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. 2021 Sep 30;16(9):e0257536. doi: 10.1371/journal.pone.0257536

Decreasing death rates and causes of death in Icelandic children—A longitudinal analysis

Marina Ros Levy 1, Valtyr Thors 1,2, Sigríður Haralds Elínardottir 3, Alma D Moller 3, Asgeir Haraldsson 1,2,*
Editor: Amir Radfar4
PMCID: PMC8483359  PMID: 34591867

Abstract

Background

Global death rate in children has been declining during the last decades worldwide, especially in high income countries. This has been attributed to several factors, including improved prenatal and perinatal care, immunisations, infection management as well as progress in diagnosis and treatment of most diseases. However, there is certainly room for further progress. The aim of the current study was to describe the changes in death rates and causes of death in Iceland, a high-income country during almost half a century.

Methods

The Causes of Death Register at The Directorate of Health was used to identify all children under the age of 18 years in Iceland that died during the study period from January 1st, 1971 until December 31st, 2018. Using Icelandic national identification numbers, individuals could be identified for further information. Hospital records, laboratory results and post-mortem diagnosis could be accessed if cause of death was unclear.

Findings

Results showed a distinct decrease in death rates in children during the study period that was continuous over the whole period. This was established for almost all causes of death and in all age groups. This reduction was primarily attributed to a decrease in fatal accidents and fewer deaths due to infections, perinatal or congenital disease as well as malignancies, the reduction in death rates from other causes was less distinct. Childhood suicide rates remained constant.

Interpretation

Our results are encouraging for further prevention of childhood deaths. In addition, our results emphasise the need to improve measures to detect and treat mental and behavioural disorders leading to childhood suicide.

Introduction

In the year 2018, 6.2 million children younger than 15 years old died worldwide, decreasing from 14.2 million in 1990 [1–3]. More than 2/3 of these children were in low and middle-income countries (LMIC), especially in sub-Saharan Africa and central and south-Asia [4]. A large part of these deaths was from preventable diseases, primarily in the youngest age groups [1].

Overall, death rates are highest during the first year of life, slowly decreasing with age but increases again between 15–18 years of age. High-income countries (HIC) generally have much lower childhood death rates [1]. In an earlier Icelandic study, the death rates and causes of death during 1941–1975 were described [5]. That study revealed a substantial reduction of childhood deaths due to infections in the first decade of the study period, i.e. during introduction of antibiotics to hospital care. Data from Iceland, ranging even further back described under five mortality rate of 360:1000 live born children in the year 1840, slowly but steadily declining to around 140:1000 children in the year 1900 [6]. The under-five mortality rate in Iceland in 2018 was 2.0:1000 and childhood death rate was 0.8:1000 live born children age 5–14 years and was comparable to the other Nordic and high income countries [2]. This data shows that death rates have fallen in Iceland over the last decades and the last century.

Causes of death in childhood differs between countries and world regions. In HIC, where many diseases in infancy can be prevented, the main causes of death are related to congenital diseases, infections and external causes such as accidents and suicide [1,7]. Important changes in death rates in children and causes of death have been recognised worldwide during the last decades [1]. In the current study we investigated the main hypothesis that an important decrease in the childhood death rates in Iceland during almost fifty years was primarily driven by fewer fatal infections in young children and childhood accidents and lower neonatal mortality.

The aim of the current study was to describe changes in childhood death rates in Iceland and evaluate causes of death over almost five decades. The underlying hypothesis was that that the declining death rates are primarily driven by decreases in fatal infections, childhood accidents, and neonatal mortality, especially in the under-five age group. From the results we attempt to determine specific risk factors and identify potential interventions to further prevent childhood deaths.

Material and methods

In the current study, causes of death in children (from birth until their 18th birthday) were collected from The National Causes of Death register in Iceland. Death rates were calculated and classified according to year of death, age-groups and gender. Death rates were calculated and given as rates of death per thousand children. Information on number of living children each year and stratified to age and gender was obtained from Statistics Iceland (statice.is).

The study period was from January 1st, 1971 until December 31st, 2018. The National causes of death register in Iceland, kept at the Directorate of Health, Iceland is maintained by qualified personnel. All deaths are registered and coded under Icelandic national identification numbers which were used to identify all deceased individuals. Classification of diseases was done using International Classification of Diseases ICD-8 during 1971–1981, ICD-9 during 1981–1996 and ICD-10 from 1996. If cause of death was classified as “other ill-defined and unspecified causes of mortality” (ICD 10: R99) by the register, hospital records, laboratory and post-mortem results were accessed by the authors.

Causes of death were categorised according to the following groups: perinatal causes, congenital diseases, cardiovascular diseases, malignancies, infections, neurological and degenerative diseases, other diseases, accidents, suicide and other causes [8]. Congenital malformations of the heart, nervous system and urinary tract were all grouped under congenital diseases with other congenital malformations. When a child with malignancy died, malignancy was registered as the cause of death even if a complication of the underlying disease or treatment was a strong contributing factor.

