Impact of COVID-19 Pandemic Interventions on Sudden Unexpected Death in Infancy Incidence in France.

OBJECTIVE: To study the impact of non-pharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic on the monthly incidence of sudden unexpected death in infancy (SUDI) cases overall and those with a viral or bacterial identification. STUDY DESIGN: We conducted an interrupted time-series analysis using seasonally adjusted Poisson regression models from the French national prospective and multicenter SUDI registry, that included all SUDI cases under age one year who died from 2016 to 2021 in mainland France. RESULTS: Of 998 SUDI cases analyzed, 750 were recorded during the pre-pandemic period (January 2016 through March 2020) and 248 during the NPI period (April 2020 through December 2021). We found a significant seasonal pattern of overall monthly SUDI incidence, with a peak observed periodically from November to February. The monthly SUDI incidence decreased significantly from the pre-pandemic to NPI periods (adjusted incidence rate ratio 0.83 [95% confidence interval 0·72-0·96]). In particular, the monthly incidence of SUDI cases with a viral or bacterial identification decreased, while no significant difference was found for SUDI cases without a viral or bacterial identification. CONCLUSION: NPIs were associated with a significant change in the incidence of SUDI cases with a viral or bacterial identification. Further investigations are needed to analyze the pathophysiologic role of viruses and bacteria in the SUDI.

The French registry of sudden unexpected death in infancy (SUDI): a 7-year review of available data.

The French "OMIN registry" was established in 2015 to collect nationwide standardised data concerning biological, clinical, environmental and social characteristics of sudden unexpected death in infancy (SUDI) and unexpected death in children aged 1-2 years. A biobank has existed since July 2020 to store biological samples for each case. This article aimed to detail (1) a brief history and the objectives of the registry; (2) a description of the methodology used; (3) the first results of the registry, i.e. the main characteristics of the cases included so far; (4) the process for accessing the data for research projects; and (5) issues regarding weakness and improvement and perspectives offered by the registry. On 31 May 2024, 1975 cases were included in the OMIN registry; on 31 December 2022, 4606 biological samples from 176 cases were collected. For each deceased child, different types of data are registered on an electronic case report form: socio-demographic data, personal and familial medical background, environment and feeding data, clinical data, and biological and imaging results. A strict and continuous quality control process is used to ensure the reliability of the data, in parallel with specific actions to improve the exhaustiveness of the registry. The OMIN registry database is one of the largest and the most complete databases on SUDI, especially in Europe, and the first in the world to associate a standardised biological sample collection with it. Perspectives of research provided by our registry are numerous and could be supported by national and international scientific collaborations. CONCLUSION:  This article details the objectives and methods of the French registry of SUDI. It provides initial results relating to the population included in the register and the procedure for accessing the data. WHAT IS KNOWN: • In Western Europe, France is one of the countries with the highest SUDI rate, making it the first cause of death of infants between 28 and 364 days. • The development of epidemiological tools on a national and international scale is essential to advance research into the determinants and risk factors of unexpected death in children under 2 years of age. WHAT IS NEW: • The OMIN registry was created in France in 2015 to collect nationwide standardised social, environmental, clinical, and paraclinical data for cases of unexpected death in children aged 0 to 2 years. • To date, the OMIN registry has included 680 data from almost 2000 children unexpectedly deceased, completed by a biocollection since 2020. • Data from the OMIN registry, unique in its field, are freely available for scientific research teams, after acceptation by the scientific committee of the registry.

Risk factors for unexpected infant death among very premature infants in France.

