Bronchopulmonary Dysplasia (BPD)NCT06940856
Chloride Imbalance in Preterm Infants
An observational study of Bronchopulmonary Dysplasia (BPD) and Mortality Prediction, run by Kanuni Sultan Suleyman Training and Research Hospital at 1 site in Turkey (Türkiye).
Trial summary
In adults and children low or high blood chloride levels are linked to the risk of death. The aim of this observational study is to determine whether there is a relationship between low or high blood chloride levels and the risk of death or long-term lung problems. Read more about this study
- Who is it for?
- Ages 1 hour to 6 weeks
- Conditions the study is for
- Bronchopulmonary Dysplasia (BPD), Mortality Prediction, Chloride Disorder
- What is being tested?
- Incomplete response, Complete response and Bad response
- How many people
- 500 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 15 May 2025to 15 Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 hour to 6 weeks
- All sexes
- No healthy volunteers
- Child
Study population: Study population includes infants admitted to the Neonatal Intensive Care Unit at Kanuni Sultan Suleyman Training and Research Hospital over the past 5 years.
Who may be able to join
- Infants born <32 weeks PMA or <1500 grams
- Infants admitted to NICU within the first 24 hours
Who cannot join
- Infants with major congenital anomalies
- Infants with chromosomal anomalies
- Infants who have undergone enterostomy operation
- Infants admitted to NICU after the first 24 hours
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Turkey (Türkiye)1 site, 1 recruiting
- Recruiting
Kanuni Sultan Suleyman Education and Research Hospital
Istanbul, Turkey
Gokhan Buyukkale, +905057743497, gbuyukkale@hotmail.com
Murat Köstü, MD, +905323932616, murat.kostu@saglik.gov.tr
About this study
Official title: The Impact of Chloride Imbalance on BPD Development and Mortality in Preterm Infants
In adults and children low or high blood chloride levels are linked to the risk of death. The aim of this observational study is to determine whether there is a relationship between low or high blood chloride levels and the risk of death or long-term lung problems. We will also learn the risk factors and associated conditions of high or low blood chloride levels. We will include infants born before 32 weeks of pregnancy or have a birth weight of less than 1500 grams in the study. The main question it aims to answer is:
Is there a relationship between low or high blood chloride levels in the first 4-6 weeks of life and risk of death or long-term lung problems in premature babies? We will examine the medical reports of babies who were followed up in neonatal intensive care unit over the past 5 years.
Read the detailed description
Chloride balance usually parallels that of sodium, and it is strictly correlated to the extracellular volume balance. In addition plasma chloride and bicarbonate concentrations are inversely regulated through the chloride-bicarbonate exchange pump in renal collecting ducts, independent of sodium. Consequently, plasma chloride levels are closely correlated with pH (hypochloremia/metabolic alkalosis, hyperchloremia/metabolic acidosis).
In adults, dyschloremia is associated with mortality, acute kidney injury, and prolonged hospital stay. Hyperchloremia is often associated with severe sepsis. It has been shown that resuscitation with high-chloride fluids (eg: saline solution) instead of balanced fluids (e.g., Ringer's lactate) increases the need for inotropes in critically ill adults. Similarly, hyperchloremia in septic pediatric patients is linked to acute renal injury requiring dialysis, increased inotropic support, and mortality. In 1979, infants fed with chloride-deficient formula were reported to develop impaired head growth and neurologic sequelae.
Although serum chloride is routinely measured in neonatal intensive care units, its clinical significance is often overlooked. For this reason unlike sodium, literature on chloride metabolism in preterm infants is exceedingly limited.
Advancements in perinatal care over the past 50 years have significantly improved survival rates in preterm infants. However, a large proportion of very preterm infants who survive the neonatal period develop bronchopulmonary dysplasia (BPD). BPD, a chronic lung disease, manifests clinically through persistent respiratory support and/or oxygen dependency. Despite efforts to optimize neonatal care -such as controlled oxygen usage, non-invasive ventilation, volume-guarantee techniques, high-frequency ventilation, and caffeine therapy- BPD remains the most common complication among preterm infants and is associated with increased morbidity and mortality.
It has been suggested that extracellular volume expansion (edema) plays a role in the pathophysiology of BPD. Perlman et al.'s 1986 study demonstrated that infants who died from BPD exhibited hypochloremia, metabolic alkalosis, and complications like inadequate head growth, more frequently than those who survived. These findings highlight the critical importance of chloride imbalance in neonates, similar to findings in adult and pediatric populations.
This study aims to investigate the relationship between chloride balance and two major outcomes-mortality and the development of BPD-in preterm infants. Infants <32 weeks postmentruel age (PMA) or weighing less than 1500 grams will be enrolled in the study. We also plan to explore the relationship of dyschloremia with other outcomes of prematurity (eg: patent ductus arteriosus, ventilator dependency, retinopathy of prematurity (ROP), necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia, hospital stay. Lastly we plan to explore the risk factors and clinical/laboratory conditions that are associated with chloride level abnormalities.
