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.

A Novel Predictive Machine Learning Model Integrating Cytokines in Cervical-Vaginal Mucus Increases the Prediction Rate for Preterm Birth.

Preterm birth (PB) is a leading cause of perinatal morbidity and mortality. PB prediction is performed by measuring cervical length, with a detection rate of around 70%. Although it is known that a cytokine-mediated inflammatory process is involved in the pathophysiology of PB, none screening method implemented in clinical practice includes cytokine levels as a predictor variable. Here, we quantified cytokines in cervical-vaginal mucus of pregnant women (18-23.6 weeks of gestation) with high or low risk for PB determined by cervical length, also collecting relevant obstetric information. IL-2, IL-6, IFN-γ, IL-4, and IL-10 were significantly higher in the high-risk group, while IL-1ra was lower. Two different models for PB prediction were created using the Random Forest machine-learning algorithm: a full model with 12 clinical variables and cytokine values and the adjusted model, including the most relevant variables-maternal age, IL-2, and cervical length- (detection rate 66 vs. 87%, false positive rate 12 vs. 3.33%, false negative rate 28 vs. 6.66%, and area under the curve 0.722 vs. 0.875, respectively). The adjusted model that incorporate cytokines showed a detection rate eight points higher than the gold standard calculator, which may allow us to identify the risk PB risk more accurately and implement strategies for preventive interventions.

Use of a screening questionnaire for systemic lupus erythematosus among pregnant women in a Mexican population.

OBJECTIVE: To conduct a diagnostic assessment of pregnant women using a screening questionnaire for SLE. MATERIALS AND METHODS: This was an analytical cross-sectional study carried out at the National Institute of Perinatology between 1 November 2019 and 28 February 2020, using a screening questionnaire for SLE. Antinuclear antibody and anti-double stranded DNA antibody tests and a clinical assessment by a rheumatologist were conducted for participants who obtained ≥4 positive responses on the questionnaire. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the screening questionnaire for SLE were calculated. RESULTS: The questionnaire survey was conducted with 540 pregnant patients, 22 of whom (4.1%) had ≥4 positive responses. An antinuclear antibody test was conducted in all aforementioned 22 patients; 17 (77.3%) showed titres of ≥1:80. Of the 22 patients, 19 (86.4%) underwent clinical assessment by a rheumatologist. The patients were classified according to the SLE classification criteria: 7/19 (36.9%) met the revised 1997 American College Rheumatology (ACR) criteria, 8/19 (42.1%) met the Systemic Lupus International Collaborating Clinics criteria and 7/19 (36.9%) met the 2019 ACR/EULAR criteria (sensitivity=0.86, specificity=0.97, PPV=0.77 and NPV=1 for antinuclear antibody titre of ≥1:80; sensitivity=0.88, specificity=0.98, PPV=0.37 and NPV=1 for SLE according to the 2019 ACR/EULAR criteria). CONCLUSIONS: The questionnaire showed high sensitivity and specificity in the diagnosis of SLE. Given its usability and cost:benefit ratio, this strategy should be used for all patients coming in for their first visit to determine who requires antinuclear antibody testing and who needs to be referred to a rheumatologist.

Cambios morfológicos en las placentas de pacientes con preeclampsia o restricción del crecimiento intrauterino e interpretación de los desenlaces perinatales / Morphological changes in placentas of patients with preeclampsia or intrauterine growth restriction and interpretation of perinatal outcomes

Resumen OBJETIVO: Determinar las diferencias morfológicas macro y microscópicas en las placentas de pacientes con preeclampsia o restricción del crecimiento intrauterino con las de pacientes sanas. MATERIALES Y MÉTODOS: Estudio de casos y controles, retrospectivo, observacional y comparativo. Se revisaron las bases de datos del servicio de Medicina Materno Fetal del Instituto Nacional de Perinatología (INPer) de febrero de 2018 a marzo de 2020 en busca de pacientes con embarazo único y diagnóstico de preeclampsia temprana o restricción del crecimiento temprano y finalización del embarazo en el INPer. El análisis de los datos se llevó a cabo en el programa estadístico SPSS versión 25. Las variables categóricas se compararon entre grupos con χ2 y los resultados se representaron en porcentajes. Para la evaluación estadística analítica se utilizó ANOVA para una muestra independiente para contrastar las asociaciones entre las diversas variables. RESULTADOS: Se incluyeron 52 pacientes que se dividieron en: grupo 1: preeclampsia temprana sin restricción del crecimiento intrauterino (n = 13), grupo 2: preeclampsia y restricción del crecimiento intrauterino temprano (n = 13), grupo 3: restricción del crecimiento intrauterino temprano (n = 13) y grupo 4 (control) pacientes sanas (n = 13). Se demostró una diferencia estadísticamente significativa en el peso de la placenta, con un valor de p < 0.05 pero sin diferencia en el diámetro del cordón umbilical entre los cuatro grupos. CONCLUSIONES: El estudio histopatológico placentario es una oportunidad para obtener información detallada de la base fisiopatológica de la enfermedad y, así, ofrecer una asesoría y seguimiento preciso a la paciente y al neonato.

Abstract OBJECTIVE: To determine the macro and microscopic morphologic differences in placentas of patients with preeclampsia or intrauterine growth restriction with those of healthy patients. MATERIALS AND METHODS: A retrospective, observational and comparative case-control study. The databases of the Maternal Fetal Medicine service of the National Institute of Perinatology (INPer) from February 2018 to March 2020 were reviewed for patients with singleton pregnancy and diagnosis of early preeclampsia or early growth restriction and termination of pregnancy at the INPer. Data analysis was performed in the statistical program SPSS version 25. Categorical variables were compared between groups with χ2 and the results were represented in percentages. For the analytical statistical evaluation, ANOVA for an independent sample was used to contrast the associations between the various variables. RESULTS: Fifty-two patients were included and divided into: group 1: early preeclampsia without intrauterine growth restriction (n = 13), group 2: preeclampsia and early intrauterine growth restriction (n = 13), group 3: early intrauterine growth restriction (n = 13) and group 4 (control) healthy patients (n = 13). A statistically significant difference in placental weight was demonstrated, with a p value < 0.05 but no difference in umbilical cord diameter among the four groups. CONCLUSIONS: Placental histopathologic study is an opportunity to obtain detailed information on the pathophysiologic basis of the disease and thus provide accurate counseling and follow-up to the patient and neonate.