Children were categorised in age groups according to age at death, <1 year (infant), 1 to <5 years (under five), 5 to <13 years and 13 to <18 years of age.

Statistical analyses were done with R (ed 3.6.2) and R-studio (ed 1.2.5033) [9]. From The National Causes of Death register in Iceland and from population data from Statistics Iceland, death rate for each year, age groups and gender were calculated. This ratio was also calculated for the total mortality rate as well as for under five mortality rates. For analysing changes in death rates over the study period, Poisson regression (logarithmic transformed) was used with robust standard error. Two regression models were applied, one for all children 0–18 years old and another one for children under 5 years of age. The regression model for children of all ages was done with an interaction variable between genders. ANOVA was done to compare the results with and without that variable. To calculate changes in death rates and gender ratios within the groups of causes of death as well as changes within age groups, a Chi-squared test was used comparing the first decade (1971–1980) to the last one (2009–2018). Statistical significance was set at p<0.05 and a 95% confidence interval not crossing 1 for risk ratios.

The study was approved by the National Bioethics Committee (VSNb2019110034/03.01), The University Hospital’s research committee and the Directorate of Health in Iceland.

Results

The total number of children that died during the study period 1971–2018 was 2003, 1209 boys (60.4%) and 794 girls (39.6%). More than half of the children died before one year of age (1060, 53%), 57% of them were boys (599). Deceased children between one and five years of age were 285 (14% of total deaths, 58% boys), children between five and thirteen years old were 294 (15%, 63% boys) and 13 to 18 years were 364 (18%, 72% boys) (Fig 1). The death rate decreased significantly over the study period. For boys the ratio decreased from 1.5:1000 boys in 1971 to 0.18 in 2018 and for girls from 0.9 to 0.17:1000 girls in the same years (Table 1). The gender death ratio (boys:girls) was 1.5 for the whole period, declining from 1.6 in the first period to 1.1 in the last one. Boys were more likely to die during the whole period (RR: 1.45, CI: 1.33–1.59).

Fig 1. Mortality rate in Icelandic children according to age groups from January 1st, 1971 until December 31st 2018.

Fig 1

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Table 1. Causes of death in Icelandic children according to disease categories, gender and time periods from January 1st, 1971 until December 31st 2018.

