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.

Trends in preterm birth in women living with HIV in Switzerland over the last three decades: A multicentric, prospective, cohort study.

BACKGROUND: HIV infection and its management during pregnancy to reduce perinatal transmission has been associated with preterm birth (PTB). This management has drastically changed. We aimed to evaluate changes in rates of PTB over 34 years in women living with HIV (WLWH) in Switzerland, and to identify factors and interventions associated with these changes. METHODS: We analysed data from 1238 singleton pregnancies, prospectively collected by the Swiss Mother and Child HIV Cohort Study (MoCHiV) and the Swiss HIV Cohort Study (SHCS) between 1986 and 2020. Rates of PTB in this cohort were compared with that of the general Swiss population for three time periods according to changing treatment strategies recommended at the time. We evaluated the association of PTB with sociodemographic, HIV infection and obstetric variables in uni- and multivariate logistic regression. RESULTS: Rate of PTB in WLWH was highest prior to 2010 (mean 20.4%), and progressively decreased since then (mean 11.3%), but always remained higher than in the general population (5%). Older maternal age, lower CD4 count and detectable viraemia at third trimester (T3), drug consumption and mode of delivery were all significantly associated with both PTB and period of study in univariate analysis. There was no association between PTB and type of antiretroviral regimen. No difference was found in the rate of spontaneous labor between PTB and term delivery groups. Only higher CD4 count at T3 and vaginal delivery were significantly associated with a decrease in PTB over time in multivariate analysis. CONCLUSIONS: Preterm birth in WLWH in Switzerland has drastically decreased over the last three decades, but remains twice the rate of that in the general population. Improved viral control and changes in mode of delivery (vaginal birth recommended if viral loads are low near birth) have led to this progress.

Influence of Timing of Maternal Pertussis Immunization on the Avidity of Transferred Antibodies in Term and Preterm Neonates.

The timing of maternal pertussis vaccination influences the titers of cord-blood anti-pertussis antibodies. Whether it affects their avidity is unknown. We demonstrate in 298 term and 72 preterm neonates that antibody avidity is independent of the timing of maternal vaccination, whether comparing second with third trimester or intervals before birth.

[Multidisciplinary management of postpartum headaches]. / Prise en charge multidisciplinaire des céphalées du postpartum.

Headache is a common complaint in the postpartum period and is benign in most cases. Physiological adaptations during pregnancy and childbirth put women at risk of secondary headaches and the clinician must be able to identify them at an early stage. The management algorithm described in this article provides a systematic assessment based on 4 key points: the clinical presentation, which refers to specific clinical pictures or severity criteria, the clinical context and the evolution of symptoms focusing on potential complications and known associations between different diseases. Indications for imaging (CT or MRI) and possible treatments during breastfeeding are also detailed.

Les céphalées (primaires et secondaires) sont une plainte courante durant la période du postpartum et sont, dans la majorité des cas, bénignes. Les modifications physiologiques liées à la grossesse et à l'accouchement entraînent un risque de céphalées secondaires et le praticien doit savoir les identifier précocement. L'algorithme de prise en charge décrit dans cet article permet une évaluation systématisée et repose sur quatre points essentiels : la présentation clinique, qui oriente vers des tableaux cliniques spécifiques ou des critères de gravité, le contexte clinique et l'évolution de la symptomatologie, en insistant sur les complications potentielles, ainsi que les associations connues entre différentes pathologies. Les indications pour une imagerie (scanner ou IRM) sont détaillées ainsi que les traitements possibles durant l'allaitement.

Dual effect of nifedipine on pregnant human myometrium contractility: Implication of TRPC1.

Nifedipine, an L-type voltage-gated Ca2+ channel (L-VGCC) blocker, is one of the most used tocolytics to treat preterm labor. In clinical practice, nifedipine efficiently decreases uterine contractions, but its efficacy is limited over time, and repeated or maintained nifedipine-based tocolysis appears to be ineffective in preventing preterm birth. We aimed to understand why nifedipine has short-lasting efficiency for the inhibition of uterine contractions. We used ex vivo term pregnant human myometrial strips treated with cumulative doses of nifedipine. We observed that nifedipine inhibited spontaneous myometrial contractions in tissues with high and regular spontaneous contractions. By contrast, nifedipine appeared to increase contractions in tissues with low and/or irregular spontaneous contractions. To investigate the molecular mechanisms activated by nifedipine in myometrial cells, we used the pregnant human myometrial cell line PHM1-41 that does not express L-VGCC. The in vitro measurement of intracellular Ca2+ showed that high doses of nifedipine induced an important intracellular Ca2+ entry in myometrial cells. The inhibition or downregulation of the genes encoding for store-operated Ca2+ entry channels from the Orai and transient receptor potential-canonical (TRPC) families in PHM1-41 cells highlighted the implication of TRPC1 in nifedipine-induced Ca2+ entry. In addition, the use of 2-APB in combination with nifedipine on human myometrial strips tends to confirm that the pro-contractile effect induced by nifedipine on myometrial tissues may involve the activation of TRPC channels.

Transfer of antiretroviral drugs into breastmilk: a prospective study from the Swiss Mother and Child HIV Cohort Study.

