Cardiovascular Risk Factors Among First-Degree Relatives of Patients with Premature Cardiovascular Disease in Malta. Baseline Findings from the CRISO Project.

Purpose: A family history of premature atherosclerotic cardiovascular disease (ASCVD) confers a greater risk of developing ASCVD. However, the prevalence of ASCVD risk factors among asymptomatic Maltese adults with parental or fraternal history of premature ASCVD is unknown. The study aimed to evaluate and compare their risk with the general population. Patients and Methods: Posters to market the project were distributed in cardiac rehabilitation areas. Patients with premature cardiovascular disease facilitated recruitment by informing their relatives about the project. Medical doctors and cardiac rehabilitation nurses referred first-degree relatives. Posters were put up in community pharmacies, and an explanatory video clip was shared on social media for interested individuals to contact researchers. Those eligible were enrolled in a preventive cardiology lifestyle intervention. Their data were compared with the risk in the general population. Results: Many first-degree relatives had a suboptimal risk profile, with 60% (N = 89) having a total cholesterol level of >5.0 mmol/L; 54% having a low-density lipoprotein-cholesterol level of >3 mmol/L; 70.5% being overweight/obese, with 62% having a waist circumference greater than the recommended values; 34.8% having hypertension; 56.2% being inadequately adherent to the Mediterranean diet; 62% being underactive, with 18% being sedentary; and 25.8% being smokers. First-degree relatives had significantly higher proportions of underactive lifestyle (p = 0.00016), high body mass index (>25kg/m2) (p = 0.006), and systolic blood pressure (p = 0.001) than the general population, with 30% having metabolic syndrome. Conclusion: This study determined the prevalence of lifestyle, biochemical, physiological, and anthropometric cardiovascular risk factors among asymptomatic first-degree relatives of Maltese patients with premature ASCVD. First-degree relatives had considerable prevalences of an underactive lifestyle, hypertension, and obesity, suggesting better screening and early risk factor intervention are needed to modify their risk of ASCVD.

This study was done to evaluate factors that can increase the risk of heart disease in siblings and offspring of Maltese patients who developed atherosclerotic cardiovascular disease (ASCVD) at a young age. Relatives were invited to meetings during which a risk evaluation was performed. The researchers found that relatives had a high prevalence of cardiometabolic risk factors, meaning they were at increased risk of developing the disease. The researchers have concluded that reducing the risk of ASCVD in individuals at increased risk requires developing and testing potentially sustainable risk factor modification strategies.

Association between a polygenic lipodystrophy genetic risk score and diabetes risk in the high prevalence Maltese population.

BACKGROUND: Type 2 diabetes (T2DM) is genetically heterogenous, driven by beta cell dysfunction and insulin resistance. Insulin resistance drives the development of cardiometabolic complications and is typically associated with obesity. A group of common variants at eleven loci are associated with insulin resistance and risk of both type 2 diabetes and coronary artery disease. These variants describe a polygenic correlate of lipodystrophy, with a high metabolic disease risk despite a low BMI. OBJECTIVES: In this cross-sectional study, we sought to investigate the association of a polygenic risk score composed of eleven lipodystrophy variants with anthropometric, glycaemic and metabolic traits in an island population characterised by a high prevalence of both obesity and type 2 diabetes. METHODS: 814 unrelated adults (n = 477 controls and n = 337 T2DM cases) of Maltese-Caucasian ethnicity were genotyped and associations with phenotypes explored. RESULTS: A higher polygenic lipodystrophy risk score was correlated with lower adiposity indices (lower waist circumference and body mass index measurements) and higher HOMA-IR, atherogenic dyslipidaemia and visceral fat dysfunction as assessed by the visceral adiposity index in the DM group. In crude and covariate-adjusted models, individuals in the top quartile of polygenic risk had a higher T2DM risk relative to individuals in the first quartile of the risk score distribution. CONCLUSION: This study consolidates the association between polygenic lipodystrophy risk alleles, metabolic syndrome parameters and T2DM risk particularly in normal-weight individuals. Our findings demonstrate that polygenic lipodystrophy risk alleles drive insulin resistance and diabetes risk independent of an increased BMI.