Time period* 1971–1978 1979–1988 1989–1998 1999–2009 2009–2018 Total
Boys Girls Boys Girls Boys Girls Boys Girls Boys Girls Boys Girls
  (n = 425) (n = 248) (n = 320) (n = 197) (n = 238) (n = 172) (n = 132) (n = 96) (n = 94) (n = 81) (n = 1209) (n = 794)
Perinatal causes                        
  Total deaths 121 (28%) 84 (34%) 62 (19%) 52 (26%) 66 (28%) 44 (26%) 33 (25%) 26 (27%) 19 (20%) 18 (22%) 301 (25%) 224 (28%)
Mortality rate† 0,375 0,273 0,160 0,140 0,167 0,117 0,082 0,068 0,046 0,046 0,157 0,122
Accidents                        
  Traffic 49 (42%) 21 (60%) 52 (50%) 18 (62%) 31 (53%) 16 (62%) 15 (58%) 18 (86%) 10 (62%) 12 (75%) 157 (49%) 85 (67%)
Drowning 30 (26%) 2 (6%) 20 (19%) 4 (14%) 14 (24%) 5 (19%) 4 (15%) 1 (5%) 1 (6%) 2 (12.5%) 69 (22%) 14 (11%)
Other 37 (32%) 12 (34%) 31 (30%) 7 (24%) 14 (24%) 5 (19%) 7 (27%) 2 (9%) 5 (31%) 2 (12.5%) 94 (29%) 28 (22%)
  Total deaths 116 (27%) 35 (14%) 103 (32%) 29 (15%) 59 (25%) 26 (15%) 26 (20%) 21 (22%) 16 (17%) 16 (20%) 320 (26%) 127 (16%)
Mortality rate† 0,359 0,114 0,265 0,078 0,149 0,069 0,065 0,055 0,039 0,041 0,167 0,069
Congenital diseases                        
  Circulatory system 26 (40%) 21 (37%) 28 (39%) 21 (40%) 17 (45%) 14 (40%) 3 (21%) 5 (42%) 4 (36%) 5 (33%) 78 (39%) 66 (39%)
Nervous system 12 (18%) 13 (23%) 14 (19%) 8 (15%) 2 (5%) 4 (11%) 2 (14%) 2 (17%) 1 (9%) 6 (40%) 31 (15.5%) 33 (19%)
Other 27 (42%) 23 (40%) 30 (42%) 23 (44%) 19 (50%) 17 (49%) 9 (64%) 5 (42%) 6 (55%) 4 (27%) 91 (45.5%) 72 (42%)
  Total deaths 65 (15%) 57 (23%) 72 (22%) 52 (26%) 38 (16%) 35 (20%) 14 (11%) 12 (12%) 11 (12%) 15 (19%) 200 (17%) 171 (22%)
Mortality rate† 0,201 0,185 0,185 0,140 0,096 0,093 0,035 0,031 0,027 0,038 0,104 0,093
Infections                        
  Respiratory 23 (45%) 12 (40%) 4 (27%) 1 (6%) 5 (45%) 4 (33%) 1 (17%) 3 (38%) 1 (20%) 1 (33%) 34 (39%) 21 (30%)
Sepsis 15 (29%) 8 (27%) 2 (13%) 2 (12%) 2 (18%) 4 (33%) 0 (0%) 3 (38%) 3 (60%) 1 (33%) 22 (25%) 18 (26%)
Other 13 (25%) 10 (33%) 9 (60%) 13 (81%) 4 (36%) 4 (33%) 5 (83%) 2 (25%) 1 (20%) 1 (33%) 32 (36%) 30 (43%)
  Total deaths 51 (12%) 30 (12%) 15 (5%) 16 (8%) 11 (5%) 12 (7%) 6 (5%) 8 (8%) 5 (5%) 3 (4%) 88 (7%) 69 (9%)
Mortality rate† 0,158 0,098 0,039 0,043 0,028 0,032 0,015 0,021 0,012 0,008 0,046 0,038
Malignancies                        
  Central nervous system 5 (21%) 7 (41%) 3 (17%) 4 (36%) 2 (33%) 4 (44%) 5 (33%) 4 (44%) 4 (44%) 2 (50%) 20 (28%) 21 (42%)
Leukemia 9 (38%) 5 (29%) 9 (50%) 3 (27%) 3 (50%) 2 (22%) 2 (13%) 3 (33%) 2 (22%) 2 (50%) 25 (35%) 15 (30%)
Other 10 (42%) 5 (29%) 6 (33%) 4 (36%) 1 (17%) 3 (33%) 8 (53%) 2 (22%) 3 (33%) 0 (0%) 27 (38%) 14 (28%)
  Total deaths 24 (6%) 17 (7%) 18 (6%) 11 (6%) 6 (3%) 9 (5%) 15 (11%) 9 (9%) 9 (10%) 4 (5%) 72 (6%) 50 (6%)
Mortality rate† 0,074 0,055 0,046 0,030 0,015 0,024 0,037 0,023 0,022 0,010 0,038 0,027
Neurological and degenerative diseases                      
  Total deaths 10 (2%) 8 (3%) 8 (2%) 4 (2%) 12 (5%) 5 (3%) 9 (7%) 2 (2%) 9 (10%) 9 (11%) 48 (4%) 28 (4%)
Mortality rate† 0,031 0,026 0,021 0,011 0,030 0,013 0,022 0,005 0,022 0,023 0,025 0,015
Other diseases                        
  Total deaths 14 (3%) 11 (4%) 5 (2%) 6 (3%) 7 (3%) 6 (3%) 4 (3%) 7 (7%) 5 (5%) 4 (5%) 35 (3%) 34 (4%)
Mortality rate† 0,043 0,036 0,013 0,016 0,018 0,016 0,010 0,018 0,012 0,010 0,018 0,019
Suicide                        
  Total deaths 6 (1%) 1 (0%) 11 (3%) 0 (0%) 14 (6%) 6 (3%) 6 (5%) 1 (1%) 9 (10%) 2 (2%) 46 (4%) 10 (1%)
Mortality rate† 0,019 0,003 0,028 0,000 0,035 0,016 0,015 0,003 0,022 0,005 0,024 0,005
Cardiovascular diseases                        
  Total deaths 6 (1%) 2 (1%) 4 (1%) 5 (3%) 1 (0%) 4 (2%) 5 (4%) 2 (2%) 5 (5%) 1 (1%) 21 (2%) 14 (2%)
Mortality rate† 0,019 0,007 0,010 0,013 0,003 0,011 0,012 0,005 0,012 0,003 0,011 0,008
Other causes                        
  Total deaths 12 (3%) 3 (1%) 22 (7%) 22 (11%) 24 (10%) 25 (15%) 14 (11%) 8 (8%) 6 (6%) 9 (11%) 78 (6%) 67 (8%)
Mortality rate† 0,037 0,010 0,057 0,059 0,061 0,066 0,035 0,021 0,015 0,023 0,041 0,037
Total deaths 425 (100%) 248 (100%) 320 (100%) 197 (100%) 238 (100%) 172 (100%) 132 (100%) 96 (100%) 94 (100%) 81 (100%) 1209 (100%) 794 (100%)
Mortality rate† 1,316 0,806 0,824 0,532 0,601 0,456 0,329 0,249 0,230 0,207 0,630 0,433
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*From 1.jan 1971–31. dec 2018. †Per 1000 live births (0–18 years).

A significant decrease in death rate was seen for all age groups (p<0.0001) (Fig 1). The death rate was highest for under one year of age, being 5.1:1000 live born infants but declined from 10.5 in the first decade to 1.8 in the last decade.

