence in maternal, the severity of the disease, or the time when the infection had occurred. CONCLUSIONS: Since anti-SARS-CoV-2 antibodies are found in the colostrum irrespective of the time of infection during pregnancy, but the virus itself is not detected in human breast milk, our study found no indications to withhold breastfeeding, taking contact precautions when there is active disease.

Level of agreement between midwives and obstetricians performing ultrasound examination during labor.

OBJECTIVE: To evaluate the level of agreement between ultrasound measurements to evaluate fetal head position and progress of labor by attending midwives and obstetricians after appropriate training. METHODS: In this prospective study, women in the first stage of labor giving birth to a single baby in cephalic presentation at our Obstetric Unit between March 2018 and December 2019 were invited to participate; 109 women agreed. Transperineal and transabdominal ultrasound was independently performed by a trained midwife and an obstetrician. Two paired measurements were available for comparisons in 107 cases for the angle of progression (AoP), in 106 cases for the head-to-perineum distance (HPD), in 97 cases for the cervical dilatation (CD), and in 79 cases for the fetal head position. RESULTS: We found a good correlation between the AoP measured by obstetricians and midwives (intra-class correlation coefficient [ICC] = 0.85; 95% confidence interval [CI] 0.80-0.89). There was a moderate correlation between the HPD (ICC = 0.75; 95% CI 0.68-0.82). There was a very good correlation between the CD measured (ICC = 0.94; 95% CI 0.91-0.96). There was a very good level of agreement in the classification of the fetal head position (Cohen's κ = 0.89; 95% CI 0.80-0.98). CONCLUSIONS: Ultrasound assessment of fetal head position and progress of labor can effectively be performed by attending midwives without previous experience in ultrasound.

Efficiency of the Cerebroplacental Ratio in Identifying High-Risk Late-Term Pregnancies.

Background and Objectives: Over the last few years, great interest has arisen in the role of the cerebroplacental ratio (CPR) to identify low-risk pregnancies at higher risk of adverse pregnancy outcomes. This study aimed to assess the predictive capacity of the CPR for adverse perinatal outcomes in all uncomplicated singleton pregnancies attending an appointment at 40-42 weeks. Materials and Methods: This is a retrospective cohort study including all consecutive singleton pregnancies undergoing a routine prenatal care appointment after 40 weeks in three maternity units in Spain and the United Kingdom from January 2017 to December 2019. The primary outcome was adverse perinatal outcomes defined as stillbirth or neonatal death, cesarean section or instrumental delivery due to fetal distress during labor, umbilical arterial cord blood pH < 7.0, umbilical venous cord blood pH < 7.1, Apgar score at 5 min < 7, and admission to the neonatal unit. Logistic mixed models and ROC curve analyses were used to analyze the data. Results: A total of 3143 pregnancies were analyzed, including 537 (17.1%) with an adverse perinatal outcome. Maternal age (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01 to 1.04), body mass index (OR 1.04, 95% CI 1.03 to 1.06), racial origin (OR 2.80, 95% CI 1.90 to 4.12), parity (OR 0.36, 95% CI 0.29 to 0.45), and labor induction (OR 1.79, 95% CI 1.36 to 2.35) were significant predictors of adverse perinatal outcomes with an area under the ROC curve of 0.743 (95% CI 0.720 to 0.766). The addition of the CPR to the previous model did not improve performance. Additionally, the CPR alone achieved a detection rate of only 11.9% (95% CI 9.3 to 15) when using the 10th centile as the screen-positive cutoff. Conclusions: Our data on late-term unselected pregnancies suggest that the CPR is a poor predictor of adverse perinatal outcomes.

Intrapartum ultrasound in maternal lateral versus semi-recumbent posture. A repeated measures study.

