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Abstract
Background The neonatal mortality rate is a main indicator of the health and development of a country. Having insight into the cause of neonatal deaths may be the first step to reducing it. This paper depicts the cause of newborn deaths in Iran.
Methods This cross-sectional study was performed on data from the national Iranian Maternal And Neonatal network to investigate all neonatal deaths in the country during the year 2019. The cause of death data were reported according to categories of birth weight, gestational age (GA), death time and place.
Results The main causes of the 9959 neonatal deaths during the study period were respiratory distress syndrome (RDS) (37%), malformation (21%), prematurity of <26 weeks (20%), others (12%), asphyxia (7%) and infection (3%). The major causes of neonatal mortality in delivery rooms were prematurity of <26 weeks and in the inpatient wards the RDS. By increasing the GA and birth weight towards term babies, the rate of RDS gets lower, while that of malformation gets higher.
Conclusions RDS was the main cause of neonatal mortality in Iran which is seen mainly in preterm babies. Prematurity of <26 weeks was another main cause. Thus, suggestions include reducing prematurity by preconception and pregnancy care and, on the other hand, improving the care of preterm infants in delivery rooms and inpatient wards.
- Infant
- Mortality
- Neonatology
Data availability statement
Data may be obtained from a third party and are not publicly available.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Causes of neonatal mortality have been studied in different places, and different causes have been pointed out as the major ones. The main causes of death may differ based on the situation.
WHAT THIS STUDY ADDS
This study reported the causes of neonatal mortality in Iran and investigated it based on birth weight, gestational age (GA), and time and place of death. Differences were observed between categories of birth weight and GA, and the time and place of death.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Findings of this study shed light on the major causes of newborn death in a developing country. Based on these results, the newborn health policy makers can prioritise the interventions to address the major causes and to get better results in the reduction of neonatal mortality.
Introduction
In the way towards the sustainable development goals, one main challenge is newborn health.1 Reducing neonatal mortality is the main part of reducing the mortality of children under 5 years old.2 The humans are most sensitive and vulnerable in the neonatal period and have the highest risk of death.3 Neonatal mortality is also an indicator of health system assessment for the countries.4 5
Most neonatal deaths (75%) occur in the first week of life, and annually, about one million neonatal deaths occur in the first 24 hours of life.6 According to WHO, about 2.5 million newborns died in 2018 during the neonatal period.6 Considering the importance of the subject, WHO and UNICEF provided the ENAP guide for reducing preventable neonatal deaths.7
Having knowledge on the cause of death and the major causes can be helpful in developing proper intervention measures.8 In prioritising the interventions, the major causes of death should be taken into account for easy, fast and inexpensive achievement of the goals.1 Since a considerable share of neonatal deaths is preventable, proper and timely interventions are important.3 Having accurate data about neonatal mortality and the cause of death data, we can be able to develop and execute proper plans.4 7
To the best of our knowledge and as the search results show, the previous studies on the cause of neonatal mortality in Iran are hospital based and with limited sample size.8 9 Thus, in this study, we investigated the cause of death for all neonatal mortalities of the country. The comprehensive picture that comes from the findings of the study can be used to develop interventions and to make evidence-informed decisions at the national level. This paper also describes the system by which the cause of neonatal mortality is determined in Iran. The system of determining the cause of death, its findings and the interpretation of national data can also be helpful for other countries.
Methods
This descriptive study was conducted cross-sectionally at the national level. The study period was 1 year: 21 March 2019 to 19 March 2020 which is beginning till the end of a year in the local Shamsi calendar. The study population was all babies born in Iran. No sampling was performed, and thus all newborns were counted as census. All babies born in hospitals in Iran were eligible to be included in the study, including those with other nationalities. Neonatal death was defined by WHO as those live-born babies babies with GA of 22 week and more who had died before 28 days of life.
The required data were obtained from the Iranian Maternal And Neonatal (IMAN) network. It is a national network in which all births, hospitalisations and deaths of newborns are recorded from all around the country. The data entry occurs in delivery rooms and inpatient wards of the hospitals, and then the network provides several reports for programmers and policy makers at local, regional and national levels.
A staircase system exists in Iran to determine the cause of neonatal death. The system is developed by a board of experts at the national level. It is simple and easy to use so that for determining the cause of death of a newborn, the questions are asked from top to down, and wherever you got a ‘Yes’, that is the cause of death. When you get a ‘Yes’ answer, you stop asking further questions; otherwise, you keep asking the next questions. For example, if a particular newborn had respiratory problems (question 4) and infection (question 5), the cause of death should be determined as RDS based on question 4, and thus, question 5 should be ignored. Figure 1 shows the flowchart of determining the cause of neonatal mortality in Iran. This system was announced by the Ministry of Health and Medical Education (MOHME) and is in use all around the country.