Children under five years of age who died during the period were 1345 (67%), 57% of whom were boys (763). Under five mortality rates declined from 3.14 to 0.36:1000 over the study period, a reduction of 88.6%. These rates decreased from 3.5 to 0.4:1000 for boys and for girls from 2.8 to 0.32:1000. The gender ratio was 1.3 for the whole period, declining from 1.3 to 0.9.

The most common causes of death over the study period were perinatal causes or complications thereof (Table 1, Fig 2), accounting for 525 children (26%), almost all of whom died during the first year of life.

Fig 2. Number of deaths in Icelandic children according to disease categories from January 1st, 1971 until December 31st 2018.

Fig 2

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Over the study period, 447 children (22%) died in accidents, of which 72% were boys (320). Traffic accidents were most common, 242 (54%). The death rate caused by accidents was the highest for the age group 13-<18 years, 18.9:1000 children (Fig 2, Table 1). The gender ratio in accidents (boys:girls) was 3.42 (p<0.0001) in the first decade but 0.96 (p = 0.91) in the last decade. The death rate from accidents declined from 0.24:1000 children (n = 188) in the first decade to 0.04 (n = 32) in the last decade (p<0.0001).

The gender ratios are seen for all causes and four different categories in Fig 3.

Fig 3. Gender ratios for all causes of childhood deaths and four different categories in Iceland during 1971–2018.

Fig 3

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Congenital diseases were the cause of death in 371 children (18.5% 54% boys), 76% of them died during the first year of life (282). The death rate due to congenital diseases decreased from 0.2:1000 children in the first decade to 0.03:1000 children in the last decade (Table 1). Under five mortality rates due to congenital diseases decreased from 0.7 to 0.1:1000 children. Congenital heart diseases were the most common (39%, 144), followed by malformations of the nervous system (17%, 64) and the urinary tract (7%, 25).

When comparing the first decade to the last one, a significant decrease in death rate was observed for infections (p<0.0001) and malignancies (p<0.0001). A decrease in death rates, although not significant was found for neurological and degenerative diseases (76, 4%) and cardiovascular diseases (35, 2%) (Tables 1 and S1).

During the study period, 56 children (82% boys) committed suicide. The death rate due to suicide did not decline over the study period (p = 0.51).

In the category “Other causes” (145, 7%), sudden infant death accounted for 100 deaths (69%) in this group and avalanches caused 16 deaths (11%), of those 12 occurred in the same year in two different avalanches. Undefined causes of death were 22 (15% of this group, 1% of total) and violence caused seven deaths (5%).

Underlying, anonymised data is accessible at https://osf.io/jy2h8/.

Discussion

The main finding of this study was a striking decrease in death rates among children up to 18 years of age during the study period of almost fifty years. This was established for almost all causes of death and in all age groups. The trend appears to be consistently negative over the period.

The gender ratio clearly revealed higher risk of death for boys than girls, most obvious in the adolescent age group and more pronounced in the first decades of the study period. These ratios have been described by others [10,11]. This gender difference is less clear in under five mortality rates as has also been described by UNICEF in HIC [1]. In our study, a decline in male/female ratio was seen from 1.6 to 1.2 and deserves special attention. The reason may be due to behavioural differences as well as physiological, social and environmental factors. This is reflected in the higher death rate for boys due to accidents. The changes in gender ratios were clearly reflected in the decreasing death ratio caused by accidents among boys. These causes have been identified in several countries [8]. During the study period, several safety measures for accident prevention were implemented, especially regarding traffic safety. These safety measures as well as increased awareness are probably the main factors leading to the decreased childhood mortality due to accidents.

Under five mortality rates have been declining, especially in HIC according to WHO and UNICEF [1]. This is in accordance with our findings. In a recent report from WHO [1], the decrease in under five mortality rates in Europe and USA in 1990–2018 was 72% and 42% respectively. In our study this decline was 67% during the same period. Several factors contribute to this decline; improved prenatal health care and perinatal survival, infection control and progress in health care in general being the most obvious reasons [1,11]. Perinatal and neonatal deaths in Iceland have been substantially decreasing over the period and is currently among the lowest in Europe [12]. This obviously contributes to the improved survival in this age group.

The highest risk of mortality was in the age group less than one year of age followed by the oldest age group, 13 to <18 years. This is comparable to other studies in HIC [13,14]. The reason for the relative high death rate in the youngest group may be attributed to perinatal and neonatal events as well as congenital disease. In HIC, premature births have become more common, but the survival rate of premature babies has improved. This has also been found in Iceland [12]. Nevertheless, perinatal events may still cause some of these early deaths [2,14,15]. The causes of death in the oldest age group are most often related to long term illnesses, accidents or suicide.

