The individual and global impact of copy-number variants on complex human traits.

The impact of copy-number variations (CNVs) on complex human traits remains understudied. We called CNVs in 331,522 UK Biobank participants and performed genome-wide association studies (GWASs) between the copy number of CNV-proxy probes and 57 continuous traits, revealing 131 signals spanning 47 phenotypes. Our analysis recapitulated well-known associations (e.g., 1q21 and height), revealed the pleiotropy of recurrent CNVs (e.g., 26 and 16 traits for 16p11.2-BP4-BP5 and 22q11.21, respectively), and suggested gene functionalities (e.g., MARF1 in female reproduction). Forty-eight CNV signals (38%) overlapped with single-nucleotide polymorphism (SNP)-GWASs signals for the same trait. For instance, deletion of PDZK1, which encodes a urate transporter scaffold protein, decreased serum urate levels, while deletion of RHD, which encodes the Rhesus blood group D antigen, associated with hematological traits. Other signals overlapped Mendelian disorder regions, suggesting variable expressivity and broad impact of these loci, as illustrated by signals mapping to Rotor syndrome (SLCO1B1/3), renal cysts and diabetes syndrome (HNF1B), or Charcot-Marie-Tooth (PMP22) loci. Total CNV burden negatively impacted 35 traits, leading to increased adiposity, liver/kidney damage, and decreased intelligence and physical capacity. Thirty traits remained burden associated after correcting for CNV-GWAS signals, pointing to a polygenic CNV architecture. The burden negatively correlated with socio-economic indicators, parental lifespan, and age (survivorship proxy), suggesting a contribution to decreased longevity. Together, our results showcase how studying CNVs can expand biological insights, emphasizing the critical role of this mutational class in shaping human traits and arguing in favor of a continuum between Mendelian and complex diseases.

Cytomegalovirus infection during pregnancy: cross-sectional survey of knowledge and prevention practices of healthcare professionals in French-speaking Switzerland.

BACKGROUND: Lack of Cytomegalovirus (CMV) knowledge among healthcare professionals has been proven to be the main threat to pregnant women's awareness, preventing them from reducing the risk of infection. The aims of this study were to assess the knowledge and practices of French-speaking Swiss perinatal professionals in terms of CMV prevention, as well as the sociodemographic-professional factors that influence them. METHODS: This observational study used a cross-sectional design to collect data-via an anonymous electronic questionnaire in French distributed to gynecologists-obstetricians, general practitioners and midwives via various channels: e-mails and social networks of partner centers, professional associations, and conferences. The 41-item questionnaire collected data on sociodemographic and professional characteristics, general CMV knowledge, national recommendation knowledge and prevention practices. Univariable and multivariable analyses were performed. RESULTS: A total of 110 gynecologist-obstetricians, 5 general practitioners and 226 midwives participated in the study. While more than 80% of practitioners were familiar with protective hygiene measures, significant gaps were highlighted concerning the transmission routes, as well as the signs of short- and long-term congenital CMV infection. Regarding practice, 63.3% of participants provided information on CMV to their patients, mainly during the first antenatal visit. Among those who did not, lack of knowledge and forgetfulness were the two main reasons cited. Concerning systematic screening, 45.7% of participants offered it to their patients, and 37.3% only offered it to "at risk" groups. The existence of national guidelines on CMV was known by 62.0% of participants. Multivariable analysis revealed that working as a gynecologist-obstetrician was independently associated with higher score of preventive practices, while performing ultrasound or preconception consultations was independently associated with a higher score of general CMV knowledge, and working in a university hospital was independently associated with a higher score of Swiss recommendation knowledge. A level of training higher than the basic medical or midwifery diploma and participation in fetal medicine symposia both promote a higher score of CMV knowledge and prevention practices in line with current recommendations. CONCLUSION: This study confirms the significant gaps in CMV knowledge among French-speaking Swiss caregivers along with the heterogeneity of their prevention practices. To raise awareness among pregnant women and reduce the burden of congenital CMV infections, improving professional knowledge through access to specific training and standardizing practices should be a national priority.

Time to redefine prolonged third stage of labor? A systematic review and meta-analysis of the length of the third stage of labor and adverse maternal outcome after vaginal birth.