If this study yields findings that underscore the clinical significance of chloride levels in preterm infants, similar to adults and children, then close monitoring of chloride balance and appropriate interventions could potentially reduce mortality and BPD incidence in preterm infants. Conversely, if results indicate that chloride balance lacks clinical significance in preterm infants, this will also contribute valuable information to the current literature.
- Being tested
- Incomplete response, Complete response, Bad response
- Keywords
- Bronchopulmonary dysplasia, Preterm infant, Mortality, Chloride imbalance
- Medical subject headings
- Bronchopulmonary Dysplasia, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Incomplete responseOther
Infants died before 36 weeks PMA, infants diagnosed to have BPD at 36 weeks PMA and infants developed major complications before 36 weeks PMA:
- >Stage 2 necrotizing enterocolitis according to Bell classification
- Hemodynamically significant patent ductus arteriosus
- >Grade 2 intraventricular hemorrhage,
- Retinopathy of prematurity, ICROP classification stage >2
- >Stage 2 cystic periventricular leukomalacia
- Ventricular dilatation/hydrocephalus requiring intervention
Complete responseOther
Infants discharged before 36 weeks PMA and infants who reached 36 weeks PMA without BPD and major complications:
- >Stage 2 necrotizing enterocolitis according to Bell classification
- Hemodynamically significant patent ductus arteriosus
- >Grade 2 intraventricular hemorrhage,
- Retinopathy of prematurity, ICROP classification stage >2
- >Stage 2 cystic periventricular leukomalacia
- Ventricular dilatation/hydrocephalus requiring intervention
Bad responseOther
Infants died before 36 weeks PMA and infants diagnosed to have BPD at 36 weeks PMA
| Study group | Role | What they receive |
|---|---|---|
| Infants without dyschloremia | Infants with serum chloride levels within reference range before 36 weeks PMA Receives: Other: Incomplete response; Other: Complete response; Other: Bad response | |
| Infants with dyschloremia | Infants with serum chloride levels <96 mEq/l and >110 mEq/l before 36 weeks PMA Receives: Other: Incomplete response; Other: Complete response; Other: Bad response |
What is being measured
The primary outcome is the main question the study is designed to answer.
BPD
BPD at 36 weeks PMA
Measured: From enrollment to the end of 36 weeks PMA
Secondary outcomes (1)
Mortality
Mortality within 36 weeks PMA
Measured: From enrollment to the end of 36 weeks PMA
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2025
- Study start15 May 2025
- Primary completion15 Apr 2027 (estimated)
- Study completion15 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Bronchopulmonary Dysplasia (BPD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kanuni Sultan Suleyman Training and Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Murat Köstü, Kanuni Sultan Suleyman Training and Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06940856
- Sponsor's protocol ID
- Murat Kostu
- Status last verified
- Aug 2025
- First submitted
- 7 Apr 2025
- Last updated
- 6 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: We are not sure that local ethics committee that approved our study will allow IPD sharing
Publications
Perlman JM, Moore V, Siegel MJ, Dawson J. Is chloride depletion an important contributing cause of death in infants with bronchopulmonary dysplasia? Pediatrics. 1986 Feb;77(2):212-6.
PubMed 2935779Thebaud B, Goss KN, Laughon M, Whitsett JA, Abman SH, Steinhorn RH, Aschner JL, Davis PG, McGrath-Morrow SA, Soll RF, Jobe AH. Bronchopulmonary dysplasia. Nat Rev Dis Primers. 2019 Nov 14;5(1):78. doi: 10.1038/s41572-019-0127-7.
PubMed 31727986Chutorian AM, LaScala CP, Ores CN, Nass R. Cerebral dysfunction following infantile dietary chloride deficiency. Pediatr Neurol. 1985 Nov-Dec;1(6):335-41. doi: 10.1016/0887-8994(85)90067-0.
PubMed 3880419Khan AH, Gai J, Faruque F, Bost JE, Patel AK, Pollack MM. Pediatric Mortality and Acute Kidney Injury Are Associated with Chloride Abnormalities in Intensive Care Units in the United States: A Multicenter Observational Study. J Pediatr Intensive Care. 2020 Nov 23;11(2):91-99. doi: 10.1055/s-0040-1719172. eCollection 2022 Jun.
PubMed 35734213Kalikkot Thekkeveedu R, Ramarao S, Dankhara N, Alur P. Hypochloremia Secondary to Diuretics in Preterm Infants: Should Clinicians Pay Close Attention? Glob Pediatr Health. 2021 Feb 4;8:2333794X21991014. doi: 10.1177/2333794X21991014. eCollection 2021.