Accidents were the second most common cause of death over the study period. An impressive decrease in deaths due to accidents, especially traffic accidents, was noted. The gender difference was particularly obvious in the first decade of the study but was almost equal in the final decade. Similar findings have been described in other Nordic and European countries [16,17]. Traffic accidents were the most common cause of accidents and accounted for more than half of the fatal accidents. Similar results for the youngest age groups have been reported from other Nordic countries [8]. The fact that boys are more prone to fatal accidents probably reflect gender differences in risk taking behaviour [7,10,11,18]. Although the number of fatal accidents in children are still too high, the rate has declined significantly. The reason for this is presumably higher risk awareness, better training and education of young drivers, improved traffic and car safety measures. Nevertheless, this still leaves room for improvement.

In our study, sixteen children lost their lives in avalanches. These children were classified separately as natural disaster rather than accidents as they are different in nature and harder to prevent or predict.

Congenital diseases make up for the third most common cause of death in our study, almost all occurring before the age of five and most were cardiac malformations. However, there was a substantial decline during the study period. This is in accordance with other findings, especially in countries where prenatal diagnosis of severe diseases is applied with a possibility of preparing for delivery of a baby with severe congenital malformations or termination of the pregnancy [19–22].

Death caused by infections declined significantly during the study period. This can be attributed to better diagnosis and improved antibiotic treatment as well as introduction of new vaccines in universal immunisations schedules. An earlier Icelandic study, describing death rate and causes of death during 1941–1975, revealed a substantial reduction of fatal infections in the first decade of that study, i.e. during increasingly widespread use of antibiotics [5]. The last measles epidemic in Iceland was in 1977 and immunisation coverage in Iceland is very high [23,24]. This has obviously contributed to declining incidence of fatal infections in Icelandic children [25–27]. This clearly underlines the success of immunisations and appropriate antibiotic usage.

A decline in deaths due to all categories of childhood malignancies was confirmed in our study. The Nordic Society of Pediatric Haematology and Oncology (NOPHO) reports incidence and treatment results of childhood malignancies in the Nordic countries [28]. The results in our study are in context with the findings from NOPHO and other HIC [8,28–30]. As the incidence of malignancies in children has not decreased, this success must be attributed to improved cancer treatment as well as better supportive care, including infection management.

The decline in deaths due to cardiovascular diseases and neurological disorders was not statistically significant. However, these are small numbers and results must be interpreted with caution.

The rate of children dying due to suicide did not change significantly during the study period. Similar findings have been reported by others [31,32] although other Nordic countries have reported a decreasing incidence [33]. As in other studies, boys are at much higher risk than girls [31–33]. This finding is of a grave concern. We recognise that determining whether a cause of death should be categorised as suicide is often difficult. The available data may not always be sufficient to distinguish between accidents (e.g. by drug overdose) and suicides. Suicide may therefore possibly be underestimated, especially in teenagers. However, heightened awareness of suicidal risk in teenagers is important for implementing preventive measures. This finding of no or slim reductions in death rates due to suicide in our study must be a strong encouragement to increase our awareness of the importance of mental health and psychological disorders in children in order to prevent these tragic events. A working group on suicide preventions issued by the Icelandic government released a program of action in 2018 with one of the goals being to ensure regular and evidence-based education on mental health in day-care centres, as well as primary and secondary schools. This, among other measures, will hopefully lead to better awareness and bring us one step closer to intervene and provide help to those who need it before it is too late.

A major strength of this study is the utilisation of nationwide and complete data source of causes of death over an almost fifty-year period. The Causes of Death register is kept at the Directorate of Health in Iceland. The register contains individual-level information from all death certificates and from autopsy reports if any autopsy was performed. Every death is coded manually by one specially trained personnel. Cases of uncertain cause of death were reviewed by a specially trained physician. In order to support the categorisation of underlying cause of death the Acme user interface programme is used to check manual coding. In addition, using the national identification numbers, we were able to find hospital records, laboratory results or post-mortem diagnosis in cases where the death certificate was unclear. We therefore maintain that the results are comprehensive and reflect nationwide childhood fatality rates with minimal errors of classifications.

Although we are confident of the accuracy of the data and the total number of cases reviewed exceeded two thousand, some of the categories are rather small. This is inevitable in a small country as Iceland. Nevertheless, our findings are in concordance with other published studies.

The results of this study show a clear reduction in death rates in children over an almost fifty-year period. This reduction is primarily attributed to a decrease in fatal accidents, but also to fewer deaths due to infections, perinatal or congenital disease and malignancies although a reduction in other causes was also noted. Our results should be encouraging to improve this outcome even further but also to increase emphasis on further preventing childhood mortality, including measures to detect mental and behavioural disorders which may lead to childhood suicide.

Supporting information

S1 Table. Causes of death in Icelandic children according to disease categories and sub-categories, gender and time periods from January 1st, 1971 until December 31st 2018.

(DOCX)

Click here for additional data file. (667.1KB, docx)

Acknowledgments

Benedikt Th Sigurjonsson at The University of Iceland contributed to the statistical analysis.

