A number of sclerosis (MS) is one in all a number of persistent immune illnesses with an rising incidence,1 and nearly all of sufferers are girls recognized between the ages of 20 and 40 years. Through the previous 25 years, the therapy choices have improved, and with the introduction of disease-modifying remedy (DMT), individuals residing with MS are actually inspired to pursue the life they wish to stay. With many females being recognized at childbearing age, this may increasingly embody beginning a household.2 Questions associated to copy are naturally of nice concern within the increasing inhabitants of younger girls with MS and it has turn out to be an necessary space of scientific care and analysis. Ladies with MS traditionally have fewer youngsters than the final inhabitants,3 and this can be due to durations of energetic illness and coverings. Whether or not fertility is impaired remains to be debated,3,4 however it’s sure that some sufferers with a persistent illness make an energetic alternative to not have youngsters.5 It has progressively turn out to be extra routine for neurologists to debate being pregnant when planning medical therapy in younger girls. Sufferers had been beforehand involved concerning the heritability of MS, however neuroepidemiological research on this space have produced reassuring outcomes. Earlier research have instructed that susceptibility to MS is a fancy interaction of heritability and surroundings, and the query about heritability is an ongoing analysis subject.6–9 A meta-analysis from 2012 discovered the age-adjusted threat of recurrence amongst offspring with a dad or mum with MS to be 1.45% (95% CI 1.23–1.67).10
As well as, sufferers are naturally fearful concerning the affect of MS as a illness and its corresponding medicines on the well being of their offspring, which has led to rising calls for for conception counseling. The affiliation between in utero publicity to maternal MS, with its accompanying medical therapies, and opposed short- and long-term offspring outcomes has been studied to a restricted extent amongst researchers in neurology and obstetrics over the previous 20 years.11–14
The authors are conscious of two evaluations,15,16 which, from a neurological angle, summarize proof on MS and short-term opposed delivery outcomes. One other evaluation examined the developmental trajectories of offspring and requested additional research on long-term outcomes in offspring.17 We carried out this evaluation as a result of there have been no different evaluations with a deal with long-term somatic well being outcomes within the offspring of girls with MS.
Materials and Strategies
Protocol and Registration
The evaluation protocol was registered on the Worldwide Potential Register of Systematic Critiques (PROSPERO.org) with ID quantity CRD42022338414, previous to initiation of the evaluation course of.
Search Technique and Eligibility Standards
A complete literature search was undertaken in Embase and Medline together with a reference screening of the included research performed in PubMed, to pursue a whole protection of the subject. The search working dates had been 05.02.2022–06.15.2022 and all searches had been repeated on 08.23.2022, which didn’t contribute any new publications assembly the inclusion and exclusion standards. The final up-to-date search, performed on 02.06.2023, added one new research.18 The search technique was developed by MLA along with a educated librarian on the College of Southern Denmark, making use of the PICOS format (inhabitants, intervention, comparability and outcomes of curiosity) and arranged in search blocks. For the search string, see the Supportive File. For the connections between search blocks, the Boolean operators AND and OR had been used.
The search outcomes are offered in Determine 1. Each major knowledge assortment and research together with secondary sources of information (eg claims databases, interviews with moms) had been thought of. Duplicates had been eliminated in Endnote. Abstracts, evaluations, case reviews, case sequence and spontaneous reviews had been excluded, as had been different sorts of research with no reference group. Offspring delivery, neonatal, childhood and adolescence somatic and psychological well being outcomes had been of curiosity. We included solely research reporting on youngster outcomes with a threat estimate (absolute or relative threat estimates [hazard ratio (HR), odds ratio (OR), relative risk (RR)]). After reviewing the search outcomes, abstracts had been screened and full-text articles learn. Lastly, applicable research had been included based mostly on the exclusion and inclusion standards. Causes for exclusion of papers had been recorded in a desk. The research had been sorted into three teams: 1) maternal MS and short-term outcomes within the offspring (delivery and neonatal), 2) in utero publicity to medicines used to deal with maternal MS and short-term outcomes within the offspring (delivery and neonatal), and three) maternal MS and long-term well being outcomes within the offspring (from 1 month to maturity).
Determine 1 Search technique and flowchart of exclusion and inclusion of research.
The eligibility standards for this evaluation had been as follows.
