*2.2. AKI*

AKI events occurring during the 6-week postnatal period were detected by the neonatal modified KIDGO sCr criteria [5,16,18] (Table 1). Measuring a chemistry panel including sCr q 1–3 days is usual at our NICU if the infant's condition is critical during the first few weeks of life, and increasing the interval up to q 1–2 weeks, if the infant's condition has become stabilized. Although we did not adopt urine amount criteria to classify stage, we calculated urine output from flow sheets, and reported the incidence of oliguria (<0.5 mL/kg/day) at each stage of AKI.


**Table 1.** The maximum AKI stage within a first month after birth according to neonatal acute kidney injury KDIGO classification.

a Reference SCr will be considered as the lowest prior SCr value. b SCr value of 2.5 mg/dL corresponds to GFR less than 10 mL/min/1.73 m2. AKI, acute kidney injury; SCr, serum creatinine; KDIGO, Kidney Disease Improving Global Outcomes.

#### *2.3. HS PDA*

We defined HS PDA as more than 2 mm in ductal diameter plus predominant left to right flow on echocardiography initially performed at average postnatal day 7; requiring ventilator support accompanying signs and symptoms consistent with symptomatic PDA, such as hypotension with mean airway pressure below GA; grade ≥ 2 cardiac murmur; pulse pressure widening (>30 mmHg); or need for increased respiratory support [31,32]. We deferred until postnatal day 7 as spontaneous ductal closures could occur even in EPT for the first postnatal week [17,34]. Follow-up echocardiography was conducted regularly at 2–4 weeks intervals until PDA closure. During the study period, 50/54 (93%) and 47/74 (64%) in the EPT of 23–26 weeks of gestation were diagnosed with HS PDA, respectively.

#### *2.4. Fluid Therapy*

We managed all EPT with HS PDA with non-interventional conservative managemen<sup>t</sup> without any pharmacologic and/or surgical intervention. We judiciously restricted the fluid intake starting with the first-day mean fluid volume around 67 mL/kg/day, and maintaining mean fluid intake around 107–115 mL/kg/day from days 7 to 28 for the first two months of life [31,32]. We individualized and adjusted the target fluid volume for each EPT q 24 h after assessment of volume status by body weight, serum sodium level, urine output and specific gravity, or cardiomegaly. In this present study, we could obtain judicious fluid restriction in EPT through meticulous NICU care including better room care delivery, minimal handling, and high humidification [35,36].

#### *2.5. Data Collection and Definition*

We analyzed clinical characteristics, which included sex, birth weight, GA, Apgar score at 1-min and 5-min, mode of delivery, chorioamnionitis, use of inotropic drugs, antenatal steroid use, and oliguria. We determined GA using the last menstrual period of mother and modified Ballard score. We confirmed chorioamnionitis using placental pathology. We reported oliguria when urine amount is less than 0.5 mL/kg for a day.

We analyzed adverse outcomes including≥ moderate BPD [37], cystic periventricular leukomalacia, IVH (grade ≥ 3) [38], NEC (Bell's stage ≥ 2b) [39], retinopathy of prematurity (ROP) (stage ≥ 3) [40], and mortality.

To present the time course of sCr and AKI by gestational age, cumulative incidence rates of AKI in EPT at gestational age of 23–24 and 25–26 weeks were evaluated. We measured the adjusted odds ratios (ORs) of mortality and morbidities by the presence and/or persistence (per increase of week) of AKI stage 3 using multivariate regression analyses.

#### *2.6. Statistical Analyses*

We analyzed the categorical variables by χ2 tests and Fisher's exact test. For continuous variables, we analyzed data through Student's *t*-tests and Mann–Whitney *U* tests. We also did multivariable analyses by binary logistic regression to measure adjusted ORs and 95% CI of the association between the duration of stage 3 AKI and adverse outcomes including mortality within the entire cohort. We considered a *p* value less than 0.05 as statistically significant. We used SPSS version 21 (SPSS Inc., Chicago, IL, USA) in all data analyses.
