Trial Outcomes & Findings for Laparotomy vs. Drainage for Infants With Necrotizing Enterocolitis (NCT NCT01029353)

NCT ID: NCT01029353

Last Updated: 2024-07-18

Results Overview

Death or NDI at 18-22 months corrected age

Recruitment status

COMPLETED

Study phase

Target enrollment

529 participants

Primary outcome timeframe

at 18-22 months corrected age

Results posted on

2024-07-18

Participant Flow

Participant milestones

Participant milestones
Measure	Randomized Trial: Initial Laparotomy Under general anesthesia in the neonatal intensive care unit (NICU) or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Initial Laparotomy Under general anesthesia in the neonatal intensive care unit (NICU) or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Overall Study STARTED	148	162	100	119
Overall Study Included in ITT Analysis	146	162	100	119
Overall Study Reached Network Status	146	162	100	119
Overall Study COMPLETED	141	154	93	115
Overall Study NOT COMPLETED	7	8	7	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Randomized Trial: Initial Laparotomy Under general anesthesia in the neonatal intensive care unit (NICU) or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Initial Laparotomy Under general anesthesia in the neonatal intensive care unit (NICU) or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Overall Study Lost to Follow-up	4	5	5	4
Overall Study Consent Withdrawn	2	0	0	0
Overall Study Primary Outcome Indeterminate	1	3	2	0

