Risk factors of patent ductus arteriosus in preterm infants in neonatal intensive care unit of dubai hospital and latifa hospitals

Aim: To describe the risk factors of patent ductus arteriosus in preterm infants in neonatal intensive care unit, Dubai, UAE and Latifa hospitals. Study Design: A retrospective descriptive study on all neonates admitted to Neonatal Intensive Care Unit in Dubai Hospital and Latifa Hospitals were diagnosed with Patent ductus arteriosus from July 2017 to December 2018. Setting: Neonatal Intensive Care Unit in Dubai and Latifa Hospitals Subjects: 59 with PDA were included in study while the age limit on admission was 24 hours. Results: In the total sample of 59, 30 (51 %) were females while 29 (49 %) were females. Preterm neonates with PDA were subjected to medical therapy and one case led to surgical ligation. List of Figures and Tables Figure 1: Distribution of gender in study population 9 Figure 2: Distribution by Mode of Delivery………………………………………….

…………10 Table 1: summary of 1 minute Apgar test score…………………………………………………11 Table 2: summary of 5 min Apgar test score……………………………………………………. 11 Table 3:Summary incorporating birth weights, platelet count, and preterm ductus arteriosus…. 12 Table 4: Demographic Incidences in Gestation age, VLBW and Platelet Count………………. 14 Table 5: Demographic Incidences in Gestation age, ELBW and Platelet Count………………. In preterm infants, sensitivity for oxygen is reduced while the sensitivity to PGE2, nitric oxide (NO), and perhaps endothelin 1 is increased [6]. Glucocorticoids appear to change DA’s sensitivity to PGE2. For example, hydrocortisone given to preterm lambs facilitates ductal constriction, probably by decreasing the sensitivity of the ductus to the dilating action of PGE2 [7]. This may explain the lower incidence of patent ductus arteriosus in VLBW infants whose mothers received antenatal glucocorticoid treatment [8]. Recently, Echtler et al.

The target population was taken from Dubai hospital/ neonatal intensive care unit and Latifa hospital/ neonatal intensive care unit. Furthermore, methodology sampling was taken from the neonatal intensive care unit registry book for both hospitals (since all the cases of congenital heart disease were recorded in the registry book). Moreover, the inclusion criteria included all preterm infants with gestational age < 37 weeks who got admitted to Dubai and Latifa hospitals/ Neonatal intensive care unit with a confirmed diagnosis of patent ductus arteriosus with ECHO (Gestational age was defined according to the New Ballard Score when the last menstrual period date was unknown). Exclusion criteria included congenital heart defects other than patent ductus arteriosus and full blood count not done in first 24 hours of life.

The data collection sheet included the following: 1. At 95 % Confident Interval, the significance that was accepted was p< 0. Data Analysis and Results Patent ductus arteriosus(PDA) is majorly a common problem affecting preterm neonates. 98neonates were admitted to Neonatal intensive care unit and Latifa hospitals in Dubai from July 2017 to December 2018. Out of these, 54 (55 %) were males while 44 (45 %) were females. Also out of 98 infants, 90 (92 %) were preterm infants with gestational age < 37 weeks whereas 8 (8%) were excluded from the study since their gestational ages were not < 37 weeks. In addition, 33 (56 %) out of 59 preterm infants administered 1 minute Apgar test showed results between 4-6, indicating need for breathing assistance. Also, 18 (30 %) of preterm infants showed result ranging between 7-10 after 1-minute Apgar test, showing that the neonates only needed routine post-delivery.

In addition, need for Apgar test led to prevalence to PDA summing to 15 cases in preterm neonates. Table 1 below shows results. 1 minute Apgar score Below 4 4–6 7 – 10 No of preterm infants 8 33 18 Percentages 14 % 56 % 30 % With PDA 1 7 7 Table 1: summary of 1 minute Apgar test score On the other hand, when 5-minute Apgar test was conducted on 59 preterm infants, 52 (88 %) showed results ranging between 7and 10 thereby showing normal conditions of infants. It was noted that 5 preterm infants with ELBW and patent ductus arteriosus had results ranging from 135000 / µl – 197000 / µl. Meanwhile 23 preterm infants of ELBW with closed ductus arteriosus had platelet count ranging from 92000 / µl – 514000 / µl. Moreover, platelet count was then conducted to 18 preterm infants with VLBW. It was notable that 5 preterm infants of VLBW with patent ductus arteriosus had platelet count ranging from 145000 / µl – 295000 / µl while other 13preterm infants of VLBW and having closed ductus arteriosus had platelet count ranging from 89000 – 336000 / µl.

