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.

Efficacy and safety of hydroxychloroquine for treatment of mild SARS-CoV-2 infection and prevention of COVID-19 severity in pregnant and postpartum women: A randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Pregnant women have an increased risk of severe COVID-19. Evaluation of drugs with a safety reproductive toxicity profile is a priority. At the beginning of the pandemic, hydroxychloroquine (HCQ) was recommended for COVID-19 treatment. MATERIAL AND METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted in eight teaching hospitals in Spain to evaluate the safety and efficacy of HCQ in reducing viral shedding and preventing COVID-19 progression. Pregnant and postpartum women with a positive SARS-CoV-2 PCR (with or without mild COVID-19 signs/symptoms) and a normal electrocardiogram were randomized to receive either HCQ orally (400 mg/day for 3 days and 200 mg/day for 11 days) or placebo. PCR and electrocardiogram were repeated at day 21 after treatment start. Enrollment was stopped before reaching the target sample due to low recruitment rate. Trial registration EudraCT #: 2020-001587-29, on April 2, 2020. CLINICAL TRIALS: gov # NCT04410562, registered on June 1, 2020. RESULTS: A total of 116 women (75 pregnant and 41 post-partum) were enrolled from May 2020 to June 2021. The proportion of women with a positive SARS-CoV-2 PCR at day 21 was lower in the HCQ group (21.8%, 12/55) than in the placebo group (31.6%, 18/57), although the difference was not statistically significant (P = 0.499). No differences were observed in COVID-19 progression, adverse events, median change in QTc, hospital admissions, preeclampsia or poor pregnancy and perinatal outcomes between groups. CONCLUSIONS: HCQ was found to be safe in pregnant and postpartum women with asymptomatic or mild SARS-CoV-2 infection. Although the prevalence of infection was decreased in the HCQ group, the statistical power was insufficient to confirm the potential beneficial effect of HCQ for COVID-19 treatment.

Maternal COVID-19 Serological Changes-Comparison between Seroconversion Rate in First and Third Trimesters of Pregnancy and Subsequent Obstetric Complications: A Cohort Study.

Pregnant women are especially vulnerable to respiratory diseases. We aimed to study seroconversion rates during pregnancy in a cohort of consecutive pregnancies tested in the first and third trimesters and to compare the maternal and obstetric complications in the women who seroconverted in the first trimester and those who did so in the third. This was an observational cohort study carried out at the Hospital Universitario de Torrejón, in Madrid, Spain, during the first peak of the COVID-19 pandemic. All consecutive singleton pregnancies with a viable fetus attending their 11-13-week scan between 1 January and 15 May 2020 were included and seropositive women for SARS-CoV2 were monthly follow up until delivery. Antibodies against SARS-CoV-2 (IgA and IgG) were analyzed on stored serum samples obtained from first- and third-trimester routine antenatal bloods in 470 pregnant women. Antibodies against SARS-CoV-2 were detected in 31 (6.6%) women in the first trimester and in 66 (14.0%) in the third trimester, including 48 (10.2%) that were negative in the first trimester (seroconversion during pregnancy). Although the rate of infection was significantly higher in the third versus the first trimester (p = 0.003), no significant differences in maternal or obstetric complications were observed in women testing positive in the first versus the third trimester.

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.

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.

Application of a new protocol for providing obstetric care in an outpatient service during the COVID-19 pandemic in a public hospital in Madrid, Spain.

