Table 1:

Demographic characteristics of infants who survived ≥7 days and were exposed to varying durations of moderate-to-large PDA shunts that persisted beyond the first week. Infants with small or closed ductus at postnatal day 7 were assumed to have not been exposed to a moderate-to-large PDA during the first 7 days. Infants with moderate-to-large PDAs at postnatal day 7 were assumed to have been exposed to a moderate-to-large PDA for the entire 7 days.

	Duration of exposure to a moderate-to-large PDA
Variable	Closed/Small 1	<7 days 2	7-13 days 3	≥14 days 4	p-value
N=	231	19	56	117
Prenatal Variables:
Multiple Gestation - %	29	37	39	36	0.310
Preeclampsia - %	23	16	27	23	0.808
Maternal Diabetes - %	11	21	11	16	0.383
Chorioamnionitis - %	23	58	16	15	<0.001
Betamethasone <24 hours - %	26	26	36	26	0.498
Caesarian Section - %	66	58	70	72	0.560
Neonatal Variables:
Gestation-weeks (m±sd) 5	26.4±1.0	25.6±0.9	26.1±1.2	25.9±1.1	<0.001
Gestation ≤25 weeks - %	31	63	48	49	≤0.001
Birthweight – grams (m±sd)	852±201	773±126	805±195	779±189	0.005
Small for Gestational Age - % 6	12	0	9	13	0.678
Outborn - %	21	26	36	23	0.149
Caucasian - %	36	42	45	42	0.542
Male - %	51	42	50	44	0.592
5 minute Apgar ≤5 - %	30	37	41	39	0.250
Intubated during 1st 24 hours - %	82	95	89	79	0.209
Mechanical Ventilation at 24 hours - %	52	74	73	66	0.005
ICH (grades 3 or 4) - % 7	10	16	9	11	0.808
Net Fluid Gain 1st 72 hours – ml (m±sd) 8	156±99	134±78	148±108	136±103	0.327
Early Onset Infection - % 9	4	11	7	3	0.316
Late Onset Infection - % 10	34	47	36	27	0.293
Birth Epoch: (2005-2008/2009-2013/2014-2018) - %	52/24/24	63/26/11	27/28/45	8/30/62	<0.001
Necrotizing Enterocolitis - % 11	14	11	14	17	0.768
PDA Variables:
Prophylactic Indomethacin - %	73	79	29	21	<0.001
PDA Ligation - %	0	58	23	18	<0.001
Any PDA Treatment - % 12	74	100	96	74	<0.001
PDA Reopened after 1st week - % 13	0	100	20	12	<0.001
Outcomes:
BPD/Death - % 14	28	16	45	50	<0.001
BPD - % 15	23	16	33	47	<0.001
Death - % 16	9	0	20	7	0.052

¹Closed/Small, infants who either closed their ductus permanently during the first week or had a small PDA at the end of the first week that either closed or remained small throughout the hospitalization

²<7 days, infants with constricted ductus during the first postnatal week (with small or closed ductus at postnatal day 7) who subsequently reopened their PDA after the initial ductus constriction and were exposed to the reopened moderate-to-large PDA shunt for <7 days

³7-13 days, total exposure to a moderate-to-large PDA for 7-13 days: among infants who had a moderate-to-large PDA during the first week that persisted beyond 7 days and among infants with constricted ductus during the first week that later reopened, becoming moderate-to-large after the first week

⁴≥14 days, total exposure to a moderate-to-large PDA for ≥14 days: among infants who had a moderate-to-large PDA during the first week that persisted beyond 7 days and among infants with constricted ductus during the first week that later reopened, becoming moderate-to-large after the first week

⁵Gestation, gestational age was determined by the date of last menstrual period and early ultrasounds (before 24 weeks gestation)

⁶Small for Gestational Age, Fenton birthweight-for-gestational-age z-scores <1.29 ¹⁵

⁷ICH (grades 3 or 4), serious intraventricular hemorrhages were defined as grades 3 or 4 intraventricular hemorrhage (using the four-level grading system) ¹⁶.

⁸Net Fluid Gain 1^st 72 hours, total fluid intake during first 3 days minus total urine output during first 3 days

⁹Early Onset Infection, culture-positive bacteremia prior to 4 days of life

¹⁰Late Onset Infection, culture-positive bacteremia or pneumonia after 3 days of life (pneumonia = sudden respiratory deterioration in arterial blood gases associated with a) new progressive infiltrates in the chest radiograph that persist for more than 3 days and b) either blood leukocytosis, leukopenia, or an increase in immature neutrophil forms, and/or c) associated temperature and/or glucose instability)

¹¹Necrotizing Enterocolitis, Bell’s classification II or greater (this included necrotizing enterocolitis that was treated medically or surgically, and “spontaneous perforations” that occurred before 10 days of life) ¹⁷.

¹²Any PDA Treatment, infants who received prophylactic indomethacin and/or later pharmacologic PDA treatment

¹³PDA Reopened after 1^st week, ductus that were constricted during the first week, but then reopened after the first week developing a moderate-to-large shunt

¹⁴BPD/Death, bronchopulmonary dysplasia or death before 36 weeks. Bronchopulmonary dysplasia was defined using a modified room air challenge test between 36^0/7 and 36^6/7 weeks’ corrected age ¹⁴

¹⁵BPD, bronchopulmonary dysplasia: n=393 (Closed small (n=216), <7 days (n=19), 7-13 days (n=46), ≥14 days (n=112)): several infants died after 7 days and prior to completion of the room air challenge test at 36 weeks:

¹⁶Death, death after 7 days and prior to hospital discharge