PubMed 33614850Iacobelli S, Kermorvant-Duchemin E, Bonsante F, Lapillonne A, Gouyon JB. Chloride Balance in Preterm Infants during the First Week of Life. Int J Pediatr. 2012;2012:931597. doi: 10.1155/2012/931597. Epub 2012 Mar 8.
PubMed 22505945
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Chloride Imbalance on BPD Development and Mortality in Preterm Infants
- ClinicalTrials.gov ID
- NCT06940856
- Acronym / sponsor ID
- Murat Kostu
- Keywords
- Bronchopulmonary dysplasia, Preterm infant, Mortality, Chloride imbalance
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Kanuni Sultan Suleyman Training and Research HospitalUniversity, hospital or other
- Study start
- 15 May 2025 (actual)
- Primary completion
- 15 Apr 2027 (estimated)
- Study completion
- 15 Dec 2027 (estimated)
- First posted
- 23 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In adults and children low or high blood chloride levels are linked to the risk of death. The aim of this observational study is to determine whether there is a relationship between low or high blood chloride levels and the risk of death or long-term lung problems. We will also learn the risk factors and associated conditions of high or low blood chloride levels. We will include infants born before 32 weeks of pregnancy or have a birth weight of less than 1500 grams in the study. The main question it aims to answer is:
Is there a relationship between low or high blood chloride levels in the first 4-6 weeks of life and risk of death or long-term lung problems in premature babies? We will examine the medical reports of babies who were followed up in neonatal intensive care unit over the past 5 years.
Detailed description
Chloride balance usually parallels that of sodium, and it is strictly correlated to the extracellular volume balance. In addition plasma chloride and bicarbonate concentrations are inversely regulated through the chloride-bicarbonate exchange pump in renal collecting ducts, independent of sodium. Consequently, plasma chloride levels are closely correlated with pH (hypochloremia/metabolic alkalosis, hyperchloremia/metabolic acidosis).
In adults, dyschloremia is associated with mortality, acute kidney injury, and prolonged hospital stay. Hyperchloremia is often associated with severe sepsis. It has been shown that resuscitation with high-chloride fluids (eg: saline solution) instead of balanced fluids (e.g., Ringer's lactate) increases the need for inotropes in critically ill adults. Similarly, hyperchloremia in septic pediatric patients is linked to acute renal injury requiring dialysis, increased inotropic support, and mortality. In 1979, infants fed with chloride-deficient formula were reported to develop impaired head growth and neurologic sequelae.
Although serum chloride is routinely measured in neonatal intensive care units, its clinical significance is often overlooked. For this reason unlike sodium, literature on chloride metabolism in preterm infants is exceedingly limited.
Advancements in perinatal care over the past 50 years have significantly improved survival rates in preterm infants. However, a large proportion of very preterm infants who survive the neonatal period develop bronchopulmonary dysplasia (BPD). BPD, a chronic lung disease, manifests clinically through persistent respiratory support and/or oxygen dependency. Despite efforts to optimize neonatal care -such as controlled oxygen usage, non-invasive ventilation, volume-guarantee techniques, high-frequency ventilation, and caffeine therapy- BPD remains the most common complication among preterm infants and is associated with increased morbidity and mortality.
It has been suggested that extracellular volume expansion (edema) plays a role in the pathophysiology of BPD. Perlman et al.'s 1986 study demonstrated that infants who died from BPD exhibited hypochloremia, metabolic alkalosis, and complications like inadequate head growth, more frequently than those who survived. These findings highlight the critical importance of chloride imbalance in neonates, similar to findings in adult and pediatric populations.
This study aims to investigate the relationship between chloride balance and two major outcomes-mortality and the development of BPD-in preterm infants. Infants <32 weeks postmentruel age (PMA) or weighing less than 1500 grams will be enrolled in the study. We also plan to explore the relationship of dyschloremia with other outcomes of prematurity (eg: patent ductus arteriosus, ventilator dependency, retinopathy of prematurity (ROP), necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia, hospital stay. Lastly we plan to explore the risk factors and clinical/laboratory conditions that are associated with chloride level abnormalities.
If this study yields findings that underscore the clinical significance of chloride levels in preterm infants, similar to adults and children, then close monitoring of chloride balance and appropriate interventions could potentially reduce mortality and BPD incidence in preterm infants. Conversely, if results indicate that chloride balance lacks clinical significance in preterm infants, this will also contribute valuable information to the current literature.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Infants without dyschloremia | – | Other: Incomplete response, Other: Complete response, Other: Bad responseInfants with serum chloride levels within reference range before 36 weeks PMA |
| Infants with dyschloremia | – | Other: Incomplete response, Other: Complete response, Other: Bad responseInfants with serum chloride levels <96 mEq/l and >110 mEq/l before 36 weeks PMA |
Who may qualify
- Ages
- 1 hour to 6 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Study population includes infants admitted to the Neonatal Intensive Care Unit at Kanuni Sultan Suleyman Training and Research Hospital over the past 5 years.
