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| Name | Class |
|---|---|
| Swiss Neonatal Network | NETWORK |
| SwissPedNet | OTHER |
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The aim of this study is to determine whether restricted fluid intake (135 ±5 mL/kg/day) compared to liberal fluid intake (165 ±5 mL/kg/day) from day 8 of life reduces the incidence of bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age or prior death in preterm infants born <30 weeks gestational age.
Complications of preterm birth remain the leading cause of death in children under five years of age worldwide, accounting for approximately one million deaths annually. Among the survivors, bronchopulmonary dysplasia (BPD) is the most common severe complication. BPD is a chronic lung disease characterized by prolonged need for respiratory support and oxygen therapy, poor postnatal growth, and long-term impairments in lung function and neurodevelopment.
Despite advancements in neonatal care, BPD is the most common chronic lung disease in infancy and associated with increased mortality, repeated hospitalisation throughout childhood, impaired lung function up into adulthood, and long-term neurodevelopmental impairment. The incidence of BPD has remained stable over the past 15 years. This is likely due to the improved survival of extremely preterm infants, who are at the highest risk for BPD.
A key feature of evolving BPD is the accumulation of interstitial pulmonary edema, which reduces lung compliance and increases the need for respiratory support, thereby perpetuating a cycle of lung damage.
Currently, diuretics are sometimes used to manage pulmonary edema in preterm infants. While they can improve lung function in the short term, they come with potential risks including bone demineralization, nephrotoxicity, electrolyte imbalances, and impaired growth.
As a potentially safer alternative, fluid restriction is sometimes used to prevent or manage pulmonary edema. It is hypothesized to improve lung mechanics and reduce the need for respiratory support, without the adverse effects associated with medications. However, there is no robust evidence on optimal fluid targets in these patients.
SwissNeoNet, consisting of all nine Swiss NICUs, is a mandatory national registry, where data on all infants born before 32 weeks of gestation and/or with a birth weight < 1501 g are collected. Fluid management practices vary among Swiss neonatal intensive care units (NICUs) following international guidelines recommending 135 to 180 mL/kg/day of fluids. This variation may contribute to the differing rates of BPD and mortality observed across centers, but fluid intake is not routinely captured in SwissNeoNet data, making it difficult to assess its impact.
In summary, although fluid restriction shows potential as a simple and low-risk intervention to reduce the incidence of BPD, current evidence is insufficient to support its routine use. There is a clear need for a robust, contemporary, and pragmatic trial to evaluate whether fluid restriction, started after the first week of life, can safely and effectively reduce the incidence of BPD or death in very preterm infants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fluid restriction | Experimental | Fluid restriction strategy (fluid target 135 ±5 mL/kg/d). This is standard of care. |
|
| Liberal fluid intake | Active Comparator | Liberal fluid intake strategy (fluid target 165 ± 5 mL/kg/d) in line with international best practice recommendations on nutrition. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fluid restriction | Other | Fluid restriction strategy (fluid target 135 ±5 mL/kg/d) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Bronchopulmonary dysplasia (BPD) | Proportion of infants with BPD measured at 36 weeks postmenstrual age or prior death. | From enrolment to 36 weeks postmenstrual age |
| Measure | Description | Time Frame |
|---|---|---|
| Complications of prematurity | Major complications of prematurity including necrotising enterocolitis ≥ Bell's stage 2, retinopathy of prematurity requiring treatment, patent ductus arteriosus requiring treatment, abnormal brain ultrasound, late onset sepsis | From enrolment to 36 weeks postmenstrual age |