Baseline Characteristics

Laparotomy vs. Drainage for Infants With Necrotizing Enterocolitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Randomized Trial: Initial Laparotomy n=146 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=162 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Initial Laparotomy n=100 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain n=119 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Total n=527 Participants Total of all reporting groups
Age, Continuous	11.6 days STANDARD_DEVIATION 10 • n=5 Participants	12.1 days STANDARD_DEVIATION 9.9 • n=7 Participants	79.9 days STANDARD_DEVIATION 125.4 • n=5 Participants	49.9 days STANDARD_DEVIATION 111.7 • n=4 Participants	33.3 days STANDARD_DEVIATION 81.0 • n=21 Participants
Sex/Gender, Customized Female	66 Participants n=5 Participants	63 Participants n=7 Participants	48 Participants n=5 Participants	53 Participants n=4 Participants	230 Participants n=21 Participants
Sex/Gender, Customized Male	80 Participants n=5 Participants	98 Participants n=7 Participants	52 Participants n=5 Participants	66 Participants n=4 Participants	296 Participants n=21 Participants
Sex/Gender, Customized Missing	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Black	62 Participants n=5 Participants	67 Participants n=7 Participants	31 Participants n=5 Participants	42 Participants n=4 Participants	202 Participants n=21 Participants
Race/Ethnicity, Customized Missing	5 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	12 Participants n=21 Participants
Race/Ethnicity, Customized Other	6 Participants n=5 Participants	8 Participants n=7 Participants	9 Participants n=5 Participants	6 Participants n=4 Participants	29 Participants n=21 Participants
Race/Ethnicity, Customized White	73 Participants n=5 Participants	82 Participants n=7 Participants	59 Participants n=5 Participants	70 Participants n=4 Participants	284 Participants n=21 Participants
Maternal hispanic ethnicity Missing	1 Participants n=5 Participants	9 Participants n=7 Participants	3 Participants n=5 Participants	9 Participants n=4 Participants	22 Participants n=21 Participants
Infant mean blood pressure	37.1 mmHG STANDARD_DEVIATION 10.3 • n=5 Participants	37.0 mmHG STANDARD_DEVIATION 11.5 • n=7 Participants	39.0 mmHG STANDARD_DEVIATION 11.3 • n=5 Participants	36.1 mmHG STANDARD_DEVIATION 11.7 • n=4 Participants	37.2 mmHG STANDARD_DEVIATION 11.2 • n=21 Participants
Infant lowest platelet count	155.7 1000 platelets per microliter STANDARD_DEVIATION 96 • n=5 Participants	150.4 1000 platelets per microliter STANDARD_DEVIATION 80.9 • n=7 Participants	156.2 1000 platelets per microliter STANDARD_DEVIATION 91.4 • n=5 Participants	131.5 1000 platelets per microliter STANDARD_DEVIATION 79.6 • n=4 Participants	148.7 1000 platelets per microliter STANDARD_DEVIATION 87.3 • n=21 Participants
Maternal hispanic ethnicity No	107 Participants n=5 Participants	120 Participants n=7 Participants	75 Participants n=5 Participants	95 Participants n=4 Participants	397 Participants n=21 Participants
Maternal hispanic ethnicity Yes	38 Participants n=5 Participants	33 Participants n=7 Participants	22 Participants n=5 Participants	15 Participants n=4 Participants	108 Participants n=21 Participants
Infant gestational age	25 weeks STANDARD_DEVIATION 1.7 • n=5 Participants	24.9 weeks STANDARD_DEVIATION 1.7 • n=7 Participants	24.6 weeks STANDARD_DEVIATION 1.1 • n=5 Participants	24.5 weeks STANDARD_DEVIATION 1.2 • n=4 Participants	25 weeks STANDARD_DEVIATION 1.7 • n=21 Participants
Infant birth weight	721.2 gram STANDARD_DEVIATION 138.4 • n=5 Participants	711.4 gram STANDARD_DEVIATION 135.9 • n=7 Participants	719.8 gram STANDARD_DEVIATION 150.5 • n=5 Participants	675.6 gram STANDARD_DEVIATION 161.7 • n=4 Participants	707.6 gram STANDARD_DEVIATION 146.2 • n=21 Participants
Infant was small for gestational age Missing	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Infant was small for gestational age No	131 Participants n=5 Participants	145 Participants n=7 Participants	84 Participants n=5 Participants	98 Participants n=4 Participants	458 Participants n=21 Participants
Infant was small for gestational age Yes	15 Participants n=5 Participants	16 Participants n=7 Participants	16 Participants n=5 Participants	21 Participants n=4 Participants	68 Participants n=21 Participants
Inborn status In born	82 Participants n=5 Participants	90 Participants n=7 Participants	65 Participants n=5 Participants	75 Participants n=4 Participants	312 Participants n=21 Participants
Inborn status Out born	64 Participants n=5 Participants	72 Participants n=7 Participants	35 Participants n=5 Participants	44 Participants n=4 Participants	215 Participants n=21 Participants
Infant Apgar score at 1 minute	3 units on a scale n=5 Participants	3 units on a scale n=7 Participants	4 units on a scale n=5 Participants	4 units on a scale n=4 Participants	3 units on a scale n=21 Participants
Infant Apgar score at 5 minute	6 units on a scale n=5 Participants	6 units on a scale n=7 Participants	7 units on a scale n=5 Participants	7 units on a scale n=4 Participants	7 units on a scale n=21 Participants
Infant had patent ductus arteriosus (PDA) prior to enrollment Missing	10 Participants n=5 Participants	15 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants	31 Participants n=21 Participants
Infant had patent ductus arteriosus (PDA) prior to enrollment No	77 Participants n=5 Participants	85 Participants n=7 Participants	52 Participants n=5 Participants	56 Participants n=4 Participants	270 Participants n=21 Participants
Infant had patent ductus arteriosus (PDA) prior to enrollment Yes	59 Participants n=5 Participants	62 Participants n=7 Participants	46 Participants n=5 Participants	59 Participants n=4 Participants	226 Participants n=21 Participants
