Enterocolitis, Necrotizing, Infant, Low Birth Weight, Infant, Newborn, Infant, Premature, Infant, Small for Gestational Age, Intestinal Perforation
Conditions
Keywords
NICHD Neonatal Research Network, Very Low Birth Weight (VLBW), Extremely Low Birth Weight (ELBW), Prematurity, Laparotomy, Drainage, Isolated intestinal perforation, Focal intestinal perforation
Brief summary
This study will compare the effectiveness of two surgical procedures -laparotomy versus drainage - commonly used to treat necrotizing enterocolitis (NEC) or isolated intestinal perforations (IP) in extremely low birth weight infants (≤1,000 g). Infants diagnosed with NEC or IP requiring surgical intervention, will be recruited. Subjects will be randomized to receive either a laparotomy or peritoneal drainage. Primary outcome is impairment-free survival at 18-22 months corrected age.
Detailed description
Necrotizing enterocolitis (NEC) is a condition, generally affecting premature infants, in which the intestines become ischemic (lack oxygen and/or blood flow). NEC occurs in up to 5-15% of extremely low birth weight (ELBW) infants. Isolated or focal intestinal perforation (IP) is a less common condition, affecting an estimated 4% of ELBWs, in which a hole develops in the intestines leaking fluid into the abdominal cavity. Outcome for infants with NEC and/or IP is poor: 49% die and half of the surviving infants are neurodevelopmentally impaired. Surgical options for NEC and IP include two possible procedures: peritoneal drainage, in which a tube is placed in the abdominal cavity through a small incision for fluid to drain out; or laparotomy, in which an incision is made in the abdomen and necrotic intestine is removed. Drainage may be followed by a laparotomy. The Neonatal Research Network's observational study of 156 ELBW infants with NEC or IP (Pediatrics. 2006 Apr; 117(4): e680-7) showed comparable outcomes for the two procedures before hospital discharge, but suggested an advantage of laparotomy over drainage at 18-22 months corrected age with lower rates of death or neurodevelopmental impairment. However, the infants that underwent laparotomy were more mature; infants with drains were smaller and more premature. We hypothesize that initial laparotomy may improve an infant's long-term neurodevelopmental outcome, potentially by reducing the maximum severity or duration of inflammation. This study included a randomized controlled trial to compare the effectiveness of laparotomy versus drainage for treating NEC or IP in extremely low birth weight infants. Target enrollment is 300 infants diagnosed with NEC or IP for randomization to receive initially either a laparotomy or drainage. Subsequent laparotomies may be performed on infants in either group, if their condition continues to deteriorate. Surviving infants will return for a follow-up assessment at 18-22 months corrected age. This study also attempted to use a comprehensive cohort design that would have added additional information beyond the conventional randomized trial component. The cohort component included trial data among eligible, non-randomized infants with NEC/IP, who consented for the non-randomized cohort, would be collected and analyzed as a secondary specific aim. This additional cohort was called the preference cohort.
Interventions
PROCEDURELaparotomy
Initial laparotomy will be performed. Standard procedures will be used, including inspection of the bowel with removal of diseased areas, creation of stoma(s), and other procedures deemed indicated by the surgeon.
PROCEDUREDrainage
Initial drainage will involve placing a Penrose drain in the abdomen.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Center for Research Resources (NCRR)
NICHD Neonatal Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 8 Weeks
Healthy volunteers
No
Inclusion criteria
* Infants born at ≤1,000 g birth weight * Infant is ≤8 0/7 weeks of age at the time of eligibility assessment * Pediatric surgeon decision to perform surgery for suspected NEC or IP * Subject is at a center able to perform both laparotomy and drainage
Exclusion criteria
* Major anomaly that influences likelihood of developing primary outcome or affects surgical treatment considerations * Congenital infection * Prior laparotomy or peritoneal drain placement * Prior NEC or IP * Infant for whom full support is not being provided * Follow-up unlikely
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Death or Neurodevelopmental Impairment (NDI) | at 18-22 months corrected age | Death or NDI at 18-22 months corrected age |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Death | by 18-22 months corrected age | Death by 18-22 months corrected age |
| Death or Moderate to Severe Cerebral Palsy | up to the follow-up visit completed within the 18-22 months corrected age window | Death within 18-22 months corrected age or moderate to severe cerebral palsy at 18-22 months corrected age |
| Death or Bayley Cognitive Composite Score Less Than 85 | up to the follow-up visit completed within the 18-22 months corrected age window | Death within 18-22 months corrected age or Bayley cognitive composite score less than 85 at 18-22 months corrected age. Higher values of the Bayley cognitive composite score is better than lower values. Normal values are greater than or equal to 85. A moderate value is in the 70-84 range, and a severe value is \<70. |
| Death or Blindness | up to the follow-up visit completed within the 18-22 months corrected age window | Death within 18-22 months corrected age or blindness at 18-22 months corrected age |
| Death or Hearing Loss | up to the follow-up visit completed within the 18-22 months corrected age window | Death within 18-22 months corrected age or hearing loss at 18-22 months corrected age |
| Subsequent Laparotomy | between initial surgery and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Subsequent laparotomy after initial surgery |
| Any Intraoperative Complications During Any Surgery | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Any intraoperative complications during any surgery |
| Any Wound Dehiscence | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Any wound dehiscence during any surgery |
| Any Intra-abdominal Abscess | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Any intra-abdominal abscess during any surgery |
| Any Intestinal Stricture | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Any intestinal stricture during any surgery |
| Any Late Onset Sepsis | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Any late onset sepsis after randomization |
| Any Parenteral Nutrition (PN)-Associated Cholestasis | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Any Parenteral nutrition (PN)-associated cholestasis during any surgery |
| Any Severe IVH | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Any severe IVH ater randomization |
| Duration of Mechanical Ventilation | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Duration of mechanical ventilation while on study |
| Duration of Parenteral Nutrition | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Duration of parenteral nutrition while on study |
| Final Bowel Length | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Final bowel length after last surgery |