OBJECTIVE: This study aimed (1) to assess the association between the length of the third stage of labor and adverse maternal outcome after vaginal birth and (2) to evaluate whether earlier manual placenta removal reduces the risk of adverse outcome. DATA SOURCES: PubMed, MEDLINE, Embase, ClinicalTrials.gov, the Cochrane Library, Journals@Ovid, and the World Health Organization International Clinical Trials Registry were searched from January 1, 2000, to June 13, 2023. STUDY ELIGIBILITY CRITERIA: All studies that assessed adverse maternal outcome, defined as any maternal complication after vaginal birth, concerning the length of the third stage of labor and the timing of manual placenta removal were included. METHODS: The included studies were evaluated using the Conducting Systematic Reviews and Meta-Analyses of Observational Studies of Etiology methodology. Pooled odds ratios with 95% confidence intervals were calculated. Heterogeneity (I2 test) was assessed, subgroup analyses were performed, and 95% prediction intervals were calculated. RESULTS: To meet the first objective, 18 cohort studies were included. The assessed cutoff values for the length of the third stage of labor were 15, 30, and 60 minutes. Women with a third stage of labor of ≥15 minutes had an increased risk of postpartum hemorrhage compared with those with a third stage of labor of <15 minutes (odds ratio, 5.55; 95% confidence interval, 1.74-17.72). For women without risk factors for postpartum hemorrhage, the odds ratio was 2.20 (95% confidence interval, 0.75-6.49). Among women with a third stage of labor of ≥60 minutes vs women with a third stage of labor of <60 minutes, the odds ratio was 3.72 (95% confidence interval, 2.36-5.89). The incidence of red blood cell transfusion was higher for a third stage of labor of ≥30 minutes than for a third stage of labor of <30 minutes (odds ratio, 3.23; 95% confidence interval, 2.26-4.61). Of note, 3 studies assessed the timing of placenta removal and the risk of adverse maternal outcome. However, the results could not be pooled because of the different outcome measures. Moreover, 1 randomized controlled trial (RCT) reported a significantly higher incidence of hemodynamic compromise in women with manual placenta removal at 15 minutes than in women with manual placenta removal at 10 minutes (30/156 [19.2%] vs 10/156 [6.4%], respectively), whereas 2 observational studies reported a lower risk of bleeding among women without manual placenta removal. CONCLUSION: Although the risk of adverse maternal outcome after vaginal birth increases when the third stage of labor exceeds 15 minutes, there is no convincing supporting evidence that reducing the length of the third stage of labor by earlier manual removal of the placenta can reduce the incidence of adverse maternal outcome.

Contribution of fetal blood sampling to determining the prognosis of congenital cytomegalovirus infections: a case-cohort study in Switzerland.

BACKGROUND: Cytomegalovirus is responsible for the most common congenital infection, affecting 0.5% to 1.0% of live births in Europe. Congenital cytomegalovirus infection can be diagnosed during pregnancy by viral DNA amplification in the amniotic fluid, but the prognosis of fetuses without severe brain abnormalities remains difficult to establish on the basis of prenatal imaging alone. OBJECTIVE: To identify predictors of moderate to severe symptomatic cytomegalovirus infection among fetal blood parameters and to propose an algorithm on the basis of these parameters and on prenatal imaging that would provide the best positive and negative predictive values. STUDY DESIGN: Fetal blood sampling at 21-28 weeks gestation was performed in fetuses with congenital cytomegalovirus infection confirmed by amniocentesis after maternal infection in the first-trimester or periconceptional period. We compared the levels of hemoglobin, thrombocytes, γ-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, ß2-microglobulin, immunoglobulins G and M, and cytomegalovirus DNA viral loads in amniotic fluid and fetal blood between those with moderate to severe symptomatic infection and those with asymptomatic to mild infection (median follow-up of 36 months for live births). RESULTS: Among 58 fetuses included, 25 (43%) had a moderate to severe symptomatic infection: 16 with severe cerebral abnormalities, 5 with multiple signs or symptoms at birth, 2 with bilateral sensorineural hearing loss, and 2 with neurodevelopmental delay. The values of thrombocytes, aspartate aminotransferase, ß2 microglobulin, Immunoglobulin M, and cytomegalovirus viral loads differed significantly between fetuses with moderate to severe symptomatic infection and those with asymptomatic to mild infection. The optimal strategy to predict moderate to severe symptomatic infection was to first perform fetal brain imaging, followed by fetal blood sampling with the following cutoffs: thrombocytes <120,000/mL, viremia ≥5 log10/mL, and ß2 microglobulin ≥12 mg/L). This recursive algorithm had a negative predictive value of 100% for moderately to severely symptomatic infection. CONCLUSION: The combination of thrombocytes, ß2-microglobulin, and cytomegalovirus viral load in fetal blood can be used for prognosis determination, particularly in cytomegalovirus-infected fetuses without severe brain abnormalities at the time of prenatal diagnosis. Future studies should evaluate whether these parameters remain useful in infected fetuses who have been treated with valacyclovir before fetal blood sampling.

