Early neonatal deaths with perinatal asphyxia in very low birth weight Brazilian infants

Abstract

Objective:

The objective of this study was to assess the frequency of early deaths associated with birth asphyxia of very low birth weight infants between 2005 and 2010, in Brazil.

Study Design:

This population study enrolled all live births with birth weight from 400 to 1499 g, gestational age ⩾22 weeks, without malformations that died up to 6 days after birth with perinatal asphyxia. Asphyxia was defined if intrauterine hypoxia, asphyxia at birth or meconium aspiration syndrome were written in any line of the death certificate. Active search was carried out in 27 Brazilian federative units.

Result:

For every 1000 live births of very low birth weight infants without congenital malformations, 40.25 and 32.38 died with birth asphyxia in the first week after birth, respectively, in 2005 and 2010 (P<0.001). The contribution of birth asphyxia to early neonatal death of these infants was approximately 10 to 12% all study years.

Conclusion:

Reduction of birth asphyxia in very low birth weight infants is essential to reducing neonatal mortality in Brazil.

Introduction

The Millennium Development Goal 4 envisioned a two-third reduction in the global mortality of children under 5 years of age between 1990 and 2015.¹ The most recent estimate of the performance of several countries in meeting this goal indicates that mortality in children under 5 years of age decreased by 49% between 1990 and 2013, with 6.3 million deaths still occurring worldwide. It has been suggested that the established goal was not met mainly because of a slower reduction in neonatal mortality compared with other age groups: the global neonatal mortality rate decreased by only 40% between 1990 and 2013.^{2, 3} Deaths on the day of birth and within the first week of life correspond to 36% and 73%, respectively, of the 2.8 million neonatal deaths that occurred worldwide in 2013.² Birth asphyxia and prematurity are the leading causes of early neonatal deaths, and both conditions can be reduced with therapeutic interventions.^{4, 5}

In 2012, Brazil ranked tenth among the countries with the highest number of preterm births and sixteenth in the number of deaths resulting from preterm birth complications.⁶ Approximately three million children are born per year in Brazil, with 45 000 of these with gestational age of less than 32 weeks and 40 000 with a birth weight less than 1500 g. Considering only the basic cause of deaths between 0 and 6 days of life in infants with birth weights less than 1500 g in 2013, intrauterine hypoxia and birth asphyxia were responsible for 5.4% of them.⁷ However, these data do not consider the overall contribution of birth asphyxia to the early neonatal deaths among the very low birth weight infants. In addition, there are no studies focused on the epidemiological data of newborns who present both prematurity and birth asphyxia, which are the two most important conditions associated with early neonatal deaths.

Accordingly, the present study aimed to assess the frequency and the primary epidemiological characteristics of early deaths associated with birth hypoxia/asphyxia of very low birth weight infants between 2005 and 2010 in Brazil.

Methods

This is a population-based study of all live births of infants weighing between 400 and 1499 g with a gestational age greater than or equal to 22 weeks who died with birth asphyxia up to 168 h after birth from 1 January 2005 to 31 December 2010 in Brazil. Data were obtained from each Brazilian federative unit. The project was approved by the Research Ethics Committee of Federal University of São Paulo, which was the leading center for this project.

The deaths associated with the presence of birth asphyxia included in the study were reported in any line of the death certificate as any of the following according to the International Classification of Diseases—10th Revision (ICD 10): P20.0—intrauterine hypoxia diagnosed before the onset of labor; P20.1—intrauterine hypoxia diagnosed during labor and delivery; P20.9—intrauterine hypoxia, unspecified; P21.0—severe birth asphyxia; P21.1—mild or moderate birth asphyxia; P21.9—birth asphyxia, unspecified; or P24.0—neonatal aspiration of meconium.⁸

This study did not include deaths caused by neonatal aspiration of secretions other than meconium, deaths described as neonatal cerebral depression or fetal deaths. The analysis excluded all newborns with a congenital malformation reported in any line of the death certificate.

The data were obtained from the State Health Departments of the 26 Brazilian states and from the Data Analysis System State Foundation (Fundação Sistema Estadual de Análise de Dados) for the state of São Paulo. The analyzed variables were compiled from electronic files and/or the original death certificates from each federative unit and were collected in files without identification of the patients who died or their mothers.