Flowchart of determining the cause of neonatal death in Iran. HIE, hypoxic ischaemic encephalopathy.
Congenital anomaly: if there was a fatal anomaly like diaphragmatic hernia, tracheoesophageal fistula, intestinal obstruction and myelomeningocele. Minor and non-fatal anomalies such as cleft lip and polydactyly should be ignored.
Extreme prematurity (<26 weeks): if a baby has no fatal anomaly and the gestational age (GA) is below 26 weeks, then the cause of death is extreme prematurity <26 weeks.
Asphyxia: if the answer to questions 1 and 2 is ‘No’, and the baby has the criteria of being categorised as hypoxic ischaemic encephalopathy (HIE), then the causes of death is asphyxia.
Respiratory distress syndrome (RDS): if the baby has no fatal anomaly or symptoms of HIE, and the GA is 26 weeks and above, and the baby suffers from respiratory problems, then the cause of death should be determined as RDS. This is in spite that the baby died due to pulmonary haemorrhage, pneumothorax or other consequences of the RDS.
Infection (sepsis): if the answer to all questions 1–4 is ‘No’, and the baby had an infection, then the cause of death is infection. Criteria for having infection are clinical signs of infection with positive culture or with laboratory findings suggesting an infection.
Others: if the answer to all questions 1–5 is ‘No’, the cause of death is others. This category includes:
Pneumothorax: if pneumothorax exists without respiratory problems
Pulmonary haemorrhage: if it exists without respiratory problems
Intraventricular haemorrhage
Disseminated intravascular coagulation
Hydrops fetalis
Metabolic disorders
None of the mentioned categories
The variables of interest in this study were the cause of death, place of death (delivery/operation room and inpatient wards), birth weight and GA. Data were entered into SPSS V.19 software and tested with a significant level of 0.05. The χ2 test was used for the qualitative variables. Results were explained by descriptive statistics of frequency and relative frequency for qualitative data. MS Excel 2019 software was used to draw the charts. Since all the variables of interest are mandatory at the IMAN, there were no missing data.
Research ethics approval
Since no human subjects were involved in this study and the aggregated data were used, informed consent was not applicable. No ethical approval was obtained. The permission to access the data was obtained from the MOHME.
Results
According to the IMAN network, a total of 9959 neonatal deaths occurred in hospitals in Iran during the study course. Table 1 shows some characteristics of these cases. About 57% of the deaths occurred in newborns with a birth weight of <1500 g. Similarly, about 59% of the deaths occurred in newborns with GA of <32 completed weeks. In terms of place of residence, three-fourths of all neonatal deaths in the country were in the urban population.
Characteristics of the study subjects: neonatal mortality in Iran in 2019
The data on the cause of all neonatal deaths are depicted in figure 2. As seen in this figure, the major cause of neonatal deaths in Iran was RDS which stands for 37% of total mortality. The next major causes were malformation (21%) and extreme prematurity of <26 weeks (20%). These three categories equal to 78% of the total neonatal mortalities in the country.
Causes of neonatal mortality in Iran according to IMAN, 2019.
Table 2 compares the cause of neonatal mortality in the delivery/operation room and the inpatient wards. It shows that the causes of death in the delivery/operation room differ from those of inpatient wards, and this difference is statistically significant (p<0.001). The main causes of death in delivery/operation rooms were extreme prematurity (GA <26 weeks) and RDS in the inpatient wards. Table 2 also shows the causes of neonatal deaths based on the time of death. Among the babies who died in the early neonatal period (first week of life), the major causes were extreme prematurity (GA <26 weeks) (34%), RDS (31%) and malformation (20%). But among the babies who died in the late neonatal period (day 8–28 of life), the major causes of death were RDS (45%), malformation (29%) and extreme prematurity (GA <26 weeks) (11%). Infection is responsible for 1% of neonatal deaths in the first week and 4% in the second to fourth weeks.
Comparison of causes of death in Iranian newborns in 2019 in terms of place and time of death
The cause of neonatal deaths was also assessed in terms of GA, and the results showed it was different in various GA groups (p<0.001). The major causes of death in term newborns were malformation while RDS and malformation among 32–36-week babies and RDS and extreme prematurity (GA <26 weeks) in babies below 32 weeks (table 3).
Comparison of causes of death in Iranian newborns in 2019 in terms of birth weight and gestational age and the region of residence
Table 3 compares the causes of neonatal mortality based on birth weight groups. The table shows that the causes of death in birth weight groups are similar to those of GA groups (p<0.001). The causes of death of newborns with GA of ≥37 weeks were similar to newborns with a birth weight of ≥2500 g. Causes of deaths of newborns with GA of 32–36 weeks were similar to those with a birth weight of 1500–2500 g. And the causes of neonatal deaths among babies with GA of <32 weeks were similar to those with a birth weight of <1500 g. In contrast to GA groups, the causes of death were different in groups of birth weight (p<0.001). The major causes of death among babies with a birth weight of >2500 g were malformation, RDS and malformation in newborns with a birth weight of 1500–2500 g and RDS and extreme prematurity (GA <26 weeks) among newborns with a birth weight below 1500 g.