OBJECTIVE: This study aimed to assess whether intrapartum ultrasound (ITU) measurements in maternal lateral posture are superimposable to ITU measurements in semi-recumbent position. STUDY DESIGN: A single-center, repeated measures design was used. Women in the second stage of labor were randomized to ITU first in semi-recumbent followed by ITU in side-lying posture without and with contraction, or inversely. The angle of progression (AOP) and the head-perineum distance (HPD) between contractions (AOP1 and HPD1) and with contraction (AOP2 and HPD2) were measured in each maternal posture. The differences between AOP1 and AOP2 (dAOP), and between HPD1 and HPD2 (dHPD) were calculated. RESULTS AND CONCLUSIONS: Forty-two women participated in the study. A generalized estimating equation model showed that AOP1 (-3.00°; 95 % CI -5.77 to -0.23; p = 0.03) and AOP2 (-4.14°; 95 % CI -7.20 to -1.08; p = 0.008) were lower in semi-recumbent compared to maternal lateral posture. HPD1 (+1.43 mm; 95 % CI 0.05-2.81; p = 0.042) and HPD2 (+1.53 mm; 95 % CI 0.17-2.89; p = 0.03) were higher in semi-recumbent position. Differences in the ITU measurements in maternal lateral posture compared to semi-recumbent position are small. Monitoring the second stage of labor with ITU in lateral maternal posture is possible.

Fetal and maternal Doppler adaptation to maternal exercise during pregnancy: a randomized controlled trial.

BACKGROUND: Regular and supervised exercise during pregnancy is worldwide recommended due to its proven benefits, but, during exercise, maternal blood flow is redirected from the viscera to the muscles and how fetal wellbeing may be affected by this redistribution is still not well known. OBJECTIVE: To analyze the longitudinal effect of a supervised moderate physical exercise program during pregnancy on uteroplacental and fetal Doppler parameters. METHODS: This is a planned secondary analysis of an randomized controlled trial (RCT), performed at Hospital Universitario de Torrejón, Madrid, Spain, including 124 women randomized from 12+0 to 15+6 weeks of gestation to exercise vs. control group. Fetal umbilical artery (UA), middle cerebral artery, and uterine artery pulsatility index (PI), were longitudinally collected by Doppler ultrasound assessment throughout gestation, and derived cerebroplacental ratio (normalized by z-score), and maternal mean PI in the uterine arteries (normalized by multiplies of the median). Obstetric appointments were scheduled at 12 (baseline, 12+0 to 13+5), 20 (19+0 to 24+2), 28 (26+3 to 31+3) and 35 weeks (32+6 to 38+6) of gestation. Generalized estimating equations were adjusted to assess longitudinal changes in the Doppler measurements according to the randomization group. RESULTS: No significant differences in the fetal or maternal Doppler measurements were found at any of the different checkup time points studied. The only variable that consistently affected the Doppler standardized values was gestational age at the time of assessment. The evolution of the UA PI z-score during the pregnancy was different in the two study groups, with a higher z-score in the exercise group at 20 weeks and a subsequent decrease until delivery while in the control group it remained stable at around zero. CONCLUSIONS: A regular supervised moderate exercise program during pregnancy does not deteriorate fetal or maternal ultrasound Doppler parameters along the pregnancy, suggesting that the fetal well-being is not compromised by the exercise intervention. Fetal UA PI z-score decreases during pregnancy to lower levels in the exercise group compared with the control group.