Data Availability

All relevant data are within the paper and its Supporting Information files. (personalized data is not available). In addition, the following has been added to the paper: Underlying, anonymized data is accessible at https://osf.io/jy2h8/.

Funding Statement

The authors received no specific funding for this work.

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Decision Letter 0

Amir Radfar

Transfer Alert

This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present.

11 Mar 2021

PONE-D-20-37583

Decreasing death rates and causes of death in Icelandic children - A longitudinal analysis

PLOS ONE

Dear Dr. Haraldsson,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Specifically :

  • Please elaborate your answer to all of the methodology section comments.

  • Please make sure the data underlying the findings in this manuscript are fully available.

Please submit your revised manuscript by Apr 10 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

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We look forward to receiving your revised manuscript.

Kind regards,

Amir Radfar, MD,MPH,MSc,DHSc

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: No

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: In the manuscript “Decreasing death rates and causes of death in Icelandic children—A longitudinal analysis”, the authors analyze a near 50 year dataset of mortality data to ascertain how death rates have changed over the study period. More specifically, the authors subset the data into sex and age groups, calculate mortality rates for various causes of death, and compare how and/or model how how rates have changed over the period. This is an interesting topic and use of public health data, as it has the potential to evaluate the affect of past public health policies. However, several major aspects of the current paper prevents me from recommending it for publication in this journal.

First, the trove of data the authors use is certainly worth analysis, and Figures 1 and 2 are interesting in and of themselves. However, the authors do not establish any sort of questions or hypotheses that they wish to answer or evaluate by doing the analysis. Thus, it feels more like a preliminary data exploration exercise than a mature, hypothesis driven analysis. There is an implicit hypothesis, captured in one of the statistical methods used (Chi-square), that the mortality rates at the end of the study period differ from those at the beginning. However, the lack of explicit questions or hypotheses results in a disappointingly short exploration of some of the more surprising results, such as the marginal increase in death rates due to suicide in recent decades. I would recommend re-examining the whole of the data, and more thoroughly considering which patterns are expected versus ones that are not, and thus suggest the need for re-evaluation of public health policy.

Second, the statistical methods chosen seem reasonable given the data, but how the data were processed, how rates were calculated, and how the statistical methods were applied to the data are very much unclear. I was also frequently uncertain whether the presented results pertained to the Chi-square or the Poisson regression analyses. Further, some of the results discussed in the text did not seem to align with the data in the tables. For example, in paragraph 1 of the results, it says “The death rate decreased significantly over the study period, for boys the ratio decreased from 1·5:1000 boys to 0·18 and for girls from 0·9 to 0·17:1000 girls Table I)”. However, the table shows different values for boys and girls in the first and last decade examined. I suppose this sentence was referring to the first and last years, but this isn't clear. And, the figure does not differentiate between girls and boys, so that doesn't help clarify things. To evaluate the rigor of a study, it is imperative that statistical methodologies are clearly explained, and that there is an unambiguous connection between analyses conducted and results presented.

Next, the results are presented in a “laundry-list” sort of manner that may be more appropriate for a journal of public health statistics. In addition, organization of the results section into subsections would significantly improve the readability of that section.

Lastly, the discussion section does discuss results in the context of other HIC, and some reasonable interpretations for how past interventions could have resulted in the patterns shown are made. However, it does not “determine specific risk factors and analyse possible interventions” as suggested in the introduction. The determination of risk factors and determining important contributors to mortality rates could be done via appropriate multivariate modeling. This is not done here, as I far as I can tell. In addition, the discussion of interventions for some causes of mortality, such as from accidents, are discussed only vaguely and lack citations.

Minor comments: there are no line numbers on the PDF of the submission. This makes it difficult to refer to specific sections. Therefore, I will refer to paragraphs of sections.

Abstract: The word “impressive” in inappropriate here, as it has an emotional connotation.

Findings section: what does “a less impressive reductions was seen in other causes” mean?

Introduction: the last paragraph is a single sentence. It should be split into several sentences for clarity.

Methods:

1st paragraph: causes of death weren't described in this study, they were compiled from records.

2nd paragraph: What is the ICD-8 through 10 system? Is it a relevant detail here?

1. In the case of “ill-defined and unspecified causes of mortality”, how were hospital records used to assign cause of death? Was this done in a consistent way by a qualified person? Is there uncertainty in this process, and what proportion of the data is made up of this classification

3rd paragraph:Were these categories determined using a previously published methodology, or was it done in an adhoc way?

5th paragraph: Since the entire study is about mortality rates, I would suggest explicitly writing how all rates were calculated(year, decade, group, sex, age), and which rates were used in what analysis.

Results:

1st paragraph: “Children aged 1-<5 years were 285 (14%, 58% boys), aged 5-<13 years old were 294 (15%, 63% boys) and 13-<18 years were 364 (18%, 72% boys) (Figure 1).” Is this referring to children who died?

2nd paragraph: “Boys were 41% more likely to die during the whole period (CI: 0·51-0·67).” How was this calculation made?