- Publicity: Maternal MS prognosis verified with the McDonald standards or by Worldwide Classification of Ailments (ICD) prognosis codes.19 Comparability with wholesome controls was most popular. In research with DMT publicity, stratification on every sort of medicine was necessary, and comparability with girls with MS however with out DMT therapy was most popular.
- Research with knowledge from pharmacovigilance databases managed by pharmaceutical producers had been excluded, along with research the place the contributing authors had been completely employed by the trade.
- Outcomes: In all research with the end result of preterm delivery, this was outlined as delivery earlier than gestational age 37 weeks; low Apgar was outlined as an Apgar rating <7 at 5 minutes; and small for gestational age (SGA) was outlined as a delivery weight beneath –2 SD or <2500 g at accomplished 37 gestational weeks, based on the WHO definition. In distinction to low delivery weight, SGA relates the delivery weight to gestational week, intercourse and singleton or a number of gestation, and is influenced by the intrauterine development situations and genetic potential.20 No standardized nomenclature was used for the end result of congenital anomalies, which had been simply known as “congenital malformations”, “congenital anomalies” or “delivery defects”.
- Presentation of outcomes: Danger estimates ought to be accessible within the article. Research presenting solely descriptive outcomes, corresponding to prevalence, proportions or percentages, had been excluded.
Screening was initially carried out based mostly on the title and summary, adopted by a full textual content screening by MLA. For the inclusion of information, the eligibility standards had been utilized by two reviewers (MLA and LRJ) who independently screened the information for inclusion. To extend the reproducibility and accuracy of the evaluation, the literature screening was performed in accordance with the Most popular Reporting Gadgets for Systematic evaluations and Meta-Analyses (PRISMA 2020) guidelines and utilizing the web-based program covidence.org on the College Library of Southern Denmark. Disagreements had been resolved by means of dialogue and consensus with a 3rd reviewer (BMN).
Knowledge extracted from the included research are offered in Tables 1–3. The analyses encompass summarizing the dangers of opposed delivery, childhood and adolescence well being outcomes amongst offspring of girls with MS. We thought of a meta-analysis, however the variety of research recognized inside every group was too low, too few research reported on particular outcomes and the exposures had been too inhomogeneous. The authors had been conscious of some present systematic evaluations and meta-analyses on delivery outcomes amongst girls with MS and DMT from 2000–2019,21,22 and determined to conduct an up-to-date search on this subgroup of research.
Desk 1 Maternal A number of Sclerosis and the Impact on Neonatal Outcomes
Desk 2 Ladies with A number of Sclerosis Handled with Illness-Modifying Remedy and the Impact on Neonatal Outcomes
Desk 3 In Utero Publicity to Maternal A number of Sclerosis Well being Outcomes Throughout Childhood and Adolescence (1 Month to 18 Years)
The standard of the included research was assessed utilizing the Newcastle–Ottawa Scale (NOS) software for cohort research, evaluating the danger of bias as a result of choice, comparability and final result. A research could possibly be awarded a most of 1 star for every numbered merchandise within the choice and final result classes.23 A most of two stars will be given for comparability. A most of 9 factors will be given to research of the very best high quality. Two authors (MLA and LRJ) carried out the evaluation independently. In conditions of disagreement, consensus was reached by way of dialogue. The assessments of the danger of bias are offered in Tables 1–3.
Literature Search and Examine Choice
The preliminary literature search recognized 1035 research by title, of which 944 had been exterior the scope of the evaluation. A complete of 91 research had been screened by summary, and 77 had been assessed in full. Solely 21 research had been included, and 5 of them had been newly revealed in 2021/2022. An up-to-date search added yet one more research in group 2. Traits and abstract knowledge from the included research are offered in Tables 1–3.
We discovered 10 research that belonged to group 1: Maternal MS and short-term outcomes within the offspring (delivery and neonatal). We discovered 9 research that belonged to Group 2: In utero publicity to medicines used to deal with maternal MS and short-term outcomes within the offspring (delivery and neonatal). We discovered 4 research that belonged to Group 3: Maternal MS and long-term well being outcomes within the offspring (from 1 month to 18 years). One research had outcomes that belonged to a couple of group.