Accuracy of placental growth factor alone or in combination with soluble fms-like tyrosine kinase-1 or maternal factors in detecting preeclampsia in asymptomatic women in the second and third trimesters: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to: (1) identify all relevant studies reporting on the diagnostic accuracy of maternal circulating placental growth factor) alone or as a ratio with soluble fms-like tyrosine kinase-1), and of placental growth factor-based models (placental growth factor combined with maternal factors±other biomarkers) in the second or third trimester to predict subsequent development of preeclampsia in asymptomatic women; (2) estimate a hierarchical summary receiver-operating characteristic curve for studies reporting on the same test but different thresholds, gestational ages, and populations; and (3) select the best method to screen for preeclampsia in asymptomatic women during the second and third trimester of pregnancy by comparing the diagnostic accuracy of each method. DATA SOURCES: A systematic search was performed through MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform databases from January 1, 1985 to April 15, 2021. STUDY ELIGIBILITY CRITERIA: Studies including asymptomatic singleton pregnant women at >18 weeks' gestation with risk of developing preeclampsia were evaluated. We included only cohort or cross-sectional test accuracy studies reporting on preeclampsia outcome, allowing tabulation of 2×2 tables, with follow-up available for >85%, and evaluating performance of placental growth factor alone, soluble fms-like tyrosine kinase-1- placental growth factor ratio, or placental growth factor-based models. The study protocol was registered on the International Prospective Register Of Systematic Reviews (CRD 42020162460). METHODS: Because of considerable intra- and interstudy heterogeneity, we computed the hierarchical summary receiver-operating characteristic plots and derived diagnostic odds ratios, ß, θi, and Λ for each method to compare performances. The quality of the included studies was evaluated by the QUADAS-2 tool. RESULTS: The search identified 2028 citations, from which we selected 474 studies for detailed assessment of the full texts. Finally, 100 published studies met the eligibility criteria for qualitative and 32 for quantitative syntheses. Twenty-three studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the second trimester, including 16 (with 27 entries) that reported on placental growth factor test alone, 9 (with 19 entries) that reported on the soluble fms-like tyrosine kinase-1-placental growth factor ratio, and 6 (16 entries) that reported on placental growth factor-based models. Fourteen studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the third trimester, including 10 (with 18 entries) that reported on placental growth factor test alone, 8 (with 12 entries) that reported on soluble fms-like tyrosine kinase-1-placental growth factor ratio, and 7 (with 12 entries) that reported on placental growth factor-based models. For the second trimester, Placental growth factor-based models achieved the highest diagnostic odds ratio for the prediction of early preeclampsia in the total population compared with placental growth factor alone and soluble fms-like tyrosine kinase-1-placental growth factor ratio (placental growth factor-based models, 63.20; 95% confidence interval, 37.62-106.16 vs soluble fms-like tyrosine kinase-1-placental growth factor ratio, 6.96; 95% confidence interval, 1.76-27.61 vs placental growth factor alone, 5.62; 95% confidence interval, 3.04-10.38); placental growth factor-based models had higher diagnostic odds ratio than placental growth factor alone for the identification of any-onset preeclampsia in the unselected population (28.45; 95% confidence interval, 13.52-59.85 vs 7.09; 95% confidence interval, 3.74-13.41). For the third trimester, Placental growth factor-based models achieved prediction for any-onset preeclampsia that was significantly better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1-placental growth factor ratio (placental growth factor-based models, 27.12; 95% confidence interval, 21.67-33.94 vs placental growth factor alone, 10.31; 95% confidence interval, 7.41-14.35 vs soluble fms-like tyrosine kinase-1-placental growth factor ratio, 14.94; 95% confidence interval, 9.42-23.70). CONCLUSION: Placental growth factor with maternal factors ± other biomarkers determined in the second trimester achieved the best predictive performance for early preeclampsia in the total population. However, in the third trimester, placental growth factor-based models had predictive performance for any-onset preeclampsia that was better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1-placental growth factor ratio. Through this meta-analysis, we have identified a large number of very heterogeneous studies. Therefore, there is an urgent need to develop standardized research using the same models that combine serum placental growth factor with maternal factors ± other biomarkers to accurately predict preeclampsia. Identification of patients at risk might be beneficial for intensive monitoring and timing delivery.

Performance of Screening Strategies for Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease: Results from the ENEIDA Registry of GETECCU.

(1) Aims: Patients receiving antitumor necrosis factor (anti-TNF) therapy are at risk of developing tuberculosis (TB), usually due to the reactivation of a latent TB infection (LTBI). LTBI screening and treatment decreases the risk of TB. This study evaluated the diagnostic performance of different LTBI screening strategies in patients with inflammatory bowel disease (IBD). (2) Methods: Patients in the Spanish ENEIDA registry with IBD screened for LTBI between January 2003 and January 2018 were included. The diagnostic yield of different strategies (dual screening with tuberculin skin test [TST] and interferon-×¥-release assay [IGRA], two-step TST, and early screening performed at least 12 months before starting biological treatment) was analyzed. (3) Results: Out of 7594 screened patients, 1445 (19%; 95% CI 18−20%) had LTBI. Immunomodulator (IMM) treatment at screening decreased the probability of detecting LTBI (20% vs. 17%, p = 0.001). Regarding screening strategies, LTBI was more frequently diagnosed by dual screening than by a single screening strategy (IGRA, OR 0.60; 95% CI 0.50−0.73, p < 0.001; TST, OR 0.76; 95% CI 0.66−0.88, p < 0.001). Two-step TST increased the diagnostic yield of a single TST by 24%. More cases of LTBI were diagnosed by early screening than by routine screening before starting anti-TNF agents (21% [95% CI 20−22%] vs. 14% [95% CI 13−16%], p < 0.001). The highest diagnostic performance for LTBI (29%) was obtained by combining early and TST/IGRA dual screening strategies in patients without IMM. (4): Conclusions: Both early screening and TST/IGRA dual screening strategies significantly increased diagnostic performance for LTBI in patients with IBD, with optimal performance achieved when they are used together in the absence of IMM.