The epidemiology of CHD in Malta.

BACKGROUND: CHD refers to structural cardiac abnormalities which comprise the commonest group of congenital malformations. Malta is a small island in the central Mediterranean with excellent diagnostic and therapeutic facilities. It is unique in the European population as termination of pregnancy is illegal. This study was carried out to ascertain patterns in CHD prevalence in comparison with EUROCAT data (European Surveillance of Congenital Anomalies). METHODS: Anonymised data were obtained from the EUROCAT website for 1993-2020. RESULTS: There were a total of 22,833,032 births from all EUROCAT Registries, of which 121,697 were from Malta. The prevalence rate for Malta CHD was 32.38/10,000 births (at the higher end of the range). Malta had a significant excess of commoner, comparatively non-severe CHDs. For most of the severe lesions analysed rates reported were higher than EUROCAT average, however, apart from Ebstein's anomaly, they all fell within the ranges reported from the different registries. DISCUSSION: Wide variations in reported CHD prevalence are known, and the Malta rates may be higher for milder defects due to quicker pickup prior to spontaneous resolution. There may also be a higher pickup of milder forms of more severe conditions. For the more severe conditions, lack of termination may be the explanation. These factors may result in the higher neonatal mortality observed in Malta.

Addressing childhood obesity through policy: A cross-sectional study in Malta.

Introduction: Childhood overweight and obesity are major public health challenges, with Malta having one of the highest prevalences among European countries. The COVID-19 pandemic may further worsen this epidemic. The food and physical activity environments impact children's behaviours. This study looks at barriers to maintain a healthy weight, responsibility to address obesity, and assesses parental support for 22 policies aimed at addressing childhood obesity. Public support for policy is key because it influences which policies are adopted and their success. Methods: A cross-sectional, paper-based, quantitative survey was conducted amongst parents of primary school-aged children in Malta in 2018-2019. Ethical approval was obtained. Statistical analysis was performed using SPSS. Results: 1,169 parents participated. The food environment was more commonly identified as a barrier to maintain a healthy weight than the physical activity environment. Parents were least supportive of taxation policies, and most in favour of increasing spaces available for safe physical activity (94.0%), followed by providing free weight management services for children (90.8%). The level of support varied significantly by various socio-demographic/economic characteristics; parents with a higher educational level were significantly more supportive of most policies. Most findings were consistent with the international literature. Conclusions: Most policies supported are trans-sectoral; a health-in-all policies approach is needed to address the obesogenic environment. The strong public support identified for several policies should embolden policymakers to consider policy options that were not previously considered.

Clinical features and diagnostic challenges of mpox (monkeypox) outbreak in Malta: a retrospective cohort study.

BACKGROUND: In May of 2022, an mpox (formerly known as monkeypox) outbreak was reported from countries where the disease is not endemic, rising worldwide concern. Malta, the smallest European Union member state, faced unique challenges, with high infection rates compared to the rest of Europe. The aim of the study is to describe the clinical characteristics, diagnostic challenges, and unique demographics of mpox patients diagnosed in Malta. METHODS: This is a retrospective analysis of medical records of all mpox cases recorded from May to September 2022. Demographic data, sexual behaviors and practices, travel history, comorbidities, and HIV status were investigated. RESULTS: In the study period, we recorded 33 mpox cases, 97% of them were male, in the age group 30-39 (39%). Ninety percent were gay or bisexual men and 76% non-Maltese. The most common clinical presentations included skin rash (78%), lymphadenopathy (71%), anogenital lesions (67%), and fever (67%). Twenty-seven percent of the patients were people living with HIV. In terms of coinfection with STIs, 27% of patients tested positive for gonorrhea, 12% for syphilis, 15% for chlamydia, 9% for herpes simplex virus, and 3% for hepatitis C virus. CONCLUSION: The results shed light on unique challenges faced by the local sexual health clinic and call for more resources in response to the global emerging of infectious diseases.