The research had been all cohort research and several other of them had been population-based cohorts, they usually represented 4 continents (North and South America, Asia and Europe). There have been 15 European research and eight of them had been based mostly on Scandinavian nationwide registers: Andersen et al studied the Danish population18,24,39,40 Dahl et al and Strom et al studied the Norwegian inhabitants,11,25,26 and Korjagina et al used knowledge from Finland and Sweden of their register research.27 Two of the three German research had been based mostly on the identical dataset, however with completely different timeslots and exposures,28,29 and the 2 research from Italy got here from the identical registry, however with completely different timeslots.30,31 One research from the UK reported as part of the Oxford Report Linkage Examine on a cohort from 1970–1989.32 Chen et al studied the inhabitants of Taiwan12 and Soler et al studied a cohort in Chile.13 The Canadian research group of Razaz et al performed two population-based register research from British Columbia on long-term outcomes in youngsters.33,34 Three research got here from the USA: two cohort research from Boston, utilizing knowledge from the identical administrative claims database,14,35 and one research from Washington.36
Group 1 Research: Maternal MS and Brief-Time period Outcomes within the Offspring (Start and Neonatal)
We discovered 10 research in whole on this class. These research examined the affiliation between maternal MS recognized earlier than the time of conception and delivery and neonatal outcomes within the offspring. The bulk centered on short-term delivery outcomes, together with 5-minute Apgar <7, SGA/low delivery weight, preterm delivery, congenital anomalies and stillbirth, among the many offspring of girls with MS.
9 of the group 1 research reported on the end result of preterm delivery. Two of those research discovered a considerably elevated threat of preterm delivery in girls with MS.12,14 MacDonald et al used the Truven Well being MarketScan Database (2011–2015; Truven Well being Analytics Inc, Ann Arbor, Michigan) and the Nationwide Inpatient Pattern (2007–2011) to determine delivery cohorts. Ladies with MS had been in contrast with the background inhabitants, they usually discovered an RR of 1.19 (95% CI 1.04–1.35) for preterm delivery within the Truven Database and RR 1.30 (95% CI 1.16–1.44) for preterm delivery within the Nationwide Inpatient Pattern.14 The principle limitation of the Truven Well being MarketScan Database was that 728,337 pregnancies (39.8%) had been excluded owing to non-continuous enrollment in the course of the interval from 90 days earlier than the final menstrual interval to the supply date, which might introduce choice bias. Nevertheless, they’ve made a comparability of a number of the covariates on the included and excluded girls, stating them to be related beside 12 months of delivery. In a research by Chen et al from Taiwan, the OR for preterm delivery was 2.25 (95% CI 1.37–3.70).12 Comparability was made with an age-matched management group with none illnesses. From our perspective, the 2 research missed adjustment for some necessary potential confounders, corresponding to maternal comorbidities, smoking, physique mass index (BMI) and medical therapy. Not one of the different six research reporting on preterm delivery as an final result had ample statistical energy to attract conclusions on the danger of preterm delivery.24,25,32,36–38
SGA and Low Start Weight
Six research reported SGA and three of them discovered a considerably elevated threat, with OR 1.29–1.89, amongst youngsters of girls with MS in comparison with a reference group with out MS.12,24,25 The research by Chen et al discovered an elevated threat of SGA, with OR 1.89 (95% CI 1.29–2.70). It’s value noting that the research is classed as being nationwide and inhabitants based mostly, however the cohort consists of solely 174 girls with MS in contrast with 1392 wholesome controls, and the inhabitants of the island consists of 23 million individuals.12 One should subsequently assume that the cohort constitutes solely a small proportion of the ladies on the island with MS giving delivery. A research by Dahl et al discovered an elevated threat of SGA, with OR 1.45 (95% CI 1.14–1.84), within the MS group in comparison with the background inhabitants.25 A research by Goldacre et al discovered an elevated threat of low delivery weight <2000 g, with OR 2.7 (95% CI 1.10–6.60), however based mostly on solely 5 instances within the MS group, which ought to in all probability be interpreted as a random distribution.32 In distinction to those research, three different research reporting on SGA didn’t discover any vital variations. Goldacre et al discovered an equal distribution, with OR 1.0 (95% CI 0.60–1.80), of their dataset from 1970–1989.32 Dahl et al discovered OR 1.20 (95% CI 0.99–1.45) of their research on a pattern of MS sufferers in Norway.25 Mueller et al reported on the end result of low delivery weight <2500 g unadjusted for gestational age, and located RR 0.9 (95% CI 0.50–1.70).36 MacDonald et al reported on the end result of poor fetal development (recognized earlier than delivery) of their two research cohorts from completely different databases, and located OR 1.03 (95% CI 0.87–1.19) and OR 1.23 (95% CI 0.94–1.54). They didn’t current knowledge on delivery weight ends in their research.14
