Determination of the Prevalence of Patent Ductus Arteriosus in Infants with Very Low Birth Weight Admitted in Hospital during 2011-2016 View PDF

The ductus arteriosus is a fetal vascular connection between the pulmonary artery and the aorta which transmit blood from the pulmonary artery to the systemic circulation during the fetal period. The duct contracts and usually close up to 72 hours after birth. If this contraction does not occur after birth, the ductus arteriosus will remain patent, which results in patent ductus arteriosus (PDA), leading to inappropriate blood transmission between the aorta and the pulmonary artery [1,2].

Usually, this contraction causes the functional closure of the ductus arteriosus within 10 to 15 hours after birth that starts from the pulmonary artery and ultimately progresses to the aortic end. Such changes do not occur in patent ductus arteriosus, which indicates the presence of specific anatomical differences in the ductus arteriosus tissue [3]

Very low birth weight (VLBW) is considered as a term to define babies who are less than 1500 grams. Approximately 1% of infants are VLBW, but they account for 50% of infant mortality. VLBW infants face a 200-fold risk of death compared with other infants [4]. The incidence of PDA is inversely associated with gestational age. A large PDA with a left to right shunt in the VLBW infant can cause pulmonary edema, congestive heart failure (CHF), pulmonary hemorrhage, and an increased risk of pulmonary dysplasia [5].

Drug therapy with indomethacin or ibuprofen is successful in 75- 80% of newborns, but also has an adverse effect on neonates, such as gastrointestinal bleeding, perforation, and necrotizing enterocolitis [6].

Studies have shown that the incidence of congenital heart defects is about 1 in 200 births in normal populations. Recent statistics indicate that the incidence of congenital heart defects is 12 to 14 per 1,000 live births. PDA as a single congenital defect in neonates is estimated to account for 5-10% of all congenital heart defects [7]. A study indicated that clinical symptoms alone were not sufficient to detect PDA. In addition, routine echocardiography was necessary for early detection of PDA in premature babies in the first few days after birth [8]. Another studyreported that the ductus arteriosus is closed spontaneously at the beginning of the infancy in most of the newborns with VLBW and PDA [9]. Another study looked at the extent of the spontaneous closure of the ductus arteriosus in the VLBW neonates in an observational and prospective manner in which ductus arteriosus was closed in 49% of the newborns on day 7, based on echocardiographic findings [10]. There is no detailed data on the association between PDA and VLBW in Iran and the need for accurate diagnostic procedures seems to be necessary for proper treatment with regard to various supportive, pharmaceutical and surgical treatments.

The study of companion (VLBW) and PDA in Iran’s largest referral centers (Iranian maternity hospitals) can be the basis for further studies in favor of appropriate treatment and reduction of the mortality rate in these infants. Therefore, in this study, the prevalence of PDA was evaluated in VLBW infants admitted to Shahid Akbar Abadi Hospital in 2011-2016.

In this observational and cross-sectional study, the data were collected from medical records of 286 VLBW neonates (<1000 grams) admitted to the NICU of Shahid Akbar Abadi Hospital during the years 2011 to 2016. In the present study, a checklist was used in which variables such as gender (boy, girl), gestational age (week), birth weight (g), neonate Apgar score, need for respiration (requiring auxiliary ventilation; positive, negative) Cardiac anomalies (positive, negative), sepsis (positive, negative), PDA (neg, closing, small, medium, large), treatment (positive, negative) and response to treatment (positive, negative) were recorded. Echo was performed by a skilled pediatric cardiologist after the first 48 hours of birth and before 72 hours in all extremely low birth weight (ELBW) infants.

If there were indications (hemodynamic instability, oxygen dependence and large PDA), the infant with open ductus arteriosus was treated with ibuprofen for 3 days at a dose of 10 mg/kg and then 5 mg/kg for the next two doses at intervals of 24 hours. After the end of the treatment period, the echocardiographywas performed again, if the PDA still remained, a re-treatment course with ibuprofen was performed. In the absence of treatment indication, the baby was reechoed for 7 days. In the absence of treatment indication, the echo was repeated for the baby at 7 days of age.

In the presence of contraindications for the use of ibuprofen, the baby was excluded from the study Contraindications include: internal bleeding such as gastrointestinal or pulmonary hemorrhage or IVH grade 3 and 4, platelets less than 50,000, creatinine above 1.2, or jaundice close to or near the exchange transfusion based on the Bhutani curve. In addition, diagnosis of sepsis in the newborn was performed based on positive blood culture.

Inclusion criteria included; all infants less than 1000 gr who were admitted to Shahid Akbar Abadi hospital during 2011-2012.

Exclusion criteria included contraindication of ibuprofen administration, incidence of complications such as gastrointestinal bleeding, abdominal distension, necrotizing enterocolitis during study, infant death for any reason during the study.

In this research, ethicalprinciples were fully followed, first the ethical codewas taken from the Ethics Committee and the information extracted from the cases remained confidential.

ANOVA and Chi-square analyses were conducted using the statistical software SPSS for Windows, version 13.0 with a significance level of 0.05.

In the present study, the mean (SD) of the gestational age, birth weight, Apgar score were determined to be 27.27 ± 0.15 weeks, 835.20 ± 42.6 and 5.31 ± 0.13, respectively. Frequency distribution and frequency of qualitative variables are shown in Table 1.