A glimpse into Long COVID characteristics and the mental health impact within a highly vaccinated population: a Malta observational study.

BACKGROUND: Post-acute COVID-19 consequences are gaining global recognition. This study explores Long COVID characteristics and associated mental health impact/s among the highly vaccinated adult population of Malta. METHODS: A social media survey gathered demographics, vaccination, and COVID-19 data. Generalised Anxiety Disorder and Patient Health Questionnaire-9 assessment tools were used for anxiety and depression. Quantitative analyses were performed. RESULTS: 41% reported Long COVID, mostly female, 30-39 years, absence of chronic disease/s and vaccinated. Shortness of breath commonest persistent symptom among males, and fatigue for females. Significantly higher depression scores were present in Long COVID cohort compared to no persistent symptoms (p=0.001) and never acquiring COVID-19 (p=<0.01). A significant higher anxiety scores was present for Long COVID cohort than never acquiring COVID-19 (p=<0.01). CONCLUSIONS: Long COVID occurs even in healthy individuals and vaccinated, while exacerbating mental health burdens. Urgent action is required to manage Long COVID and preventing the sequela.

Hybrid immunity and protection against infection during the Omicron wave in Malta.

By December 2021, administration of the third dose of COVID-19 vaccinations coincided with the spread of the Omicron variant in Europe. Questions had been raised on protection against infection conferred by previous vaccination and/or infection. Our study population included 252,433 participants from the COVID-19 vaccination registry in Malta. Data were then matched with the national testing database. We collected vaccination status, vaccine brand, vaccination date, infection history, and age. Using logistic regression, we examined different combinations of vaccine dose, prior infection status and time, and the odds of infection during the period when the Omicron variant was the dominant variant in Malta. Participants infected with Sars-Cov-2 prior to the Omicron wave had a significantly lower odds of being infected with the Omicron variant. Additionally, the more recent the infection and the more recent the vaccination, the lower the odds of infection. Receiving a third dose within 20 weeks of the start of the Omicron wave in Malta offered similar odds of infection as receiving a second dose within the same period. Time since vaccination was a strong determinant against infection, as was previous infection status and the number of doses taken. This finding reinforces the importance of future booster dose provision especially to vulnerable populations.

Genetic landscape of ALS in Malta based on a quinquennial analysis.

Genetic risk for amyotrophic lateral sclerosis (ALS) is highly elevated in genetic isolates, like the island population of Malta in the south of Europe, providing a unique opportunity to investigate the genetics of this disease. Here we characterize the clinical phenotype and genetic profile of the largest series of Maltese ALS patients to date identified throughout a 5-year window. Cases and controls underwent neuromuscular assessment and analysis of rare variants in ALS causative or risk genes following whole-genome sequencing. Potentially damaging variants or repeat expansions were identified in more than 45% of all patients. The most commonly affected genes were ALS2, DAO, SETX and SPG11, an infrequent cause of ALS in Europeans. We also confirmed a significant association between ATXN1 intermediate repeats and increased disease risk. Damaging variants in major ALS genes C9orf72, SOD1, TARDBP and FUS were however either absent or rare in Maltese ALS patients. Overall, our study underscores a population that is an outlier within Europe and one that represents a high percentage of genetically explained cases.

Assessing the impact of the four COVID-19 variants and the vaccine coverage on mortality in Malta over 2 years: An observational case study.