Objective: To evaluate the clinical implementation of a preventive COVID-19 protocol regarding re-organization of appointments and documented infections among health workers in an obstetric outpatient service. Methods: Descriptive analysis of the antenatal care at our obstetric outpatient service and infection rates among health care providers from March 19th to May 22nd, 2020. Appointments were divided into telephone calls or face-to-face examinations. A pre-consultation triage was implemented to identify suspected SARS-CoV2 infected women to reschedule them 14 days later or, if the consultation was non-delayable, to use complete Personal Protective Equipment (PPE). Firstly, the number of face-to-face appointments, telephone appointments, and COVID-19 diagnoses in pregnant women were analyzed. Secondly, the number of obstetricians and nurses diagnosed with SARS-CoV2 infection and their serologic status during universal screening in May 2020 were recorded. Results: One thousand eight hundred forty-two obstetric appointments were scheduled during this period, including 432 (23.5%) telephone appointments (96.53% according to clinical protocol, 1.62% symptomatic patients advised to stay at home, and 1.85% COVID-19 confirmed cases), and 1,410 (76.5%) face-to-face appointments (9.7% did not attend due to fear of getting the infection, 3.1% were lost-to-follow-up, 0.5% were rescheduled due to COVID-19 symptoms and 86.7% who did attend). Of the 1,223 women attending their hospital appointment, 3.6% screened positive at the triage (72.7% rescheduled and 27.3% seen with PPE). 43 rRT-PCR-SARS-CoV2 tests were performed, and two tested positive. No COVID-19 symptoms were reported among health workers at the outpatient obstetric service, and only one nurse presented immunoglobulin (Ig)G anti-SARS-CoV2. Conclusion: A prompt implementation of a preventive protocol in a hospital obstetric outpatient service, including triage, hygienic and preventive measurements, and rescheduling pregnancy appointments, reduces the percentage of health workers affected by SARS-CoV2.

Multisite assessment of the impact of a prenatal testing educational App on patient knowledge and preparedness for prenatal testing decision making.

In this study, we wanted to assess the impact of the use of a patient educational app on patient knowledge about noninvasive prenatal testing (NIPT) and preparedness for prenatal screening decision-making. A randomized control study was carried out at three international sites between January 2019 and October 2020. Study participants completed a pre-consultation survey and post-consultation survey to assess knowledge, satisfaction, and preparedness for prenatal screening consultation. Providers completed a post-consultation survey. In the control arm, the pre-consultation survey was completed prior to consultation with their prenatal care provider. In the intervention arm, the pre-consultation survey was completed after using the app but prior to consultation with their prenatal care provider. Mean knowledge scores in the 203 participants using the app were significantly higher pre-consultation (p < 0.001) and post-consultation (p < 0.005) than those not using the app. Higher pre-consultation knowledge scores in the intervention group were observed at all sites. Most (86%) app users stated they were "Satisfied" or "Very Satisfied" with it as a tool. Providers rated the intervention group as more prepared than controls (p = 0.027); provider assessment of knowledge was not significantly different (p = 0.073). This study shows that clinical implementation of a patient educational app in a real-world setting was feasible, acceptable to pregnant people, and positively impacted patient knowledge.

Clinical and Economic Evaluation after Adopting Contingent Cell-Free DNA Screening for Fetal Trisomies in South Spain.

INTRODUCTION: Contingent cell-free (cf) DNA screening on the basis of the first-trimester combined test (FCT) results has emerged as a cost-effective strategy for screening of trisomy 21 (T21). OBJECTIVES: To assess performance, patients' uptake, and cost of contingent cfDNA screening and to compare them with those of the established FCT. METHODS: This is a prospective cohort study including all singleton pregnancies attending to their FCT for screening of T21 at 2 university hospitals in South Spain. When the FCT risk was ≥1:50, there were major fetal malformations, or the nuchal translucency was ≥3.5 mm, women were recommended invasive testing (IT); if the risk was between 1:50 and 1:270, women were recommended cfDNA testing; and for risks bellow 1:270, no further testing was recommended. Detection rate (DR), false-positive rate (FPR), patients' uptake, and associated costs were evaluated. RESULTS: We analyzed 10,541 women, including 46 T21 cases. DR of our contingent strategy was 89.1% (41/46) at 1.4% (146/10,541) FPR. Uptake of cfDNA testing was 91.2% (340/373), and overall IT rate was 2.0%. The total cost of our strategy was €1,462,895.7, similar to €1,446,525.7 had cfDNA testing not been available. CONCLUSIONS: Contingent cfDNA screening shows high DR, low IT rate, and high uptake at a similar cost than traditional screening.

Maternal physiological changes at rest induced by exercise during pregnancy: A randomized controlled trial.

