Risk Factors of Respiratory Diseases Among Neonates in Neonatal Intensive Care Unit of Qena University Hospital, Egypt

Background: Respiratory diseases in newborns are considered major causes of neonatal morbidity and mortality especially in developing countries. Its causes are diverse and require early detection and management. This study aimed for detection of the prevalence and risk factors of respiratory diseases in addition to outcome among neonates admitted in neonatal intensive care unit. Methods: Our study was a prospective observational study that was undertaken at the neonatal intensive care unit of Qena University Hospital, Egypt from July 2017 to July 2018. Demographic and clinical data of newborns and their mothers were evaluated and tabulated. Results: In this period, 312 neonates were admitted to the neonatal intensive care unit, out of them 145 suffered respiratory diseases giving a prevalence of (46.5%), and (55.9%) were males. The mean neonatal age at admission was 4.33 ± 7.19 days and mean gestational age was 34.49 ± 3.31 weeks. The most common detected respiratory diseases were respiratory distress syndrome (RDS; 49.6%), transient tachypnea of newborn (TTN; 22%), neonatal pneumonia (17.2%) and meconium aspiration syndrome (MAS; 6.21%). Premature rupture of membrane (PROM), maternal diabetes and fetal prematurity had the highest risk factors for respiratory diseases occurrence in neonates. Neonatal mortality rate was 26.2%, mainly due to hyaline membrane disease and pneumonia. Conclusion: Respiratory diseases constitute major part of total admission in neonatal intensive care unit especially RDS, TTN, pneumonia and MAS. Prematurity and maternal diabetes were the most important risk factors associated with respiratory diseases. Respiratory distress syndrome carried the highest risk of mortality and TTN carried the highest survival rate.

diovascular and neuromuscular diseases. A tremendous decrease in mortality rate of neonatal respiratory diseases has occurred over the past six decades in developed countries due to renovations in neonatology care that are lacking in developing ones [9].

Patients and Methods
The current study was a prospective observational study that was done at the neonatology care unit, Qena University hospital from July 2017 and July 2018 to evaluate the prevalence of respiratory diseases among neonates in neonatal care unit. The study included both full-term and preterm neonates with respiratory diseases. Demographic, clinical and laboratory data were evaluated. Out of total 312 neonates admitted to neonatal intensive care unit, 145 neonates were diagnosed with respiratory diseases; 81 males, 61 females and 3 undefined sex. Through interviewed questionnaires to parents and physical examination of neonates, we studied socio-demographic characteristics, antenatal history, intrapartum history, history of prematurity, gestational age, postnatal age, age of onset of the respiratory disease and clinical findings of neonates. Maternal data obtained included age of mother, status of mother according to gravidity, parity, abortion and live Births. Any obstetric complications like ante-partum hemorrhage (APH), premature rupture of membranes (PROM), preeclampsia, eclampsia or diabetes were recorded. Presence of fetal distress, presence of meconium, place and mode of delivery and whether pregnancy was single, twin or triple gestation also were recorded. Clinical examination included general, chest, cardiac and neurological examination. Regarding radiological investigations, chest x-ray, abdominal ultrasound, CT chest and Echocardiography were done in selected cases when indicated. Regarding laboratory investigations, complete blood count with differential, C-reactive protein and blood culture were done in selected cases when indicated. The study was approved by scientific and ethical committee of Qena Faculty of Medicine, South Valley University. An informed consent was obtained from the parents of the newborn.

Statistical analysis
Analysis of data was evaluated using SPSS version 20. Values that were recorded as mean and standard deviation were compared using Student's t test. Differences in proportions were compared by applying the chi-square test. Finally, the univariate linear regression Pearson correlation was performed as indicated. P value <0·05 was considered significant.