The characteristics of the death included the following: death occurring in the same municipality where the mother lived, the institution, time of death (night: 7 pm to 7 am) and age at death. Also, maternal and neonatal demographic data were recorded.

Each death was entered by two independent professionals into an electronic file that was specifically created for the study. The following yearly rates were calculated: (i) number of early neonatal deaths found in the study per total number of very low birth weight live births; (ii) number of early neonatal deaths found in the study per total number of early neonatal deaths. The denominators were obtained at DATASUS (www.datasus.gov.br), a national open-access public health system database maintained by the Brazilian Ministry of Health.⁷ Such frequencies were analyzed for the country as a whole and for each of the five regions of Brazil. Subsequently, the death, maternal and neonatal characteristics were compared over the years of the study.

All comparisons used descriptive statistical analysis with chi-square test for trend with SPSS software (IBM SPSS Statistics for Windows, Version 21.0. IBM Corp, Armonk, NY, USA).

Results

This study found 27 800 deaths associated with birth asphyxia between 2005 and 2010 in Brazil, of which 25033 (90%) did not have any congenital malformations. Of this group, 2892 (12%) did not have gestational age and birth weight data. Among the 22 141 deaths with the required information, 7082 (32%) had a gestational age ⩾22 weeks and a birth weight of 400 to 1499 g.

The rates of early neonatal deaths associated with birth asphyxia per 1000 live births of very low birth weight infants without congenital malformations decreased from 40.25 in 2005 to 32.38 in 2010, in Brazil (P<0.001). This reduction was significant in the Northeast (P<0.001), Southeast (P<0.001) and South (P=0.002) regions of the country (Figure 1).

Figure 1

Rate of early neonatal deaths associated with birth asphyxia per thousand live births with birth weight of 400 to 1499 g and without malformations according to year of death and region of Brazil.

The ratios of early neonatal deaths associated with birth asphyxia in relation to the total early neonatal deaths of very low birth weight infants without congenital malformations according to the Brazilian regions and year of occurrence are shown in Figure 2. Early neonatal deaths associated with birth asphyxia accounted for 10 to 12% of the mortality of very low birth weight infants in Brazil in all the years analyzed. A decrease in this ratio was observed in Northeast Brazil: from 13.37% in 2005 to 10.02% in 2010 (P=0.001).

Figure 2

Proportion of early neonatal deaths associated with birth asphyxia in relation to total early neonatal deaths of infants with birth weight of 400 to 1499 g and without malformations according to year of death and region of Brazil.

In Brazil, 28.3% of infants without congenital malformations who died between 0 and 6 days after birth owing to birth asphyxia had a birth weight less than 1500 g (Table 1). The chance that an infant who died from 0 to 6 days after birth in the country owing to birth asphyxia of being a very low birth weight neonate was 22% greater in 2010 than in 2005 (P<0.001).

Table 1 Proportion of early neonatal deaths with very low birth weight and without congenital anomalies associated with perinatal asphyxia by Brazilian regions and by year of occurrence

Among the 7082 deaths analyzed, 28% of the mothers were less than 20 years of age (mean 25±7 years); 46% of them had fewer than 8 years of education, and 62% were housewives; 52% of the mothers were primiparous, while 15% had multiple births; furthermore, 30% of the mothers delivered their child by cesarean section. The neonatal characteristics were as follows: 58% of the infants were male; 61% were born at a gestational age of 22 to 27 weeks, and 27% were born at 28 to 31 weeks; 30% had a birth weight ⩾1000 g, with a mean birth weight of 851±282 g. Among the deaths, 44% occurred in the state capital cities, but in half of these, the mothers had their residence in the countryside; 77% occurred in federal, state, municipal or charitable public hospitals that provide care within the public system held by the Unified Health System (Sistema Único de Saúde—SUS), and 73% occurred within 24 h after birth. The characteristics of the 7082 very low birth weight infants without malformations who had an early neonatal death associated with perinatal asphyxia according to year of the death are shown in Table 2.

Table 2 Characteristics of the 7082 very low birth weight infants without malformations that had an early neonatal death associated with perinatal asphyxia according to year of death

Discussion

This time series indicates that, for every 1000 very low birth weight live births without congenital malformations, 30 to 40 infants die with birth asphyxia in the first week after birth. These values decreased from 40.25 in 2005 to 32.38 per 1000 live births in 2010. The contribution of birth asphyxia to the early neonatal death of these infants was approximately 10 to 12%. very low weight infants represent 28% of patients who die 0 to 6 days after birth with asphyxia.