| Days to reach full feeds |
| Measure | Description | Time Frame |
|---|---|---|
| Growth | Growth (weight, length, and head circumference z-score) | from 36 weeks postmenstrual age, 6-12 and 18-24 months post-term |
| Respiratory outcome | Respiratory outcome as per Basel-Bern-Infant-Lung-Development cohort study questionnaire |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Anne Carrer | Contact | +4161 704 2853 | anne.carrer@ukbb.ch | |
| Michel Schrutt | Contact | relief@ukbb.ch |
| Name | Affiliation | Role |
|---|---|---|
| Sven Schulzke, Prof.MD | University Children's Hospital Basel | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kantonsspital Aarau AG, Klinik für Kinder u. Jugendliche | Recruiting | Aarau | 5001 | Switzerland |
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Pragmatic, registry-linked, multicentre, open-label, cluster-randomised, multiple period, cross-over, effectiveness trial
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| Liberal fluid intake |
| Other |
Liberal fluid intake strategy (fluid target 165 ± 5 mL/kg/d) |
|
Days to reach full feeds defined as 150 ml/kg/d or being off parenteral nutrition |
| From enrolment to 36 weeks postmenstrual age |
| Need of diuretics | Treatment with diuretics (days on diuretics) | From enrolment to 36 weeks postmenstrual age |
| Need of corticosteroids | Systemic postnatal corticosteroids for prevention or treatment of bronchopulmonary dysplasia | From enrolment to 36 weeks postmenstrual age |
| Need of respiratory support | Duration of mechanical ventilation, non-invasive respiratory support, total positive pressure support, supplemental oxygen support, supplemental home oxygen, home ventilation | At first discharge home, on average 37 weeks postmenstrual age |
| Growth | difference in weight, length, and head circumference z-score at 36 weeks postmenstrual age and at birth, respectively | at birth and 36 weeks postmenstrual age |
| Daily caloric intake | Daily caloric intake from day 8 of life to 36 weeks postmenstrual age | From enrolment to 36 weeks postmenstrual age |
| Dehydration | Dehydration (sodium level ≥ 150 mmol/L plus clinical signs of dehydration) | From enrolment to 36 weeks postmenstrual age |
| Fluid overload | Fluid overload (sodium level ≤ 130 mmol/L plus clinical signs of fluid overload) | From enrolment to 36 weeks postmenstrual age |
| Age at discharge | Postmenstrual age at discharge home | At first discharge home, on average 37 weeks postmenstrual age |
| Tube feeding | Tube feeding at discharge home | At first discharge home, on average 37 weeks postmenstrual age |
| from 36 weeks postmenstrual age, 6-12 and 18-24 months post-term |
| Visits to the emergency | Visits to the emergency department from discharge to 6-12 months for any reason | From discharge to 6-12 and 18-24 months |
| Neurodevelopmental outcome | Neurodevelopmental outcome as per PARCA-R questionnaire | from enrolment to 18-24 months post-term |
| University Children's Hospital Basel (UKBB) | Recruiting | Basel | 4056 | Switzerland |
|
| Inselspital Bern, Kinderklinik | Recruiting | Bern | 3010 | Switzerland |
|
| Kantonsspital Graubünden, Departement Kinder- und Jugendmedizin | Recruiting | Chur | 7000 | Switzerland |
|
| Hôpitaux universitaires de Genève (HUG), Unité de Néonatologie | Recruiting | Geneva | 1205 | Switzerland |
|
| Centre hospitalier universitaire vaudois (CHUV) - Service de néonatologie | Recruiting | Lausanne | 1011 | Switzerland |
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| Luzerner Kantonsspital, Kinderspital | Recruiting | Lucerne | 6000 | Switzerland |
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| Ostschweizer Kinderspital & Neonatologie und Frauenklinik KSSG, Perinatalzentrum St. Gallen | Recruiting | Sankt Gallen | 9006 | Switzerland |
|
| UniversitätsSpital Zürich, Klinik für Neonatologie | Recruiting | Zurich | 8091 | Switzerland |
|
| ID | Term |
|---|---|
| D001997 | Bronchopulmonary Dysplasia |
| ID | Term |
|---|---|
| D055397 | Ventilator-Induced Lung Injury |
| D055370 | Lung Injury |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007235 | Infant, Premature, Diseases |
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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