High prevalence of severe circulatory complications with diazoxide in premature infants.
BACKGROUND
Since diazoxide was approved for clinical use in Japan in 2008, its prescription for the treatment of infants with hyperinsulinemic hypoglycemia (HIH) has rapidly expanded. Concomitantly, reports of complications associated with diazoxide are increasing.


OBJECTIVE
To clarify the trends and problems associated with the treatment of infants with HIH, we planned a nationwide surveillance in Japan.


METHODS
Questionnaires were sent to 255 institutions belonging to the Japanese Neonatologist Association inquiring about neonatal cases of HIH from 2009 to 2011.


RESULTS
One hundred nineteen cases of neonates with transient HIH (THIH) related to perinatal problems and 15 cases with permanent HIH (PHIH; hypoglycemia persisting beyond a year) or genetic HIH were reported. Sixty-four infants (53.8%) with THIH were administered diazoxide, and the administration was completed within 3 months in 46 infants (71.9%). Fourteen of the PHIH or genetic cases were treated with diazoxide and 7 of them (50%) had hypoglycemia persisting beyond a year. Circulatory complications were reported in 15 infants, i.e. 10 with THIH and 5 with PHIH. Multiple regression analysis revealed that a younger gestational age at birth and higher maximum doses of diazoxide were significant risk factors for circulatory complications.


CONCLUSIONS
Diazoxide is widely prescribed for infants with HIH as a first-line medicine in Japan, but prophylactic diuretics are uncommon. Under these circumstances, a high prevalence of severe circulatory complications in very-low-birth-weight infants was reported.
Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kayo
K
Yoshida
Masahiko
M
Kawai
Chieko
C
Marumo
Hoshinori
H
Kanazawa
Takashi
T
Matsukura
Satoshi
S
Kusuda
Tohru
T
Yorifuji
Toshio
T
Heike
D001724:Birth Weight; D001775:Blood Circulation / Q000187:drug effects*; D044903:Congenital Hyperinsulinism / Q000188:drug therapy* / Q000453:epidemiology; D003981:Diazoxide / Q000009:adverse effects*; D004374:Ductus Arteriosus, Patent / Q000453:epidemiology / Q000503:physiopathology / Q000628:therapy; D004487:Edema / Q000139:chemically induced / Q000453:epidemiology / Q000503:physiopathology; D005260:Female; D005865:Gestational Age; D019538:Health Care Surveys; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D007564:Japan / Q000453:epidemiology; D008297:Male; D009846:Oliguria / Q000139:chemically induced / Q000453:epidemiology / Q000503:physiopathology; D015995:Prevalence; D012008:Recurrence; D012307:Risk Factors; D011795:Surveys and Questionnaires
D003981:Diazoxide