Low Apgar Rating
Three research reported on low 5-minute Apgar rating. None of those discovered an elevated threat amongst youngsters of girls with MS.24,32,36 The Danish cohort research by Andersen et al reported an final result referred to as “indicators of asphyxia”, together with components from the Apgar analysis along with umbilical wire blood pattern. This final result was decrease within the uncovered group of kids born to girls with MS, with OR 0.87 (95% CI 0.78–0.97).24
Six of the group 1 research reported on the end result of congenital anomalies. MacDonald et al discovered OR 0.85 (95% CI 0.59–1.12) for congenital anomalies amongst offspring of girls with MS,14 however solely reported on main anomalies, whereas Weber-Schoendorfer and Schaefer reported OR 3.34 (95% CI 0.62–11.55) within the MS group, they usually counted each minor and main anomalies.37 The boldness interval exhibits the low statistical precision, and the research was too small to supply agency conclusions. Within the largest cohort research, by Andersen et al, the OR for congenital anomalies was 1.02 (95% CI 0.87–1.19).24 Mueller et al discovered RR 0.6 (95% CI 0.10–2.30) for congenital anomalies.36 The 2 Norwegian research by Dahl et al didn’t report on the variety of congenital anomalies, however simply reported that they didn’t discover any variations concerning congenital anomalies.11,25 Soler et al in contrast girls with “pre-MS” and “post-MS”, however had no wholesome controls of their research.13 They discovered OR 0.66 (95% CI 0.30–1.14) for congenital anomalies in girls with being pregnant previous to MS prognosis, in contrast with girls who grew to become pregnant after MS was recognized.
Stillbirth was outlined in another way within the seven research that reported on this final result. The research by Fong et al discovered a threat of “fetal demise” within the MS group, with OR 1.6 (95% CI 0.90–3.10),38 whereas the biggest research cohort, by Andersen et al (n=2930 girls with MS), discovered OR 1.17 (95% CI 0.68–2.00) for stillbirth.24 Each cohort research are, nonetheless, not giant sufficient to attract a major conclusion on this uncommon final result. Mueller et al studied a cohort of in another way insured MS sufferers giving delivery at non-federal hospitals in Washington State, and located OR 1.1 (95% CI 0.30–5.10) on the end result “toddler loss of life”, however didn’t additional outlined whether or not loss of life was earlier than or after delivery.36 Goldacre et al discovered no stillbirths of their research group32 and Dahl et al reported “no distinction” on the end result “perinatal mortality”, however didn’t current their outcomes as numbers.11,25 MacDonald et al discovered OR 0.82 (95% CI 0.23–1.52) and OR 0.96 (95% CI 0.50–1.48) of their two research cohorts.14,35
Group 2 Research: In Utero Publicity to Drugs to Deal with Maternal MS and Brief-Time period Outcomes within the Offspring (Start and Neonatal)
We discovered 9 research matching group 2 standards. Eight reported on the end result of congenital anomalies and preterm delivery. 4 research reported on the end result of SGA, low delivery weight or intrauterine development restriction (IUGR). Two research assembly our standards reported on the end result of stillbirth. A scientific evaluation and meta-analysis of being pregnant and fetal outcomes amongst girls with MS and DMT was revealed in 2020.21 Right here, Lopez-Leon et al included research from the interval January 2000 to August 2019 and reviewed the present literature on the affect of DMT. In distinction to this evaluation, research with out calculated threat estimates had been included. Of their meta-analyses, they discovered no elevated threat of preterm delivery after stratification based on glatiramer acetate (two research, n=288), with RR 0.79 (95% CI 0.56–1.12), interferon-β (4 research, n=704), with RR 0.92 (95% CI 0.58–1.46), or natalizumab (two research, n=79), with RR 0.82 (95% CI 0.57–1.18). In all research, the uncovered youngsters had been in contrast with youngsters of moms with MS who didn’t take DMT earlier than or throughout being pregnant. Relating to main congenital anomalies, they discovered 4 research reporting this final result amongst youngsters uncovered to interferons (n=423), with RR 0.70 (95% CI 0.3–1.6), and glatiramer acetate (n=188), RR 0.58 (95% CI 0.16–2.12).