Infant received postnatal steroids No	119 Participants n=5 Participants	115 Participants n=7 Participants	67 Participants n=5 Participants	83 Participants n=4 Participants	384 Participants n=21 Participants
Infant received postnatal steroids Yes	27 Participants n=5 Participants	47 Participants n=7 Participants	33 Participants n=5 Participants	36 Participants n=4 Participants	143 Participants n=21 Participants
Infant received indomethacin before or on Randomization Missing	3 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants	19 Participants n=21 Participants
Infant received indomethacin before or on Randomization No	69 Participants n=5 Participants	74 Participants n=7 Participants	51 Participants n=5 Participants	38 Participants n=4 Participants	232 Participants n=21 Participants
Infant received indomethacin before or on Randomization Yes	74 Participants n=5 Participants	82 Participants n=7 Participants	46 Participants n=5 Participants	74 Participants n=4 Participants	276 Participants n=21 Participants
Infant received enteral feedings before or on enrollment Missing	33 Participants n=5 Participants	38 Participants n=7 Participants	16 Participants n=5 Participants	25 Participants n=4 Participants	112 Participants n=21 Participants
Infant received enteral feedings before or on enrollment No	23 Participants n=5 Participants	29 Participants n=7 Participants	5 Participants n=5 Participants	11 Participants n=4 Participants	68 Participants n=21 Participants
Infant received enteral feedings before or on enrollment Yes	90 Participants n=5 Participants	95 Participants n=7 Participants	79 Participants n=5 Participants	83 Participants n=4 Participants	347 Participants n=21 Participants
Infant had early onset sepsis before or on enrollment Missing	2 Participants n=5 Participants	5 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	8 Participants n=21 Participants
Infant had early onset sepsis before or on enrollment No	143 Participants n=5 Participants	151 Participants n=7 Participants	98 Participants n=5 Participants	117 Participants n=4 Participants	509 Participants n=21 Participants
Infant had early onset sepsis before or on enrollment Yes	1 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	10 Participants n=21 Participants
Infant had late onset sepsis before or on enrollment Missing	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Infant had late onset sepsis before or on enrollment No	109 Participants n=5 Participants	113 Participants n=7 Participants	72 Participants n=5 Participants	76 Participants n=4 Participants	370 Participants n=21 Participants
Infant had late onset sepsis before or on enrollment Yes	37 Participants n=5 Participants	47 Participants n=7 Participants	27 Participants n=5 Participants	43 Participants n=4 Participants	154 Participants n=21 Participants
Infant had severe intraventricular hemorrhage (IVH) (grade 3 or 4) Missing	6 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants	16 Participants n=21 Participants
Infant baseline risk of death or neurodevelopmental impairment (NDI)	63.4 Percent probability STANDARD_DEVIATION 27 • n=5 Participants	70.7 Percent probability STANDARD_DEVIATION 23.7 • n=7 Participants	88.1 Percent probability STANDARD_DEVIATION 20.7 • n=5 Participants	85.8 Percent probability STANDARD_DEVIATION 23.1 • n=4 Participants	70.3 Percent probability STANDARD_DEVIATION 25.0 • n=21 Participants
Infant had severe intraventricular hemorrhage (IVH) (grade 3 or 4) No	123 Participants n=5 Participants	134 Participants n=7 Participants	86 Participants n=5 Participants	88 Participants n=4 Participants	431 Participants n=21 Participants
Infant had severe intraventricular hemorrhage (IVH) (grade 3 or 4) Yes	17 Participants n=5 Participants	23 Participants n=7 Participants	13 Participants n=5 Participants	27 Participants n=4 Participants	80 Participants n=21 Participants
Infant on vasopressors at Enrollment No	105 Participants n=5 Participants	103 Participants n=7 Participants	55 Participants n=5 Participants	71 Participants n=4 Participants	334 Participants n=21 Participants
Infant on vasopressors at Enrollment Yes	41 Participants n=5 Participants	59 Participants n=7 Participants	45 Participants n=5 Participants	47 Participants n=4 Participants	192 Participants n=21 Participants
Infant on vasopressors at Enrollment Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Infant received HFOV or HFJV at randomization No	114 Participants n=5 Participants	114 Participants n=7 Participants	51 Participants n=5 Participants	66 Participants n=4 Participants	345 Participants n=21 Participants
Infant received HFOV or HFJV at randomization Yes	32 Participants n=5 Participants	48 Participants n=7 Participants	49 Participants n=5 Participants	53 Participants n=4 Participants	182 Participants n=21 Participants
Infant pH closest to enrollment	7.2 pH STANDARD_DEVIATION 0.1 • n=5 Participants	7.2 pH STANDARD_DEVIATION 0.1 • n=7 Participants	7.2 pH STANDARD_DEVIATION 0.1 • n=5 Participants	7.2 pH STANDARD_DEVIATION 0.2 • n=4 Participants	7.2 pH STANDARD_DEVIATION 0.1 • n=21 Participants
Infant fraction of inspired oxygen (FiO2) closest to enrollment	44.8 Percent STANDARD_DEVIATION 26.3 • n=5 Participants	45.9 Percent STANDARD_DEVIATION 24.1 • n=7 Participants	57.8 Percent STANDARD_DEVIATION 29.7 • n=5 Participants	53.5 Percent STANDARD_DEVIATION 30.0 • n=4 Participants	49.6 Percent STANDARD_DEVIATION 27.6 • n=21 Participants
Infant preoperative diagnosis (NEC or IP) IP	104 Participants n=5 Participants	109 Participants n=7 Participants	25 Participants n=5 Participants	72 Participants n=4 Participants	310 Participants n=21 Participants
Infant preoperative diagnosis (NEC or IP) NEC	42 Participants n=5 Participants	53 Participants n=7 Participants	75 Participants n=5 Participants	47 Participants n=4 Participants	217 Participants n=21 Participants