5th paragraph: This should be split into several paragraphs with different sections to guide the reader.

Overall: I would suggest additional tables and/or figures to help cross walk the age and gender information. As it is, you cannot tell at what age boys and girls diverge in terms of suicide-based mortality. But this is important to a prevention measures.

Figure 1: Why are there only three lines when 4 age classes are considered. Also, the age classes shown in the legend are the not the same as in the text.

Supplemental Table: This table appears to contain the same information as the Table 1 along with addition information. Why not just have 1 table?

Discussion:

2nd paragraph: “The gender ratio revealed clearly a higher risk for boys than girls, most obvious in the oldest age group and more pronounced in earlier periods”. This seems contradictory.

4th paragraph: “In HIC, the number of prenatal births has increased”; do you mean premature births?

Overall: there are several assertions made without citations or data. For example “The reason for this gender difference may be due to behavioural differences as well as physiological, social and environmental factors. The decreasing gender ratio is primarily due to less fatal accidents among boys, probably through increased awareness and accident prevention.” While speculations about mechanisms of sex-based mortality differences or intervention success have to be made here, they should be made based on literature-based sources.

Reviewer #2: This is an important study on the changes in death rates in children in Iceland. My comments are as follows

1. The manuscript is written in standard English but I do feel that some sentences are long or a little bit unclear and clarity could be improved throughout by a thorough edit.

2. Methods: Could 'cardio- vascular' just be 'cardiovascular'?

3. Methods: Could the authors provide a reference or further justification for why they grouped causes of death as they did?

4. Results: Could the authors be consistent when they provide number and when they provide per cent? Sometimes they provide both and sometimes they just provide per cent. For example, in the first sentence, both numbers and percentages are provide, while in the second, only percentages are provided.

5. Results: Paragraph 3. Sorry I may be misreading this, but I would have assumed the 95% CIs would be above 1 if boys were 41% more likely to die (1.59, 95% CI 1.51-1.67)? Could the authors put the RR with the CIs for clarity?

6. Results: I would prefer to see a p-value, rather than n.s. when the ratio is not significant.

7. Results/Discussion: Why are avalanches not grouped with accidents?

8. Discussion: In the second paragraph, the authors say the gender ratio declined from 1.8 to 1.2. In the results, it says it declined from 1.6 to 1.1. Which is correct?

9. Discussion: Second paragraph. The last sentence "This deserves special attention", leaves me asking 'why?' I would recommend the authors either delete or add more detail on why.

10. Discussion: Fourth paragraph. I got a little lost here. Weren't perinatal causes the most common cause of death? Could the authors clarify?

Reviewer #3: This manuscript presents interesting analyses of changes in death rates over time in Iceland. These analyses contain some valuable contributions, though I would suggest some changes to the analyses to make them more robust.

I also feel as though this manuscript could take the analyses further in the examples presented. Maybe this is just the epidemiologist in me, but, for instance, could the measles vaccination rates be included as a covariate in a model to determine if the rates are correlated with the declines in measles infections. For the decrease in accidents, maybe there were specific government campaigns to improving driving education or maybe just safer cars were released.

1. For the Poisson distribution, the mean and variance are the same parameter, i.e., the mean equals the variance. That can be a very poor assumption in regression models and I would strongly urge you to try a quasipossion or negative binomial model. Those distributions decouple the mean and variance and allow for the variance to be estimated independent of the mean.

2. My understanding is that you've modeled the rates. I would suggest trying to model the death counts instead of the rates with the population as an offset. This is a more natural way to model this, and you can obtain the death rates from the model and convert them to deaths per 1000.

3. I also wasn't sure why a Chi-squared test was used especially after you've been working with a model that is testing trends over time. You could utilize the model to estimate the changes from the start of the interval to the end, probably with contrast statements.

4. In the results, I would be a little more explicit about some of the sample sizes presented. The sentence about deaths from accidents is great, but it's hard to tell what the time frame is for the other diseases.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2021 Sep 30;16(9):e0257536. doi: 10.1371/journal.pone.0257536.r002

Author response to Decision Letter 0

1 Jun 2021

All comments by the reviewers have been addressed.

Underlying data has been made available online as stated in the manuscript

Table II has been removed.

Attachment

Submitted filename: PLOS-response to revieweres.docx

Click here for additional data file. (347.8KB, docx)

Decision Letter 1

Amir Radfar

23 Jun 2021

PONE-D-20-37583R1

Decreasing death rates and causes of death in Icelandic children - A longitudinal analysis

PLOS ONE

Dear Dr. Haraldsson,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Specifically ,please address all comments made by reviewer #1

Please submit your revised manuscript by Aug 07 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Amir Radfar, MD,MPH,MSc,DHSc

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #3: (No Response)

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #3: (No Response)

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #3: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #3: (No Response)

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have reasonably responded to most of my comments and have significantly improved their manuscript. However, there are still some import issues that need to be addressed before I can recommend this manuscript for publication.