Table 3 also compares the causes of neonatal mortality in provinces that have a neonatal mortality rate (NMR) above the country average with those with NMR near and below the country average. It can be seen that the major causes of death are similar in all categories, but the rate of each cause differs. In general, in provinces that have lower NMR, the rate of RDS is lower, and the rate of extreme prematurity is higher (p=0.02).
Discussion
This study was conducted to investigate the causes of neonatal deaths in Iran and assessed the cause of about 10 000 neonatal deaths during a 1-year course. Three major causes of death of Iranian newborns during the study period were RDS (37%), congenital malformation (21%) and extreme prematurity (<26 weeks) (20%). Prevention, identification, and timely intervention and management can reduce mortality and morbidity of newborns.10
Nearly 60% of all neonatal mortalities in the country had occurred in newborns with a birth weight of <1500 g and/or GA of <32 weeks (table 1). This shows the role of prematurity and low birth weight in neonatal mortality. In line with this result is the finding that RDS and extreme prematurity of <26 weeks are among the major causes of death (figure 2). In general, the major cause of neonatal mortality in Iran was RDS. Previous studies have shown that RDS is related to prematurity.11 The findings of our study also showed that the RDS was considerable in newborns with GA below 37 weeks (table 3). Thus, the main intervention for reducing neonatal mortality due to RDS would be reducing prematurity.12 Prepregnancy care has a significant role in reducing premature birth.13 So, extending the coverage and improving the quality of prepregnancy care can be a priority in Iran to reduce neonatal mortality. According to the statistics of WHO, the coverage of pregnancy care in Iran is 96.9%,14 but it seems that there are some problems in the coverage of prepregnancy care. A study in the north of Iran reported the full coverage of prepregnancy care to be 32.7% in 2017.15 Thus, we emphasised on prepregnancy care. On the other hand, since 99% of childbirths in Iran take place in health facilities (2020),16 a proper use of antenatal corticosteroids in preterm deliveries12 and timely administration of surfactant in preterm babies14 can help lower the respiratory problems in these newborns. The antenatal corticosteroids also increase the survival of the newborns.15 A proper use of this medication according to defined indications can prevent RDS and thus prevent the death of the newborn due to RDS.14 Production of a domestic pulmonary surfactant named Beraksurf in Iran (2019)17 assures that all hospitals have access to a sufficient amount of this medication. Other studies have recommended the promotion of non-invasive mechanical ventilation and limiting the invasive one so this intervention can be helpful in reducing neonatal deaths due to RDS.16
The next major cause of neonatal deaths in Iran was congenital malformation. Previous studies have shown that the causes of death differ in various countries. comparison of the findings of this study in Europe and in other countries17 18 showed a lower rate of malformation in neonatal mortality in Iran while about 90% of congenital malformations occur in low-income and middle-income countries.19 Congenital malformation is also reported to be correlated with low birth weight,19 and the use of folic acid before pregnancy can reduce the risk of malformation.20 However, the consumption of folic acid in some areas may not be optimal.15 Providing access to tests and sonographic screenings can be helpful in this regard by identifying the problematic pregnancies and then the timely termination of it.21 In countries with a higher rate of neonatal mortality, the major cause of death is infection (including sepsis/pneumonia, tetanus and diarrhoea), and as we look at countries with lower NMR, the rate of prematurity and malformation becomes lower.22
Almost 99% of the global neonatal mortality occurs in developing countries, and this is considerable.23 Neonatal mortality in African countries was related to RDS, perinatal asphyxia, meconium aspiration syndrome and infection.24 In Pakistan with an NMR of 47.3 neonatal deaths per 1000 live births, the causes of death consist of prematurity, asphyxia and infection.25 Table 3 shows that in provinces with lower NMR, the rate of the congenital anomalies is a little bit higher, the rate of RDS and asphyxia is much lower and the rate of extreme prematurity of <26 weeks is higher compared with provinces with higher NMR. It can be concluded that in areas with lower NMR, there are few preventable neonatal deaths, and thus, the rate of extreme prematurity of <26 weeks and congenital anomalies, which are non-preventable deaths, gets higher.
