Research Article: Neonatal factors related to center variation in the incidence of late-onset circulatory collapse in extremely preterm infants

Date Published: June 12, 2018

Publisher: Public Library of Science

Author(s): Yume Suzuki, Yumi Kono, Takahiro Hayakawa, Hironori Shimozawa, Miyuki Matano, Yukari Yada, Ming Dao.


Although late-onset circulatory collapse (LCC) is widely recognized in Japan, its etiology and the reason for center variation in its incidence remain unclear. This study’s objectives were to identify the perinatal and neonatal factors related to LCC and to estimate the factors related to the center variation in the incidence of LCC.

Extremely preterm infants born between 2008 and 2012 who were registered in the database of the Neonatal Research Network, Japan were retrospectively analyzed. LCC was defined as a clinical diagnosis of LCC and the administration of steroids. We first identified the factors that were significantly related to LCC. We then examined the cause of the center variation in the incidence of LCC, using the standardized incidence ratios (SIRs) of LCC and individual factors.

The factors significantly associated with LCC included low gestational age (odds ratio [OR]: 1.13), small for date (OR: 1.43), male sex (OR: 1.26), antenatal steroid use (OR: 1.19), respiratory distress syndrome (OR: 1.25), chronic lung disease at 36 weeks (OR: 1.16), periventricular leukomalacia (PVL) (OR: 2.57), necrotizing enterocolitis (OR: 0.59), retinopathy of prematurity (ROP) (OR: 1.73), high-frequency oscillating ventilation (HFOV) use (OR: 1.31), parenteral nutrition (OR: 1.38), and red blood cell (RBC) transfusion (OR: 1.94). The SIR of LCC ranged from 0.05 to 2.94, and was positively correlated with SIRs of PVL, ROP, HFOV use and RBC transfusion.

PVL, ROP, HFOV use and RBC transfusion were found to be correlated with the center variation in the incidence of LCC.

Partial Text

Prematurity of adrenal function is recognized as transient adrenocortical insufficiency of prematurity (TAP) or glucocorticoid responsive hypotension in preterm infants [1–3]. In Japan, late-onset circulatory collapse (LCC) was recognized in 2000, and tentative diagnostic criteria were established. In the established criteria, LCC is defined as acute-onset hypotension or oliguria occurring after the transitional period. The incidence of LCC in very low birth weight (VLBW) infants and extremely low birth weight infants is 6.3%, and 11.6%, respectively [4]. Prematurity of adrenal function is an important cause of LCC, and certain drugs, including levothyroxine, may be related to the onset of LCC; however, the etiology remains unclear [5]. The reported incidence of LCC varies among Japanese perinatal centers; however, the cause of such center variation remains unclear [6].

We examined the perinatal and neonatal factors associated with LCC in EP infants using the NRNJ database. GA, SFD, male sex, ANS use, RDS, CLD at 36 weeks, PVL, NEC, ROP, HFOV use, PN and RBC transfusion significantly correlated with LCC. The center variation for LCC remained after standardizing the incidence at every 2 weeks of gestation. The SIR of LCC significantly correlated with the SIRs of PVL, ROP, HFOV use and RBC transfusion.




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