[Neonatal Fc receptor : role and implications in maternal fetal medicine]. / Récepteur Fc néonatal : rôle et ­implications en médecine ­fœto-maternelle.

During pregnancy, the mother's IgG immunoglobulins cross the -placenta via the neonatal Fc receptor (FcRn), enabling the fetus to acquire passive immunity. In the presence of maternal allo- or auto-antibodies, placental transfer of these pathogenic antibodies mediated by FcRn can cause diseases in the fetus and/or the newborn. FcRn blockade therefore appears to be a therapeutic strategy in these high-risk pregnancies, firstly by reducing IgG recycling, -thereby reducing its concentration in the maternal circulation, and secondly by blocking placental transfer. The promising results of a recent trial testing nipocalimab, a monoclonal antibody targeting FcRn, in very severe erythrocyte alloimmunisation, has opened the way to new targeted therapeutic approaches for perinatal diseases mediated by maternal IgG.

Durant la grossesse, les immunoglobulines de type G (IgG) de la mère franchissent le placenta via le récepteur Fc néonatal (FcRn), permettant au fœtus d'acquérir une immunité passive. En présence d'allo ou d'autoanticorps maternels, ce passage peut entraîner des pathologies fœtales et/ou néonatales. Ainsi, le blocage du FcRn apparaît comme une stratégie thérapeutique dans ces grossesses à risque, d'une part en diminuant le recyclage des IgG, réduisant ainsi leur concentration dans la circulation maternelle, et d'autre part en bloquant leur transfert placentaire. Les résultats prometteurs d'un essai récent testant le nipocalimab, anticorps monoclonal ciblant le FcRn, dans les allo-immunisations érythrocytaires très sévères, a ouvert la voie à de nouvelles approches thérapeutiques ciblées pour les pathologies périnatales médiées par des IgG maternelles.

Reproductive Safety of Trazodone After Maternal Exposure in Early Pregnancy: A Comparative ENTIS Cohort Study.

PURPOSE/BACKGROUND: Trazodone is indicated for the treatment of major depressive disorder, but more frequently prescribed off-label at lower doses for insomnia in women of childbearing age. The aim of this study was to assess the risks linked to trazodone exposure during pregnancy for which limited safety data are available. METHODS/PROCEDURES: This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to trazodone in early pregnancy against those in a reference group of women exposed to a selective serotonin reuptake inhibitors (SSRIs) between 1996 and 2021. FINDINGS/RESULTS: The sample included 221 trazodone and 869 SSRI-exposed pregnancies. Exposure to trazodone in the first trimester was not associated with a significant difference in the risk of major congenital anomalies (trazodone [1/169, 0.6%]; SSRI [19/730, 2.6%]; adjusted odds ratio, 0.2; 95% confidence interval, 0.03-1.77). The cumulative incidences of live birth were 61% and 73% in the trazodone and reference group, respectively (25% vs 18% for pregnancy loss and 14% vs 10% for pregnancy termination). Trazodone exposure was not associated with a significantly increased risk of pregnancy termination and pregnancy loss. The rate of small for gestational age infants did not differ between the groups. IMPLICATIONS/CONCLUSIONS: This study did not reveal a significant difference in the risk of major congenital anomalies after first trimester exposure to trazodone, compared with SSRI exposure. Although this study is the largest so far, these results call for confirmation through further studies.