| Time to Full Feeds | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Time to full feeds while on study |
| Length of Hospital Stay | from randomization up to 1 year following birth | Length of hospital stay while on study |
| Death or NDI Stratified by Pre-operative Diagnosis | at 18-22 months corrected age | Death or NDI at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Survival With Neurodevelopmental Impairment (NDI) | by 18-22 months corrected age | NDI at 18-22 months corrected age (among survivors) |
| Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis | by 18-22 months corrected age | NDI at 18-22 months corrected age (among survivors). Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis | up to the follow-up visit completed within the 18-22 months corrected age window | Death within 18-22 months corrected age or moderate to severe cerebral palsy at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis | up to the follow-up visit completed within the 18-22 months corrected age window | Death within 18-22 months corrected age or Bayley cognitive composite score less than 85 at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). Higher values of the Bayley cognitive composite score is better than lower values. Normal values are greater than or equal to 85. A moderate value is in the 70-84 range, and a severe value is \<70. |
| Death or Blindness Stratified by Pre-operative Diagnosis | up to the follow-up visit completed within the 18-22 months corrected age window | Death within 18-22 months corrected age or blindness at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Death or Hearing Loss Stratified by Pre-operative Diagnosis | up to the follow-up visit completed within the 18-22 months corrected age window | Death within 18-22 months corrected age or hearing loss at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Subsequent Laparotomy Stratified by Pre-operative Diagnosis | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Subsequent laparotomy after initial surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Any intraoperative complications during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Any Wound Dehiscence Stratified by Pre-operative Diagnosis | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Any wound dehiscence during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Any intra-abdominal abscess during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Any Intestinal Stricture Stratified by Pre-operative Diagnosis | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Any intestinal stricture during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Any Late Onset Sepsis Stratified by Pre-operative Diagnosis | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Any late onset sepsis after randomization. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Any Parenteral nutrition (PN)-associated cholestasis during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Any Severe IVH Stratified by Pre-operative Diagnosis | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Any severe IVH ater randomization. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Duration of Mechanical Ventilation Stratified by Pre-operative Diagnosis | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Duration of mechanical ventilation while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Duration of Parenteral Nutrition Stratified by Pre-operative Diagnosis | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Duration of parenteral nutrition while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Final Bowel Length Stratified by Pre-operative Diagnosis | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Final bowel length after last surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Time to Full Feeds Stratified by Pre-operative Diagnosis | between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth | Time to full feeds while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Length of Hospital Stay Stratified by Pre-operative Diagnosis | from randomization up to 1 year following birth | Length of hospital stay while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
| Death Stratified by Pre-operative Diagnosis | by 18-22 months corrected age | Death within 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Randomized Trial: Initial Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. | 146 |
| Randomized Trial: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation. | 162 |
| Preference Cohort: Initial Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. | 100 |
| Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation. | 119 |
| Total | 527 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Consent Withdrawn | 2 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 4 | 5 | 5 | 4 |
| Overall Study | Primary Outcome Indeterminate | 1 | 3 | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Randomized Trial: Initial Laparotomy | Randomized Trial: Initial Peritoneal Drain | Preference Cohort: Initial Laparotomy | Preference Cohort: Initial Peritoneal Drain |
|---|---|---|---|---|---|
| Age, Continuous | 33.3 days STANDARD_DEVIATION 81 | 11.6 days STANDARD_DEVIATION 10 | 12.1 days STANDARD_DEVIATION 9.9 | 79.9 days STANDARD_DEVIATION 125.4 | 49.9 days STANDARD_DEVIATION 111.7 |
| Inborn status In born | 312 Participants | 82 Participants | 90 Participants | 65 Participants | 75 Participants |
| Inborn status Out born | 215 Participants | 64 Participants | 72 Participants | 35 Participants | 44 Participants |
| Infant Apgar score at 1 minute | 3 units on a scale | 3 units on a scale | 3 units on a scale | 4 units on a scale | 4 units on a scale |
| Infant Apgar score at 5 minute | 7 units on a scale | 6 units on a scale | 6 units on a scale | 7 units on a scale | 7 units on a scale |
| Infant baseline risk of death or neurodevelopmental impairment (NDI) | 70.3 Percent probability STANDARD_DEVIATION 25 | 63.4 Percent probability STANDARD_DEVIATION 27 | 70.7 Percent probability STANDARD_DEVIATION 23.7 | 88.1 Percent probability STANDARD_DEVIATION 20.7 | 85.8 Percent probability STANDARD_DEVIATION 23.1 |
| Infant birth weight | 707.6 gram STANDARD_DEVIATION 146.2 | 721.2 gram STANDARD_DEVIATION 138.4 | 711.4 gram STANDARD_DEVIATION 135.9 | 719.8 gram STANDARD_DEVIATION 150.5 | 675.6 gram STANDARD_DEVIATION 161.7 |
| Infant fraction of inspired oxygen (FiO2) closest to enrollment | 49.6 Percent STANDARD_DEVIATION 27.6 | 44.8 Percent STANDARD_DEVIATION 26.3 | 45.9 Percent STANDARD_DEVIATION 24.1 | 57.8 Percent STANDARD_DEVIATION 29.7 | 53.5 Percent STANDARD_DEVIATION 30 |
| Infant gestational age | 25 weeks STANDARD_DEVIATION 1.7 | 25 weeks STANDARD_DEVIATION 1.7 | 24.9 weeks STANDARD_DEVIATION 1.7 | 24.6 weeks STANDARD_DEVIATION 1.1 | 24.5 weeks STANDARD_DEVIATION 1.2 |
| Infant had early onset sepsis before or on enrollment Missing | 8 Participants | 2 Participants | 5 Participants | 0 Participants | 1 Participants |
| Infant had early onset sepsis before or on enrollment No | 509 Participants | 143 Participants | 151 Participants | 98 Participants | 117 Participants |
| Infant had early onset sepsis before or on enrollment Yes | 10 Participants | 1 Participants | 6 Participants | 2 Participants | 1 Participants |