OBJECTIVE: to analyse maternal physiological changes in several areas (cardiovascular, metabolic, renal and hepatic) related to the regular practice of a supervised exercise program. METHODS: This is an unplanned secondary analysis from a randomized controlled trial carried out in a single maternity unit in Madrid, Spain (NCT 02,756,143). From November 2014 to June 2015, 92 women were randomly assigned to perform a mild-moderate supervised exercise program during pregnancy (Intervention group, IG) or to continue with their routine pregnancy care (control group, CG). For the purpose of this study we collected clinical and analytical data (heart blood pressure, weight, blood glucose, AST, ALT, blood Creatinine and blood Uric acid) available from all obstetric visits and examined the differences between groups. RESULTS: We did not find any differences in: pregnancy weight (IG: 11.4 ± 4.4 Kg vs. CG: 10.1 ± 5.3 Kg; p = 0.173); fasting glucose at 10+0-12+6 weeks (IG: 78.48±8.34 vs. CG: 76±13.26, p = 0.305) or at 34+0-36+4 weeks (IG: 73.25±10.27 vs CG: 73.45± 8.29,p = 0.920), and 50 gs glucose tolerance at 24+4-26+6weeks (IG: 116.23±35.07 vs CG: 116.36±25.98, p = 0.984); Aspartate-amino-transferase at 10+0-12+6 weeks (IG: 15.38±4.17 vs CG: 17.33±7.05, p = 0.124) and at 34+0-36+4 weeks (IG: 21.65±5.25 vs CG: 19.53±8.32, p = 0.165) or Alanine-amino- transferase at 10+0-12+6 weeks (IG: 27.50±10.63 vs CG: 28.27±11.77, p = 0.746) or at 34+0-36+4 weeks (IG: 22.93±9.23 vs CG: 20.84±13.49, p = 0.407); blood Creatinine concentrations at 34+0-36+4 weeks (IG: 0.595±0.401 vs CG: 0.575±0.100, p = 0.757) and blood uric acid concentrations at 34+0-36+4 weeks (IG: 3.526 ± 0.787 vs CG: 3.262±0.672, p = 0.218). Heart blood pressure was similar between groups except at 27+0-28+6 weeks, where systolic blood pressure was significantly lower in the CG in comparison to the IG (116.31±10.8 mmHg vs. 120.22 ± 10.3 mmHg, p = 0.010). CONCLUSION: Regular supervised exercise during pregnancy does not alter normal maternal physiology.

Prenatal screening and diagnosis of genetic abnormalities: SEGO, SEQCML, AEDP consensus recommendations.

In this paper, the scientific societies SEGO, SEQCML and AEDP provide a series of consensus-based recommendations for prenatal screening and diagnosis of genetic abnormalities. A set of evaluation indicators are also proposed as a means to improve the quality of the biochemical, ultrasound, and genetic processes involved in prenatal screening and diagnosis of genetic anomalies. Some recommendations are also proposed in relation to invasive prenatal diagnostic procedures, more specifically regarding sample collection and genetic testing. The purpose of this proposal is to unify performance criteria and quality indicators at national level, with audits performed on a regular basis. It is strongly recommended that a national prenatal screening strategy be established and provided with the resources necessary to evaluate the performance of quality indicators and diagnostic procedures under the supervision of health authorities. Protocols should be revised on a regular basis to consider the incorporation of new cost-effective technologies.

Physical exercise programme during pregnancy decreases perinatal depression risk: a randomised controlled trial.

INTRODUCTION: The incidence of depression is high during the perinatal period. This mood disorder can have a significant impact on the mother, the child and the family. OBJECTIVE: To examine the effect of an exercise programme during pregnancy on the risk of perinatal depression. METHODS: Healthy women who were <16 weeks pregnant were randomly assigned to two different groups. Women in the intervention group participated in a 60 min exercise programme throughout pregnancy, 3 days per week, which was conducted from October 2014 to December 2016. The Center for Epidemiological Studies-Depression Scale was used to measure the risk of depression at the beginning of the study (12-16 weeks), at gestational week 38 and at 6 weeks postpartum. RESULTS: One hundred and twenty-four pregnant women were allocated to either the intervention (IG=70) or the control (CG=54) group. No differences were found in the percentage of depressed women at baseline (20% vs 18.5%) (χ2=0.043; p=0.836). A smaller percentage of depressed women were identified in the IG compared with the CG at 38 gestational weeks (18.6% vs 35.6%) (χ2=4.190; p=0.041) and at 6 weeks postpartum (14.5% vs 29.8%) (χ2=3.985; p=0.046) using the per-protocol analysis. No significant differences were found using the intention-to-treat analyses, except in the multiple imputation analysis at week 38 (18.6% vs 34.4%) (χ2=4.085; p=0.049). CONCLUSION: An exercise programme performed during pregnancy may reduce the prevalence of depression in late pregnancy and postpartum. TRIAL REGISTRATION NUMBER: NCT02420288; Results.