Maternal Age, Continuous	27.6 years STANDARD_DEVIATION 6.7 • n=5 Participants	27.3 years STANDARD_DEVIATION 6.3 • n=7 Participants	26.7 years STANDARD_DEVIATION 6.3 • n=5 Participants	26.8 years STANDARD_DEVIATION 6.2 • n=4 Participants	27.2 years STANDARD_DEVIATION 6.4 • n=21 Participants
Married, Customized Missing	1 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	15 Participants n=21 Participants
Married, Customized No	81 Participants n=5 Participants	95 Participants n=7 Participants	50 Participants n=5 Participants	62 Participants n=4 Participants	288 Participants n=21 Participants
Married, Customized Yes	64 Participants n=5 Participants	61 Participants n=7 Participants	46 Participants n=5 Participants	53 Participants n=4 Participants	224 Participants n=21 Participants
Maternal Education, Customized College graduate	18 Participants n=5 Participants	21 Participants n=7 Participants	19 Participants n=5 Participants	25 Participants n=4 Participants	83 Participants n=21 Participants
Maternal Education, Customized High school graduate	42 Participants n=5 Participants	38 Participants n=7 Participants	19 Participants n=5 Participants	25 Participants n=4 Participants	124 Participants n=21 Participants
Maternal Education, Customized Less than high school	21 Participants n=5 Participants	28 Participants n=7 Participants	22 Participants n=5 Participants	12 Participants n=4 Participants	83 Participants n=21 Participants
Maternal Education, Customized Missing	42 Participants n=5 Participants	51 Participants n=7 Participants	25 Participants n=5 Participants	38 Participants n=4 Participants	156 Participants n=21 Participants
Maternal Education, Customized Some college	23 Participants n=5 Participants	24 Participants n=7 Participants	15 Participants n=5 Participants	19 Participants n=4 Participants	81 Participants n=21 Participants
Mother had private insurance Missing	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Mother had private insurance No	98 Participants n=5 Participants	113 Participants n=7 Participants	71 Participants n=5 Participants	65 Participants n=4 Participants	347 Participants n=21 Participants
Mother had private insurance Yes	48 Participants n=5 Participants	46 Participants n=7 Participants	29 Participants n=5 Participants	53 Participants n=4 Participants	176 Participants n=21 Participants
Mother received prenatal care Missing	1 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	15 Participants n=21 Participants
Mother received prenatal care No	3 Participants n=5 Participants	10 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants	20 Participants n=21 Participants
Mother received prenatal care Yes	142 Participants n=5 Participants	149 Participants n=7 Participants	92 Participants n=5 Participants	109 Participants n=4 Participants	492 Participants n=21 Participants
Mother received antibiotics Missing	28 Participants n=5 Participants	37 Participants n=7 Participants	15 Participants n=5 Participants	18 Participants n=4 Participants	98 Participants n=21 Participants
Mother received antibiotics No	39 Participants n=5 Participants	42 Participants n=7 Participants	19 Participants n=5 Participants	19 Participants n=4 Participants	119 Participants n=21 Participants
Mother received antibiotics Yes	79 Participants n=5 Participants	83 Participants n=7 Participants	66 Participants n=5 Participants	82 Participants n=4 Participants	310 Participants n=21 Participants
Rupture of membranes > 18 hours Missing	22 Participants n=5 Participants	29 Participants n=7 Participants	7 Participants n=5 Participants	6 Participants n=4 Participants	64 Participants n=21 Participants
Rupture of membranes > 18 hours No	101 Participants n=5 Participants	108 Participants n=7 Participants	69 Participants n=5 Participants	97 Participants n=4 Participants	375 Participants n=21 Participants
Rupture of membranes > 18 hours Yes	23 Participants n=5 Participants	25 Participants n=7 Participants	24 Participants n=5 Participants	16 Participants n=4 Participants	88 Participants n=21 Participants
Maternal hypertension Missing	26 Participants n=5 Participants	31 Participants n=7 Participants	10 Participants n=5 Participants	13 Participants n=4 Participants	80 Participants n=21 Participants
Maternal hypertension No	85 Participants n=5 Participants	98 Participants n=7 Participants	65 Participants n=5 Participants	84 Participants n=4 Participants	332 Participants n=21 Participants
Maternal hypertension Yes	35 Participants n=5 Participants	33 Participants n=7 Participants	25 Participants n=5 Participants	22 Participants n=4 Participants	115 Participants n=21 Participants
Mother received antenatal magnesium Missing	52 Participants n=5 Participants	68 Participants n=7 Participants	59 Participants n=5 Participants	66 Participants n=4 Participants	245 Participants n=21 Participants
Mother received antenatal magnesium No	17 Participants n=5 Participants	21 Participants n=7 Participants	6 Participants n=5 Participants	7 Participants n=4 Participants	51 Participants n=21 Participants
Mother received antenatal magnesium Yes	77 Participants n=5 Participants	73 Participants n=7 Participants	35 Participants n=5 Participants	46 Participants n=4 Participants	231 Participants n=21 Participants
Mother received steroids Missing	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Mother received steroids No	22 Participants n=5 Participants	31 Participants n=7 Participants	11 Participants n=5 Participants	18 Participants n=4 Participants	82 Participants n=21 Participants
Mother received steroids Yes	124 Participants n=5 Participants	130 Participants n=7 Participants	89 Participants n=5 Participants	101 Participants n=4 Participants	444 Participants n=21 Participants