Background: Mortality may quantify a population's disease burden. Malta, like other European countries, experienced COVID-19 surges in cases and mortality across the pandemic. This study assesses COVID-19's mortality impact, while exploring the effects of the four dominant COVID-19 variants and that of the vaccination coverage on the Maltese population. Methods: COVID-19 data (cases, mortality, positivity, and vaccination rates) was obtained from the websites of the European Center for Disease Prevention and Control and the Malta Ministry of Health. Data was categorized into the four periods according to reported dominant COVID-19 variant. Years of life lost (YLL) and Case-Fatality-Ratio (CFR) for each period were estimated. CFR was also estimated for the pre-vaccine and post-vaccine periods. Results: The original COVID-19 period (36 weeks) had the highest YLL (4,484), followed by the Omicron variant period (12 weeks; 1,398). The Alpha variant period (7 weeks) had the highest CFR (1.89%) followed by the Original COVID-19 (1.35%). The pre-vaccine (1.59%) period had higher CFR than the post-vaccine period (0.67%). Conclusion: Various factors contributed to mortality, but the variant's infectivity, transmissibility, and the effectiveness of the vaccine against the variant play an important role. Reducing mortality by embracing mass vaccination that targets current variants along with other non-pharmaceutical interventions remains paramount.

Digitalizing and Upgrading Severe Acute Respiratory Infections Surveillance in Malta: System Development.

BACKGROUND: In late 2020, the European Centre for Disease Prevention and Control and Epiconcept started implementing a surveillance system for severe acute respiratory infections (SARI) across Europe. OBJECTIVE: We sought to describe the process of digitizing and upgrading SARI surveillance in Malta, an island country with a centralized health system, during the COVID-19 pandemic from February to November 2021. We described the characteristics of people included in the surveillance system and compared different SARI case definitions, including their advantages and disadvantages. This study also discusses the process, output, and future for SARI and other public health surveillance opportunities. METHODS: Malta has one main public hospital where, on admission, patient data are entered into electronic records as free text. Symptoms and comorbidities are manually extracted from these records, whereas other data are collected from registers. Collected data are formatted to produce weekly and monthly reports to inform public health actions. From October 2020 to February 2021, we established an analogue incidence-based system for SARI surveillance. From February 2021 onward, we mapped key stakeholders and digitized most surveillance processes. RESULTS: By November 30, 2021, 903 SARI cases were reported, with 380 (42.1%) positive for SARS-CoV-2. Of all SARI hospitalizations, 69 (7.6%) were admitted to the intensive care unit, 769 (85.2%) were discharged, 27 (3%) are still being treated, and 107 (11.8%) died. Among the 107 patients who died, 96 (89.7%) had more than one underlying condition, the most common of which were hypertension (n=57, 53.3%) and chronic heart disease (n=49, 45.8%). CONCLUSIONS: The implementation of enhanced SARI surveillance in Malta was completed by the end of May 2021, allowing the monitoring of SARI incidence and patient characteristics. A future shift to register-based surveillance should improve SARI detection through automated processes.

On the way between Africa and Europe: Molecular taxonomy of ticks collected from birds in Malta.

The Maltese Archipelago is situated in the middle of the Mediterranean Basin, between Europe and Africa, therefore representing an important stopover site for migratory birds between these two continents. Despite this, up-to-date information is not available on tick species associated with birds in Malta. Therefore, in this study, birds mist-netted for ringing by BirdLife Malta were examined for the presence of ticks between September, 2019 and May, 2021. Ticks were identified morphologically and molecularly, using three genetic markers. During the study period, 57 individuals of 22 bird species were found tick-infested, from which altogether 113 ixodid ticks were collected. The majority of developmental stages were nymphs, but 13 larvae and one female were also found. These ticks belonged to nine species: Ixodes cumulatimpunctatus (n=1), Ixodes ricinus (n=2), Ixodes acuminatus (n=2), Ixodes frontalis (n=5), Ixodes festai (n=1), one species of the Amblyomma marmoreum complex (n=8), Hyalomma rufipes (n=78), Hyalomma marginatum (n=7) and Hyalomma lusitanicum (n=1). Eight Hyalomma sp. ticks could only be identified on the genus level. Regarding seasonality, all Palearctic Ixodes species were carried by birds exclusively in the autumn (i.e., north to south), whereas H. rufipes (with predominantly Afrotropical distribution) was exclusively collected in the spring (i.e., carried south to north). Two tick species that occurred on birds in Malta, i.e., a species of the A. marmoreum complex and I. cumulatimpunctatus are only indigenous in the Afrotropical zoogeographic region. This is the first finding of the latter tick species in Europe, and four tick species were identified for the first time in Malta. In conclusion, the diversity of tick species regularly arriving in Europe from Africa is most likely higher than reflected by data obtained in Mediterranean countries of mainland Europe. Most notably, ticks of the genus Amblyomma appear to be underrepresented in previous datasets. Ticks of the subgenus Afrixodes (represented by I. cumulatimpunctatus) might also be imported into Europe by migratory birds.