COVID-19-related medicine utilization study in pregnancy: The COVI-PREG cohort.

AIM: The objective of this study was to describe the use of COVID-19-related medicines during pregnancy and their evolution between the early/late periods of the pandemic. METHODS: Pregnant women who tested positive for SARS-CoV-2 from March 2020 to July 2021 were included using the COVI-PREG registry. Exposure to the following COVID-19-related medicines was recorded: antibiotics, antivirals, hydroxychloroquine, corticosteroids, anti-interleukin-6 and immunoglobulins. We described the prevalence of medicines used, by trimester of pregnancy, maternal COVID-19 severity level and early/late period of the pandemic (before and after 1 July 2020). FINDINGS: We included 1964 pregnant patients who tested positive for SARS-CoV-2. Overall, 10.4% (205/1964) received at least one COVID-19-related medicine including antibiotics (8.6%; 169/1694), corticosteroids (3.2%; 62/1964), antivirals (2.0%; 39/1964), hydroxychloroquine (1.4%; 27/1964) and anti-interleukin-6 (0.3%; 5/1964). The use of at least one COVID-19-related medicine was 3.1% (12/381) in asymptomatic individuals, 4.2% (52/1233) in outpatients, 19.7% (46/233) in inpatients without oxygen, 72.1% (44/61) in those requiring standard oxygen, 95.7% (22/23) in those requiring high flow oxygen, 96.2% (25/26) in patients who required intubation and 57.1% (4/7) among patients who died. The proportion who received medicines to treat COVID-19 was higher before than after July 2020 (16.7% vs. 7.7%). Antibiotics, antivirals and hydroxychloroquine had lower rates of use during the late period. CONCLUSION: Medicine use in pregnancy increased with disease severity. The trend towards increased use of corticosteroids seems to be aligned with changing guidelines. Evidence is still needed regarding the effectiveness and safety of COVID-19-related medicines in pregnancy.

Postpartum haemorrhage in high-resource settings: Variations in clinical management and future research directions based on a comparative study of national guidelines.

OBJECTIVE: To compare guidelines from eight high-income countries on prevention and management of postpartum haemorrhage (PPH), with a particular focus on severe PPH. DESIGN: Comparative study. SETTING: High-resource countries. POPULATION: Women with PPH. METHODS: Systematic comparison of guidance on PPH from eight high-income countries. MAIN OUTCOME MEASURES: Definition of PPH, prophylactic management, measurement of blood loss, initial PPH-management, second-line uterotonics, non-pharmacological management, resuscitation/transfusion management, organisation of care, quality/methodological rigour. CONCLUSIONS: Our study highlights areas where strong evidence is lacking. There is need for a universal definition of (severe) PPH. Consensus is required on how and when to quantify blood loss to identify PPH promptly. Future research may focus on timing and sequence of second-line uterotonics and non-pharmacological interventions and how these impact maternal outcome. Until more data are available, different transfusion strategies will be applied. The use of clear transfusion-protocols are nonetheless recommended to reduce delays in initiation. There is a need for a collaborative effort to develop standardised, evidence-based PPH guidelines. RESULTS: Definitions of (severe) PPH varied as to the applied cut-off of blood loss and incorporation of clinical parameters. Dose and mode of administration of prophylactic uterotonics and methods of blood loss measurement were heterogeneous. Recommendations on second-line uterotonics differed as to type and dose. Obstetric management diverged particularly regarding procedures for uterine atony. Recommendations on transfusion approaches varied with different thresholds for blood transfusion and supplementation of haemostatic agents. Quality of guidelines varied considerably.

What do mothers think about their antenatal classes? A mixed-method study in Switzerland.