PRIMARY outcome

Timeframe: 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.

Death or NDI at 18-22 months corrected age

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=141 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=154 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy n=93 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain n=115 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Death or Neurodevelopmental Impairment (NDI) No	44 Participants	46 Participants	27 Participants	28 Participants
Death or Neurodevelopmental Impairment (NDI) Yes	97 Participants	108 Participants	66 Participants	87 Participants

SECONDARY outcome

Timeframe: 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.

Death by 18-22 months corrected age

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=146 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=162 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Death No	105 Participants	114 Participants	—	—
Death Yes	41 Participants	48 Participants	—	—

SECONDARY outcome

Timeframe: 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.

NDI at 18-22 months corrected age (among survivors)

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=100 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=106 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Survival With Neurodevelopmental Impairment (NDI) No	44 Participants	46 Participants	—	—
Survival With Neurodevelopmental Impairment (NDI) Yes	56 Participants	60 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Death within 18-22 months corrected age or moderate to severe cerebral palsy at 18-22 months corrected age

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=142 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=157 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Death or Moderate to Severe Cerebral Palsy No	84 Participants	78 Participants	—	—
Death or Moderate to Severe Cerebral Palsy Yes	58 Participants	79 Participants	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=141 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=151 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Death or Bayley Cognitive Composite Score Less Than 85 No	46 Participants	51 Participants	—	—
Death or Bayley Cognitive Composite Score Less Than 85 Yes	95 Participants	100 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Death within 18-22 months corrected age or blindness at 18-22 months corrected age

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=142 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=157 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Death or Blindness No	101 Participants	105 Participants	—	—
Death or Blindness Yes	41 Participants	52 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Death within 18-22 months corrected age or hearing loss at 18-22 months corrected age

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=141 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=156 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Death or Hearing Loss No	98 Participants	105 Participants	—	—
Death or Hearing Loss Yes	43 Participants	51 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Subsequent laparotomy after initial surgery

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=145 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=162 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Subsequent Laparotomy No	110 Participants	81 Participants	—	—
Subsequent Laparotomy Yes	35 Participants	81 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Any intraoperative complications during any surgery

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=145 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=162 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Any Intraoperative Complications During Any Surgery No	116 Participants	141 Participants	—	—
Any Intraoperative Complications During Any Surgery Yes	29 Participants	21 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Any wound dehiscence during any surgery

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=146 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=162 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Any Wound Dehiscence No	135 Participants	154 Participants	—	—
Any Wound Dehiscence Yes	11 Participants	8 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Any intra-abdominal abscess during any surgery

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=146 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=162 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Any Intra-abdominal Abscess No	141 Participants	158 Participants	—	—
Any Intra-abdominal Abscess Yes	5 Participants	4 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Any intestinal stricture during any surgery

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=146 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=162 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Any Intestinal Stricture No	139 Participants	153 Participants	—	—
Any Intestinal Stricture Yes	7 Participants	9 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Any late onset sepsis after randomization

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=146 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=160 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Any Late Onset Sepsis No	123 Participants	126 Participants	—	—
Any Late Onset Sepsis Yes	23 Participants	34 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Any Parenteral nutrition (PN)-associated cholestasis during any surgery

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=146 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=162 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Any Parenteral Nutrition (PN)-Associated Cholestasis No	110 Participants	116 Participants	—	—
Any Parenteral Nutrition (PN)-Associated Cholestasis Yes	36 Participants	46 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Any severe IVH ater randomization

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=140 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=157 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Any Severe IVH No	122 Participants	132 Participants	—	—
Any Severe IVH Yes	18 Participants	25 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Duration of mechanical ventilation while on study

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=107 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=120 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Duration of Mechanical Ventilation	33.3 days Standard Deviation 25.6	38.9 days Standard Deviation 26.7	—	—

SECONDARY outcome

Timeframe: 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.

Duration of parenteral nutrition while on study

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=135 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=149 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Duration of Parenteral Nutrition	55.5 days Standard Deviation 34.1	64.1 days Standard Deviation 36.4	—	—

SECONDARY outcome

Timeframe: 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.

Final bowel length after last surgery

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=28 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=16 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Final Bowel Length	74.4 cm Standard Deviation 24.6	68.7 cm Standard Deviation 35.7	—	—

SECONDARY outcome

Timeframe: 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.