INTRODUCTION

The end of the second paragraph and the last paragraphs are a bit confusing. The author’s state that the main hypothesis that childhood death rates are decreasing due to fewer fatal infections. But then the author’s say that the underlying hypothesis is that death rates are declining. I think that what the authors are aiming to say is that the data show that death rates have fallen over the previous 5 decades and it is a hypothesis is that these declines are primarily driven by decreases in fatal infections, childhood accidents, and neonatal mortality. If this is correct, this should be clarified.

METHODS

In the statistical analysis section, the authors say they have stated how rates were calculated, but they only say in the methods that “death rate for each year, age groups and gender were calculated”. In the results, it can be seen that rates are listed per 1000 children. However, providing a simple equation for rate calculation, and/or stating that they are rates of death per thousand children in the methods section would be helpful to clear up ambiguity.

RESULTS

There is still uncertainty about the Poisson regression model that was applied to the data. Was a separate regression model fit for each group, or was a single model used with age and gender groups as factors? Which factors were significant and which factors weren’t? If multiple models were applied, was there a correction for multiple p-values. These issues could be addressed by simply reporting the terms of the model used in the text. In addition, PLoSOne guidelines for regression analyses suggest that they should be included, at least as part of the supplementary data:

Regression analyses. Include the full results of any regression analysis performed as a supplementary file. Include all estimated regression coefficients, their standard error, p-values, and confidence intervals, as well as the measures of goodness of fit.

On the same topic, providing the details of all the Chi-square analyses performed would also be helpful to fully appreciate the scope of the analysis that the authors conducted.

DISCUSSION

The statement that “the decrease was continuous over the period” does not appear to be true. There is clear variation from year to year with increases in some groups occurring several years in a row (e.g. Figure 1, group 13-18, 1982-1987). However, the trend appears to be consistently negative over the period, which is what the Poisson regression (I think?) showed.

Did the authors quantify that “The decreasing gender ratio was in fact primarily driven by fewer fatal accidents among boys”? While it is mentioned in the results that there was a dramatic decrease in the boys:girls death ratio of accidents, and figure 3 is provided to show this, I don’t see any sort of quantification of the contribution of accidents, relative to other causes of death, to differences in boy:girl death ratios between the two decades of comparison. In addition, figure 3 is at a very low resolution, making the y-axis largely unreadable. Although I can see that accidents are the only cause of death for which male and female death rates (maybe counts?) do not obviously overlap, the y-axes are clearly on different scales. A quantification here would make the author’s argument on this point stronger.

In the sentence “The reason for the relative high death rate in the youngest group may be contributed to perinatal and neonatal events as well as congenital disease”, I think the authors might want to use the word “attributed” instead of “contributed”.

For the statement “Traffic accidents were the most common cause of accidents and accounted for more than half of the fatal accidents. In the younger age groups, most victims were pedestrians, but older children were more often car passengers”, I don’t see where this is shown, as the supplementary table is not stratified by age. Since there are no limits on the size of supplementary files, it seems reasonable to include this information if it is reported in the text. Also, is the implication here that older boys would have higher traffic mortality as the drivers of cars than girls? If so, that should be stated.

In the sentence “The available data may not always be sufficient to distinguish between accidents e.g. by drug overdose and suicides”, I believe that the authors need to add a parentheses: “…accidents (e.g., by drug overdose) and suicides”.

Reviewer #3: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2021 Sep 30;16(9):e0257536. doi: 10.1371/journal.pone.0257536.r004

Author response to Decision Letter 1

21 Aug 2021

All questions have been addressed in the file Decreasing death rates in children - Resp to reviewers II

Attachment

Submitted filename: Decreasing death rates in children - Resp to reviewers II.docx

Click here for additional data file. (23.3KB, docx)

Decision Letter 2

Amir Radfar

7 Sep 2021

Decreasing death rates and causes of death in Icelandic children - A longitudinal analysis

PONE-D-20-37583R2

Dear Dr. Haraldsson,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Acceptance letter

Amir Radfar

22 Sep 2021

PONE-D-20-37583R2

Decreasing death rates and causes of death in Icelandic children - A longitudinal analysis

Dear Dr. Haraldsson:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

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on behalf of

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Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Table. Causes of death in Icelandic children according to disease categories and sub-categories, gender and time periods from January 1st, 1971 until December 31st 2018.

    (DOCX)

    Click here for additional data file. (667.1KB, docx)
    Attachment

    Submitted filename: PLOS-response to revieweres.docx

    Click here for additional data file. (347.8KB, docx)
    Attachment

    Submitted filename: Decreasing death rates in children - Resp to reviewers II.docx

    Click here for additional data file. (23.3KB, docx)

    Data Availability Statement

    All relevant data are within the paper and its Supporting Information files. (personalized data is not available). In addition, the following has been added to the paper: Underlying, anonymized data is accessible at https://osf.io/jy2h8/.

    Articles from PLoS ONE are provided here courtesy of PLOS

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