| Infant had late onset sepsis before or on enrollment Missing | 3 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants |
| Infant had late onset sepsis before or on enrollment No | 370 Participants | 109 Participants | 113 Participants | 72 Participants | 76 Participants |
| Infant had late onset sepsis before or on enrollment Yes | 154 Participants | 37 Participants | 47 Participants | 27 Participants | 43 Participants |
| Infant had patent ductus arteriosus (PDA) prior to enrollment Missing | 31 Participants | 10 Participants | 15 Participants | 2 Participants | 4 Participants |
| Infant had patent ductus arteriosus (PDA) prior to enrollment No | 270 Participants | 77 Participants | 85 Participants | 52 Participants | 56 Participants |
| Infant had patent ductus arteriosus (PDA) prior to enrollment Yes | 226 Participants | 59 Participants | 62 Participants | 46 Participants | 59 Participants |
| Infant had severe intraventricular hemorrhage (IVH) (grade 3 or 4) Missing | 16 Participants | 6 Participants | 5 Participants | 1 Participants | 4 Participants |
| Infant had severe intraventricular hemorrhage (IVH) (grade 3 or 4) No | 431 Participants | 123 Participants | 134 Participants | 86 Participants | 88 Participants |
| Infant had severe intraventricular hemorrhage (IVH) (grade 3 or 4) Yes | 80 Participants | 17 Participants | 23 Participants | 13 Participants | 27 Participants |
| Infant lowest platelet count | 148.7 1000 platelets per microliter STANDARD_DEVIATION 87.3 | 155.7 1000 platelets per microliter STANDARD_DEVIATION 96 | 150.4 1000 platelets per microliter STANDARD_DEVIATION 80.9 | 156.2 1000 platelets per microliter STANDARD_DEVIATION 91.4 | 131.5 1000 platelets per microliter STANDARD_DEVIATION 79.6 |
| Infant mean blood pressure | 37.2 mmHG STANDARD_DEVIATION 11.2 | 37.1 mmHG STANDARD_DEVIATION 10.3 | 37.0 mmHG STANDARD_DEVIATION 11.5 | 39.0 mmHG STANDARD_DEVIATION 11.3 | 36.1 mmHG STANDARD_DEVIATION 11.7 |
| Infant on vasopressors at Enrollment Missing | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Infant on vasopressors at Enrollment No | 334 Participants | 105 Participants | 103 Participants | 55 Participants | 71 Participants |
| Infant on vasopressors at Enrollment Yes | 192 Participants | 41 Participants | 59 Participants | 45 Participants | 47 Participants |
| Infant pH closest to enrollment | 7.2 pH STANDARD_DEVIATION 0.1 | 7.2 pH STANDARD_DEVIATION 0.1 | 7.2 pH STANDARD_DEVIATION 0.1 | 7.2 pH STANDARD_DEVIATION 0.1 | 7.2 pH STANDARD_DEVIATION 0.2 |
| Infant preoperative diagnosis (NEC or IP) IP | 310 Participants | 104 Participants | 109 Participants | 25 Participants | 72 Participants |
| Infant preoperative diagnosis (NEC or IP) NEC | 217 Participants | 42 Participants | 53 Participants | 75 Participants | 47 Participants |
| Infant received enteral feedings before or on enrollment Missing | 112 Participants | 33 Participants | 38 Participants | 16 Participants | 25 Participants |
| Infant received enteral feedings before or on enrollment No | 68 Participants | 23 Participants | 29 Participants | 5 Participants | 11 Participants |
| Infant received enteral feedings before or on enrollment Yes | 347 Participants | 90 Participants | 95 Participants | 79 Participants | 83 Participants |
| Infant received HFOV or HFJV at randomization No | 345 Participants | 114 Participants | 114 Participants | 51 Participants | 66 Participants |
| Infant received HFOV or HFJV at randomization Yes | 182 Participants | 32 Participants | 48 Participants | 49 Participants | 53 Participants |
| Infant received indomethacin before or on Randomization Missing | 19 Participants | 3 Participants | 6 Participants | 3 Participants | 7 Participants |
| Infant received indomethacin before or on Randomization No | 232 Participants | 69 Participants | 74 Participants | 51 Participants | 38 Participants |
| Infant received indomethacin before or on Randomization Yes | 276 Participants | 74 Participants | 82 Participants | 46 Participants | 74 Participants |
| Infant received postnatal steroids No | 384 Participants | 119 Participants | 115 Participants | 67 Participants | 83 Participants |
| Infant received postnatal steroids Yes | 143 Participants | 27 Participants | 47 Participants | 33 Participants | 36 Participants |
| Infant was small for gestational age Missing | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Infant was small for gestational age No | 458 Participants | 131 Participants | 145 Participants | 84 Participants | 98 Participants |
| Infant was small for gestational age Yes | 68 Participants | 15 Participants | 16 Participants | 16 Participants | 21 Participants |
| Married, Customized Missing | 15 Participants | 1 Participants | 6 Participants | 4 Participants | 4 Participants |
| Married, Customized No | 288 Participants | 81 Participants | 95 Participants | 50 Participants | 62 Participants |
| Married, Customized Yes | 224 Participants | 64 Participants | 61 Participants | 46 Participants | 53 Participants |
| Maternal Age, Continuous | 27.2 years STANDARD_DEVIATION 6.4 | 27.6 years STANDARD_DEVIATION 6.7 | 27.3 years STANDARD_DEVIATION 6.3 | 26.7 years STANDARD_DEVIATION 6.3 | 26.8 years STANDARD_DEVIATION 6.2 |
| Maternal Education, Customized College graduate | 83 Participants | 18 Participants | 21 Participants | 19 Participants | 25 Participants |
| Maternal Education, Customized High school graduate | 124 Participants | 42 Participants | 38 Participants | 19 Participants | 25 Participants |
| Maternal Education, Customized Less than high school | 83 Participants | 21 Participants | 28 Participants | 22 Participants | 12 Participants |
| Maternal Education, Customized Missing | 156 Participants | 42 Participants | 51 Participants | 25 Participants | 38 Participants |
| Maternal Education, Customized Some college | 81 Participants | 23 Participants | 24 Participants | 15 Participants | 19 Participants |
| Maternal hispanic ethnicity Missing | 22 Participants | 1 Participants | 9 Participants | 3 Participants | 9 Participants |
| Maternal hispanic ethnicity No | 397 Participants | 107 Participants | 120 Participants | 75 Participants | 95 Participants |
| Maternal hispanic ethnicity Yes | 108 Participants | 38 Participants | 33 Participants | 22 Participants | 15 Participants |
| Maternal hypertension Missing | 80 Participants | 26 Participants | 31 Participants | 10 Participants | 13 Participants |
| Maternal hypertension No | 332 Participants | 85 Participants | 98 Participants | 65 Participants | 84 Participants |
| Maternal hypertension Yes | 115 Participants | 35 Participants | 33 Participants | 25 Participants | 22 Participants |
| Mother had private insurance Missing | 4 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants |
| Mother had private insurance No | 347 Participants | 98 Participants | 113 Participants | 71 Participants | 65 Participants |
| Mother had private insurance Yes | 176 Participants | 48 Participants | 46 Participants | 29 Participants | 53 Participants |
| Mother received antenatal magnesium Missing | 245 Participants | 52 Participants | 68 Participants | 59 Participants | 66 Participants |