ELBW VLBW No of preterm infants 28 18 PDA result 5 5 Closed ductus arteriosus 23 13 Platelet count in first 24 hours of life (PDA) ( /µl) 135000 – 147000 145000– 295000 Platelet count in first 24 hours (closed DA) ( /µl ) 92000 – 514000 89000 – 336000 Table 3: Summary incorporating birth weights, platelet count, and preterm ductus arteriosus Therefore, from above analyses it is notable that thrombocytopenia in the first 24 hours of life shows linkage with ductal tone whereas at higher platelet count ductus arteriosus (DA) tends to close. Therefore, it is noteworthy from analysis that birth weights significantly depend on gestation ages of preterm neonates. Nevertheless, there is no association between platelet count in the first 24 hours of life with either gestation or birth weights in preterm neonates. On the other hand, analyses incorporating gestational ages, ELBW and platelet counts were also conducted to explore risk factors for patent ductus arteriosus in preterm neonates and then results recorded in table 5 below.

No. Gestational age (weeks) ELBW (grams) Platelet count (per µl) 1. 01 Female 9 (50 %) 7 (58 %) 2 (33 %) 6 (43 %) 9 (50 %) 0. 25 Male 9 (50 %) 5 (42 %) 4 (67 %) 8 (57 %) 9 (50 %) 0. 03 BW (g) 1166 1173 1153 1158 1166 0. 01 GA (weeks) 28 28 28 29 29 0. 01 PLT > 250/nL 4 (22. 5 (56 %) out of 9 male infants never had PDA. On the other hand, another 9 (50 %) out of 18 VLBW infants were females, of these 9 female infants, 2 (22 %) had a PDA, 6 (67 %) out of 9 infants received antenatal corticotherapy to control the need of oxygen. In addition, 9 (100 %) underwent surfactant administration, thus prevented worsening of RDS. 7 (78 %) out of 9 female infants did not have PDA at the end. In addition, it is worth noting that the frequency of PDA was significantly higher in male preterm patients than in female preterm patients. On the other hand 23 (82 %) out of 28 infants never had patent ductus arteriosus out of which 9 (39 %) were female and 14 (61 %) were male infants. Also out of 28 ELBW preterm infants, 20 (71 %) got diagnosed for antenatal corticotherapy out of which 8 (40 %) were female infants whereas 12 (60 %) were male infants.

Antenatal corticotherapy helps in COX inhibition that regulates on excess need to oxygen since glucocorticoids changes DA’s sensitivity to PGE2. Thus hydrocortisone given to preterm neonates facilitates ductal constriction by decreasing the sensitivity of the ductus to the dilating action of PGE2. Besides, 23 (82 %) out of ELBW preterm infants under study were subjected to surfactant administration. LBW) have prevalence to patent ductus arteriosus thus contributes to significant morbidity and mortality in preterm infants since at 95 % confidence level it had significance p<0. 01, thus showing a strong relation with PDA risk. In addition, in VLBW many preterm infants (78 %) received antenatal corticotherapy treatment versus 71 % in ELBW preterm infants who obtained same antenatal corticotherapy treatment. Moreover, in VLBW preterm infants, all (100 %) infants underwent surfactant administration unlike in ELBW preterm infants where only 82 % of infants were subjected to surfactant administration.

On the other hand, platelet count did not show any difference between VLBW infants with or without PDA. 0 % of ELBW infants with or without patent ductus arteriosus. This observation suggested that all preterm neonates in ELBW underwent antenatal corticotherapy and surfactant administration leading to few cases of DA closure. Therefore from above analyses it is noticeable that very low birth weight (VLBW) is one of the key risks to PDA in preterm neonates. Besides, among the 3 VLBW infants with thrombocytopenia (platelet count < 150, 000 /µL) within the first 24 hours of life, 1 (33. 3 %) had a PDA whereas 4 (36. On the other hand, out of 3 thrombocytopenic ELBW infants (platelet count < 150, 000 /µL) in the first 24 hours after birth,1 (33. 3 %) had PDA where 4 (18. 2 %) non-thrombocytopenic infants (platelet count < 250, 000 /µL) out of 22 showed presence of PDA even after treatments.

Furthermore, out of 3 ELBW infants without thrombocytopenia (platelet count > 250, 000 /µL) in the first 24 hours after birth, none (0 %) showed presence of PDA. This was due to exposure of infants to medical treatments that as a result might have facilitated ductal constriction leading to no PDA. However, platelet count (Thrombocytopenia) in the first 24 hours after birth is not associated with the incidences of delayed ductus arteriosus closure since functional closure of ductus arteriosus mostly occurs in 72 hours after birth with higher proportion of hemodynamically significant patent ductus arteriosus (H - PDA)at 72 hours and 7 days of life. On the other hand, another retrospective analysis was done that involved gestation ages, birth weight, gender, multiplicity and administration of both 1 and 5– minute Apgar scores in preterm neonates.

