1. Background
Neonatal period is a critical time for infant survival. Fetal life as the main period of human development is a continuous period potentially influenced by various genetic, environmental, and social factors (1). In this period, many physiological adaptation processes necessary for extra-uterine life are formed. Thus, the fetus is very vulnerable with high rates of mortality and morbidity. Neonatal mortality rate is often used as a standard for the development of health care systems as well as achieving optimal educational and social conditions (2, 3). Neonatal mortality rate is directly associated with high risk pregnancy and therefore the major reasons for neonatal death can be revealed in relation to complications of risky pregnancy including prematurity, intrauterine growth retardation, congenital abnormalities and other disabilities (3-5).
Every year more than four million neonates die worldwide and more than ten thousand deaths occur in the first day of life (6). Almost all cases of deaths occur in low-income or middle-income countries (7). Neonatal mortality is largely preventable and has been considerably reduced in developed countries using proper techniques and appropriate preventive approaches (8-10). Therefore, in addition to determining the rate of infant mortality, identifying factors associated with neonatal death may lead to the prevention of life-threatening neonatal events (11). In fact, preventive health education, prenatal cares, nutritional planning, social supports, identifying potential risk factors and obstetric cares can effectively reduce early neonatal death in neonatal period (12). In this context, prematurity has a major role and its proper management results in increasing infant survival (13). About 15 million infants are born preterm each year worldwide and the incidence is rising (14). In the United State, prematurity causes approximately one third of infant deaths (15).
Unfortunately, we are still far from international standards for prevention and management of neonatal mortality, especially in premature state. In a recent report in our country, the most important cause of newborn death was prematurity in about 64% of affected cases (16). However, mortality rate in premature infants in different areas of the country remained unknown. Furthermore, the main determinants of premature infant death are already questioned.
2. Objectives
Thus, we aimed to determine mortality rate and its main indicators among premature neonates in our region to make better decisions to improve public health and reduce neonatal mortality.
3. Patients and Methods
Fifty-hundred consecutive premature neonates hospitalized in neonatal intensive care unit at Fatemieh hospital in Hamadan, Iran during 2012 entered this cross-sectional study. The definitional criterion of prematurity was gestational age below 37 weeks based on last menstrual period (LMP). Thus, those with unknown LMP were excluded. In this regard, 492 neonates were finally evaluated. Baseline characteristics were extracted from hospital recorded files. A special questionnaire was designed to record required information of preterm infants in the neonatal intensive care unit (NICU) including birth weight, gestational age at birth, Apgar score, gender, need for resuscitation in the delivery room, need for surfactant, need for mechanical ventilation, causes of preterm birth, disease history in the mother and cause of infant death such as respiratory distress syndrome, sepsis or congenital anomalies. Results were reported as mean ± standard deviation (SD) for quantitative variables and percentages for categorical variables. The groups were compared using Student’s t-test or Mann-Whitney U test for continuous variables and chi-square test (or Fisher’s exact test if required) for categorical variables. Predictors exhibiting a statistically significant relation with neonatal death in Univariate analyses (with a P Value > 0.1) were taken for a Multivariable logistic regression analysis to investigate their independence as predictors. P values of 0.05 or less considered statistically significant. All the statistical analyses were performed using SPSS version 19.0 (SPSS Inc., Chicago, IL, USA) and SAS version 9.1 for Windows (SAS Institute Inc., Cary, NC, USA).
4. Results
The average of gestational age was 31.97 ± 2.99 weeks ranged 23 to 36 weeks. Mothers had the mean age of 27.59 ± 6.08 years ranged 14 to 50 years. The mean of neonatal weight at birth was 1810.15 ± 665.00 grams. Average of first and fifth minutes Apgar scores were 6.43 ± 1.92 (median 7.0) and 7.79 ± 1.73 (median 8.0), respectively. One-hundred and forty-one infants (28.7%) were the result of multiple pregnancies. Table 1 describes premature neonates and compares baseline characteristics between survived and death premature neonates. Except for mother’s age and infection status as complication, which were both comparable in the two survived and non-survived neonates, other characteristics such as gestational age less than 28 weeks, low weight at birth, low first and fifth minutes Apgar scores, need for intensive supports including mechanical ventilation, instillation of surfactant, resuscitation at delivery room, history of disease in mother and occurrence of pneumothorax were all more observed in non-survived group. Moreover, male to female ratio was significantly higher in dead neonates than survived ones.