BACKGROUND: Prematurity is one of the risk factors for sudden unexpected infant death (SUID), a phenomenon that remains poorly explained. MATERIALS AND METHODS: The analysis of specific factors associated with SUID among very premature infants (VPI) was performed through a retrospective review of data collected in the French SUID registry from May 2015 to December 2018. The factors associated with SUID among VPI were compared with those observed among full-term infants (FTI). Results are expressed as means (standard deviation [SD]) or medians (interquartile range [IQR)]. RESULTS: During the study period, 719 cases of SUID were included in the registry, 36 (incidence: 0.60 ‰) of which involved VPI (gestational age: 29.2 [2] weeks, 1157 [364]) g] and 313 (0.18 ‰) involved FTI (gestational age: 40 [0.8] weeks, 3298 [452] g). The infants' postnatal age at the time of death was similar in the two groups: 15.5 (12.2-21.8) vs. 14.5 (7.1-23.4) weeks. We observed low breastfeeding rates and a high proportion of fathers with no occupation or unemployment status among the VPI compared to the FTI group (31% vs. 55 %, p = 0.01 and 32% vs. 13 %, p = 0.05, respectively). Among the VPI, only 52 % were in supine position, and 29 % were lying prone at the time of the SUID (compared to 63 % and 17 %, respectively, in the FTI group). CONCLUSION: This study confirms prematurity as a risk factor for SUID with no difference in the SUID-specific risk factors studied except for breastfeeding and socioeconomic status of the fathers. VPI and FTI died at similar chronological ages with a high proportion of infants dying in prone position. These results argue for reinforcement of prevention strategies in cases of prematurity.

Inconsistency Between Pictures on Baby Diaper Packaging in Europe and Safe Infant Sleep Recommendations.

OBJECTIVE: To describe the level of inconsistency between pictures on baby diaper packaging and safe infant sleep recommendations (SISRs) in Europe. STUDY DESIGN: We attempted to identify all packaging of baby diapers sold in 11 European countries for infants weighing less than 5 kg through internet searches from July 2022 through February 2023. For each type of package, we extracted whether there was a picture depicting a baby, whether the baby was sleeping, and whether the picture of the sleeping baby was inconsistent with ≥1 of 3 SISRs: (i) nonsupine sleeping position, (ii) soft objects or loose bedding, or (iii) sharing a sleep surface with another person. Data were aggregated at the country level, and a random-effects meta-analysis of proportions was used to obtain summary estimates. The outcome was the summary estimate of the proportion of pictures that were inconsistent with SISRs. RESULTS: We identified 631 baby diaper packaging types of which 49% (95% CI: 42-57; n = 311) displayed a picture of a sleeping baby. Among those 311 packages, 79% (95% CI 73-84) were inconsistent with ≥1 SISR, including a nonsupine sleeping position, 45% (95% CI 39-51), soft objects or loose bedding such as pillows or blankets, 51% (95% CI 46-57), and sharing a sleep surface with another person, 10% (95% CI 4-18). CONCLUSIONS: Pictures on baby diaper packaging in Europe are often inconsistent with SISRs. The prevention of sudden unexpected death in infancy requires action from manufacturers and legislators to stop parents' exposure to misleading images that may lead to dangerous practices.

Procalcitonin is associated with sudden unexpected death in infancy due to infection.

Infection is an important cause of death during infancy worldwide and is a frequent etiology of sudden unexpected death in infancy (SUDI). Procalcitonin (PCT) is a useful marker to diagnose infection in patients, and several studies report the stability of PCT after death. The added value of a biological marker, such as the PCT level in the blood, remains controversial in investigating SUDI. The aim of this study was to determine if PCT can help clinicians determine whether infection caused SUDI. We conducted a retrospective, multicenter study with the French SUDI registry (Observatoire National des Morts Inattendues du Nourrisson; OMIN). We collected data from this registry on children who died between May 2015 and June 2021. The levels of PCT in the blood of 540 SUDI patients were measured. We compared PCT and other biological tests performed in terms of infection status, autopsy results, and cause of death using clinical and biological data compiled by pediatricians at the SUDI referral center. PCT levels were significantly higher in the children who died from infection than in those who did not (0.12 µg/L vs. 0.08 µg/L, p < 0.001). A PCT blood level exceeding 0.2 µg/L was more frequently observed when infection was present than in the absence of infection (44.3% vs. 15.4%, p < 0.001). The same data were obtained with a 0.5 µg/L cut-off (36.1% with infection vs. 9.2% without, p < 0.001).  Conclusions: PCT is a sensitive biomarker for detecting infections postmortem; thus, additional samples may be necessary during autopsy. What is known: • PCT is a stable marker postmortem and increases earlier than CRP, i.e., 2-4 h after the beginning of an infection vs. 6 h. • PCT can be measured up to 140 h after death. What is new: • PCT is a sensitive marker for detecting infection in SUDI patients postmortem. • This test can reveal an infection from non-standardized samples obtained during autopsy if such an infection was not determined before death.