PROBLEM: Research so far has evaluated the effect of antenatal classes, but few studies have investigated its usefulness from the perspective of mothers after birth. BACKGROUND: Antenatal classes evolved from pain management to a mother-centred approach, including birth plans and parenting education. Evaluating the perception of the usefulness of these classes is important to meet mother's needs. However, so far, research on the mothers' perception of the usefulness of these classes is sparse, particularly when measured after childbirth. Given that antenatal classes are considered as adult education, it is necessary to carry out this evaluation after mothers have had an opportunity to apply some of the competences they acquired during the antenatal classes during their childbirth. AIM: This study investigated mothers' satisfaction and perceived usefulness of antenatal classes provided within a university hospital in Switzerland, as assessed in the postpartum period. METHODS: Primiparous mothers who gave birth at a Swiss university hospital from January 2018 to September 2020 were contacted. Those who had attended the hospital's antenatal classes were invited to complete a questionnaire consisting of a quantitative and qualitative part about usefulness and satisfaction about antenatal classes. Quantitative data were analysed using both descriptive and inferential statistics. Qualitative data were analysed using thematic analysis. FINDINGS: Among the 259 mothers who answered, 61% (n = 158) were globally satisfied with the antenatal classes and 56.2% (n = 145) found the sessions useful in general. However, looking at the utility score of each theme, none of them achieved a score of usefulness above 44%. The timing of some of these sessions was questioned. Some mothers regretted the lack of accurate information, especially on labour complications and postnatal care. DISCUSSION: Antenatal classes were valued for their peer support. However, in their salutogenic vision of empowerment, they did not address the complications of childbirth, even though this was what some mothers needed. Furthermore, these classes could also be more oriented towards the postpartum period, as requested by some mothers. CONCLUSION: Revising antenatal classes to fit mothers' needs could lead to greater satisfaction and thus a better impact on the well-being of mothers and their families.

Informing about childbirth without increasing anxiety: a qualitative study of first-time pregnant women and partners' perceptions and needs.

BACKGROUND: Complications requiring medical interventions during childbirth are far from rare, even after uncomplicated pregnancies. It is often a challenge for maternity healthcare professionals to know how to prepare future parents for these eventualities without causing unnecessary anxiety. Studies on traumatic birth experiences have shown that feelings of loss of control, insufficient information, and lack of participation in medical decisions during childbirth are factors of difficult experiences. However, little is known about the information and communication needs of expectant parents about childbirth during the prenatal period. To gain a deeper understanding of the information and communication needs of first-time pregnant women and partners, we explored their perceptions and expectations for their upcoming childbirth, and the actions they initiated to prepare for it. METHODS: Semi-structured interviews were conducted individually with first-time pregnant women and partners of pregnant women aged 18 years or older, with an uncomplicated pregnancy. Thematic analysis was used to identify themes and sub-themes. RESULTS: Twenty expectant parents (15 pregnant women and five partners of pregnant women) were interviewed. Six themes were identified: Childbirth event; Childbirth experience; Childbirth environment; Organisation of care; Participation in decision making; Roles within the couple and transition to parenthood. CONCLUSIONS: This study contributes to a better understanding of the information needs of future parents expecting their first child. Results highlighted that the notion of "childbirth risks" went beyond the prospect of complications during birth, but also encompassed concerns related to a feeling of loss of control over the event. Expectant parents showed an ambivalent attitude towards consulting risk information, believing it important to prepare for the unpredictability of childbirth, while avoiding information they considered too worrying. They expressed a desire to receive concrete, practical information, and needed to familiarise themselves in advance with the birth environment. Establishing a respectful relationship with the healthcare teams was also considered important. The findings suggest that information on childbirth should not be limited to the transmission of knowledge, but should primarily be based on the establishment of a relationship of trust with healthcare professionals, taking into account each person's individual values and expectations.

Human Male Genital Tract Microbiota.

The human body is vastly colonised by microorganisms, whose impact on health is increasingly recognised. The human genital tract hosts a diverse microbiota, and an increasing number of studies on the male genital tract microbiota suggest that bacteria have a role in male infertility and pathological conditions, such as prostate cancer. Nevertheless, this research field remains understudied. The study of bacterial colonisation of the male genital tract is highly impacted by the invasive nature of sampling and the low abundance of the microbiota. Therefore, most studies relied on the analysis of semen microbiota to describe the colonisation of the male genital tract (MGT), which was thought to be sterile. The aim of this narrative review is to present the results of studies that used next-generation sequencing (NGS) to profile the bacterial colonisation patterns of different male genital tract anatomical compartments and critically highlight their findings and their weaknesses. Moreover, we identified potential research axes that may be crucial for our understanding of the male genital tract microbiota and its impact on male infertility and pathophysiology.