Table 1. Baseline Characteristics in Survived and non-Survived Neonates
| Characteristics | All Neonates (n = 492) | Survived Neonates (n = 358) | Non-Survived neonates (n = 134) | P Value |
|---|---|---|---|---|
| Age of gestation,wk | < 0.001 | |||
| < 28 | 68 (13.8) | 24 (6.7) | 44 (32.8) | |
| 28 - 32 | 185 (37.6) | 130 (36.3) | 55 (41.1) | |
| > 32 | 239 (48.6) | 204 (57.0) | 35 (26.1) | |
| Weight at birth, gr | < 0.001 | |||
| < 1000 | 64 (13) | 11 (3.1) | 53 (39.6) | |
| 1000 - 1500 | 128 (26) | 97 (27.1) | 31 (23.1) | |
| 1501 - 2000 | 137 (28) | 108 (30.2) | 29 (21.6) | |
| 2001 - 2500 | 89 (18) | 80 (22.3) | 9 (6.7) | |
| > 2500 | 74 (15) | 62 (17.3) | 12 (10.0) | |
| Mother age, y | 0.789 | |||
| < 15 | 1 (0.2) | 1 (0.3) | 0 (0.0) | |
| 15 - 35 | 429 (87.2) | 311 (86.9) | 118 (88.1) | |
| > 35 | 62 (12.6) | 46 (12.8) | 16 (11.9) | |
| First minute Apgar score | < 0.001 | |||
| 0 - 3 | 42 (8.6) | 6 (1.7) | 36 (26.9) | |
| 4 - 6 | 172 (34.9) | 111 (31.0) | 61 (45.5) | |
| 7 - 10 | 278 (56.5) | 241 (67.3) | 37 (27.6) | |
| Fifth minute Apgar score | < 0.001 | |||
| 0 - 3 | 20 (4.1) | 4 (1.1) | 16 (11.9) | |
| 4 - 6 | 71 (14.4) | 31 (8.7) | 40 (29.9) | |
| 7 - 10 | 401 (81.5) | 323 (90.2) | 78 (58.2) | |
| Gender of neonate | < 0.001 | |||
| Male | 305 (62.8) | 209 (58.4) | 96 (71.6) | |
| Female | 181 (37.2) | 144 (40.2) | 37 (27.6) | |
| Need to resuscitation | 115 (23.4) | 34 (10.0) | 81 (60.4) | < 0.001 |
| Need to surfactant | 124 (25.2) | 38 (10.6) | 86 (64.2) | < 0.001 |
| Need to ventilation | 177 (35.9) | 52 (14.5) | 125 (93.3) | < 0.001 |
| Complicated by infection | 36 (7.4) | 24 (6.7) | 12 (8.9) | 0.404 |
| Complicated by pneumothorax | 31 (6.3) | 4 (1.1) | 27 (20.1) | < 0.001 |
| History of disease in mother | 26 (5.3) | 10 (2.8) | 16 (11.9) | 0.001 |
As shown in Table 2, the most frequent causes of preterm labor were premature rupture of membranes (11.2%) followed by preeclampsia (9.3%), multiple pregnancy (8.5%) and fetal distress (7.5%). Neonatal death rate was overall 27.4% (134 of 489 neonates), which was significantly higher in gestational age subgroup of less than 28 weeks compared with other gestational age subgroups (P < 0.001). The most prevalent etiologies of neonatal death were respiratory distress syndrome (73.8%), congenital abnormalities (13.8%) and sepsis (5.4%), respectively. Regarding etiologies of preterm labor, preeclampsia and history of multiple pregnancies were significantly more prevalent in non-survived neonates; however, two survived and non-survived patients were similar in other causes including premature rupture of membranes, fetal distress, oligohydramnios, eclampsia and previous history of various disorders in mothers (Table 2). According to multivariable logistic regression modeling (Table 3), low birth weight, need for intensive supports including resuscitation and ventilation, occurrence of pneumothorax, pregnancy complications such as preeclampsia and fetal distress could all strongly predict occurrence of death in premature infants. Moreover, male gender was associated with increased risk of death in these neonates.
Table 2. Etiologies of Preterm Labor in Survived and Non-Survived Groups
| Etiology | All Neonates (n = 492) | Survived Neonates (n = 358) | Non-Survived Neonates (n = 134) | P Value |
|---|---|---|---|---|
| PROM | 55 (11.2) | 39 (10.9) | 16 (11.9) | 0.754 |
| Fetal distress | 37 (7.5) | 26 (7.3) | 11 (8.2) | 0.737 |
| Oligohydramnios | 6 (1.2) | 4 (1.1) | 2 (1.5) | 0.718 |
| Preeclampsia | 46 (9.3) | 22 (6.1) | 24 (17.9) | < 0.001 |
| Multiple pregnancy | 42 (8.5) | 40 (11.1) | 2 (1.5) | < 0.001 |
| Eclampsia | 1 (0.2) | 0 (1.1) | 1 (0.7) | 0.69 |
| Mother’s disease | 3 (0.6) | 0 (1.1) | 3 (2.2) | 0.355 |
Table 3. Odds Ratio for Neonatal Mortality According to the Risk Factors a
| Risk Factors | OR (95% CI) | P Value |
|---|---|---|
| Weight at birth, gr | ||
| < 1000 | 30.2 (2.3 ~ 390) | 0.009 |
| > 2500 | 1 | |
| Pregnancy complications | ||
| Fetal Distress | 46.1 (5.9 ~ 358) | < 0.0001 |
| Pre eclampsia | 9.3 (1.6 ~ 52) | 0.011 |
| Gender of neonate | ||
| Male | 5.7 (1.9 ~ 16) | 0.001 |
| Female | 1 | |
| Need to resuscitation | ||
| Yes | 6.4 (1.6 ~ 25.7) | 0.008 |
| No | 1 | |
| Need to ventilation | ||
| Yes | 48 (14 ~ 162) | < 0.0001 |
| No | 1 | |
| Complicated by pneumothorax | ||
| Yes | 10.4 (1.7 ~ 62) | 0.009 |
| No | 1 |
a ORs and 95% CIs were calculated by performing logistic regression analysis to determine the risk of neonatal mortality according to the presence of maternal and neonatal risk factors.
