A Randomized, Controlled Trial of Very Early Prophylactic Ligation of the Ductus Arteriosus in Babies Who Weighed 1000 g or Less at Birth

Abstract

We speculated that prophylactic ligation of the ductus arteriosus would reduce mortality and morbidity in very-low-birth-weight infants. To test this hypothesis, we randomly assigned 84 babies who weighed 1000 g or less at birth and required supplemental oxygen either to receive standard treatment (n = 44) or to undergo prophylactic surgical ligation of the ductus arteriosus on the day of birth (n = 40). The ductus was ligated in babies in the control group only if the shunt was hemodynamically important. All the babies were followed for one year. The incidence of necrotizing enterocolitis was reduced in the group that underwent prophylactic ligation (3 of 40 [8 percent]) as compared with the control group (13 of 44 [30 percent]; P = 0.002). The frequency of death, bronchopulmonary dysplasia, retinopathy of prematurity, and intraventricular hemorrhage was similar in both groups. Because early enteral feeding may have increased the incidence of necrotizing enterocolitis, we analyzed separately the babies who were fed early. Among the infants who were fed within 14 days of birth, those who underwent prophylactic ligation had a lower incidence of necrotizing enterocolitis (1 of 11 [9 percent]) than those who did not (13 of 24 [54 percent]; P = 0.001). Within the control group, the infants who were fed within 14 days of birth and whose ductus was ligated for medical reasons within 5 days of birth had a lower incidence of necrotizing enterocolitis (2 of 10 [20 percent]) than those whose ductus was ligated later or not at all (11 of 14 [79 percent]; P = 0.004). We conclude that early surgical closure of the ductus arteriosus reduces the risk of necrotizing enterocolitis in infants of very low birth weight who require supplemental oxygen.

Treatment of persistent patent ductus arteriosus in preterm infants: time to accept the null hypothesis?

“…36 Of 25 studies reporting the combined outcome of death or BPD, only one showed a reduction. 78 A single trial of prophylactic ligation described a decrease in NEC, 64 and one trial of ibuprofen prophylaxis found more NEC, 87 but most found no effect. IVH rates were lower in 3 trials of prophylactic indomethacin, 91,96,98 2 trials reported lower rates of IVH>grade 2, 100,106 and 30 found no effect.…”

“…29 Analysis of data from the Trial of Indomethacin Prophylaxis in Preterms trial suggested that ductal ligation compared with medical therapy alone is associated with more neurosensory impairment, BPD, and severe ROP. 34 Re-examining data from a randomized trial of prophylactic ligation, 64 Clyman et al 36 found that ligation increased the likelihood of requiring oxygen at 36 weeks PMA. In a retrospective regression analysis of factors associated with morbidity in infants treated for PDA, Chorne et al 35 found that chronic lung disease (oxygen use at 36 weeks PMA) is associated with ductal ligation, but not with use of >3 indomethacin doses, persistent PDA after indomethacin prophylaxis, or symptomatic PDA.…”

“…The other 23 trials reporting these endpoints, including 2002 subjects, failed to show reduction in either oxygen or ventilator use; one described prolongation of ventilation in the treatment group. 95 In the sole trial comparing ligation with nonintervention, Cassady et al 64 noted that infants who underwent ligation required longer ventilation (18 vs 12 days), supplemental oxygen (34 vs 24 days), and hospitalization (51 vs 43 days) than control subjects. Those differences were not statistically significant, but more surgically treated babies required ventilation for >45 days 64 and more required oxygen or mechanical ventilation at 36 weeks PMA.…”

“…95 In the sole trial comparing ligation with nonintervention, Cassady et al 64 noted that infants who underwent ligation required longer ventilation (18 vs 12 days), supplemental oxygen (34 vs 24 days), and hospitalization (51 vs 43 days) than control subjects. Those differences were not statistically significant, but more surgically treated babies required ventilation for >45 days 64 and more required oxygen or mechanical ventilation at 36 weeks PMA. 36 Closing the ductus does not shorten the duration of respiratory support required by preterm infants.…”

Avanços em enterocolite necrosante

“…54 In a controlled and randomized trial with premature infants with birth weights less than or equal to 1,000 g, Cassady et al observed that early surgical ligature of the ductus arteriosus reduces the chance of NEC developing. 55 From the eighties onwards indomethacin began to be used prophylactically for closing ductus arteriosus and prevention of intracranial hemorrhage. The research that followed showed an effective action in reducing these situations although side effects such as reduced splenic blood flow put a check on the universal recommendation for their usage.…”