All these were studied versus platelet counts in the first 24 hours after birth in preterm neonates. In addition, this cross sectional study was aimed at assessing any relationship between platelet count in the first 24 hours of life and delayed closure of patent ductus arteriosus. Thus groups were developed into A, B and C for various platelet count in the first 24 hours of life and also the symbol ‘n’ represents number of preterm infants per given group. 10 Without PDA 11 (73. 15 Table 8: Summary of Base Characteristics 20 5 24 10 28 11 8 4 24 8 Figure 3: Summary of Base characteristics From table 8 above, gestation ages and birth weights for the groups are calculated by working the averages. Moreover, it is noticeable that 15 (25. 4 %) preterm neonates in group A of average gestation age of 31 weeks had platelet count > 250, 000 per µL.

In addition, for group B in the first 24 hours after birth, preterm neonates had average gestation age of 29 weeks with platelet count < 250, 000 per µL. 7 %) were males. In addition, out of 11 female infants, 3 (27. 3 %) had patent ductus arteriosus while 8 (53. 3 %) of female infants never had PDA. However, 1 (25 %) out of 4 male infants had PDA whereas 3 (75 %) never had PDA. Furthermore, in group C, it was noteworthy that out of 12 (20. 3 %) of 59 preterm infants, 7 (58. 3 %) were females while 5 (41. 7 %) were males. Moreover, out of these 7 female infants, 2 (28. Out of 7, 4 (57. 1 %) were female whereas 3 (42. 9 %) were male infants. Out of these 4 female infants none had patent ductus arteriosus whereas of 3 male infants with < 7 Apgar score, 1 (33. 3 %) had PDA. 4 %) were males out of which 1 (50 %) had patency of ductus arteriosus. Apgar score of > 6 indicates normal life condition after birth.

Therefore in the first 24 hours of life, 13 (86. 7 %) of 15 preterm neonates had platelet count of < 150, 000 per µL with 5 (38. 5 %) cases of delayed closure o ductus arteriosus in the Neonatal intensive care unit and Latifa hospital in Dubai. 3 %) received I minute Apgar score below 7, where 5 (50 %) were female of which 3 (50 %) had PDA whereas 5 (50 %) out of 10 were male infants, of which 2 (40 %) had PDA in the first 24 hours of life. On the other hand, 11 (91. 7%) received 5 minute Apgar score > 6, where 7 (63. 6 %) were females of which 2 (28. 6 %) had PDA and 4 (36. Also, from multiplicity it is notable that singleton births are highest at group B at platelet count < 250, 000 per µL in the first 24 hours after birth. Additionally, most births are singletons with twin births moderate as triplet births showing the least occurrence among the three groups.

Moreover, in the three groups, singleton births record the highest cases of PDA of 16 (62. 5 %) as twin birth records 6 (37. 5 %) PDA cases with triplet births showing no case of PDA. However, platelet dysfunction due to critical illness or immaturity rather than platelet counts was found to contribute to pathogenesis of PDA. Furthermore, in regard to management and outcome, it was notable that four management system were performed with three possible outcomes. Moreover, the management methods included medical therapy (antenatal corticotherapy), surfactant administration, both medical and surgical ligation and surgical ligation. On the other hand outcomes included discharge with closed ductus arteriosus and discharge with patent ductus arteriosus. It is also worth noting that medical treatment was majorly applied in all cases (100 %). 6 and 5 cases respectively.

Therefore VLBW is observed to be a risk factor to patent ductus arteriosus. On the other hand, 15 preterm infants with thrombocytopenia (PLT < 150 000 / µL), 4 infants had PDA whereas 32 infants with normal platelet count between 150 000 / µL to 250 000 / µL, 8 had PDA. Also, 12 infants with very normal platelet of count >250 000 / µL, 4 had PDA according to table 6. Thus it was noticeable that infants with thrombocytopenia had equal cases with infants with very normal platelet count. However, impaired platelet function resulting from critical illness an immaturity rather than platelet number may contribute to PDA. In addition, thrombocytopenic neonates have been observed to be showing PDA cases that are even lower than preterm neonates with normal platelets. Moreover, lower gestational ages, extremely low birth weights and very low birth weights have been found to have association with platelet counts.

On the other hand, one interesting finding was that PDA significantly has prevalence on male neonates than female neonates. Thus this finding signals for studies to determine relationships between PDA and gender in order to establish best measures to execute for either gender. Finally, some tests were not performed that could show even the functions of platelets. References 1. Martin JA, Osterman MJ, Kirmeyer SE, Gregory EC. Measuring Gestational Age in Vital Statistics Data: Transitioning to the Obstetric Estimate. Natl Vital Stat Rep 2015; 64:1. Clyman RI (2000) Ibuprofen and patent ductusarteriosus. N Engl J Med 343: 728-730. Clyman RI, Waleh N, Black SM, Riemer RK, Mauray F, et al. (1998) Regulation of ductus arteriosus patency by nitric oxide in fetal lambs: the role of gestation, oxygen tension, and vasa vasorum.