A Year of COVID-19 Pandemic Roller-Coaster: The Malta Experience, Lessons Learnt, and the Future.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic had a global impact. The study explores the various COVID-19 experiences in Malta over the past year and provides a snapshot of acute and post-acute COVID-19 symptoms, as well as national vaccination roll-out and hesitancy. METHODS: Data on medical access, lifestyle habits, acute and post-acute COVID-19 symptoms, and vaccination hesitancy was gathered through a social media survey targeting adults of Malta. COVID-19 data were gathered from the Malta Ministry of Health COVID-19 dashboard. RESULTS: Malta controlled COVID-19 spread exceptionally well initially. Since August 2020, the positivity rate, mortality, and hospital admission rates saw a fluctuating incline. From COVID-19 onset, a decrease in physical activity and an increase in body weight was reported. Most participants acquiring COVID-19 were asymptomatic but nontrivial proportion experienced post-acute symptoms. The majority opted to take the COVID-19 vaccine with only a minority expressing safety concerns. CONCLUSIONS: Malta has experienced roller coaster events over a year. The population faced elevated levels of morbidity, mortality, and economic hardship along with negative and positive risk-associated behaviors. Vaccination in combination with population adherence to social distancing, mask wearing, and personal hygiene are expected to be the beacons of hope in the coming months.

Gender, migration and violence among third country nationals accessing the sexual health clinic in Malta.

BACKGROUND: In 2020, the number of displaced people worldwide reached 41.3 million (IOM, 2020). Among them, are many migrants and refugees at risk of sexual and gender-based violence (SGBV). Healthcare providers have a key role to play in identifying migrant victims/survivors of violence. OBJECTIVES: This paper seeks to assess STIs prevalence, sexual health and sexual violence among third country nationals (TCNs) attending the GUC in Malta. METHODS: This is a mixed methods study carried out at the Genitourinary Clinic (GUC), which is the only public sexual health clinic in Malta. Demographic data, sexual history and diagnoses of patients attending the GUC between January 2018 and December 2019 were collected and retrospectively analysed. A SGBV risk assessment was performed through a semi-structured questionnaire. RESULTS: In the 24-month study period, a total of 12 654 patients accessed the GUC in Malta. Demographic data were collected on age, gender, nationality, marital status and sexual orientation. 16.4% (n = 2064) of these were extra-European migrants, predominantly male. 80 different nationalities were recorded, with the 5 most common being Nigerian, Filipino, Libyan, Syrian and Brazilian. The average age was 32.6 years. Over 110 sex workers were visited at the GUC in the study period - 20 were foreign, primarily from China. The presence of a 'massage parlour owner' during consultation, lack of control over passports and other factors were identified as warning signs of trafficking. 5 cases of sexual violence and forced prostitution involving girls from Sub-Saharan Africa and, in 2 cases, boys recently arrived in Malta by boat, were encountered. 6 African women accessing the service exhibited a type of female genital mutilation (FGM). CONCLUSIONS: Migration, sexual health and SGBV overlap in important ways. Further research and training in SGBV and migration in the healthcare setting and awareness-raising about existing services among the migrant population are required.