Time to full feeds while on study

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=92 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=92 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Time to Full Feeds	46.9 days Standard Deviation 45.8	50.6 days Standard Deviation 27.7	—	—

SECONDARY outcome

Timeframe: 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.

Length of hospital stay while on study

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=137 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=156 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Length of Hospital Stay	101.2 days Standard Deviation 71.2	113.8 days Standard Deviation 73.8	—	—

SECONDARY outcome

Timeframe: 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.

Death or NDI at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=141 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=154 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Death or NDI Stratified by Pre-operative Diagnosis IP · No	31 Participants	38 Participants	—	—
Death or NDI Stratified by Pre-operative Diagnosis IP · Yes	68 Participants	64 Participants	—	—
Death or NDI Stratified by Pre-operative Diagnosis NEC · No	13 Participants	8 Participants	—	—
Death or NDI Stratified by Pre-operative Diagnosis NEC · Yes	29 Participants	44 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Death within 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=146 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=162 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Death Stratified by Pre-operative Diagnosis IP · No	80 Participants	88 Participants	—	—
Death Stratified by Pre-operative Diagnosis IP · Yes	24 Participants	21 Participants	—	—
Death Stratified by Pre-operative Diagnosis NEC · No	25 Participants	26 Participants	—	—
Death Stratified by Pre-operative Diagnosis NEC · Yes	17 Participants	27 Participants	—	—

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=100 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=106 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis NEC · Yes	12 Participants	17 Participants	—	—
Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis IP · No	31 Participants	38 Participants	—	—
Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis IP · Yes	44 Participants	43 Participants	—	—
Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis NEC · No	13 Participants	8 Participants	—	—

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=142 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=157 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis IP · No	64 Participants	64 Participants	—	—
Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis NEC · No	20 Participants	14 Participants	—	—
Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis NEC · Yes	22 Participants	38 Participants	—	—
Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis IP · Yes	36 Participants	41 Participants	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=141 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=151 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis NEC · Yes	28 Participants	41 Participants	—	—
Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis IP · No	32 Participants	42 Participants	—	—
Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis IP · Yes	67 Participants	59 Participants	—	—
Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis NEC · No	14 Participants	9 Participants	—	—

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=142 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=157 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Death or Blindness Stratified by Pre-operative Diagnosis IP · No	76 Participants	83 Participants	—	—
Death or Blindness Stratified by Pre-operative Diagnosis IP · Yes	24 Participants	22 Participants	—	—
Death or Blindness Stratified by Pre-operative Diagnosis NEC · No	25 Participants	22 Participants	—	—
Death or Blindness Stratified by Pre-operative Diagnosis NEC · Yes	17 Participants	30 Participants	—	—