[Obstetrics and Gynecology - Femtech: how digital technologies are serving women's healthcare]. / Gynécologie ­ Obstétrique - FemTech : les nouvelles technologies au service de la santé de la femme.

Over the past ten years, a growing number of technological tools have been developed to improve women's health and well-being, grouped under the name FemTech. This growing field has the potential to improve gynecological care and covers solutions that are less invasive and more personalized to the patient's needs. Thanks to its world-renowned universities and hospitals, its high involvement in the research field and its strong biopharmaceutical sector, Romandy has demonstrated the rapid rise of start-ups dedicated to women's health, thus providing a promising landscape in the FemTech industry. Several Swiss FemTech companies yield innovative solutions related to fertility, menopause and gynecological instruments. This article aims to present the emerging Femtech companies in Romandy over the past years and their use among young women.

Au cours des 10 dernières années ont été développés un nombre croissant d'outils technologiques destinés à améliorer la santé et le bien-être des femmes, regroupés sous le nom de FemTech. Ce domaine qui ne cesse de croître a le potentiel d'améliorer la prise en charge gynécologique, de rendre les soins plus personnalisés et moins invasifs. Grâce à ses hôpitaux universitaires, ses instituts de recherche et son industrie pharmaceutique très développée, la Suisse romande compte des acteurs novateurs dans le secteur et a vu apparaître des start-up prometteuses. Plusieurs FemTech suisses proposent des solutions innovantes liées à la fertilité, à la ménopause ou aux instruments gynécologiques. Dans cet article, nous avons investigué les FemTech émergentes ces dernières années en Suisse romande et leur utilisation chez les jeunes femmes.

[Ureaplasma urealyticum, Ureaplasma parvum, and Mycoplasma hominis: commensals or pathogens?] / Ureaplasma urealyticum, Ureaplasma parvum et Mycoplasma hominis: commensaux ou pathogènes?

Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum are bacteria commonly found in the urogenital tract. However, their pathogenicity in sexually active or obstetrical patients remains controversial. Therefore, determining the significance of screening and treatment for these organisms is challenging, unlike Mycoplasma genitalium which now has well-defined management guidelines. We conducted a review of the literature to clarify the clinical significance of detecting these micro-organisms. It is crucial to carefully select the few cases that warrant further investigations, in order to mitigate the risks of overdiagnosis and overtreatment.

Mycoplasma hominis, Ureaplasma urealyticum et Ureaplasma parvum sont des bactéries couramment retrouvées au niveau de la sphère urogénitale. Toutefois, leur pathogénicité chez le patient sexuellement actif ou la femme enceinte reste encore controversée. Il est dès lors difficile de déterminer l'intérêt du dépistage et du traitement pour ces germes, à l'inverse de Mycoplasma genitalium dont la prise en charge est maintenant très encadrée. Nous avons effectué une revue de la littérature afin de clarifier la pertinence clinique de la recherche de ces microorganismes. Il est impératif de sélectionner précisément les situations nécessitant des investigations plus poussées, afin de modérer le risque de surdiagnostic et de surtraitement.

[Hematological workup in cases of recurrent early miscarriages: what evidences?] / Bilan hématologique en cas de fausses couches précoces à répétition : quelles évidences ?

Recurrent miscarriages have a major psychological and somatic impact, as well as a significant economic burden. An etiological work-up should be offered after two or three miscarriages, the threshold varying from one scientific society to another. However, the proposed biological work-up must be justified by scientific evidence. A simple blood count, basic coagulation tests including fibrinogen assay and anti-phospholipid antibodies testing should be performed initially. Hereditary thrombophilia testing should only be carried out if there is a history of maternal thrombosis. In the event of an abnormality, management should be multidisciplinary, and the prescription of medication should follow recommended guidelines. Prophylactic treatment is not justified in the absence of a known etiology.