| Mother received antenatal magnesium No | 51 Participants | 17 Participants | 21 Participants | 6 Participants | 7 Participants |
| Mother received antenatal magnesium Yes | 231 Participants | 77 Participants | 73 Participants | 35 Participants | 46 Participants |
| Mother received antibiotics Missing | 98 Participants | 28 Participants | 37 Participants | 15 Participants | 18 Participants |
| Mother received antibiotics No | 119 Participants | 39 Participants | 42 Participants | 19 Participants | 19 Participants |
| Mother received antibiotics Yes | 310 Participants | 79 Participants | 83 Participants | 66 Participants | 82 Participants |
| Mother received prenatal care Missing | 15 Participants | 1 Participants | 3 Participants | 6 Participants | 5 Participants |
| Mother received prenatal care No | 20 Participants | 3 Participants | 10 Participants | 2 Participants | 5 Participants |
| Mother received prenatal care Yes | 492 Participants | 142 Participants | 149 Participants | 92 Participants | 109 Participants |
| Mother received steroids Missing | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Mother received steroids No | 82 Participants | 22 Participants | 31 Participants | 11 Participants | 18 Participants |
| Mother received steroids Yes | 444 Participants | 124 Participants | 130 Participants | 89 Participants | 101 Participants |
| Race/Ethnicity, Customized Black | 202 Participants | 62 Participants | 67 Participants | 31 Participants | 42 Participants |
| Race/Ethnicity, Customized Missing | 12 Participants | 5 Participants | 5 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 29 Participants | 6 Participants | 8 Participants | 9 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 284 Participants | 73 Participants | 82 Participants | 59 Participants | 70 Participants |
| Rupture of membranes > 18 hours Missing | 64 Participants | 22 Participants | 29 Participants | 7 Participants | 6 Participants |
| Rupture of membranes > 18 hours No | 375 Participants | 101 Participants | 108 Participants | 69 Participants | 97 Participants |
| Rupture of membranes > 18 hours Yes | 88 Participants | 23 Participants | 25 Participants | 24 Participants | 16 Participants |
| Sex/Gender, Customized Female | 230 Participants | 66 Participants | 63 Participants | 48 Participants | 53 Participants |
| Sex/Gender, Customized Male | 296 Participants | 80 Participants | 98 Participants | 52 Participants | 66 Participants |
| Sex/Gender, Customized Missing | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 41 / 146 | 48 / 162 | 48 / 100 | 60 / 119 |
| other Total, other adverse events | 0 / 146 | 0 / 162 | 0 / 100 | 0 / 119 |
| serious Total, serious adverse events | 41 / 146 | 49 / 162 | 49 / 100 | 60 / 119 |
Outcome results
Primary
Death or Neurodevelopmental Impairment (NDI)
Death or NDI at 18-22 months corrected age
Time frame: at 18-22 months corrected age
Population: Analysis of randomized trial data included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization. Analysis of preference cohort data included all eligible participants who were consented, enrolled, did not withdraw consent, and who provided outcome data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Death or Neurodevelopmental Impairment (NDI) | No | 44 Participants |
| Randomized Trial: Initial Laparotomy | Death or Neurodevelopmental Impairment (NDI) | Yes | 97 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Neurodevelopmental Impairment (NDI) | Yes | 108 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Neurodevelopmental Impairment (NDI) | No | 46 Participants |
| Preference Cohort: Laparotomy | Death or Neurodevelopmental Impairment (NDI) | No | 27 Participants |
| Preference Cohort: Laparotomy | Death or Neurodevelopmental Impairment (NDI) | Yes | 66 Participants |
| Preference Cohort: Initial Peritoneal Drain | Death or Neurodevelopmental Impairment (NDI) | No | 28 Participants |
| Preference Cohort: Initial Peritoneal Drain | Death or Neurodevelopmental Impairment (NDI) | Yes | 87 Participants |
Comparison: A frequentist analysis. Model included treatment, baseline risk of death or NDI, and pre-operative diagnosis (Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP)) as covariates.95% CI: [0.87, 1.14]
Comparison: A frequentist analysis. Using Robust Poisson regression with log link and center as repeated measure, and effect coding, test for an interaction between treatment (Initial Laparotomy/Initial Peritoneal Drain) and pre-operative diagnosis (Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP)) as covariates. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-operative diagnosis as covariates.p-value: 0.03Robust Poisson regression
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Comparison: A frequentist analysis. Model included treatment, baseline risk of death or NDI, and pre-operative diagnosis (Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP)) covariates.95% CI: [0.75, 1.26]
Secondary
Any Intestinal Stricture
Any intestinal stricture during any surgery
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Any Intestinal Stricture | No | 139 Participants |
| Randomized Trial: Initial Laparotomy | Any Intestinal Stricture | Yes | 7 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intestinal Stricture | No | 153 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intestinal Stricture | Yes | 9 Participants |
Comparison: A frequentist analysis.95% CI: [0.34, 2.2]
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Any Intestinal Stricture Stratified by Pre-operative Diagnosis
Any intestinal stricture during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Any Intestinal Stricture Stratified by Pre-operative Diagnosis | IP | No | 101 Participants |
| Randomized Trial: Initial Laparotomy | Any Intestinal Stricture Stratified by Pre-operative Diagnosis | IP | Yes | 3 Participants |
| Randomized Trial: Initial Laparotomy | Any Intestinal Stricture Stratified by Pre-operative Diagnosis | NEC | No | 38 Participants |
| Randomized Trial: Initial Laparotomy | Any Intestinal Stricture Stratified by Pre-operative Diagnosis | NEC | Yes | 4 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intestinal Stricture Stratified by Pre-operative Diagnosis | NEC | Yes | 3 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intestinal Stricture Stratified by Pre-operative Diagnosis | IP | No | 103 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intestinal Stricture Stratified by Pre-operative Diagnosis | NEC | No | 50 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intestinal Stricture Stratified by Pre-operative Diagnosis | IP | Yes | 6 Participants |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.95% CI: [0.35, 8.05]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.95% CI: [0.1, 2.44]
Secondary
Any Intra-abdominal Abscess
Any intra-abdominal abscess during any surgery
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Any Intra-abdominal Abscess | No | 141 Participants |
| Randomized Trial: Initial Laparotomy | Any Intra-abdominal Abscess | Yes | 5 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intra-abdominal Abscess | No | 158 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intra-abdominal Abscess | Yes | 4 Participants |
Comparison: A frequentist analysis.