5. Discussion
The purpose of the present investigation was to assess neonatal in-hospital mortality and its main indicators in a sample of premature neonates in Hamadan, a big province in west of Iran. In this survey, prematurity was defined as gestational age below 37 weeks. Recently, a steadily decreasing trend of infant mortality rate has been shown worldwide; however, change in neonatal mortality, especially in premature status, remained partially constant. Prognosis of prematurity in these neonates generally depends on birth weight, gestational age, disease severity in the first hours of life and other-related pathophysiological conditions causing a wide range of neonatal premature mortality in various regions and countries. We documented a mortality rate of 27.4% in our studied premature neonates. In most similar studies, a wide varied mortality rate was documented ranged from 23% to 29% (17-19). In a study by Dong and colleagues in China, in-hospital mortality decreased from 29.8% in 2002 - 2005 to 28.1% in 2006 - 2009 with a significant trend (20). Our obtained mortality rate was inconsistent with global rate published in recent studies, however some recent reports documented dramatically higher rate of premature neonatal mortality based on definitional time of prematurity. In a study by EXPRESS Group in Sweden, overall perinatal mortality was 45% ranged from 93% at 22 weeks to 24% at 26 weeks (21). In a Swedish cohort between 1990 and 1992 on all infants with a birth weight of 1000 grams or less, most of neonates born at 23 and 24 weeks of gestation died in the delivery room and those survival to one year were only 8% and 28%, respectively (22). In a prospective, national, population-based study in France in 2011, 31.2% of neonates born at 24 weeks and 93.36% of those born at 27 - 31 weeks survived. The authors explained that although the survival rate in extremely low gestational age is improved, their long-term outcomes need more studies (23). In another study in India, 14.8% of neonates under 1500 gr died before hospital discharge (24).
Various neonatal and maternal variables have been identified affecting in-hospital death in premature neonates completely matched with previous findings. Basu and his colleagues showed that mortality rate could be increased with decreased birth weight and gestational age, vaginal bleeding, failure to administer steroid antenatally, Apgar score equal to or less than 5 at one minute, apnea, gestational age, neonatal septicemia and shock (25). In another study by Dong et al., persistent pulmonary hypertension of newborn, pulmonary hemorrhage, birth weight < 1000 grams, gestational age < 33 weeks, feeding before 3 postnatal days and enteral feeding were predictors of in-hospital mortality (20). In another study, the most important high risk factors affecting mortality of neonates were low birth weight, need for resuscitation at birth, need for ventilator use and intra-ventricular hemorrhage (26). Also in the study by Terzic et al. a significant difference was found between groups of survived and dead infants regarding gestational age, birth weight, Apgar score, Crib score, base excess, presence of respiratory distress syndrome and hemodynamic stability at birth (27). Indredavik et al. showed that lower birth weight, shorter gestation and intra-ventricular hemorrhage were risk factors for neurodevelopmental problems in very low birth weight group (28). Moreover, in Almeida et al. survey and according to the multivariate analysis, gestational age of 23 - 27 weeks, maternal hypertension, 5th minute Apgar less than 6, presence of respiratory distress syndrome and network center of birth were associated with early intra-hospital neonatal deaths (29). In total, a combination of both neonatal and maternal underlying factors can predict in-hospital mortality in Iranian premature consistent with other communities worldwide. A retrospective, population-based analysis showed that high-volume neonatal care provided at birth may reduce neonatal mortality in very preterm infant (30). It seems that wide variations in mortality rate among premature neonates are due to the time definition of prematurity and presence of one or a set of triggering maternal and neonatal parameters. Therefore, identifying and management of these predictive factors can improve planning adopted programs for pregnancy, proper prevention of life-threatening complications in mother’s and newborn’s wards and raising personal attention to the care of mothers and infants.
In summary, approximately one quarter of premature neonates had early mortality, which can be predicted by low gestational age, low birth weight, low Apgar score, need to intensive supports, postpartum complications, multiple pregnancy and history of maternal illnesses.