Sudden Unexpected Death in Infancy: Current Practices in Virological Investigations and Documentation in the French Registry.

OBJECTIVE: To describe pre-COVID-19 pandemic current practices in virological investigations, including type, frequency of samplings, and documented viruses, in sudden unexpected death in infancy (SUDI) and to compare results according to the cause of death. STUDY DESIGN: Between May 2015 and December 2019, infants under 2 years of age included in the French SUDI registry were classified in one of 4 groups by causes of death according to the classification by Goldstein et al. : unexplained (SIDS), infectious, explained but noninfectious, and undetermined. Sampling sites and viruses detected were described, and then SIDS and explained deaths (control group) were compared. RESULTS: Among 639 infants, 3.6% died of an established viral infection. From 23 sampling sites and 2238 samples, 19 virus species were detected. Overall, 43.3% of infants carried a virus, with no significant difference between SIDS infants and the control group (P = .06). We found wide variations in frequencies of samples by site (550 for nasopharynx to one for saliva). The highest positivity rate was from the nasopharynx (195/2238; 8.7%). Rhinovirus was the predominant virus detected (135/504; 26.8%), mostly in SIDS (83/254; 32.7%). We found no significant difference between positivity rates and distribution of viruses between the SIDS and control groups. At-autopsy virological analysis never contributed to determining the cause of death. CONCLUSION: Current practices in virological investigations in SUDI are heterogeneous, with wide variability despite published guidelines. Investigations should be limited to the most relevant sites, and systematic at-autopsy sampling should be reconsidered. We found no association between virus detection and SIDS.

Non-immunization associated with increased risk of sudden unexpected death in infancy: A national case-control study.

OBJECTIVE: In the context of vaccine scepticism, our study aimed to analyse the association between immunization status and the occurrence of sudden unexpected death in infancy (SUDI). STUDY DESIGN: A multi-centre case-control study was conducted between May 2015 and June 2017 with data from the French national SUDI registry (OMIN) for 35 French regional SUDI centres. Cases were infants under age 1 year who died from SUDI and who were registered in OMIN. Controls, matched to cases by age and sex at a 2:1 ratio, were infants admitted to Nantes University Hospital. All immunization data for diphtheria (D), tetanus (T), acellular pertussis (aP), inactivated poliovirus (IPV), Haemophilus influenzae b (Hib), hepatitis B (HB) and 13-valent pneumococcal conjugate vaccine (PCV13) were collected by a physician. Cases and controls were considered immunized if at least one dose of vaccine was administered. RESULTS: A total of 91 cases and 182 controls were included. The median age was 131 days (interquartile range 98-200.0) and the sex ratio (M/F) was about 1.1. For all vaccines combined (D-T-aP-IPV-Hib and PCV13), 22 % of SUDI cases versus 12 % of controls were non-immunized, which was significantly associated with SUDI after adjustment for potential adjustment factors (adjusted odds ratio 2.01 [95 % confidence interval 1.01-3.98, p = 0,047]). CONCLUSIONS: Non-immunization for D-T-aP-IPV-Hib-HB and PCV13 was associated with increased risk of SUDI. This result can be used to inform the general public and health professionals about this risk of SUDI in case of vaccine hesitancy.

Recent historic increase of infant mortality in France: A time-series analysis, 2001 to 2019.