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis
Any intra-abdominal abscess during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis | IP | No | 101 Participants |
| Randomized Trial: Initial Laparotomy | Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis | IP | Yes | 3 Participants |
| Randomized Trial: Initial Laparotomy | Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis | NEC | No | 40 Participants |
| Randomized Trial: Initial Laparotomy | Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis | NEC | Yes | 2 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis | NEC | Yes | 1 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis | IP | No | 106 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis | NEC | No | 52 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis | IP | Yes | 3 Participants |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.95% CI: [0.82, 3.86]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.95% CI: [0.42, 3.2]
Secondary
Any Intraoperative Complications During Any Surgery
Any intraoperative complications during any surgery
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Any Intraoperative Complications During Any Surgery | No | 116 Participants |
| Randomized Trial: Initial Laparotomy | Any Intraoperative Complications During Any Surgery | Yes | 29 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intraoperative Complications During Any Surgery | No | 141 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intraoperative Complications During Any Surgery | Yes | 21 Participants |
Comparison: A frequentist analysis.95% CI: [1.04, 2.36]
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis
Any intraoperative complications during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis | IP | No | 83 Participants |
| Randomized Trial: Initial Laparotomy | Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis | IP | Yes | 21 Participants |
| Randomized Trial: Initial Laparotomy | Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis | NEC | No | 33 Participants |
| Randomized Trial: Initial Laparotomy | Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis | NEC | Yes | 8 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis | NEC | Yes | 7 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis | IP | No | 95 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis | NEC | No | 46 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis | IP | Yes | 14 Participants |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.95% CI: [0.58, 3.57]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.95% CI: [1.06, 2.5]
Secondary
Any Late Onset Sepsis
Any late onset sepsis after randomization
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Any Late Onset Sepsis | No | 123 Participants |
| Randomized Trial: Initial Laparotomy | Any Late Onset Sepsis | Yes | 23 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Late Onset Sepsis | No | 126 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Late Onset Sepsis | Yes | 34 Participants |
Comparison: A frequentist analysis.95% CI: [0.37, 1.42]
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Any Late Onset Sepsis Stratified by Pre-operative Diagnosis
Any late onset sepsis after randomization. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Any Late Onset Sepsis Stratified by Pre-operative Diagnosis | IP | No | 88 Participants |
| Randomized Trial: Initial Laparotomy | Any Late Onset Sepsis Stratified by Pre-operative Diagnosis | IP | Yes | 16 Participants |
| Randomized Trial: Initial Laparotomy | Any Late Onset Sepsis Stratified by Pre-operative Diagnosis | NEC | No | 35 Participants |
| Randomized Trial: Initial Laparotomy | Any Late Onset Sepsis Stratified by Pre-operative Diagnosis | NEC | Yes | 7 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Late Onset Sepsis Stratified by Pre-operative Diagnosis | NEC | Yes | 7 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Late Onset Sepsis Stratified by Pre-operative Diagnosis | IP | No | 80 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Late Onset Sepsis Stratified by Pre-operative Diagnosis | NEC | No | 46 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Late Onset Sepsis Stratified by Pre-operative Diagnosis | IP | Yes | 27 Participants |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.95% CI: [0.62, 2.69]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.95% CI: [0.27, 1.32]
Secondary
Any Parenteral Nutrition (PN)-Associated Cholestasis
Any Parenteral nutrition (PN)-associated cholestasis during any surgery
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Any Parenteral Nutrition (PN)-Associated Cholestasis | No | 110 Participants |
| Randomized Trial: Initial Laparotomy | Any Parenteral Nutrition (PN)-Associated Cholestasis | Yes | 36 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Parenteral Nutrition (PN)-Associated Cholestasis | No | 116 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Parenteral Nutrition (PN)-Associated Cholestasis | Yes | 46 Participants |
Comparison: A frequentist analysis.95% CI: [0.7, 1.15]
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with effect coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis
Any Parenteral nutrition (PN)-associated cholestasis during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis | IP | No | 79 Participants |
| Randomized Trial: Initial Laparotomy | Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis | IP | Yes | 25 Participants |
| Randomized Trial: Initial Laparotomy | Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis | NEC | No | 31 Participants |
| Randomized Trial: Initial Laparotomy | Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis | NEC | Yes | 11 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis | NEC | Yes | 19 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis | IP | No | 82 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis | NEC | No | 34 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis | IP | Yes | 27 Participants |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.95% CI: [0.41, 1.36]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.95% CI: [0.69, 1.42]
Secondary
Any Severe IVH
Any severe IVH ater randomization
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Any Severe IVH | No | 122 Participants |
| Randomized Trial: Initial Laparotomy | Any Severe IVH | Yes | 18 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Severe IVH | No | 132 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Severe IVH | Yes | 25 Participants |
Comparison: A frequentist analysis.95% CI: [0.44, 1.36]
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Any Severe IVH Stratified by Pre-operative Diagnosis
Any severe IVH ater randomization. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Any Severe IVH Stratified by Pre-operative Diagnosis | IP | No | 84 Participants |
| Randomized Trial: Initial Laparotomy | Any Severe IVH Stratified by Pre-operative Diagnosis | IP | Yes | 17 Participants |
| Randomized Trial: Initial Laparotomy | Any Severe IVH Stratified by Pre-operative Diagnosis | NEC | No | 38 Participants |
| Randomized Trial: Initial Laparotomy | Any Severe IVH Stratified by Pre-operative Diagnosis | NEC | Yes | 1 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Severe IVH Stratified by Pre-operative Diagnosis | NEC | Yes | 3 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Severe IVH Stratified by Pre-operative Diagnosis | IP | No | 84 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Severe IVH Stratified by Pre-operative Diagnosis | NEC | No | 48 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Severe IVH Stratified by Pre-operative Diagnosis | IP | Yes | 22 Participants |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.95% CI: [0.04, 4.45]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.95% CI: [0.44, 1.49]
Secondary
Any Wound Dehiscence
Any wound dehiscence during any surgery
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Any Wound Dehiscence | No | 135 Participants |
| Randomized Trial: Initial Laparotomy | Any Wound Dehiscence | Yes | 11 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Wound Dehiscence | No | 154 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Wound Dehiscence | Yes | 8 Participants |
Comparison: A frequentist analysis.95% CI: [0.71, 3.5]
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Any Wound Dehiscence Stratified by Pre-operative Diagnosis
Any wound dehiscence during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Any Wound Dehiscence Stratified by Pre-operative Diagnosis | IP | No | 99 Participants |
| Randomized Trial: Initial Laparotomy | Any Wound Dehiscence Stratified by Pre-operative Diagnosis | IP | Yes | 5 Participants |
| Randomized Trial: Initial Laparotomy | Any Wound Dehiscence Stratified by Pre-operative Diagnosis | NEC | No | 36 Participants |
| Randomized Trial: Initial Laparotomy | Any Wound Dehiscence Stratified by Pre-operative Diagnosis | NEC | Yes | 6 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Wound Dehiscence Stratified by Pre-operative Diagnosis | NEC | Yes | 3 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Wound Dehiscence Stratified by Pre-operative Diagnosis | IP | No | 104 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Wound Dehiscence Stratified by Pre-operative Diagnosis | NEC | No | 50 Participants |
| Randomized Trial: Initial Peritoneal Drain | Any Wound Dehiscence Stratified by Pre-operative Diagnosis | IP | Yes | 5 Participants |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.95% CI: [0.84, 7.55]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.95% CI: [0.38, 2.88]
Secondary
Death
Death by 18-22 months corrected age
Time frame: by 18-22 months corrected age
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Death | Yes | 41 Participants |
| Randomized Trial: Initial Laparotomy | Death | No | 105 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death | No | 114 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death | Yes | 48 Participants |
Comparison: A frequentist analysis.95% CI: [0.69, 1.45]
Secondary
Death or Bayley Cognitive Composite Score Less Than 85
Death within 18-22 months corrected age or Bayley cognitive composite score less than 85 at 18-22 months corrected age. Higher values of the Bayley cognitive composite score is better than lower values. Normal values are greater than or equal to 85. A moderate value is in the 70-84 range, and a severe value is \<70.