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=141 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=156 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Death or Hearing Loss Stratified by Pre-operative Diagnosis IP · No	73 Participants	81 Participants	—	—
Death or Hearing Loss Stratified by Pre-operative Diagnosis IP · Yes	26 Participants	23 Participants	—	—
Death or Hearing Loss Stratified by Pre-operative Diagnosis NEC · No	25 Participants	24 Participants	—	—
Death or Hearing Loss Stratified by Pre-operative Diagnosis NEC · Yes	17 Participants	28 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Subsequent laparotomy after initial surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=145 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=162 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Subsequent Laparotomy Stratified by Pre-operative Diagnosis IP · No	81 Participants	58 Participants	—	—
Subsequent Laparotomy Stratified by Pre-operative Diagnosis IP · Yes	23 Participants	51 Participants	—	—
Subsequent Laparotomy Stratified by Pre-operative Diagnosis NEC · No	29 Participants	23 Participants	—	—
Subsequent Laparotomy Stratified by Pre-operative Diagnosis NEC · Yes	12 Participants	30 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Any intraoperative complications during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=145 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=162 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis IP · No	83 Participants	95 Participants	—	—
Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis IP · Yes	21 Participants	14 Participants	—	—
Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis NEC · No	33 Participants	46 Participants	—	—
Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis NEC · Yes	8 Participants	7 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Any wound dehiscence during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=146 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=162 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Any Wound Dehiscence Stratified by Pre-operative Diagnosis IP · No	99 Participants	104 Participants	—	—
Any Wound Dehiscence Stratified by Pre-operative Diagnosis IP · Yes	5 Participants	5 Participants	—	—
Any Wound Dehiscence Stratified by Pre-operative Diagnosis NEC · No	36 Participants	50 Participants	—	—
Any Wound Dehiscence Stratified by Pre-operative Diagnosis NEC · Yes	6 Participants	3 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Any intra-abdominal abscess during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=146 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=162 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis IP · No	101 Participants	106 Participants	—	—
Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis IP · Yes	3 Participants	3 Participants	—	—
Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis NEC · No	40 Participants	52 Participants	—	—
Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis NEC · Yes	2 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Any intestinal stricture during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=146 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=162 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Any Intestinal Stricture Stratified by Pre-operative Diagnosis IP · No	101 Participants	103 Participants	—	—
Any Intestinal Stricture Stratified by Pre-operative Diagnosis IP · Yes	3 Participants	6 Participants	—	—
Any Intestinal Stricture Stratified by Pre-operative Diagnosis NEC · No	38 Participants	50 Participants	—	—
Any Intestinal Stricture Stratified by Pre-operative Diagnosis NEC · Yes	4 Participants	3 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Any late onset sepsis after randomization. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=146 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=160 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Any Late Onset Sepsis Stratified by Pre-operative Diagnosis IP · No	88 Participants	80 Participants	—	—
Any Late Onset Sepsis Stratified by Pre-operative Diagnosis IP · Yes	16 Participants	27 Participants	—	—
Any Late Onset Sepsis Stratified by Pre-operative Diagnosis NEC · No	35 Participants	46 Participants	—	—
Any Late Onset Sepsis Stratified by Pre-operative Diagnosis NEC · Yes	7 Participants	7 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Any Parenteral nutrition (PN)-associated cholestasis during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=146 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=162 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis IP · No	79 Participants	82 Participants	—	—
Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis IP · Yes	25 Participants	27 Participants	—	—
Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis NEC · No	31 Participants	34 Participants	—	—
Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis NEC · Yes	11 Participants	19 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Any severe IVH ater randomization. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=140 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=157 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Any Severe IVH Stratified by Pre-operative Diagnosis NEC · Yes	1 Participants	3 Participants	—	—
Any Severe IVH Stratified by Pre-operative Diagnosis IP · No	84 Participants	84 Participants	—	—
Any Severe IVH Stratified by Pre-operative Diagnosis IP · Yes	17 Participants	22 Participants	—	—
Any Severe IVH Stratified by Pre-operative Diagnosis NEC · No	38 Participants	48 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Duration of mechanical ventilation while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=107 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=120 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Duration of Mechanical Ventilation Stratified by Pre-operative Diagnosis IP	34.1 days Standard Deviation 26.6	42.2 days Standard Deviation 28	—	—
Duration of Mechanical Ventilation Stratified by Pre-operative Diagnosis NEC	31 days Standard Deviation 22.6	31.7 days Standard Deviation 22.5	—	—

SECONDARY outcome

Timeframe: 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.

Duration of parenteral nutrition while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=135 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=149 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Duration of Parenteral Nutrition Stratified by Pre-operative Diagnosis IP	56.3 days Standard Deviation 35.2	63.6 days Standard Deviation 33.7	—	—
Duration of Parenteral Nutrition Stratified by Pre-operative Diagnosis NEC	53.5 days Standard Deviation 31.3	65.3 days Standard Deviation 42	—	—

SECONDARY outcome

Timeframe: 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.

Final bowel length after last surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=28 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=16 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Final Bowel Length Stratified by Pre-operative Diagnosis IP	83.1 cm Standard Deviation 20.9	74.7 cm Standard Deviation 22.4	—	—
Final Bowel Length Stratified by Pre-operative Diagnosis NEC	62.7 cm Standard Deviation 25	64 cm Standard Deviation 44.2	—	—

SECONDARY outcome

Timeframe: 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.

Time to full feeds while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=92 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=92 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Time to Full Feeds Stratified by Pre-operative Diagnosis IP	52.4 days Standard Deviation 50.4	56.3 days Standard Deviation 27.1	—	—
Time to Full Feeds Stratified by Pre-operative Diagnosis NEC	29.6 days Standard Deviation 18.9	32.3 days Standard Deviation 21.3	—	—

SECONDARY outcome

Timeframe: 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.

Length of hospital stay while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

Outcome measures

Outcome measures
Measure	Randomized Trial: Initial Laparotomy n=137 Participants Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=156 Participants Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Laparotomy Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Length of Hospital Stay Stratified by Pre-operative Diagnosis IP	109.6 days Standard Deviation 67	121.3 days Standard Deviation 64.7	—	—
Length of Hospital Stay Stratified by Pre-operative Diagnosis NEC	80.2 days Standard Deviation 77.8	99.2 days Standard Deviation 87.7	—	—