BACKGROUND: The infant mortality rate (IMR) serves as a key indicator of population health. METHODS: We used data from the French National Institute of Statistics and Economic Studies on births and deaths during the first year of life from 2001 to 2019 to calculate IMR aggregated by month. We ran joinpoint regressions to identify inflection points and assess the linear trend of each segment. Exploratory analyses were performed for overall IMR, as well as by age at death subgroups (early neonatal [D0-D6], late neonatal [D7-27], and post-neonatal [D28-364]), and by sex. We performed sensitivity analyses by excluding deaths at D0 and using other time-series modeling strategies. RESULTS: Over the 19-year study period, 53,077 infant deaths occurred, for an average IMR of 3·63/1000 (4·00 in male, 3·25 in female); 24·4% of these deaths occurred during the first day of life and 47·8% during the early neonatal period. Joinpoint analysis identified two inflection points in 2005 and 2012. The IMR decreased sharply from 2001 to 2005 (slope: -0·0167 deaths/1000 live births/month; 95%CI: -0·0219 to -0·0116) and then decreased slowly between 2005 and 2012 (slope: -0·0041; 95%CI: -0·0065 to -0·0016). From 2012 onwards, a significant increase in IMR was observed (slope: 0·0033; 95%CI: 0·0011 to 0·0056). Subgroup analyses indicated that these trends were driven notably by an increase in the early neonatal period. Sensitivity analyses provided consistent results. INTERPRETATION: The recent historic increase in IMR since 2012 in France should prompt urgent in-depth investigation to understand the causes and prepare corrective actions. FUNDING: No financial relationships with any organizations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

Prevalence of positive toxicology analysis from the French national registry for sudden unexpected infant death (Tox-MIN).

BACKGROUND: Sudden unexpected infant death (SUID) remains the leading cause of postnatal mortality in many countries. French and international guidelines recommend a thorough examination with toxicology studies. OBJECTIVES: The main objective was to determine the prevalence of toxic detection and positive analyses. The secondary objectives were to describe the different toxics and compare children with positive (Tox+) and negative results (Tox-) with other SUID risk factors. DESIGN AND METHODS: We used the data registered from May 2015 to December 2018 by the French national SUID registry (OMIN). It collects data for all SUID cases admitted to any of the 35 participating French SUID referral centers. RESULTS: Of the 624 SUID cases registered in the OMIN, a post-mortem toxicological analysis was performed in 398 infants. Thirty-six patients (9%) were positives for expected (Etox+ (n = 19 [53%], e.g., resuscitation drugs, regular treatments) and unexpected (UTox+) (n = 17 [47%]) toxics. The unexpected toxics were opioids (n = 8), cannabis (n = 4), cocaine (n = 3), cotinine (n = 2), carbon monoxide (n = 2), caffeine (n = 2), alcohol (n = 1) and GHB (n = 1). UTox + infants had a different seasonal distribution (p = .03), a higher incidence of inappropriate sleeping position and bedding at the time of death (respectively OR 3.8, p = .037 - OR 5.4, p = .026); inadequate body hygiene (OR 10.6, p = .0005), a younger maternal age (p = .045) and a higher rate of maternal drug abuse (OR 21.9, p = .0008). CONCLUSION: The high rate of positive results warrants routine toxicology testing. The imputability of identified molecules is complicated by the presence of other known risk factors for SUID.

National Variations in Recent Trends of Sudden Unexpected Infant Death Rate in Western Europe.

OBJECTIVE: To study recent epidemiologic trends of sudden unexpected death in infancy (SUDI) in Western Europe. STUDY DESIGN: Annual national statistics of death causes for 14 Western European countries from 2005 to 2015 were analyzed. SUDI cases were defined as infants younger than 1 year with the underlying cause of death classified as "sudden infant death syndrome," "unknown/unattended/unspecified cause," or "accidental threats to breathing." Poisson regression models were used to study temporal trends of SUDI rates and source of variation. RESULTS: From 2005 to 2015, SUDI accounted for 15 617 deaths, for an SUDI rate of 34.9 per 100 000 live births. SUDI was the second most common cause of death after the neonatal period (22.2%) except in Belgium, Finland, France, and the UK, where it ranked first. The overall SUDI rate significantly decreased from 40.2 to 29.9 per 100 000, with a significant rate reduction experienced for 6 countries, no significant evolution for 7 countries, and a significant increase for Denmark. The sudden infant death syndrome/SUDI ratio was 56.7%, with a significant decrease from 64.9% to 49.7% during the study period, and ranged from 6.1% in Portugal to 97.8% in Ireland. We observed between-country variations in SUDI and sudden infant death syndrome sex ratios. CONCLUSIONS: In studied countries, SUDI decreased during the study period but remained a major cause of infant deaths, with marked between-country variations in rates, trends, and components. Standardization is needed to allow for comparing data to improve the implementation of risk-reduction strategies.