Key inclusion criteria (2 listed)
- Infants born <32 weeks PMA or <1500 grams
- Infants admitted to NICU within the first 24 hours
Key exclusion criteria (4 listed)
- Infants with major congenital anomalies
- Infants with chromosomal anomalies
- Infants who have undergone enterostomy operation
- Infants admitted to NICU after the first 24 hours
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Incomplete responseInfants died before 36 weeks PMA, infants diagnosed to have BPD at 36 weeks PMA and infants developed major complications before 36 weeks PMA: 1. >Stage 2 necrotizing enterocolitis according to Bell classification 2. Hemodynamically significant patent ductus arteriosus 3. >Grade 2 intraventricular hemorrhage, 4. Retinopathy of prematurity, ICROP classification stage >2 5. >Stage 2 cystic periventricular leukomalacia 6. Ventricular dilatation/hydrocephalus requiring intervention | Other | Infants with dyschloremia, Infants without dyschloremia |
| Complete responseInfants discharged before 36 weeks PMA and infants who reached 36 weeks PMA without BPD and major complications: 1. >Stage 2 necrotizing enterocolitis according to Bell classification 2. Hemodynamically significant patent ductus arteriosus 3. >Grade 2 intraventricular hemorrhage, 4. Retinopathy of prematurity, ICROP classification stage >2 5. >Stage 2 cystic periventricular leukomalacia 6. Ventricular dilatation/hydrocephalus requiring intervention | Other | Infants with dyschloremia, Infants without dyschloremia |
| Bad responseInfants died before 36 weeks PMA and infants diagnosed to have BPD at 36 weeks PMA | Other | Infants with dyschloremia, Infants without dyschloremia |
Primary outcome
BPD
Time frame: From enrollment to the end of 36 weeks PMA
BPD at 36 weeks PMA
1 secondary outcome
Mortality
Time frame: From enrollment to the end of 36 weeks PMA
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2026.
- Results publication: PubMed 2935779Perlman JM, Moore V, Siegel MJ, Dawson J. Is chloride depletion an important contributing cause of death in infants with bronchopulmonary dysplasia? Pediatrics. 1986 Feb;77(2):212-6.
- Results publication: PubMed 31727986Thebaud B, Goss KN, Laughon M, Whitsett JA, Abman SH, Steinhorn RH, Aschner JL, Davis PG, McGrath-Morrow SA, Soll RF, Jobe AH. Bronchopulmonary dysplasia. Nat Rev Dis Primers. 2019 Nov 14;5(1):78. doi: 10.1038/s41572-019-0127-7.
- Results publication: PubMed 3880419Chutorian AM, LaScala CP, Ores CN, Nass R. Cerebral dysfunction following infantile dietary chloride deficiency. Pediatr Neurol. 1985 Nov-Dec;1(6):335-41. doi: 10.1016/0887-8994(85)90067-0.
- Results publication: PubMed 35734213Khan AH, Gai J, Faruque F, Bost JE, Patel AK, Pollack MM. Pediatric Mortality and Acute Kidney Injury Are Associated with Chloride Abnormalities in Intensive Care Units in the United States: A Multicenter Observational Study. J Pediatr Intensive Care. 2020 Nov 23;11(2):91-99. doi: 10.1055/s-0040-1719172. eCollection 2022 Jun.
- Results publication: PubMed 33614850Kalikkot Thekkeveedu R, Ramarao S, Dankhara N, Alur P. Hypochloremia Secondary to Diuretics in Preterm Infants: Should Clinicians Pay Close Attention? Glob Pediatr Health. 2021 Feb 4;8:2333794X21991014. doi: 10.1177/2333794X21991014. eCollection 2021.
- Results publication: PubMed 22505945Iacobelli S, Kermorvant-Duchemin E, Bonsante F, Lapillonne A, Gouyon JB. Chloride Balance in Preterm Infants during the First Week of Life. Int J Pediatr. 2012;2012:931597. doi: 10.1155/2012/931597. Epub 2012 Mar 8.
- Individual participant dataSharing planned: Undecided. We are not sure that local ethics committee that approved our study will allow IPD sharing
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Bronchopulmonary Dysplasia (BPD) and Mortality Prediction, run by Kanuni Sultan Suleyman Training and Research Hospital at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Murat Köstü (+905323932616, murat.kostu@saglik.gov.tr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
BPD (time frame: From enrollment to the end of 36 weeks PMA). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06940856, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2026.