Maternal Race and Stillbirth: Cohort Study and Systematic Review with Meta-Analysis.

Accurate identification of independent predictors of stillbirth is needed to define preventive strategies. We aim to examine the independent contribution of maternal race in the risk of stillbirth after adjusting for maternal characteristics and medical history. There are two components to the study: first, prospective screening in 168,966 women with singleton pregnancies coordinated by the Fetal Medicine Foundation (FMF) and second, a systematic review and meta-analysis of studies reporting on race and stillbirth. In the FMF study, logistic regression analysis found that in black women, the risk of stillbirth, after adjustment for confounders, was higher than in white women (odds ratio 1.78, 95% confidence interval 1.50 to 2.11). The risk for other racial groups was not significantly different. The literature search identified 20 studies that provided data on over 6,500,000 pregnancies, but only 10 studies provided risks adjusted for some maternal characteristics; consequently, the majority of these studies did not provide accurate contribution of different racial groups to the prediction of stillbirth. It is concluded that in women of black origin, the risk of stillbirth, after adjustment for confounders, is about twofold higher than in white women. Consequently, closer surveillance should be granted for these women.

Association of the Genetic Variation in the Long Non-Coding RNA FENDRR with the Risk of Developing Hypertrophic Cardiomyopathy.

Background: In around 40−60% of Hypertrophic Cardiomyopathy (HCM) cases pathogenic variants are not identified. Our aim was to evaluate the possible association of lncRNAs with the risk of developing HCM. Methods: We sequenced 10 lncRNAs coding genes that have been associated with cardiovascular disease in a discovery cohort (238 HCM patients and 212 controls) by NGS, and genotyped rs74035787 G>A and rs1424019 A>G polymorphism in a validation cohort (962 HCM patients and 923 controls). Finally, we sequenced the FENDRR promoter by Sanger sequencing. Results: We observed by NGS that FENDRR rs39527, rs39529 and rs40384 polymorphisms were significantly associated with HCM in our cohort (p = 0.0284; OR: 0.24, 95%CI: 0.07−0.86). NGS results were confirmed by genotyping rs74035787 polymorphism (p = 0.001; OR:0.38, 95%CI: 0.21−0.66). Moreover, it is also associated when stratification by sex (p = 0.003; OR:0.20, 95%CI: 0.06−0.53), and age (≥50 years old p = 0.001, OR:0.33, 95%CI: 0.16−0.63) Moreover, the risk of HCM in the carriers of the GG genotype of the rs1424019 polymorphism was significantly higher than that of the AA/AG genotypes carriers in the elderly subjects (p = 0.045, OR:1.24, 95%CI: 1.01−1.53). On the other hand, we observed significant differences in the rs74035787 A/rs1424019 G haplotype frequency (p = 0.0035; OR: 0.20, 95%CI: 0.07−0.59). Conclusions: Our study suggested a significant association between FENDRR gene variants and HCM.

A comprehensive formula for computing corrected QT intervals in patients with wide QRS.