Time frame: up to the follow-up visit completed within the 18-22 months corrected age window
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Death or Bayley Cognitive Composite Score Less Than 85 | No | 46 Participants |
| Randomized Trial: Initial Laparotomy | Death or Bayley Cognitive Composite Score Less Than 85 | Yes | 95 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Bayley Cognitive Composite Score Less Than 85 | No | 51 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Bayley Cognitive Composite Score Less Than 85 | Yes | 100 Participants |
Comparison: A frequentist analysis.95% CI: [0.89, 1.18]
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis
Death within 18-22 months corrected age or Bayley cognitive composite score less than 85 at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). Higher values of the Bayley cognitive composite score is better than lower values. Normal values are greater than or equal to 85. A moderate value is in the 70-84 range, and a severe value is \<70.
Time frame: up to the follow-up visit completed within the 18-22 months corrected age window
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis | IP | No | 32 Participants |
| Randomized Trial: Initial Laparotomy | Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis | IP | Yes | 67 Participants |
| Randomized Trial: Initial Laparotomy | Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis | NEC | No | 14 Participants |
| Randomized Trial: Initial Laparotomy | Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis | NEC | Yes | 28 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis | NEC | Yes | 41 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis | IP | No | 42 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis | NEC | No | 9 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis | IP | Yes | 59 Participants |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.95% CI: [0.61, 1.06]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.95% CI: [1.01, 1.37]
Comparison: A Bayesian analysis. Within pre-operative diagnosis, Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. Pre-operative diagnosis levels were NEC and IP. PROC MCMC with effect coding was used. Center (random effect), treatment, pre-operative diagnosis, baseline risk, and the treatment by Preoperative diagnosis were the covariates. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Death or Blindness
Death within 18-22 months corrected age or blindness at 18-22 months corrected age
Time frame: up to the follow-up visit completed within the 18-22 months corrected age window
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Death or Blindness | No | 101 Participants |
| Randomized Trial: Initial Laparotomy | Death or Blindness | Yes | 41 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Blindness | No | 105 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Blindness | Yes | 52 Participants |
Comparison: A frequentist analysis.95% CI: [0.64, 1.31]
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Death or Blindness Stratified by Pre-operative Diagnosis
Death within 18-22 months corrected age or blindness at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: up to the follow-up visit completed within the 18-22 months corrected age window
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Death or Blindness Stratified by Pre-operative Diagnosis | IP | No | 76 Participants |
| Randomized Trial: Initial Laparotomy | Death or Blindness Stratified by Pre-operative Diagnosis | NEC | No | 25 Participants |
| Randomized Trial: Initial Laparotomy | Death or Blindness Stratified by Pre-operative Diagnosis | NEC | Yes | 17 Participants |
| Randomized Trial: Initial Laparotomy | Death or Blindness Stratified by Pre-operative Diagnosis | IP | Yes | 24 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Blindness Stratified by Pre-operative Diagnosis | NEC | Yes | 30 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Blindness Stratified by Pre-operative Diagnosis | IP | No | 83 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Blindness Stratified by Pre-operative Diagnosis | IP | Yes | 22 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Blindness Stratified by Pre-operative Diagnosis | NEC | No | 22 Participants |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.95% CI: [0.46, 1.01]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.95% CI: [0.74, 2.01]
Comparison: A Bayesian analysis. Within pre-operative diagnosis, Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. Pre-operative diagnosis levels were NEC and IP. PROC MCMC with effect coding was used. Center (random effect), treatment, pre-operative diagnosis, baseline risk, and the treatment by Preoperative diagnosis were the covariates. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Death or Hearing Loss
Death within 18-22 months corrected age or hearing loss at 18-22 months corrected age
Time frame: up to the follow-up visit completed within the 18-22 months corrected age window
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Death or Hearing Loss | Yes | 43 Participants |
| Randomized Trial: Initial Laparotomy | Death or Hearing Loss | No | 98 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Hearing Loss | Yes | 51 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Hearing Loss | No | 105 Participants |
Comparison: A frequentist analysis.95% CI: [0.69, 1.36]
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Death or Hearing Loss Stratified by Pre-operative Diagnosis
Death within 18-22 months corrected age or hearing loss at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: up to the follow-up visit completed within the 18-22 months corrected age window
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Death or Hearing Loss Stratified by Pre-operative Diagnosis | IP | No | 73 Participants |
| Randomized Trial: Initial Laparotomy | Death or Hearing Loss Stratified by Pre-operative Diagnosis | IP | Yes | 26 Participants |
| Randomized Trial: Initial Laparotomy | Death or Hearing Loss Stratified by Pre-operative Diagnosis | NEC | No | 25 Participants |
| Randomized Trial: Initial Laparotomy | Death or Hearing Loss Stratified by Pre-operative Diagnosis | NEC | Yes | 17 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Hearing Loss Stratified by Pre-operative Diagnosis | NEC | Yes | 28 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Hearing Loss Stratified by Pre-operative Diagnosis | IP | No | 81 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Hearing Loss Stratified by Pre-operative Diagnosis | NEC | No | 24 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Hearing Loss Stratified by Pre-operative Diagnosis | IP | Yes | 23 Participants |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.95% CI: [0.51, 1.04]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.95% CI: [0.82, 1.93]
Comparison: A Bayesian analysis. Within pre-operative diagnosis, Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. Pre-operative diagnosis levels were NEC and IP. PROC MCMC with effect coding was used. Center (random effect), treatment, pre-operative diagnosis, baseline risk, and the treatment by Preoperative diagnosis were the covariates. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Death or Moderate to Severe Cerebral Palsy
Death within 18-22 months corrected age or moderate to severe cerebral palsy at 18-22 months corrected age
Time frame: up to the follow-up visit completed within the 18-22 months corrected age window
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Death or Moderate to Severe Cerebral Palsy | No | 84 Participants |
| Randomized Trial: Initial Laparotomy | Death or Moderate to Severe Cerebral Palsy | Yes | 58 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Moderate to Severe Cerebral Palsy | No | 78 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Moderate to Severe Cerebral Palsy | Yes | 79 Participants |
Comparison: A frequentist analysis.95% CI: [0.66, 1.06]
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis
Death within 18-22 months corrected age or moderate to severe cerebral palsy at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: up to the follow-up visit completed within the 18-22 months corrected age window