The majority of the investigations on contributors to early neonatal mortality use prematurity and birth asphyxia as independent variables, and therefore, these studies do not reveal how many of the premature infants developed severe morbidity or died owing to conditions associated with hypoxia or birth asphyxia.^{9, 10, 11, 12} In fact, the comparisons are even harder because of the various definitions used to characterize prematurity and birth asphyxia. The present study used a birth weight less than 1500 g in addition to the gestational age, which was available for 97% of the cases. However, because Brazilian death certificates used gestational age ranges until 2011, these data could not be further analyzed. The term ‘birth asphyxia’ is inaccurate¹⁰ and broadly defined by the World Health Organization as the failure to initiate or maintain regular breathing at birth.¹³ This definition is difficult to apply in the population of premature infants, especially those born at less than 32 weeks of pregnancy, in whom the difficulty in breathing that is observed in the transition to the extrauterine environment is not synonymous with hypoxic and/or ischemic injury during the peripartum period.

The contribution of birth asphyxia to early neonatal mortality of very low birth weight infants remained relatively constant in the five regions and in the country as a whole; however, there was a reduction of approximately 25% in the number of these deaths over the 6 years evaluated. The main factors responsible for the improvement of maternal and child health indicators in Brazil in the past 20 to 30 years include social development, with a reduction in poverty, a higher educational level among the women, urbanization, a reduction in fertility rates and universal access to health care, in addition to interventions not specifically associated with health, such as income transfer programs, the distribution of water and the sewage network.^{14, 15, 16}

During the 6 years of this study, there was a change in the characteristics of the neonatal deaths evaluated: the maternal educational level and the paid work outside home progressively increased; the rate of cesarean sections increased over the years; in addition, the occurrence of deaths in private hospitals and outside of the state capital cities also increased. In all the analyzed years, at least 70% of the deaths of very low birth weight infants without malformations associated with birth asphyxia happened on the first day after birth. These findings are in agreement with the ‘Birth in Brazil Survey’, that assessed a cohort of 23 940 postpartum women in 2011 to 2012, and showed that approximately 50% of the very low birth weight infants born in hospitals without a neonatal intensive care unit died. These data indicate problems in the organization of the perinatal care system, such as the journey of a pregnant woman in labor to find a hospital vacancy and giving birth in inadequate places.¹⁶

It is estimated that proper care by the health-care professionals during labor can reduce the neonatal mortality rates by 20 to 30%, while the use of resuscitation techniques results in an additional reduction of 5 to 20% in these rates, which can reduce neonatal deaths caused by birth asphyxia by up to 45%.¹⁷ According to Lawn et al.,^{10, 18, 19} a qualification in neonatal resuscitation by the health-care professionals who provide care during labor is a central strategy for reducing neonatal mortality. In this context, the specific impact of the Neonatal Resuscitation Program of the Brazilian Society of Paediatrics is difficult to measure. However, the training of more than 60 000 health-care professionals who work in the delivery rooms throughout Brazil according to guidelines based on the best available evidence²⁰ updated every 5 years and presented in an organized manner²¹ by a network of more than 600 instructors in all the Brazilian states since 1994, may have contributed to the reduction in birth asphyxia associated with early neonatal mortality in very low birth weight infants observed in this temporal series.

Completeness and accuracy of vital statistical databases are major issues in epidemiological research. Therefore, the main limitation of this study is that the data were obtained from information provided by physicians on the death certificates, with a likely underreporting.^{22, 23} Nevertheless, it provides, for the first time, a national overview of the large contribution of birth asphyxia to the early neonatal mortality rate of very low weight infants without congenital malformations. This study carefully excluded the unavoidable deaths, as well as the deaths of patients with birth weights less than 400 g and/or gestational ages of less than 22 weeks.

Conclusions

Although Brazil reached in 2011 the goal of reducing by two-thirds the mortality of children under 5 years of age between 1990 and 2015,²⁴ the neonatal mortality rates in the country are still high. The present study indicates that the reduction of birth asphyxia in preterm infants, especially those with very low birth weight, is an important step to decrease neonatal mortality.