INTRODUCTION: In 2018, Switzerland changed its guidelines to support women living with HIV wishing to breastfeed. The exposure of antiretroviral drugs (ARVs) in breastmilk and the ingested daily dose by the breastfed infant are understudied, notably for newer ARVs. This study aimed to quantify ARV concentrations in maternal plasma and breastmilk to determine the milk/plasma ratio, to estimate daily infant ARV dose from breastfeeding and to measure ARV concentrations in infants. METHODS: All women wishing to breastfeed were included, regardless of their ARV treatment. Breastmilk and maternal plasma samples were mostly collected at mid-dosing interval. RESULTS: Twenty-one mother/child pairs were enrolled; of those several were on newer ARVs including 10 raltegravir, 1 bictegravir, 2 rilpivirine, 2 darunavir/ritonavir and 3 tenofovir alafenamide. No vertical HIV transmission was detected (one infant still breastfed). The median milk/plasma ratios were 0.96/0.39 for raltegravir once/twice daily, 0.01 for bictegravir, 1.08 for rilpivirine, 0.12 for darunavir/ritonavir and 4.09 for tenofovir alafenamide. The median estimated infant daily dose (mg/kg) from breastfeeding was 0.02/0.25 for raltegravir once/twice daily, 0.01 for bictegravir, 0.02 for rilpivirine, 0.05 for darunavir/ritonavir and 0.007 for tenofovir alafenamide, resulting in relative infant dose <10% exposure index for all ARVs. CONCLUSIONS: ARVs were transferred to a variable extent in breastmilk. Nevertheless, the estimated daily ARV dose from breastfeeding remained low. Differential ARV exposure was observed in breastfed infants with some ARVs being below/above their effective concentrations raising the concern of resistance development if HIV infection occurs. More data on this potential risk are warranted to better support breastfeeding.

Autologous Platelet-Rich Plasma for Clitoral Reconstruction: A Case Study.

Clitoral reconstruction after female genital mutilation/cutting (FGM/C) is associated with significant post-operative pain and months-long recovery. Autologous platelet-rich plasma (A-PRP) reduces the time of healing and pain in orthopedic and burn patients and could also do so in clitoral reconstruction. In the present case, a 35-year-old Guinean woman who had undergone FGM/C Type IIb presented to our clinic for clitoral reconstruction. Her request was motivated by low sexual satisfaction and body image. We surgically reconstructed the clitoris using the Foldès method and applied plasma and glue of A-PRP. The patient was highly satisfied with the procedure. Two months post-operatively, her pain had ceased entirely and re-epithelialization was complete. We conclude that A-PRP may improve pain and healing after clitoral reconstruction. Extensive studies investigating long-term outcomes are needed.

[Cytomegalovirus screening during pregnancy : an ongoing debate still in 2022]. / Dépistage du cytomégalovirus pendant la grossesse : toujours débattu en 2022.

Cytomegalovirus infection remains the main congenital infectious cause of abnormal development, notably neurological or auditory. In case of early maternal infection, vertical transmission is lower than later in pregnancy, but fetal/neonatal sequelae are more frequent and severe. Until recently, there was no available treatment to prevent transmission and complications and only preventive measures were recommended. Based on a recent literature review, we will discuss the possible indication for CMV screening before conception and/or in the first trimester of pregnancy, in order to improve patient's information, prevention and treatment.

Le cytomégalovirus constitue la première cause infectieuse congénitale d'anomalie du développement, notamment aux niveaux neurologique et auditif. En cas d'infection maternelle précoce, le risque de transmission verticale est moindre que plus tard durant la grossesse, mais les séquelles fœtales/néonatales sont plus sévères. Jusqu'à présent, il n'existait pas de traitement efficace et seules les mesures de prévention primaire permettaient de combattre cette infection. Après une revue critique de la littérature récente, nous proposons de discuter l'intérêt d'un dépistage précoce en préconceptionnel et/ou au premier trimestre de la grossesse afin de permettre la mise en place des mesures de prévention et également l'introduction d'un traitement préventif/thérapeutique si nécessaire.

[Pregnancy and COVID-19: drugs and vaccine guidelines in 2021]. / Gynécologie-obstétrique - Grossesse et Covid-19 : recommandations médicamenteuses et vaccinales en 2021.

During this global health crisis, COVID-19 unfortunately did not spare pregnant women, who are at greater risk of becoming infected, developing severe forms and having obstetric complications. In this article we will talk about the risks associated with COVID-19 during pregnancy and in particular the existing data on the drugs to be administered in the event of illness and how to avoid infection and its complications through vaccination.

Durant cette crise sanitaire mondiale, le Covid-19 n'a malheureusement pas épargné les femmes enceintes. Celles-ci sont plus à risque d'être infectées, de développer des formes sévères et d'avoir des complications obstétricales. Dans cet article, nous allons parler des risques liés au Covid-19 durant la grossesse et notamment des données existantes sur les médicaments à administrer en cas de maladie et comment éviter l'infection et ses complications grâce à la vaccination.

[Management of maternal urologic issues during pregnancy]. / Prise en charge des pathologies urologiques maternelles durant la grossesse.

The management of urologic issues in pregnancy can be complex as the risk assessment of diagnostic and therapeutic options is often a challenge. This article aims to assist obstetrician-gynecologists and general practitioners in their follow-up of common urologic issues in pregnancy, of patients with previous urologic surgery (urinary derivation, urogenital reconstruction, etc.) or with a history of obstetrical complications (placenta percreta, urinary retention, trauma). This article will not cover urologic issues in the fetus.

La prise en charge de pathologies urologiques, même courantes, peut se révéler difficile dans le contexte de la grossesse. Le défi réside notamment dans les risques liés aux procédures d'investigation et aux options thérapeutiques pour cette population unique. Cet article a pour but d'aider les gynécologues-obstétriciens et les médecins de premiers recours dans leur prise en charge des pathologies urologiques courantes dans le contexte de la grossesse, du suivi de patientes avec des antécédents chirurgicaux urologiques (dérivation urinaire, reconstruction urogénitale, etc.) ou des complications obstétricales sur les structures urologiques (placenta percreta, rétention urinaire aiguë, trauma). Il ne traite pas des pathologies urologiques fœtales.