Les fausses couches précoces (FCP) à répétition ont un impact psychologique et somatique important, ainsi qu'un poids économique non négligeable. Un bilan étiologique devrait être proposé à partir de deux ou trois fausses couches, le seuil variant selon les sociétés savantes. Cependant, le bilan biologique doit être justifié par des évidences scientifiques. Une formule sanguine simple, des tests de coagulation de base avec le dosage du fibrinogène et une recherche d'anticorps anti-phospholipides devraient être réalisés en première intention. Une recherche de thrombophilie héréditaire ne devrait être effectuée qu'en cas d'antécédent thrombotique maternel. En cas d'anomalie, la prise en charge doit être multidisciplinaire et la prescription de médicaments doit suivre les recommandations. Un traitement prophylactique n'est pas justifié en l'absence d'étiologie retrouvée.

Impact of the first wave of the COVID-19 pandemic on birth rates in Europe: a time series analysis in 24 countries.

STUDY QUESTION: Did the first wave of the COVID-19 pandemic have an impact on monthly birth rates in Europe? SUMMARY ANSWER: Using datasets on live births per month in Europe, collected from the Human Fertility Database, we found a -14.1% decline in live births in January 2021 (i.e. 9-10 months after the epidemic peaks and first lockdowns), compared to the average number of live births in January 2018 and 2019. WHAT IS KNOWN ALREADY: Previous pandemics in the 20th and 21st centuries have been associated with a decline in birth rates 9 months after their peak, and a rebound in births over time. Lockdowns were necessary to control the first wave of the COVID-19 pandemic and may have had an impact on subsequent birth rates. STUDY DESIGN, SIZE, DURATION: Monthly time series data on live births from January 2018 to March 2021 were extracted to provide a time-series analysis of birthrates during and after the first wave of the COVID-19 pandemic in 24 European countries. PARTICIPANTS/MATERIALS, SETTING, METHODS: We conducted a random-effect generalized least squares regression to assess the seasonality of births from January 2018 to March 2021, and to identify potential differences in monthly live births after the first wave of the COVID-19 pandemic, considering the seasonality of births. To quantify these potential differences, we estimated the variation rate between the monthly live births observed during 2020 and 2021 and the mean of the 2018-2019 monthly live births in Europe. Factors potentially associated with a variation in monthly birth rates were assessed using univariable and multivariable generalized linear regressions. MAIN RESULTS AND THE ROLE OF CHANCE: When considering the seasonality of births, January 2021 was the only month with a significant difference in live births. A drop of -14.1% was observed compared to the average number of live births in January 2018 and 2019. At the national level, this drop was observed 9-10 months after the epidemic peaks in 13 countries. The duration of lockdowns was the variable that had the stronger association with this decrease, whereas higher incomes per capita could be a factor limiting this decline. A rebound in births compared to the previous years occurred in March 2021 in 13 countries. LIMITATIONS, REASONS FOR CAUTION: Our data are based on national data, limiting the power in the multivariable models used and the identification of other potential factors contributing to a decrease or an increase in birth rates. In addition, we collected only live births up to April 2021, which precludes the identification of a difference in births seasonality in 2021. WIDER IMPLICATIONS OF THE FINDINGS: As with previous pandemics, the COVID-19 outbreak was associated with a decline in births 9 months after its first wave. This trend may be associated with the duration of the lockdowns. Although there was a rebound in births in the following months, it does not seem to compensate for this decline. STUDY FUNDING/COMPETING INTEREST(S): The authors receive no external funding and have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Monkeypox in pregnancy: virology, clinical presentation, and obstetric management.