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis | IP | No | 64 Participants |
| Randomized Trial: Initial Laparotomy | Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis | NEC | No | 20 Participants |
| Randomized Trial: Initial Laparotomy | Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis | IP | Yes | 36 Participants |
| Randomized Trial: Initial Laparotomy | Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis | NEC | Yes | 22 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis | IP | Yes | 41 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis | IP | No | 64 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis | NEC | Yes | 38 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis | NEC | No | 14 Participants |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.95% CI: [0.47, 1.05]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.95% CI: [0.76, 1.19]
Comparison: A Bayesian analysis. Within pre-operative diagnosis, Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. Pre-operative diagnosis levels were NEC and IP. PROC MCMC with effect coding was used. Center (random effect), treatment, pre-operative diagnosis, baseline risk, and the treatment by Preoperative diagnosis were the covariates. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Death or NDI Stratified by Pre-operative Diagnosis
Death or NDI at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: at 18-22 months corrected age
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Death or NDI Stratified by Pre-operative Diagnosis | IP | No | 31 Participants |
| Randomized Trial: Initial Laparotomy | Death or NDI Stratified by Pre-operative Diagnosis | IP | Yes | 68 Participants |
| Randomized Trial: Initial Laparotomy | Death or NDI Stratified by Pre-operative Diagnosis | NEC | No | 13 Participants |
| Randomized Trial: Initial Laparotomy | Death or NDI Stratified by Pre-operative Diagnosis | NEC | Yes | 29 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or NDI Stratified by Pre-operative Diagnosis | NEC | Yes | 44 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or NDI Stratified by Pre-operative Diagnosis | IP | No | 38 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or NDI Stratified by Pre-operative Diagnosis | NEC | No | 8 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death or NDI Stratified by Pre-operative Diagnosis | IP | Yes | 64 Participants |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.95% CI: [0.64, 1.04]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.95% CI: [0.95, 1.31]
Comparison: A Bayesian analysis. Within pre-operative diagnosis, Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. Pre-operative diagnosis levels were NEC and IP. PROC MCMC with effect coding was used. Center (random effect), treatment, pre-operative diagnosis, baseline risk, and the treatment by Preoperative diagnosis were the covariates. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Death Stratified by Pre-operative Diagnosis
Death within 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: by 18-22 months corrected age
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Death Stratified by Pre-operative Diagnosis | IP | No | 80 Participants |
| Randomized Trial: Initial Laparotomy | Death Stratified by Pre-operative Diagnosis | IP | Yes | 24 Participants |
| Randomized Trial: Initial Laparotomy | Death Stratified by Pre-operative Diagnosis | NEC | No | 25 Participants |
| Randomized Trial: Initial Laparotomy | Death Stratified by Pre-operative Diagnosis | NEC | Yes | 17 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death Stratified by Pre-operative Diagnosis | NEC | Yes | 27 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death Stratified by Pre-operative Diagnosis | IP | No | 88 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death Stratified by Pre-operative Diagnosis | NEC | No | 26 Participants |
| Randomized Trial: Initial Peritoneal Drain | Death Stratified by Pre-operative Diagnosis | IP | Yes | 21 Participants |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.95% CI: [0.52, 1.13]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.95% CI: [0.79, 2.06]
Comparison: A Bayesian analysis. Within pre-operative diagnosis, Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. Pre-operative diagnosis levels were NEC and IP. PROC MCMC with effect coding was used. Center (random effect), treatment, pre-operative diagnosis, baseline risk, and the treatment by Preoperative diagnosis were the covariates. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Duration of Mechanical Ventilation
Duration of mechanical ventilation while on study
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Duration of Mechanical Ventilation | 33.3 days | Standard Deviation 25.6 |
| Randomized Trial: Initial Peritoneal Drain | Duration of Mechanical Ventilation | 38.9 days | Standard Deviation 26.7 |
Comparison: A frequentist analysis.95% CI: [-12.77, 0.75]
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using a hierarchical linear regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Duration of Mechanical Ventilation Stratified by Pre-operative Diagnosis
Duration of mechanical ventilation while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Duration of Mechanical Ventilation Stratified by Pre-operative Diagnosis | IP | 34.1 days | Standard Deviation 26.6 |
| Randomized Trial: Initial Laparotomy | Duration of Mechanical Ventilation Stratified by Pre-operative Diagnosis | NEC | 31 days | Standard Deviation 22.6 |
| Randomized Trial: Initial Peritoneal Drain | Duration of Mechanical Ventilation Stratified by Pre-operative Diagnosis | IP | 42.2 days | Standard Deviation 28 |
| Randomized Trial: Initial Peritoneal Drain | Duration of Mechanical Ventilation Stratified by Pre-operative Diagnosis | NEC | 31.7 days | Standard Deviation 22.5 |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to NEC.95% CI: [-14.1, 11.6]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to IP.95% CI: [-15.84, 0.13]
Secondary
Duration of Parenteral Nutrition
Duration of parenteral nutrition while on study
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Duration of Parenteral Nutrition | 55.5 days | Standard Deviation 34.1 |
| Randomized Trial: Initial Peritoneal Drain | Duration of Parenteral Nutrition | 64.1 days | Standard Deviation 36.4 |
Comparison: A frequentist analysis.95% CI: [-17.05, -0.46]
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using a hierarchical linear regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Duration of Parenteral Nutrition Stratified by Pre-operative Diagnosis
Duration of parenteral nutrition while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Duration of Parenteral Nutrition Stratified by Pre-operative Diagnosis | IP | 56.3 days | Standard Deviation 35.2 |
| Randomized Trial: Initial Laparotomy | Duration of Parenteral Nutrition Stratified by Pre-operative Diagnosis | NEC | 53.5 days | Standard Deviation 31.3 |
| Randomized Trial: Initial Peritoneal Drain | Duration of Parenteral Nutrition Stratified by Pre-operative Diagnosis | IP | 63.6 days | Standard Deviation 33.7 |
| Randomized Trial: Initial Peritoneal Drain | Duration of Parenteral Nutrition Stratified by Pre-operative Diagnosis | NEC | 65.3 days | Standard Deviation 42 |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to NEC.95% CI: [-27.15, 4.01]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to IP.95% CI: [-17.46, 2.2]
Secondary
Final Bowel Length
Final bowel length after last surgery
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Final Bowel Length | 74.4 cm | Standard Deviation 24.6 |
| Randomized Trial: Initial Peritoneal Drain | Final Bowel Length | 68.7 cm | Standard Deviation 35.7 |
Comparison: A frequentist analysis.95% CI: [-9.09, 22.27]
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using a hierarchical linear regression. The SAS procedure PROC MCMC with reference coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Final Bowel Length Stratified by Pre-operative Diagnosis
Final bowel length after last surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Final Bowel Length Stratified by Pre-operative Diagnosis | IP | 83.1 cm | Standard Deviation 20.9 |
| Randomized Trial: Initial Laparotomy | Final Bowel Length Stratified by Pre-operative Diagnosis | NEC | 62.7 cm | Standard Deviation 25 |