Results
In the period of the study, 312 neonates were admitted to our neonatal intensive care unit; of them 145 cases suffered from respiratory diseases giving an incidence of (46.5%) for neonatal respiratory diseases among total admission. Table 1 showed the socio-demographic data of the studied cases. They were 81 (55.9%) males, 61 (42%) females and 3 (2.1%) undefined sex. The mean neonatal age at admission was 4.33 ± 7.19 days, mean gestational age was 34.49 ± 3.31 weeks, mean maternal age was 27.6 ± 6.8 years and the mean duration of hospitalization at our NICU was 9.37 ± 1.59 days. Regarding the site of the delivery, 76 cases (52.4%) of those born at our hospital needed admission at our neonatal intensive care unit due to respiratory problems, 61 newborns were referred to our unit from other hospitals (42.1%) and 8 referred from private clinic (5.5%). One hundred newborns were from urban areas and 45 from rural areas. Most of cases with respiratory distress (97.24%) occurred after normal pregnancy and 4 cases (2.76%) only after assisted pregnancy. One hundred and seven newborns (73.79%) were single, 26 (17.9%) were one of twins, 9 (6.21%) were triplets and 3 newborns were one of quadruple (2.06%). The onset of respiratory distress was since birth in 91 cases (62.8%), at first day in 26 cases (17.9%) and after first day in 28 (19.3%) cases. Table 2 showed that preterms presented with RDS were 72 cases (49.6%), full-terms presented with transient tachypnea of newborn were 32 cases (22.1%), pneumonia caused respiratory distress in 25 cases (17.2%), meconium aspiration syndrome in 9 cases (6.2%), congenital diaphragmatic hernia in 3 cases (2.1%), aspiration pneumonia in two cases (1.4%) and tracheosophegeal fistula in two cases (1.4%). Table 3 showed risk factors of respiratory diseases occurrence. Regarding maternal illness, PROM was a risk factor in 32 cases (22.07%), antepartum hemorrhage in 30 cases (20.6%), maternal diabetes in 25 cases (17.24%), oligohydraminos in 20 cases (13.79%), preeclampsia in 9 cases (6.20%), placenta previa in 3 cases (2.06%) and cardiac diseases in 3 cases (2.06%). Regarding fetal conditions, prematurity was a risk factor in 103 cases (70.97%), multiple gestations in 38 cases (26.20%), meconium aspiration in 9 cases (6.21%) and abnormal fetal monitoring in 24 cases (16.55%). Prematurity had the highest risk for RDS followed by PROM, maternal diabetes and pre-eclampsia. Cesarean section had the highest risk for TTN followed by gestational diabetes and prematurity. Prematurity had the highest risk for pneumonia followed by PROM, congenital anomalies and prolonged labor. Cesarean section had the highest risk for MAS followed by abnormal fetal monitoring and post maturity. Table 4 showed the outcome in relation to different causes of respiratory diseases. Statistical significant difference was found between outcome and incidence of different causes of respiratory disorders. Death rate increased significantly as the incidence of RDS, MAS and pneumonia increased. During the period of the study the case fatality rate was 38.9% in newborns with RDS, 33.3% in MAS and 16% in pneumonia. The best outcome was significantly higher with TTN. Table 5 showed logistic regression analysis of variables affecting the outcome of neonatal respiratory diseases. Many variables had a great effect on the outcome with an odds ratio >1 as male gender, RDS, CDH, pneumonia, apnea, tachypnea >60 c/min, retraction, cyanosis and irritability. Maternal risk factors that had a great effect on the outcome were diabetes, pre-eclampsia, oligohydramnios and overcrowding condition with odds     ratio >1. Use of mechanical ventilation, C.S delivery and small for gestational age had an odds ratio >1.