The third major cause of neonatal mortality in Iran was extreme prematurity (GA <26 weeks). Premature babies are facing several problems, and the NMR of these newborns is very high.26 Literature suggests that the risk of neonatal mortality in GA below 26 weeks is much higher than those with GA of ≥26 weeks. A study in China showed that the rate of survival and living without complications was 8% in infants with GA of 25 weeks and 60% in those with GA of 26 weeks.15 Generally, the survival rate is correlated with GA, so the lower the GA, the lower the chance of survival.12 On the other hand, those preterm babies who survive spend a long time in a hospital and make huge costs for their family and in general for the health system.26 Numerous studies have reported lower socioeconomic status as a risk factor of prematurity,27 so on a vicious cycle, the prematurity and lower socioeconomic status of the family enforce each other,14 and thus, it can be said that prematurity is seen more in poorer families and pulls them more into poverty. Having preterm delivery also causes mental problems in families28 and makes them struggle with anxiety and depression.29 Furthermore, when we discuss extremely preterm infants, an important issue to keep in mind beyond mortality is morbidity. Because <26-week infants are very sensitive, if they survive, they may have several morbidities that affect their quality of life. Thus, the best intervention measure in this regard is the prevention of preterm birth via quality healthcare prior to pregnancy and during the pregnancy.
More than half (55%) of the neonatal deaths that occurred in delivery/caesarean operation rooms were due to extreme prematurity (GA<26 weeks), and 16% were due to congenital malformation. So, it is hard to prevent these deaths in delivery/caesarean rooms of the hospital, and their prevention should be searched outside the hospital by preventing preterm birth. On the other hand, are the neonatal deaths in inpatient wards. The principal cause of newborn deaths in inpatient wards was the RDS which can be highly reduced by available interventions and proper management of respiratory problems. Thus, the Iranian neonatal intensive care units should focus on improving the respiratory care of newborns.
The investigation of the cause of neonatal mortality by GA and birth weight showed that there was a similarity between causes of death in categories of birth weight and GA. So by increasing the birth weight and GA, the rate of prematurity and RDS is lower, and the rate of malformation is higher. In terms of the time of death, the major cause of early neonatal deaths was the extreme prematurity (<26 weeks), but in late neonatal mortalities, the main causes were RDS and malformation.
Figure 2 shows that ‘others’ is reported as the cause of death in 12% of neonatal mortalities. Detailed data of this category and its subcategories are qualitative (text data), and it is hard to analyse and report them in this paper. Since the data are available for several years, it can be used to modify the causation system or to make subcategories for the ‘others’. One possible reason for a high number of ‘others’ may be insufficient training of the personnel on how to use the causation system. So, providing additional training may be considered as an option. Investigating GA and the place of death (delivery room or inpatient ward) may also provide extra details for intervention to reduce the ‘others’ category.
Table 3 compares the causes of death according to the NMR categories (below country average, near country average and above country average). It showed that the rate of RDS is lower in provinces with lower NMR and higher in provinces with higher NMR. In contrast, the rate of extreme prematurity (<26 weeks) was higher in provinces with lower NMR and lower in provinces with higher NMR. The possible reason for this difference might be that those provinces with lower NMR have been successful in reducing neonatal mortality of the RDS and other provinces have not been yet. An application of this finding could be that, in order to lessen the NMR, the provinces with lower NMR should pay attention to the survival of the extremely preterm babies besides the RDS. On the contrary, provinces with higher NMR, because the rate of RDS is higher and also because saving infants with RDS is clinically easier than saving infants of <26 weeks of gestation, should focus on improving the respiratory care to elevate the survival of those infants.
Limitations
There were 111 out-of-hospital neonatal deaths in Iran during the study period which equal to 1% of total neonatal mortality in the country. The causes of these deaths are not discussed in this paper. Yet, investigating nearly 10 000 deaths which is almost all neonatal deaths in the country seems sufficient. Another issue to be mentioned is that this paper discussed the cause of neonatal deaths, but the mortality rates in the studied subcategories are different and may be subject for further studies.
Conclusion
Most neonatal mortalities in Iran were due to RDS; thus, efforts to decline neonatal mortality should be focused on reducing prematurity through improving the quality of prepregnancy and pregnancy care, promoting proper use of antenatal corticosteroids, timely administration of surfactant and promoting non-invasive mechanical ventilation. The next major cause of neonatal death was congenital malformation which is, to some extent, preventable by dietary supplements such as folic acid before pregnancy and then, to some extent, is identifiable by screening during pregnancy. In general, expanding the coverage and improving the quality of preconception and pregnancy care might be helpful for Iran, and the probable gains include decreased incidence of anomalies, decreased incidence of prematurity and decreased respiratory problems of newborns which all contribute to decreased neonatal mortality of the country. Improving antenatal care as well as childbirth care and postnatal care is necessary to synergise each other.
Data availability statement
Data may be obtained from a third party and are not publicly available.
Ethics statements
Patient consent for publication
Ethics approval
Not applicable.
References
Footnotes
Contributors Study conception and design: AH, MH, AD. Study supervision: AH. Data collection and process: MT, RV. Analysis and interpretation: AD, SG-F. Literature review and writing of the first draft: LA, AD. Critical review of the draft: all authors. Final approval for publication: all authors.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.