Only some extra papers have been revealed on this class for the reason that research by Lopez-Leon et al.21 Three research, revealed within the interval January 2019 to February 2023, met our inclusion standards. A Swedish cohort research centered on interferon-β-exposed youngsters (n=718),27 and one Danish cohort research centered on teriflunomide-exposed youngsters (n=49)39 and one other on injectable first-line therapies, dimethyl fumarate and natalizumab-exposed youngsters (n=711 liveborns).18 Not one of the three research discovered vital variations within the threat of opposed short-term delivery final result between DMT-exposed and unexposed youngsters.
Group 3 Research: Maternal MS and Lengthy-Time period Well being Outcomes within the Offspring (from 1 Month to 18 Years)
We included 4 research that reported on long-term outcomes in youngsters.26,33,34,40 Two of the research reported on psychiatric outcomes, one research reported on academic final result and one research on neurological final result. Andersen et al studied psychological well being at age 11 years amongst youngsters of girls with MS and didn’t discover an affiliation with psychiatric diagnoses, in comparison with youngsters of moms with out MS.40 A register research by Strom et al adopted a complete of 1,360,149 Norwegian youngsters for a interval of two–24 years. A complete of 3575 youngsters had been recognized with cerebral palsy within the background inhabitants (2.6 per 1000 stay births), and amongst youngsters of moms with MS, they discovered an elevated prevalence of three per 1000 stay births with cerebral palsy, RR 1.8 (95% CI 0.80–4.40). The consequence was not statistically vital.26 Razaz et al examined vulnerability within the social improvement area based on the Early Growth Instrument amongst 1- and 3-year-old youngsters of oldsters with MS. Youngsters uncovered to maternal MS had a decrease threat of vulnerability in comparison with youngsters of girls with out MS, OR 0.75 (95% CI 0.60–0.95).33 Razaz et al additionally examined temper and nervousness issues, starting from poor adjustment reactions and nervousness to phobic issues, obsessive–compulsive issues, affective psychoses and neurotic despair, amongst youngsters of oldsters with MS in one other set-up. Outcomes of curiosity had been recognized utilizing a mixture of hospital diagnoses, outpatient doctor diagnoses and prescription drug claims. In youngsters of girls with MS, the HR for the mixed final result “temper or nervousness issues” was 1.7 (95% CI 1.10–2.40), however it decreased when adjusting for maternal psychological comorbidity, HR 1.4 (95% CI 0.90–2.10).34
Our goal was to supply an summary of the present literature on the reproductive space of girls with MS and to determine the analysis gaps on this space. Strong data about short- and long-term youngster outcomes is crucial for clinicians to adequately counsel girls with MS in reproductive issues. The research pointed in direction of an elevated threat of preterm delivery and SGA amongst girls with MS. When it comes to girls with MS handled with DMT previous to or throughout being pregnant, no clear conclusions could possibly be drawn. The few research on long-term youngster outcomes centered primarily on neurodevelopmental and psychiatric impairments, and one research reported on the long-term threat of cerebral palsy amongst youngsters of girls with MS. None of those research reported any vital findings. On this systematic evaluation, we’ve highlighted the analysis gaps on the affect of maternal MS on offspring well being.
We centered on opposed offspring outcomes, corresponding to low delivery weight, SGA and preterm delivery, that are outcomes which can be necessary predictors of neonatal and childhood morbidity and mortality, but in addition predictors for morbidities in maturity.41 Lengthy-term well being outcomes usually embody the danger of illnesses and improvement within the offspring throughout childhood, adolescence or so far as the follow-up time permits. Nevertheless, the affect of maternal MS on long-term youngster outcomes has obtained minor consideration, and we discovered solely 4 research on long-term youngster outcomes. One cause why that is the case could also be associated to the excessive demand for applicable datasets with full and lengthy follow-up time on all people. We all know from the literature that youngsters of oldsters with MS have a minor elevated threat of growing MS themselves,42 however in any other case we all know little or no concerning the affect of in utero publicity to maternal MS, DMT and the affect on the danger of the offspring growing illnesses within the first years of life, and through childhood and adolescence.