Discussion
Respiratory diseases are one of the most common reasons for newborn admission to the neonatal intensive care unit [5]. Fifteen percent of term and 29% of preterm infants admitted to NICU develop significant respiratory morbidity specially in infants born before 34 weeks of gestation [10]. The etiologies of RD in newborn are large and diverse, including TTN, RDS, MAS, pneumonia and other miscellaneous causes [6,7]. As there is paucity of studies regarding the cause of respiratory diseases in our localities, our study was conducted to find out the prevalence and etiology of respiratory diseases among admitted neonates. The total cases admitted to our NICU during one year study were 312 cases; of them 145 cases were admitted due to respiratory diseases giving an incidence of (46.5%). This was relatively comparable to the incidence reported by other studies like Verma et al., (39%) and Tochie et al., (47.5%) [11,12]. The present study showed that neonatal respiratory diseases were higher in males (55.9%) than females (44.1%). This was similar to previous studies [13,14]. It is well known that lung growth and development start in the prenatal period and lung maturation is more advanced in the female fetus. Oral movement starts between the 16th and 26th weeks of gestation, reflecting fetal breathing, and this is considered a critical determinant for the development of the lung [15]. Other fundamental regulators of lung maturation are sex hormones. While testosterone secreted by fetal testes having mainly inhibitory effects and delays the surge of surfactant production, oestrogens produced by the placenta have positive effects on both the production of fetal surfactant and on the alveologenesis during neonatal and pubertal periods [16]. Additionally, our study detected that neonates born by a caesarean section have more incidence of respiratory diseases. This was evident by other studies [17][18][19]. Infants born by caesarean section have a larger residual volume of lung fluid, a smaller residual capacity and consequently secrete less surfactant into the alveolar space while during vaginal delivery, as the chest of the infant is squeezed, part of the fetal lung fluid is removed and the adrenergic stimulation associated with vaginal labor releases surfactant into the airways [20].
Respiratory distress syndrome was detected as the commonest respiratory disease and earlier workers had found similar observations [10,11]. RDS in the current study was detected in (49.66%) followed by TTN (22.07%), pneumonia in 17.2% and MAS in 6.2%. Parkash et al., reported RDS in (20.8%), pneumonia in (22.5%), MAS in (16.7%) and TTN in (11.7%) [21]. The study of Abou-Faddan and Nafisa revealed that RDS is the most common neonatal respiratory disease (45.8%) followed by pneumonia and TTN [22]. Regarding risk factors, our study showed that the most common maternal factors for occurrence of respiratory diseases were PROM (22%), antepartum hemorrhage (20.6%), maternal diabetes (17.24%) and oligohydraminos (13.8%). Some of serious complications associated with PROM include chorioamnionitis, neonatal sepsis and preterm labor leading to neonatal pulmonary hypoplasia and respiratory distress syndrome [23]. Similar to other studies, the most commonly detected fetal risk factor for respiratory disorders was prematurity (70.9%) [17,22]. It is well documented that all forms of respiratory morbidity, including TTN, RDS, pneumonia, and pulmonary hypertension, affect late-preterm infants at a higher rate than infants of more advanced GA [24]. A study by De Luca et al., revealed that more than ten folds increase in respiratory morbidity in infants of 34 weeks' GA compared with term infants [25]. A retrospective study by Kitsommart et al., revealed significantly worse respiratory outcomes including prevalence of pneumothorax, need for positive pressure therapy, and mechanical ventilation assistance in infants of 34 to 36 weeks' GA compared with infants of ≥37 weeks' GA [26]. The current study found that multiple gestation pregnancies was associated with high risk of neonatal respiratory diseases (26.2%). This was in accordance with the study of Ziadeh and Badria which reported that the second twin has a higher risk of respiratory distress compared to single newborns and added that caesarean section carried out before the onset of labor increase this risk [27]. Multifetal gestation brings a high risk of maternal complications during pregnancy and postnatal complications for babies specially when born prematurely. The risk of preterm delivery for triplet pregnancies is approximately 90% while in twin gestations is more than 50%, compared with only 10% incidence of preterm labor in single infants [28]. Regarding RDS, the most common risk factor detected in our study was prematurity (37.7%). By Indian study, researchers found that the incidence rates of RDS ranged from 86% at 24 weeks to less than 1% at 39 weeks and mentioned that RDS should be anticipated in any IDM and preterm delivery [29]. overcrowding conditions and small gestational age. Logistic regression analysis showed that premature SGA neonates were at a higher risk of mortality than premature AGA infants were. These findings were consistent with previous studies that showed premature SGA infants more liable to bronchopulmonary disease and chronic lung disease [39,40]. Strength of this research include use of a reasonable sample size for study and the situation of the study being a big referral center with a high rate of neonatal admission. Also, being a prospective study avoids bias and shortage of data in retrospective studies that depends on file records. The most important limitation of this study is that it was a single centered study and frequent missed cases that go for local centers.

Conclusions
This study indicated higher incidence of respiratory diseases in neonates admitted at NICU most commonly were RDS, TTN, MAS and pneumonia. Prematurity was the most important risk factor associated with respiratory diseases in addition to presence of antepartum hemorrhage, multiple gestation and maternal diabetes. Respiratory distress syndrome carried the highest risk of mortality and TTN carried the most survival rate. Although decreasing the incidence through preventive measures is ideal, early recognition and treatment of the common neonatal respiratory diseases will decrease both short-and long-term complications and related mortality of at-risk infants.