An Exploratory Physiological Study of Post-operative Recovery in Surgical Neonates and Dimethylarginine:Arginine Levels

NCT06731855 | Recruiting

• 1 other identifier: 349681
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

The SuNDiAL study will measure levels of two naturally occurring amino acids: Arginine and Asymmetric Dimethylarginine (ADMA) in neonates undergoing abdominal surgery in the first 5 days of life due to congenital abdominal malformations as the participants recover from surgery. The investigators hypothesise that the relationship between Arginine and ADMA may be useful in predicting recovery and complications in babies who have had abdominal surgery due to previous research published in adult patients undergoing abdominal surgery. If this relationship is found to be useful there may be options for developing treatments (such as arginine supplementation) in the future to improve recovery and reduce complications in neonates undergoing abdominal surgery. Neonates born after 35 weeks gestation who have a congenital abdominal malformation who require abdominal surgery in the first 5 days will be eligible to participate in the SuNDiAL study. Arginine and ADMA will be measured from blood samples that are left over from the participant's blood tests that are taken as part of their routine clinical care. The investigators will measure Arginine and ADMA preoperatively and at least 10 points in the 30 days following their surgery, or until the participant fully recovers from surgery (which ever comes first). There is no intervention in the SuNDiAL study, and there will be no extra blood or blood samples taken. Serums samples that are left over from the babies routine clinical blood tests will be stored securely in the hospitals laboratory until analysis for Arginine and ADMA. The levels of Arginine and ADMA will be compared to the time it takes the participants to recover from surgery and any complications that may arise following surgery. During the study the study team will use the participants electronic medical record to establish when the participant became fully established on oral feeding and monitor for any complications that occurred during their recovery.

Conditions

Gastroschisis; Congenital Diaphragmatic Hernia; Duodenal Atresia; Oesophageal Atresia With Tracheo-Oesophageal Fistula; Oesophageal Atresia; Exomphalos

Keywords

Neonatal; Abdominal Surgery; Asymmetric Dimethylarginine; ADMA; Arginine; Recovery; Neonate

Outcome Measures

Primary Outcomes (1)

• The relationship between Arginine, ADMA and the Arginine to ADMA ratio in comparison to the time taken to recover from abdominal surgery.

  The primary outcome measure will investigate the level of plasma ADMA, arginine and ARG/ADMA ratio preoperatively and in the immediate postoperative period (5 days) in infants stratified according to typical (\<21 days) or prolonged (\>21 days) postoperative PN dependency. The following measures will be compared between the typical and prolonged recover groups: 1. The pre-operative level (peak/trough as appropriate) of Arginine, ADMA and the ARG/ADMA ratio. 2. The post-operative level (peak/trough as appropriate) within 5 days of surgery of arginine, ADMA and the ARG/ADMA ratio and its relationship to postoperative PN days. 3. The maximum per-infant difference between pre-operative and post-operative levels as defined in a) and b).

  From Enrolment to 30 days following surgery

Secondary Outcomes (6)

• Develop a mathematical model to describe the entire postoperative (30 days) trajectory of Arginine, ADMA and the ARG/ADMA ratio in relation to PN dependency.

  From enrolment until day 30 post operatively.

• To study the relationship over time between nutritional intake and arginine, ADMA and the ARG/ADMA ratio.

  From enrolment until day 30 postoperatively.

• The relationship over time between clinically monitored postoperative inflammatory and biochemical markers and arginine, ADMA and the ARG/ADMA ratio

  From Enrolment to 30 days post operatively

• Impact of individual episodes (including duration) of any recognised postoperative complication (eg wound complications, bowel complications, sepsis) on the recovery time and the mathematical model described above.

  From enrolment to 30 days post operation

• Weight Gain/head growth over the study period in relationship to Arginine, ADMA and Arginine to ADMA ratio.

  Enrolment to 30 days post operation.

Study Arms (1)

Study Population

Infants born \>35 weeks gestation and have a condition requiring major gastrointestinal surgery within 5 days (120 hours) of birth. This is expected to include predominantly congenital gut malformations such as gastroschisis, gut atresias, volvulus and congenital diaphragmatic hernia (who are stable enough for surgery in this time frame).

Procedure: Abdominal Surgery for congenital gut malformation in the first 5 days of life.

Interventions

Abdominal Surgery for congenital gut malformation in the first 5 days of life. PROCEDURE

Abdominal Surgery for congenital gut malformation in the first 5 days of life. Procedure will depend on the congenital gut malformation.

Study Population

Eligibility Criteria

• Age: Up to 5 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

The study population with be of 30 infants born \>35 weeks gestation and has a condition requiring major gastrointestinal surgery within 5 days (120 hours) of birth. This is expected to include predominantly congenital gut malformations: gastroschisis, gut atresias, volvulus and congenital diaphragmatic hernia (who are stable enough for surgery in this time frame). Patient will be recruited over a 1 year period. These infants will be born at Liverpool Women's Hospital or at their local hospital in the north west of England region, and transferred to Alder Hey Children's Hospital for their operation, either directly or via Liverpool Women's Hospital Neonatal Intensive Care Unit. They will recover in Alder Hey Children's Hospital's Paediatric Intensive Care Unit or Neonatal Surgical Unit and may later be transferred back to Liverpool Women's Hospital.

You may qualify if:

• Infants born \>35 weeks gestation
• Have a condition requiring major gastrointestinal surgery
• Surgery within the first 5 days (120 hours) following birth (including congenital diaphragmatic hernia who are stable enough for surgery in this time frame).
• Parent(s)/guardian(s) must have a comprehensive understanding of written and spoken English, sufficient to provide informed using the translation services available to the research team.
• Must be willing and able to provide informed consent in order to take part in the study

You may not qualify if:

• Infants who are unlikely to survive because of poor immediate postoperative condition.
• Infants known (or suspected to have) a diagnosis of inborn error of metabolism or serious liver dysfunction.
• Parent(s)/guardian(s) who are unable to give informed consent.
• Infants who it is not possible to obtain the minimum required residual serum samples from routine biochemical blood testing as outlined in the study schedule

Sponsors & Collaborators

• Liverpool Women's NHS Foundation Trust: lead
• Alder Hey Children's NHS Foundation Trust: collaborator

Study Sites (2)

Alder Hey Childrens Hospital NSH Foundation Trust

Liverpool, Merseyside, L12 2AP, United Kingdom

RECRUITING

Liverpool Womens Hospital NHS Foundation Trust

Liverpool, Merseyside, L8 7SS, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum

MeSH Terms

Conditions

Gastroschisis; Hernias, Diaphragmatic, Congenital; Familial duodenal atresia; Esophageal atresia with or without tracheoesophageal fistula; Esophageal Atresia; Hernia, Umbilical

Condition Hierarchy (Ancestors)

Musculoskeletal Abnormalities; Musculoskeletal Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hernia, Abdominal; Hernia; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Hernia, Diaphragmatic; Internal Hernia; Digestive System Abnormalities; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Infant, Newborn, Diseases; Hernia, Ventral

Central Study Contacts

Colin Morgan

CONTACT

0151 7024382; colin.morgan@lwh.nhs.uk

Joshua Stead

CONTACT

0151 7024382; joshua.stead@nhs.net

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2024
• First Posted: December 12, 2024
• Study Start: February 5, 2024
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: September 29, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)