Managing COVID-19 in four small countries: Initial response to the pandemic in San Marino, Montenegro, Malta and Cyprus.

The aim of this paper is to compare the impact of the COVID-19 pandemic on four small countries in the southern half of Europe with similar public health systems: San Marino, Montenegro, Malta and Cyprus, the latter two being island states. There are advantages and disadvantages in being a small nation amidst this crisis. The centralized public health administration means that small countries are faster at adapting as they learn and evolve on a weekly basis. However, small countries tend to be dependent on their bigger neighbours, and the networks they belong to, for trade, food, medical supplies as well as policies. The risk threshold taken by a small country for the transition strategy has to be less than that taken by a bigger country because if things go wrong in a border region, there is less resilience in a small country, with immediate impact on the whole country. The blow to the tourism industry, which plays a main role especially in small countries, negatively impacted the economy, and it has been a feat to reach a balance between allowing the flow of inbound tourists and keeping the local infection rates under control.

A year of Covid-19: experiences and lessons learnt by small European island states-Cyprus, Iceland and Malta.

BACKGROUND: COVID-19 became a global pandemic within weeks, as every country including small states and islands experienced a surge in cases. Small islands are known to face several challenges in the quest to curb the viral spread, but with the absence of land boarders and small population size, these factors should have played to their advantage to minimize the spread. The aim of this article was to compare and contrast the COVID-19 situation, restrictions, preparedness, management and the healthcare systems between the small population island states of Cyprus, Iceland and Malta. METHODS: Data were obtained from Ministry of Health websites and COVID dashboards of the three respective Island states in Europe. Comparisons were made between the reported cases, deaths, excess deaths, years of life lost, swabbing rates, restrictive measures, vaccination roll-out and healthcare system structures. RESULTS: Cyprus and Malta contained the COVID-19 spread better than Iceland during the first wave. However, a significantly higher viral spread and mortality rates were observed in Malta during the second waves. Similar healthcare preparedness and services, restrictions and relaxation measures were implemented across the three islands with some exceptions. Covid-19 vaccination has initiated across all Islands with Malta leading the vaccination roll-out. CONCLUSION: The small population size and island status proved to be an asset during the first wave of COVID-19, but different governance approaches led to a different COVID-19 outcomes, including high mortality rates during the transition phases and the subsequent waves.

Does interpregnancy BMI change affect the risk of complications in the second pregnancy? Analysis of pooled data from Aberdeen, Finland and Malta.

OBJECTIVE: Weight management interventions during pregnancy have had limited success in reducing the risk of pregnancy complications. Focus has now shifted to pre-pregnancy counselling to optimise body weight before subsequent conception. We aimed to assess the effect of interpregnancy body mass index (BMI) change on the risk of perinatal complications in the second pregnancy. METHODS: A cohort study was performed using pooled maternity data from Aberdeen, Finland and Malta. Women with a BMI change of ±2 kg/m2 between their first and second pregnancies were compared with those who were BMI stable (remained within ±2 kg/m2). Outcomes assessed included pre-eclampsia (PE), intrauterine growth restriction (IUGR), preterm birth, birth weight, and stillbirth in the second pregnancy. We also assessed the effect of unit change in BMI for PE and IUGR. Logistic regression was used to calculate odds ratios with 95% confidence intervals. RESULTS: An increase of ≥2 kg/m2 between the first two pregnancies increased the risk of PE (1.66 (1.49-1.86)) and high birthweight (>4000 g) (1.06 (1.03-1.10)). A reduction of ≥2 kg/m2 increased the chance of IUGR (1.15 (1.01-1.31)) and preterm birth (1.14 (1.01-1.30)), while reducing the risk of instrumental delivery (0.75 (0.68-0.85)) and high birthweight (0.93 (0.87-0.98)). Reducing BMI did not significantly decrease PE risk in women with obesity or those with previous PE. A history of PE or IUGR in the first pregnancy was the strongest predictor of recurrence independent of interpregnancy BMI change (5.75 (5.30-6.24) and (7.44 (6.71-8.25), respectively). CONCLUSION: Changes in interpregnancy BMI have a modest impact on the risk of high birthweight, PE and IUGR in contrasting directions. However, a prior history of PE and IUGR is the dominant predictor of recurrence at second pregnancy.