The MYRACLE protocol study: a multicentric observational prospective cohort study of patients with multiple myeloma.

BACKGROUND: Despite recent advances in the treatment of multiple myeloma, the disease constantly relapses and is still considered as incurable. The current knowledge about the biological mechanisms underlying resistance to the different class of drugs in multiple myeloma remains poor. The primary objective of the MYRACLE (Myeloma Resistance And Clonal Evolution) cohort, a multicenter prospective cohort of patients with multiple myeloma, is to address this limitation. We here describe the study background, design and methods used for this cohort. METHODS/DESIGN: All patients (> 18 year old) diagnosed with de novo or relapsed multiple myeloma and treated in two hematology department from west of France are included in the MYRACLE cohort. Patients provide a signed informed to be included in the study. All subjects are followed until refusal to participate in the study or death. The MYRACLE cohort prospectively collects data on socio-economic status, medical status, imaging, prognosis factors, MM therapies and associated events (resistance, safety issues). Patients also complete standardized quality of life questionnaires. In addition, bone marrow samples will be collected at time of diagnosis and relapses to perform biomarkers analysis and functional assays exploring mechanisms underlying drug resistance. DISCUSSION: The "real-life" MYRACLE cohort offers the opportunity to prospectively collect epidemiological, medical, QoL and biological data from MM patients during the course of the disease (at time of diagnosis and subsequent relapses). At mid-tem, this integrative cohort will be unique at producing a large variety of data that can be used to conceive the most effective personalized therapy for MM patients. Additionally, the MYRACLE cohort will allow integrating the medical care of MM patients in a health and pharmacoeconomic perspective.

The French prospective multisite registry on sudden unexpected infant death (OMIN): rationale and study protocol.

INTRODUCTION: Even after 'back-to-sleep' campaigns, sudden unexpected infant death (SUID) continues to be the leading cause of death for infants 1 month to 1 year old in developed countries, with devastating social, psychological and legal implications for families. To sustainably tackle this problem and decrease the number of SUIDs, a French SUID registry was initiated in 2015 to (1) inform prevention with standardised data, (2) understand the mechanisms leading to SUID and the contribution of the already known or newly suggested risk factors and (3) gather a multidisciplinary group of experts to coordinate and develop innovative and urgent research in the SUID area. METHODS AND ANALYSIS: This observational multisite prospective observatory includes all cases of sudden unexpected deaths in children younger than 2 years occurring in the French territory covered by the 35 participating French referral centres. From these cases, various data concerning sociodemographic conditions, death scene, personal and family medical history, parental behaviours, sleep environment, clinical examinations, biological and imagery investigations and autopsy are systematically collected. These data will be complemented as of 2018 with a biobank of diverse biological samples (blood, hair, urine, faeces and cerebrospinal fluid), with other administrative health-related data (health claim reimbursements and hospital admissions) and socioenvironmental data. Insights from exploratory descriptive statistics and thematic analysis will be combined for the design of targeted strategies to effectively reduce preventable infant deaths. ETHICS AND DISSEMINATION: The French sudden unexpected infant death registry (Observatoire National des Morts Inattendues du Nourrisson registry;OMIN) was approved in 2015 by the French Data Protection Authority in clinical research (Commission Nationale de l'Informatique et des Libertés: number 915273) and by an independent ethics committee (Groupe Nantais d'Ethique dans le Domaine de la Santé: number 2015-01-27). Results will be discussed with associations of families affected by SUID, caregivers, funders of the registry, medical societies and researchers and will be submitted to international peer-reviewed journals and presented at international conferences.