The 2022 monkeypox outbreak, caused by the zoonotic monkeypox virus, has spread across 6 World Health Organization regions (the Americas, Africa, Europe, Eastern Mediterranean, Western Pacific, and South-East Asia) and was declared a public health emergency of international concern on July 23, 2022. The global situation is especially concerning given the atypically high rate of person-to-person transmission, which suggests viral evolution to an established human pathogen. Pregnant women are at heightened risk of vertical transmission of the monkeypox virus because of immune vulnerability and natural depletion of population immunity to smallpox among reproductive-age women, and because orthopoxviral cell entry mechanisms can overcome the typically viral-resistant syncytiotrophoblast barrier within the placenta. Data on pregnancy outcomes following monkeypox infection are scarce but include reports of miscarriage, intrauterine demise, preterm birth, and congenital infection. This article forecasts the issues that maternity units might face and proposes guidelines to protect the health of pregnant women and fetuses exposed to the monkeypox virus. We review the pathophysiology and clinical features of monkeypox infection and discuss the obstetrical implications of the unusually high prevalence of anogenital lesions. We describe the use of real-time polymerase chain reaction tests from mucocutaneous and oropharyngeal sites to confirm infection, and share an algorithm for the antenatal management of pregnant women with monkeypox virus exposure. On the basis of the best available knowledge from prenatal orthopoxvirus infections, we discuss the sonographic features of congenital monkeypox and the role of invasive testing in establishing fetal infection. We suggest a protocol for cesarean delivery to avoid the horizontal transmission of the monkeypox virus at birth and address the controversy of mother-infant separation in the postpartum period. Obstetrical concerns related to antiviral therapy with tecovirimat and vaccinia immune globulin are highlighted, including the risks of heart rate-corrected QT-interval prolongation, inaccuracies in blood glucose monitoring, and the predisposition to iatrogenic venous thromboembolism. The possibility of monkeypox vaccine hesitancy during pregnancy is discussed, and strategies are offered to mitigate these risks. Finally, we conclude with a research proposal to address knowledge gaps related to the impact of monkeypox infection on maternal, fetal, and neonatal health.

Haematological changes from conception to childbirth: An indicator of major pregnancy complications.

BACKGROUND: About 800 women die every day worldwide from pregnancy-related complications, including excessive blood loss, infections and high-blood pressure (World Health Organization, 2019). To improve screening for high-risk pregnancies, we set out to identify patterns of maternal hematological changes associated with future pregnancy complications. METHODS: Using mixed effects models, we established changes in 14 complete blood count (CBC) parameters for 1710 healthy pregnancies and compared them to measurements from 98 pregnancy-induced hypertension, 106 gestational diabetes and 339 postpartum hemorrhage cases. RESULTS: Results show interindividual variations, but good individual repeatability in CBC values during physiological pregnancies, allowing the identification of specific alterations in women with obstetric complications. For example, in women with uncomplicated pregnancies, haemoglobin count decreases of 0.12 g/L (95% CI -0.16, -0.09) significantly per gestation week (p value <.001). Interestingly, this decrease is three times more pronounced in women who will develop pregnancy-induced hypertension, with an additional decrease of 0.39 g/L (95% CI -0.51, -0.26). We also confirm that obstetric complications and white CBC predict the likelihood of giving birth earlier during pregnancy. CONCLUSION: We provide a comprehensive description of the associations between haematological changes through pregnancy and three major obstetric complications to support strategies for prevention, early-diagnosis and maternal care.

Prenatal diagnosis of Aicardi syndrome based on a suggestive imaging pattern: A multicenter case-series.

OBJECTIVES: To characterize a suggestive prenatal imaging pattern of Aicardi syndrome using ultrasound and MR imaging. METHODS: Based on a retrospective international series of Aicardi syndrome cases from tertiary centers encountered over a 20-year period (2000-2020), we investigated the frequencies of the imaging features in order to characterize an imaging pattern highly suggestive of the diagnosis. RESULTS: Among 20 cases included, arachnoid cysts associated with a distortion of the interhemispheric fissure were constantly encountered associated with complete or partial agenesis of the corpus callosum (19/20, 95%). This triad in the presence of other CNS disorganization, such as polymicrogyria (16/17, 94%), heterotopias (15/17, 88%), ventriculomegaly (14/20, 70%), cerebral asymmetry [14/20, 70%]) and less frequently extra-CNS anomaly (ocular anomalies [7/11, 64%], costal/vertebral segmentation defect [4/20, 20%]) represent a highly suggestive pattern of Aicardi syndrome in a female patient. CONCLUSION: Despite absence of genetic test to confirm prenatal diagnosis of AS, this combination of CNS and extra-CNS fetal findings allows delineation of a characteristic imaging pattern of AS, especially when facing dysgenesis of the corpus callosum.