Back pain: An aftermath of Covid-19 pandemic? A Malta perspective.

BACKGROUND: Back pain is the commonest musculoskeletal complaint across the world. The Covid-19 pandemic led to mitigating measures including remote working that enhanced a sedentary lifestyle. The aim of this study was to investigate whether back pain complaints have increased from pre-Covid-19 to during the Covid-19 period among the adult population of Malta, while exploring the possible contributing factors. METHODS: An online survey was distributed through social media targeting the adult population of Malta. Questions on sociodemographic data, occurrence of back pain pre-Covid-19 and since the onset of Covid-19 was gathered, along with changes in behavioural attitudes, daily routine and physical activity. Descriptive and multiple logistic regression analyses were performed. RESULTS: Out of the 388 responders, 30% experienced chronic back pain pre-Covid-19, 49% experienced back pain since Covid-19, with the majority of the latter claiming that they never experienced back pain before Covid-19. Significant changes were present in daily routine and physical activity (PA) patterns. Indeed, continuously sitting down (OR: 15.53; p ≤ 0.01), no PA (OR: 4.22; p ≤ <0.01), once a week PA (OR: 5.74; p ≤ <0.01), two to three times PA a week (OR: 2.58; p = 0.05) and four to five PA a week (OR: 3.46; p = 0.02) were associated with experiencing new onset back pain since the onset of Covid-19, when adjusted for sex, age, education and employment status. CONCLUSION: The pandemic has changed population behaviour resulting in an enhanced back pain occurrence. This is anticipated to impact the individual's disability adjusted life years as well as increase the burden on the economy and healthcare services. A designated multidisciplinary action plan is recommended to reduce back pain impact.

Risk of Recurrent Stillbirth in Subsequent Pregnancies.

OBJECTIVE: To compare the prospective risk of stillbirth between women with and without a stillbirth in their first pregnancy. METHODS: We conducted a cohort study using perinatal data from Finland, Malta, and Scotland. Women who had at least two singleton deliveries were included. The exposed and unexposed cohorts comprised women with a stillbirth and live birth in their first pregnancy, respectively. The risk of stillbirth in any subsequent pregnancy was assessed using a Cox proportional hazards model. Time-to-event analyses were conducted to investigate whether first pregnancy outcome had an effect on time to or the number of pregnancies preceding subsequent stillbirth. RESULTS: The pooled data set included 1,064,564 women, 6,288 (0.59%) with a stillbirth and 1,058,276 with a live birth in a first pregnancy. Compared with women with a live birth, women with a stillbirth in the first pregnancy were more likely to have a subsequent stillbirth (adjusted hazard ratio [aHR] 2.25, 95% CI 1.86-2.72). For women with more than two pregnancies, the difference in risk of subsequent stillbirth between the two groups increased with the number of subsequent pregnancies. Maternal age younger than 25 years or 40 years and older, smoking, low socioeconomic status, not having a partner, pre-existing diabetes, preeclampsia, placental abruption, or delivery of a growth-restricted neonate in a first pregnancy were independently associated with subsequent stillbirth. Compared with women with a live birth in the first pregnancy, women with a stillbirth were more likely to have another pregnancy within 1 year. The absolute risk of stillbirth in a subsequent pregnancy for women with stillbirth and live birth in a first pregnancy were 2.5% and 0.5%, respectively. CONCLUSION: Compared with women with a live birth in a first pregnancy, women with a stillbirth have a higher risk of subsequent stillbirth irrespective of the number and sequence of the pregnancies. Despite high relative risk, the absolute risk of recurrence was low.