Adverse Events

Randomized Trial: Initial Laparotomy

Serious events: 41 serious events

Other events: 0 other events

Deaths: 41 deaths

Randomized Trial: Initial Peritoneal Drain

Serious events: 49 serious events

Other events: 0 other events

Deaths: 48 deaths

Preference Cohort: Initial Laparotomy

Serious events: 49 serious events

Other events: 0 other events

Deaths: 48 deaths

Preference Cohort: Initial Peritoneal Drain

Serious events: 60 serious events

Other events: 0 other events

Deaths: 60 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Martin L Blakely, MD

Vanderbilt University Medical Center

Phone: 615-936-7211

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigators must adhere to the Neonatal Research Network Publication policies.
Publication restrictions are in place

Restriction type: OTHER

Measure	Randomized Trial: Initial Laparotomy n=146 participants at risk Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Randomized Trial: Initial Peritoneal Drain n=162 participants at risk Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.	Preference Cohort: Initial Laparotomy n=100 participants at risk Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.	Preference Cohort: Initial Peritoneal Drain n=119 participants at risk Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
Cardiac disorders Pericardial effusion	0.68% 1/146 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/162 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/100 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/119 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Gastrointestinal disorders Abdominal herniation	0.00% 0/146 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.62% 1/162 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/100 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/119 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Gastrointestinal disorders Neonatal spontaneous intestinal perforation	2.1% 3/146 • Number of events 3 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/162 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	2.0% 2/100 • Number of events 2 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	7.6% 9/119 • Number of events 9 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Gastrointestinal disorders Necrotizing enterocolitis neonatal	14.4% 21/146 • Number of events 21 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	14.8% 24/162 • Number of events 24 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	35.0% 35/100 • Number of events 35 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	21.0% 25/119 • Number of events 25 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Respiratory, thoracic and mediastinal disorders Bronchopulmonary dysplasia	0.68% 1/146 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	1.2% 2/162 • Number of events 2 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	1.0% 1/100 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	1.7% 2/119 • Number of events 2 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Nervous system disorders CNS injury	0.00% 0/146 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.62% 1/162 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/100 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/119 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Infections and infestations Neonatal sepsis	6.8% 10/146 • Number of events 10 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	9.9% 16/162 • Number of events 16 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	13.0% 13/100 • Number of events 13 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	7.6% 9/119 • Number of events 9 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Respiratory, thoracic and mediastinal disorders Neonatal respiratory distress syndrome	2.1% 3/146 • Number of events 3 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.62% 1/162 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/100 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	5.9% 7/119 • Number of events 7 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Nervous system disorders Intracranial hemorrhage	2.7% 4/146 • Number of events 4 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.62% 1/162 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/100 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	2.5% 3/119 • Number of events 3 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
General disorders Death	2.7% 4/146 • Number of events 4 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	6.8% 11/162 • Number of events 11 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	6.0% 6/100 • Number of events 6 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	6.7% 8/119 • Number of events 8 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Infections and infestations Fungal Infection	0.00% 0/146 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.62% 1/162 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/100 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/119 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Pregnancy, puerperium and perinatal conditions Prematurity	2.1% 3/146 • Number of events 3 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.62% 1/162 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/100 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	1.7% 2/119 • Number of events 2 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Respiratory, thoracic and mediastinal disorders Neonatal pneumothorax	0.00% 0/146 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	1.2% 2/162 • Number of events 2 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/100 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/119 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Respiratory, thoracic and mediastinal disorders Neonatal pulmonary haemorrhage	0.68% 1/146 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/162 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	1.0% 1/100 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.84% 1/119 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Cardiac disorders Cardiopulmonary failure	0.00% 0/146 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.62% 1/162 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/100 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	1.7% 2/119 • Number of events 2 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Metabolism and nutrition disorders Metabolic acidosis	0.00% 0/146 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/162 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/100 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.84% 1/119 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/146 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/162 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	1.0% 1/100 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/119 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Infections and infestations Neonatal infection	0.68% 1/146 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	1.2% 2/162 • Number of events 2 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/100 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	5.9% 7/119 • Number of events 7 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Renal and urinary disorders Renal failure neonatal	0.00% 0/146 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.62% 1/162 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/100 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/119 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Gastrointestinal disorders Intra-abdominal bleeding	0.68% 1/146 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/162 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/100 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/119 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
General disorders Multiorgan failure	0.68% 1/146 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.62% 1/162 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/100 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/119 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Blood and lymphatic system disorders Coagulopathies	0.00% 0/146 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/162 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	1.0% 1/100 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/119 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)
Nervous system disorders Intraventricular haemorrhage neonatal	0.00% 0/146 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.00% 0/162 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	1.0% 1/100 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)	0.84% 1/119 • Number of events 1 • Adverse events are monitored from randomization through study status (death, discharge or 120 days)