| Randomized Trial: Initial Peritoneal Drain | Final Bowel Length Stratified by Pre-operative Diagnosis | IP | 74.7 cm | Standard Deviation 22.4 |
| Randomized Trial: Initial Peritoneal Drain | Final Bowel Length Stratified by Pre-operative Diagnosis | NEC | 64 cm | Standard Deviation 44.2 |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to NEC.95% CI: [-18.84, 26.83]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to IP.95% CI: [-13.29, 31.38]
Secondary
Length of Hospital Stay
Length of hospital stay while on study
Time frame: from randomization up to 1 year following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Length of Hospital Stay | 101.2 days | Standard Deviation 71.2 |
| Randomized Trial: Initial Peritoneal Drain | Length of Hospital Stay | 113.8 days | Standard Deviation 73.8 |
Comparison: A frequentist analysis.95% CI: [-30.54, 2.63]
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using a hierarchical linear regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Length of Hospital Stay Stratified by Pre-operative Diagnosis
Length of hospital stay while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: from randomization up to 1 year following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Length of Hospital Stay Stratified by Pre-operative Diagnosis | IP | 109.6 days | Standard Deviation 67 |
| Randomized Trial: Initial Laparotomy | Length of Hospital Stay Stratified by Pre-operative Diagnosis | NEC | 80.2 days | Standard Deviation 77.8 |
| Randomized Trial: Initial Peritoneal Drain | Length of Hospital Stay Stratified by Pre-operative Diagnosis | IP | 121.3 days | Standard Deviation 64.7 |
| Randomized Trial: Initial Peritoneal Drain | Length of Hospital Stay Stratified by Pre-operative Diagnosis | NEC | 99.2 days | Standard Deviation 87.7 |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to NEC.95% CI: [-48.41, 11.55]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to IP.95% CI: [-31.96, 8.06]
Secondary
Subsequent Laparotomy
Subsequent laparotomy after initial surgery
Time frame: between initial surgery and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Subsequent Laparotomy | No | 110 Participants |
| Randomized Trial: Initial Laparotomy | Subsequent Laparotomy | Yes | 35 Participants |
| Randomized Trial: Initial Peritoneal Drain | Subsequent Laparotomy | No | 81 Participants |
| Randomized Trial: Initial Peritoneal Drain | Subsequent Laparotomy | Yes | 81 Participants |
Comparison: A frequentist analysis.95% CI: [0.35, 0.63]
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Subsequent Laparotomy Stratified by Pre-operative Diagnosis
Subsequent laparotomy after initial surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Subsequent Laparotomy Stratified by Pre-operative Diagnosis | IP | No | 81 Participants |
| Randomized Trial: Initial Laparotomy | Subsequent Laparotomy Stratified by Pre-operative Diagnosis | IP | Yes | 23 Participants |
| Randomized Trial: Initial Laparotomy | Subsequent Laparotomy Stratified by Pre-operative Diagnosis | NEC | No | 29 Participants |
| Randomized Trial: Initial Laparotomy | Subsequent Laparotomy Stratified by Pre-operative Diagnosis | NEC | Yes | 12 Participants |
| Randomized Trial: Initial Peritoneal Drain | Subsequent Laparotomy Stratified by Pre-operative Diagnosis | NEC | Yes | 30 Participants |
| Randomized Trial: Initial Peritoneal Drain | Subsequent Laparotomy Stratified by Pre-operative Diagnosis | IP | No | 58 Participants |
| Randomized Trial: Initial Peritoneal Drain | Subsequent Laparotomy Stratified by Pre-operative Diagnosis | NEC | No | 23 Participants |
| Randomized Trial: Initial Peritoneal Drain | Subsequent Laparotomy Stratified by Pre-operative Diagnosis | IP | Yes | 51 Participants |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.95% CI: [0.31, 0.89]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.95% CI: [0.29, 0.66]
Secondary
Survival With Neurodevelopmental Impairment (NDI)
NDI at 18-22 months corrected age (among survivors)
Time frame: by 18-22 months corrected age
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, survived until follow-up visit at 18-22 months, and provided sufficient information to determine if NDI occurred.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Survival With Neurodevelopmental Impairment (NDI) | No | 44 Participants |
| Randomized Trial: Initial Laparotomy | Survival With Neurodevelopmental Impairment (NDI) | Yes | 56 Participants |
| Randomized Trial: Initial Peritoneal Drain | Survival With Neurodevelopmental Impairment (NDI) | No | 46 Participants |
| Randomized Trial: Initial Peritoneal Drain | Survival With Neurodevelopmental Impairment (NDI) | Yes | 60 Participants |
Comparison: A frequentist analysis. Estimate based on model fit using only data from study survivors.95% CI: [0.78, 1.34]
Comparison: A Bayesian analysis among study survivors. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis
NDI at 18-22 months corrected age (among survivors). Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: by 18-22 months corrected age
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, survived until follow-up visit at 18-22 months, and provided sufficient information to determine if NDI occurred.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis | IP | No | 31 Participants |
| Randomized Trial: Initial Laparotomy | Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis | IP | Yes | 44 Participants |
| Randomized Trial: Initial Laparotomy | Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis | NEC | No | 13 Participants |
| Randomized Trial: Initial Laparotomy | Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis | NEC | Yes | 12 Participants |
| Randomized Trial: Initial Peritoneal Drain | Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis | NEC | Yes | 17 Participants |
| Randomized Trial: Initial Peritoneal Drain | Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis | IP | No | 38 Participants |
| Randomized Trial: Initial Peritoneal Drain | Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis | NEC | No | 8 Participants |
| Randomized Trial: Initial Peritoneal Drain | Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis | IP | Yes | 43 Participants |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.95% CI: [0.42, 1.27]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.95% CI: [0.85, 1.45]
Comparison: A Bayesian analysis. Within pre-operative diagnosis, Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. Pre-operative diagnosis levels were NEC and IP. PROC MCMC with effect coding was used. Center (random effect), treatment, pre-operative diagnosis, baseline risk, and the treatment by Pre-operative diagnosis were the covariates. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Time to Full Feeds
Time to full feeds while on study
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Time to Full Feeds | 46.9 days | Standard Deviation 45.8 |
| Randomized Trial: Initial Peritoneal Drain | Time to Full Feeds | 50.6 days | Standard Deviation 27.7 |
Comparison: A frequentist analysis.95% CI: [-13.02, 7.91]
Comparison: A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using a hierarchical linear regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
Secondary
Time to Full Feeds Stratified by Pre-operative Diagnosis
Time to full feeds while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
Time frame: between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Population: Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Trial: Initial Laparotomy | Time to Full Feeds Stratified by Pre-operative Diagnosis | IP | 52.4 days | Standard Deviation 50.4 |
| Randomized Trial: Initial Laparotomy | Time to Full Feeds Stratified by Pre-operative Diagnosis | NEC | 29.6 days | Standard Deviation 18.9 |
| Randomized Trial: Initial Peritoneal Drain | Time to Full Feeds Stratified by Pre-operative Diagnosis | IP | 56.3 days | Standard Deviation 27.1 |
| Randomized Trial: Initial Peritoneal Drain | Time to Full Feeds Stratified by Pre-operative Diagnosis | NEC | 32.3 days | Standard Deviation 21.3 |
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to NEC.95% CI: [-24.62, 18.36]
Comparison: This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to IP.95% CI: [-14.42, 9.63]