BACKGROUND: There is increasing interest in developing appropriate methods for correction of the QT intervals in patients with prolonged depolarization of the ventricles. From an experimental model of controlled heart rate and QRS widening, we aimed to develop a new formula with better performance. METHODS: After exclusions, incremental pacing was performed (AAI mode; 50-120 bpm) in 17 patients admitted for self-expanding aortic valve implantation in two different phases: before and immediately after the release of the prosthesis. Mixed linear models were built to predict variation in QRS and JT intervals, and subsequently calculate the corrected QT (QTQRS-C). Internal and external validation on a new cohort of 48 patients was performed. RESULTS: Significant QRS widening (32.5 ms; CI95%:31.5-33.6) and QT prolongation (35.4 ms; CI95%:33.4-37.4) was observed after the release of the prosthesis. The best fit formula was computed as QTQRS-C = QTmeasured - (1.058*QRSmeasured - 108.397) - (0.0496*JTmeasured - 11.038). Internal validation provided a good correlation between measured and predicted QT (Pearson's coefficient:0.76; CI95%:0.70-0.80). In an external cohort (n = 48), the QRS widening was 28.4 ms(CI95%:21.8-35.1) and the JT widening was 16.58 ms(CI95%:8.73-24.4). Compared to other formulas, our proposed formula tends to display better performance as a result of a combination of appropriate correlation (Pearson's:0.75), being the closer to identity line (slope 0.83) and minimizing the relative standard error of the estimates (RSE 0.11). CONCLUSIONS: We developed a formula with better performance for QT correction in patients with wide QRS.

Chromoendoscopy With Indigo Carmine vs Virtual Chromoendoscopy (iSCAN 1) for Neoplasia Screening in Patients With Inflammatory Bowel Disease: A Prospective Randomized Study.

INTRODUCTION: The risk of colon cancer is greater in patients with inflammatory bowel disease (IBD) than in the general population. Chromoendoscopy with dye (CE) is the currently recommended method for detecting dysplasia in screening colonoscopies in IBD patients; however, the role of virtual chromoendoscopy (VC) is not yet well defined. OBJECTIVE: The object of this study was to compare CE and VC with the iSCAN 1 system in the detection of neoplastic lesions in IBD patients. DESIGN: We conducted a prospective, single-center, randomized study in IBD patients who underwent a colonoscopy for colon cancer screening. A total of 129 patients were included and were randomized to undergo a CE (n = 67) or a VC (n = 62). The rates of detection of neoplastic lesions by the 2 endoscopic techniques were compared. RESULTS: A total of 19 neoplastic lesions (9 adenomas and 10 low-grade dysplasias [LGD]) was detected in 16 patients, 12 lesions in the CE group (17.9%), and 7 lesions in the VC group (11.3%; P = 0.2); no differences were found in the overall rate of detection of lesions (neoplastic or nonneoplastic; P = 1). The median of the total examination time and endoscope withdrawal time (minutes) was significantly lower in the VC group than in the CE group (15 vs 20 and 10 vs 14, respectively; P < 0.001). CONCLUSION: No differences occurred in the rate of detection of neoplastic lesions between CE and VC with iSCAN 1. The time spent on the technique with VC is significantly less than that with CE.

Sex-dependent grades of haematopoietic modulation in patients with major depressive episodes are associated with suicide attempts.

Suicide is the leading cause of non-natural death worldwide, and major depressive disorder (MDD) is the mood disorder with the highest prevalence among individuals with suicidal behaviour (SB). The role of inflammation and immunomodulation in mood disorders has raised interest in recent years, as inflammation biomarkers have been reported to be increased in mood disorder patients, suggesting a role of inflammation in their pathogenesis. The influence of inflammation on the haematopoietic production is well known; however, a comprehensive study of the haematopoietic production in patients with major depressive episodes (MDE) is lacking. We examined global haematopoietic parameters from complete blood counts (CBC) of patients with MDE, in search of prognostic patterns. MDE patients presented differences in several CBC parameters, differences that were clearly pronounced and/or significant in concurrence with suicide attempts (SA). Red and white blood cell lineage parameters were affected, suggesting general haematopoietic modulation or imbalance. We observed distinct haematological parameter changes in women versus men, with men presenting milder alterations than women. Interestingly, we found that the List of Threatening Experiences (LTE) score, but not the Childhood Trauma Questionnaire (CTQ), was associated with the haematopoietic alterations observed exclusively in women and, more importantly, served as a parameter to stratify female MDE patients based on concurrence or non-concurrence with SA. In conclusion, grades of haematopoietic modulation in MDE patients are associated with absence or presence of SA. Haematopoietic manifestations differ between men and women and, in the latter, are markedly influenced by late, and not early, traumatic events.