Does Exercise During Pregnancy Affect Placental Weight?: A Randomized Clinical Trial.

Placental weight (PW) is a measure commonly used to summarize growth and aspects of placental function. In a normal pregnancy, it is reasonable to assume that PW is related to aspects of the functional capacity of the placenta. The placenta, as the site for all maternal-fetal oxygen and nutrient exchange, influences birth weight and is thus central to a successful pregnancy outcome. PW is the most common way to characterize placental growth, which relates to placental function. With physical exercise becoming an integral part of life for many women, the question of whether exercise during pregnancy has an adverse effect on the growing fetus is very important. The aim was to examine the influence of an aerobic exercise program throughout pregnancy on PW among healthy pregnant women. A randomized control trial was used (registration trial number: NCT02420288). Women were randomized into an exercise group (EG; n = 33) or a control group (CG; n = 32) that received standard care. The EG trained 3 days/week (55-60 min/session) from gestational Weeks 9-11 until Weeks 38-39. The 85 training sessions involved aerobic, muscular and pelvic floor strength, and flexibility exercises. PW and other pregnancy outcomes were measured. There was high attendance to the exercise program, and no differences in the PW at delivery were observed between study groups (CG = 493.2 ± 119.6 g vs. EG = 495.4 ± 150 g, p = .95). A regular, supervised exercise program throughout pregnancy does not affect the PW in healthy pregnant women.

Sonographical predictive markers of failure of induction of labour in term pregnancy.

Predictive markers of failure of induction of labour in term pregnancy were evaluated. A prospective study including 245 women attending induction of labour was performed. The inclusion criteria were singleton pregnancies, gestational age 37-42 weeks and the main outcomes were failure of induction, induction to delivery interval and mode of delivery. Women with a longer cervical length prior to induction (CLpi) had a higher rate of failure of induction (30.9 ± 6.8 vs. 23.9 ± 9.3, p < .001). BMI was higher and maternal height was lower in the group of caesarean section compared to vaginal delivery (33.1 ± 8 vs. 29.3 ± 4.6, 160 ± 5 vs. 164 ± 5, p < .001, respectively). A shorter CLpi correlated with a shorter induction to delivery interval (R Pearson .237, p < .001). In the regression analysis, for failure of induction the only independent predictor was the CL prior to induction. Therefore, the CLpi is an independent factor for prediction of failure of induction of labour.

Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial.

BACKGROUND: Most previous studies of the use of cervical pessaries were either retrospective or case controlled and their results showed that this intervention might be a preventive strategy for women at risk of preterm birth; no randomised controlled trials have been undertaken. We therefore undertook a randomised, controlled trial to investigate whether the insertion of a cervical pessary in women with a short cervix identified by use of routine transvaginal scanning at 20-23 weeks of gestation reduces the rate of early preterm delivery. METHODS: The Pesario Cervical para Evitar Prematuridad (PECEP) trial was undertaken in five hospitals in Spain. Pregnant women (aged 18-43 years) with a cervical length of 25 mm or less were randomly assigned according to a computer-generated allocation sequence by use of central telephone in a 1:1 ratio to the cervical pessary or expectant management (without a cervical pessary) group. Because of the nature of the intervention, this study was not masked. The primary outcome was spontaneous delivery before 34 weeks of gestation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00706264. FINDINGS: 385 pregnant women with a short cervix were assigned to the pessary (n=192) and expectant management groups (n=193), and 190 were analysed in each group. Spontaneous delivery before 34 weeks of gestation was significantly less frequent in the pessary group than in the expectant management group (12 [6%] vs 51 [27%], odds ratio 0·18, 95% CI 0·08-0·37; p<0·0001). No serious adverse effects associated with the use of a cervical pessary were reported. INTERPRETATION: Cervical pessary use could prevent preterm birth in a population of appropriately selected at-risk women previously screened for cervical length assessment at the midtrimester scan. FUNDING: Instituto Carlos III.