Timing of Surgical PDA Ligation and Neonatal Outcomes

NCT ID: NCT04126512

Last Updated: 2020-06-09

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 78 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-09-25
• Study Completion Date: 2019-12-31

Brief Summary

Patent ductus arteriosus (PDA) is common among very preterm infants. If pharmacological closure is ineffective or contraindicated, surgical ligation may be required. Access to cardiothoracic surgery may influence the timing of ligation, with possible long-term clinical effects. This study protocol aims to assess the impact of different surgical management of PDA (bedside surgery vs. referral to a cardiac surgery centre) on ligation timing and neonatal clinical outcomes in two tertiary Neonatal Intensive Care Units.

Infants born at St. Orsola-Malpighi University Hospital, Bologna, Italy (group 1, bedside ligation) and Cambridge University Hospital, Cambridge, UK (group 2, referred to an off-site specialist paediatric cardiac surgical centre) who underwent PDA ligation between 2007 and 2018 will be included in this retrospective cohort study if fulfilling the following criteria: gestational age (GA) <32 weeks, birth weight (BW) <1500 g, inborn, absence of major malformation or congenital heart disease. Neonatal clinical outcomes will be collected and compared between the 2 groups.

Detailed Description

Patent ductus arteriosus (PDA) is a common condition among preterm infants, with an estimated incidence of 60% in extremely low birth weight infants (ELBW). Several factors, such as the relative oxygen hyposensitivity and increased sensitivity to prostaglandins of the immature tissues and the scarceness of ductal medial muscles, contribute to the patency of arterial duct in prematurely born neonates; as a consequence, the rate of spontaneous closure is inversely related to gestational age (GA) Over the past two decades, the persistence of a significant systemic-to-pulmonary shunt through the PDA has been associated with a higher incidence of adverse clinical outcomes, including acute pulmonary morbidities and bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC), feeding intolerance and increased mortality rates.

The management of PDA in very preterm infants first includes supportive therapy (e.g., restricted fluid intake, diuretics, increasing end-expiratory pressure) and targeted pharmacologic treatment with cyclooxygenase inhibitors (i.e., ibuprofen, indomethacin, acetaminophen) or paracetamol if spontaneous closure does not occur. However, when pharmacological closure is ineffective or contraindicated and the neonate requires extensive respiratory support, surgical ligation may be required. PDA ligation can be performed on-site, either at the infants' bedside or in the operation room, or off-site, if a paediatric cardiac surgery team is not available locally. By favouring one approach over the other, the setting may also contribute to influence the timing for PDA ligation. To date, literature comparing the effects of early vs. delayed PDA ligation on the main neonatal morbidities has led to contrasting results; hence, the optimal timing of surgical PDA closure remains a matter of debate among neonatologists.

This study aims to assess whether a different management of surgical PDA closure (on-site bedside ligation vs. referral to an off-site specialist paediatric cardiac surgical centre) may influence the timing of the intervention and the main neurological, respiratory and gastrointestinal clinical outcomes in very low birth weight (VLBW) preterm infants from two tertiary Neonatal Intensive Care Units with different paediatric cardiac surgery capabilities. Postoperative complications, mortality rates and the length of hospital stay will be also evaluated as secondary outcomes.

Methods Preterm infants <32 weeks' gestation born at the Neonatal Intensive Care Unit (NICU) of Cambridge University Hospital (CUH, Cambridge, UK) and of St. Orsola-Malpighi Hospital (SOM, Bologna, Italy) between January 1st, 2007 and June 30th, 2018 will be included in this retrospective study if, due to failed or contraindicated medical therapy, underwent surgical closure of PDA, judged hemodynamically significant (hsPDA) either on a clinical (hypotension, ventilator dependence, heart failure symptoms) or echocardiographic basis (left atrial/aortic root ratio >1.5, pulsatile left-to-right shunt and/or mean velocity in the left pulmonary artery >0.6 m/s). The presence of major congenital malformations, including congenital heart disease, was considered an exclusion criterion.

Echo-Doppler studies of each patient will be reviewed, and the following parameters from the latest pre-operative scan were will be recorded: PDA size and shunt characteristics (direction and pattern); left atrial to aortic root ratio; evidence of reversed end-diastolic flow in the descending aorta and/or in the middle or anterior cerebral artery (when evaluated). Contraindications and adverse effects of pharmacological treatment will be also reviewed. Failure of pharmacological treatment is defined by PDA persistency after at least two full pharmacological courses.

Neonatal characteristics and the following pre- and peri-operative data will be recorded: echocardiographic PDA characteristics, PDA management (supportive or pharmacological treatment, related adverse effects, rates of responsiveness and recurrence), post-conceptional age, days of life and weight at surgical intervention.

Neonatal outcomes include mortality rates, IVH, periventricular leukomalacia (PVL), NEC, sepsis (defined as relevant symptoms with positive blood culture and/or C reactive protein >25 mg/L and >5 days of antibiotic treatment), retinopathy of prematurity (ROP, any grade) and BPD (defined as any requirement for supplemental oxygen and/or positive-pressure respiratory support at 36 weeks' post-conceptional age). Length of hospital stay, time needed to achieve full enteral feeding, total duration of mechanical ventilation and the rate of supplemental oxygen need at hospital discharge will be also evaluated.

Conditions

Patent Ductus Arteriosus; Patent Ductus Arteriosus - Delayed Closure; Patent Ductus Arteriosus After Premature Birth

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Bedside ligation

Infants admitted to St. Orsola-Malpighi Hospital (SOM) NICU had their PDA ligated at bedside, with a timing of surgery dependent on the time schedule of the surgeons and anaesthesiologists.

PDA ligation

Intervention Type: OTHER

PDA ligation was performed at bedside, if a local cardiac surgery team was available, or in the case this service was not available, infants were referred to off-site specialist paediatric cardiac surgical services, where PDA ligation was performed.

Referred to specialist paediatric cardiac surgery centre

Due to the unavailability of local cardiac surgery, infants admitted to the Cambridge University Hospital (CUH) NICU were referred to specialist paediatric cardiac surgical centres, where PDA ligation was performed. In these cases, the surgical timing depended on both bed availability at the referral centre and the availability of the neonatal transfer team.

PDA ligation

Intervention Type: OTHER

PDA ligation was performed at bedside, if a local cardiac surgery team was available, or in the case this service was not available, infants were referred to off-site specialist paediatric cardiac surgical services, where PDA ligation was performed.

Interventions

PDA ligation

PDA ligation was performed at bedside, if a local cardiac surgery team was available, or in the case this service was not available, infants were referred to off-site specialist paediatric cardiac surgical services, where PDA ligation was performed.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Gestational age <32 weeks' gestation
• Surgical PDA ligation

Exclusion Criteria

• Major congenital malformations
• Congenital heart disease

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 6 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IRCCS Azienda Ospedaliero-Universitaria di Bologna

OTHER

Sponsor Role: lead

Responsible Party

Silvia Martini

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Silvia Martini, MD

Role: PRINCIPAL_INVESTIGATOR

Sant'Orsola-Malpighi University Hospital

Locations

S. Orsola-Malpighi University Hospital

Bologna, Emilia-Romagna, Italy

The Rosie Hospital, Cambridge University Hospitals

Cambridge, , United Kingdom

Countries

Italy; United Kingdom

Other Identifiers

PDA-lig-SO-CAM

Identifier Type: -

Identifier Source: org_study_id