We discovered outcomes pointing in direction of youngsters of girls with MS being at greater threat of opposed delivery outcomes, corresponding to being born preterm, SGA or with low delivery weight, however with the proviso that the related research principally had been of mediocre high quality (NOS scores 5–8). A considerably elevated threat of congenital anomalies or stillbirth was not present in any of the current research, which had been, nonetheless, typically underpowered to check this final result. Moreover, a lot of the uncovered cohorts on this class had been a combination of sufferers with and with out DMT and weren’t stratified for this, which signifies that the outcomes have a restricted applicability. Relating to the end result of congenital anomalies, this isn’t a really well-described final result within the accessible literature and, along with the end result of stillbirth, no research had the required statistical energy to conclude on the calculated threat estimates. Sometimes, the cohorts weren’t solely uncovered to MS and never in comparison with wholesome controls both, which might be the popular research design on which to attract conclusions. We conclude that not one of the current research has the statistical energy to conclude on the danger of congenital anomalies or stillbirth with certainty.
Relating to medical therapy of younger girls with MS, there are presently two preparations usually acknowledged by the European Medicines Company and the American Meals and Drug Administration as potential therapy choices throughout being pregnant. These are the 2 mostly used medication for pregnant girls with MS:35,43 glatiramer acetate, which hypothetically induces Th2 cells to launch cytokines which can be capable of suppress inflammatory processes within the MS lesions, and interferon-β, which, amongst different issues, reduces the expression of adhesion molecules of the lymphocytes and thereby the passage of activated T cells throughout the blood–mind barrier. Glatiramer acetate and interferon-β don’t seem to extend the danger of opposed delivery outcomes and are already prescribed to be used throughout being pregnant to an excellent extent, however concerning the long-term well being penalties within the offspring there’s a crucial analysis hole. These two preparations have been used for nearly 25 years, and long-term penalties after maternal use on the time of conception should have been an necessary analysis space. The problem is of course an excellent concern for younger girls with MS who’re contemplating having youngsters. To the perfect of our data, no research has but examined the affiliation between maternal use of particular MS medicine across the time of conception and long-term well being penalties within the offspring.
Research up to now decade have meant to make clear the implications within the offspring of in utero publicity to those preparations affecting the immune system, however the research have been based mostly on small cohorts, and the outcomes have been divergent and characterised by publicity and final result inhomogeneity. Subsequently, a possible unfavourable affect on the fetus nonetheless needs to be investigated. Sufferers fear concerning the affect of MS and MS medicine on short- and long-term well being penalties within the offspring, and a few girls will select to not proceed their DMT throughout pregnancy37 or will resolve to not have youngsters owing to the lack of expertise on this space.3 The authors discovered a lot of pharmacovigilance research produced by pharmaceutical firms, however since they lack management teams, these research do not need the methodological high quality to allow security conclusions to be drawn from them. As well as, we determined to exclude research that centered on biometric measures, emotional and behavioral difficulties or academic achievements within the offspring, as an alternative of threat estimates of illnesses in offspring of girls with MS.44–46
To have the ability to present exact outcomes on uncommon and severe outcomes corresponding to stillbirth and congenital anomalies, we want methodologically stable research based mostly on a bigger variety of youngsters. We will totally endorse the conclusion from the systematic evaluation and meta-analysis from 2020 by Lopez-Leon et al, that future research together with inside comparators are nonetheless wanted.21
The cumulative quantity of information is certainly sparse and there’s a nice want for extra proof on this space. There’s nonetheless a big hole within the literature with regard to research on long-term somatic well being outcomes amongst youngsters of girls with MS, and just a few research exist on the affiliation between maternal MS and long-term well being outcomes within the offspring. One research reported on the end result of cerebral palsy, however the remaining had been on psychological and social outcomes, which could possibly be associated to rising up in an surroundings with a dad or mum with MS reasonably than the intrauterine publicity to the illness. It’s difficult to advise sufferers concerning the security of medicines with regard to uncovered offspring when most research on opposed penalties within the offspring solely have a look at outcomes throughout the first 12 months of life.
Future research on long-term well being penalties within the offspring of moms with MS are necessary for these sufferers.
This work has been supported by Area of Southern Denmark [grant no. 20/14788, 2022], Odense College Hospital [grant no. 122-A5119 and 128-A5300, 2021], Jascha Basis [grant no. 3630, 2020], Advisor Schou and Spouse Else-Marie Schou, born Wanges Basis [grant no. 85832].
Dr Mette Louise Andersen reviews grants from the Area of Southern Denmark, grants from the Jascha Basis, and grants from the Advisor Schous Basis, in the course of the conduct of the research. The authors declare no competing pursuits.
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