The REFRACT-LYMA cohort study: a French observational prospective cohort study of patients with mantle cell lymphoma.

BACKGROUND: Mantle Cell Lymphoma (MCL) is often associated with progression, temporary response to therapy and a high relapse rate over time resulting in a poor long-term prognosis. Because MCL is classified as an incurable disease, therapeutic resistance is of great interest. However, knowledge about the biological mechanisms underlying resistance associated with MCL therapies and about associated predictors remains poor. The REFRACT-LYMA Cohort, a multicenter prospective cohort of patients with MCL, is set up to address this limitation. We here describe the study background, design and methods used for this cohort. METHODS/DESIGN: The REFRACT-LYMA Cohort Study aims at including all patients (>18 years old) who are diagnosed with MCL in any stage of the disease and treated in specialized oncology centers in three public hospitals in Northwestern France. Any such patient providing a signed informed consent is included. All subjects are followed up indefinitely, until refusal to participate in the study, emigration or death. The REFRACT-LYMA follow-up is continuous and collects data on socio-economic status, medical status, MCL therapies and associated events (resistance, side effects). Participants also complete standardized quality of life (QOL) questionnaires. In addition, participants are asked to donate blood samples that will support ex vivo analysis of expression and functional assays required to uncover predictive biomarkers and companion diagnostics. If diagnostic biopsies are performed during the course of the disease, extracted biological samples are kept in a dedicated biobank. DISCUSSION: To our knowledge, the REFRACT-LYMA Cohort Study is the first prospective cohort of patients with MCL for whom "real-life" medical, epidemiological and QOL data is repeatedly collected together with biological samples during the course of the disease. The integrative cohort at mid-term will be unique at producing a large variety of data that can be used to conceive the most effective personalized therapy for MCL patients. Additionally, the REFRACT-LYMA Cohort puts the medical care of MCL patients in a health and pharmacoeconomic perspective.

Using the Female Sexual Function Index (FSFI) to evaluate sexual function in women with genital mutilation undergoing surgical reconstruction: a pilot prospective study.

OBJECTIVES: Few prospective studies have evaluated sexual function in women with female genital mutilation by cutting (FGM/C) before and after clitoral reconstructive surgery, and none used a validated questionnaire. A validated questionnaire, the Female Sexual Function Index (FSFI) was used for the first time, to assess the impact of reconstructive surgery on sexual function in women with female genital mutilation/cutting (FGM/C) before and after clitoral reconstructive surgery. STUDY DESIGN: Women with FGM/C consulting at the Nantes University Hospital for clitoral reconstruction between 2013 and 2014 were prospectively included. All patients completed a questionnaire at inclusion, describing their social, demographic, and FGM/C characteristics. They were also asked to complete the FSFI as well as a questionnaire about clitoral sensations, symptoms of depression or anxiety, and self-esteem before and 3 and 6 months after the surgery. Paired Wilcoxon and McNemar tests were used to compare data. RESULTS: Of the 12 women included, 9 (75%) had type II mutilations. Results showed a global sexual dysfunction (median FSFI summary score=17) before surgery. Clitoral sensations were absent in 8 women (67%). Six months after surgery, all FSFI dimensions except lubrication had improved significantly (median FSFI summary score=29, P=0.009). Ten women had clitoral sensations, and 11 (92%) were satisfied with their surgery. CONCLUSION: This study shows that 6 months after clitoral reconstructive surgery, women reported a multidimensional positive improvement in their sexual function. The FSFI is a promising tool for routine standardized assessment of the sexual function of women with FGM/C for determining appropriate management and assessing it. Larger studies with validated questionnaires assessing self-esteem, depression, and body image are also needed to develop an integrative approach and to provide evidence-based recommendations about management of these women.