As indicated in the Table 1, 57.70% of the neonates were female, most neonates (93.40%) needed respiration, and heart anomalies were detected in most neonates (82.20%), and sepsis was negative in most neonates (92%). Most neonates (44.10%) did not show PDA, while the lowest PDA frequency was reported in neonates (3.50%). In addition, 22 neonates needed treatment, of which 12 responded to ibuprofen therapy, but 10 did not respond to treatment (Table 2).

The relationship between PDA in neonates based on qualitative variables is presented in Table 2. The results show that PDA frequency distribution was significantly different in neonates (P=0.032), which small PDA was more positive in cases of sepsis.

The relationship between PDA in neonates based on gestational age (week), birth weight (g), and neonatal Apgar score are shown in Table 3. Our findings demonstrated that PDA frequency distribution was not significantly different in terms of gestational age and birth weight (P>0.05), but the mean score of Apgar score was found to be significantly different (P=0.001), whensevere cases were found to be higher in neonates with lower Apgar score.

Ductus arteriosus closurehas been indicated to be often delayed in preterm infants, which incidence of patency at less than 30 weeks has been reported to be up to 60% [11]. PDA has been defined to be liked to an increase in the mortality of premature neonates, however, the causal correlationof these adverse situation has not been appropriately documented. The PDA may be merely considered as an intermediate stage of hemodynamic changes during the first weeks of life of the infant [12-14].

In the current study, the prevalence of PDA in newborns with

Table 1. General population characteristics and demographic data.

Table 2. Relationship between PDA in neonates and other qualitative variables.

Table 3. Relationship between PDA in neonates based on gestational age (week), birth weight (g) and neonatal Apgar scor

VLBW was investigated in Shahid Akbar Abadi Hospital during 2011- 2016. In this study, 55.9% of the infants with ELBW showed PDA. The ductus arteriosus was closed spontaneously in 14% of them, and small, moderate and large PDA were observed in 34.25%, 3.5% and 4.15%, respectively. There was a significant relationship between the PDA and sepsis, where small PDAs were found to be more positive in case of sepsis. There was also a significant difference between PDA based on Apgar score when most cases were severe in infants with low Apgar score.

Radvar et al. (2014) examined the efficacy of clinical symptoms in detecting PDA in premature neonates in Iran. They reported that Clinical signs were not reliably capable of diagnosing PDA in premature neonates; therefore, routine echocardiography is needed in this regard. Furthermore, aforementioned study indicated that hyperdynamic precordium and worsening respiratory have been found to be attributing to high sensitivity at 48-72 h of life. Furthermore, in conjunction with echocardiography are valuable tools for early detection of PDA in premature infants [15].

Recent studies suggest that supportive care should be taken during the first week and be followed by selective anti-inflammatory drugs. Spontaneous closure of PDA has been reported in more than 40-60% of VLBW infants in 7 days [16]. In our study, 7.7% of newborns were treated and the response to treatment was observed in 54.5% of infants. In addition, only 14% of the PDA cases were closed spontaneously.

Current evidence indicates that management of PDA can be wide-ranging and controversial findings have been also recorded; these conditions may even represent a diverse approach in this regard [17]. The paucity of literatures in terms of supportive care of PDA has remained controversial in very premature infants [18-20].

Another study by Herrman et al. (2009) examined spontaneous closure of the PDA and treatment of PDA-associated statues in VLBW neonates with ductal patency. They stated that spontaneous closure has been reported in most VLBW neonates with PDA at initial neonatal unitdischarge [18].

A prospective observational study by Nemerofsky (2008) evaluated the rate of spontaneous closure of PDA in VLBW neonates with birth weight (BW) <1500 g, in which echocardiography were applied for neonates on day of life 3 and 7, once a week in the first month, and bimonthly until ligation, discharge, or death. The ductus arteriosus was found to be spontaneously closed in 49% infants at day 7 (67% in weight more than 1000 and 31% in weight less than 1000 g) [10]. In our study, the spontaneous closure of the ductus arteriosus was determined to be 14% in infants weighing less than 1000 g.

Conservative management of PDA has elevated for preterm imoenates, however, assessment of PDA treatment is currently controversial, leading to remarkable heterogeneity in clinical practice [14,21,22].

It has been demonstrated that 30% of preterm neonates born at <1000 g exhibited spontaneous ductus closure in the first week of life. Nevertheless, the long-term management and treatment of PDA has yet to be confirmed [14,23,24].

A study by Lee et al. (2014) aimed at determining the usefulness and safety of surgical ligation (after 15 days) in VLBW infants undergoing surgical correction for PDA for a 6-year period [25].

Early ligation for the treatment of PDA that failed treatment or contraindicated therapeutic drug may be desirable in reducing the incidence of necrotizing enterocolitis and reducing feeding intolerance in preterm neonates [25]. Of course, Based on the data presented herein, response to treatment was observed in 54.5% of newborns.

Taken together, our results revealed that PDA is present in more than half of the infants with VLBW. However, further development requires in-depth understanding of PDA and its therapeutic approaches through conducting comprehensive and multicenter trial by considering other intervening variables.

The authors would like to thank the Shahid Akbarabadi Clinical Research Development Unit (ShACRDU), Iran University of Medical Sciences (IUMS), Tehran, Iran.

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