Newborn screening for congenital adrenal hyperplasia in Tokyo, Japan from 1989 to 2013: a retrospective population-based study

Abstract

BackgroundCongenital adrenal hyperplasia (CAH) cause life-threatening adrenal crisis. It also affects fetal sex development and can result in incorrect sex assignment at birth. In 1989, a newborn screening program for congenital adrenal hyperplasia (CAH) was introduced in Tokyo. Here we present the results of this screening program in order to clarify the efficiency of CAH screening and the incidence of CAH in Japan.MethodFrom 1989 to 2013, a total of 2,105,108 infants were screened for CAH. The cutoff level for diagnosis of CAH was adjusted for gestational age and birth weight.ResultsA total of 410 infants were judged positive, and of these, 106 patients were diagnosed with CAH, indicating a positive predictive value (PPV) of 25.8 %. Of the 106 patients, 94 (88.7 %) were diagnosed with 21-OHD. Of these 94 patients, 73 were diagnosed with the salt wasting form, 14 with the simple virilising form and 7 with the nonclassical form (NC21OHD). The mean birth weight and gestational age were 3192 ± 385 g and 38.9 ± 1.38 weeks. 11 out of 44 female patients were assigned as female according to their screening result.ConclusionsThese data suggest that the newborn screening in Tokyo was effective, especially for sex assignment and preventing fatal adrenal crisis. The incidence of CAH was similar to that measured in previous Japanese screening studies, and it was also similar to that of western countries. The incidence of NC21OHD in Japan in the present study was lower than that in western countries as previous studies reported. The screening program achieved higher PPV than previous CAH screening studies, which might be due to the use of variable cutoffs according to gestational age and birth weight. However, most of the neonates born at 37 weeks or less that were referred to hospital were false-positives. Further changes are needed to reduce the number of false positive preterm neonates.

Lower body weight and BMI at birth were associated with early adiposity rebound in 21-hydroxylase deficiency patients

“…However, our results require more careful interpretation. First, 21-OHD patients are rarely born smaller than the norm for their gestational age [25], and in our study none of the patients had a birth weight of less than 2,500 g. Further, few studies have examined the direct association between body size at birth and the age at AR onset in normal healthy subjects without intrauterine growth failure, and one birth cohort reported the absence of any association between them [26].…”

Neonatal screening for congenital adrenal hyperplasia in Southern Brazil: a population based study with 108,409 infants

“…False positive results are a long-standing concern of CAH neonatal screening programs [7, 9–11, 23, 27, 29]. In the past two decades, a decrease in false positive rates has been noted [10, 11, 23, 29, 30], possibly as a result of both improved 17-OHP detection methods and adjustment of diagnostic cut-off points to birth weight [7, 10]. Adjustment of diagnostic levels of 17-OHP according to birth weight tiers [7, 9, 10, 19] has been proposed as a useful strategy to minimize false positive.…”

“…Incidence varies according to ethnicity and geographical region [1, 6]. In addition, 17-OHP levels in neonates are affected by factors such as gestational age at birth, birth weight, and age at the time of 17-OHP testing [7–11]. Perinatal stress has been associated with high values of 17-OHP on screening [8, 12], while maternal use of corticosteroids towards the end of pregnancy and early sample collection seem to reduce these values [10, 13].…”

Congenital adrenal hyperplasia and violation of newborn screening procedures

“…An important aim of newborn screening is the prevention of life‐threatening adrenal crises during the neonatal period. Newborn screening has been effectively performed in Tokyo and has contributed to a reduction in mortality due to SW because it has decreased the time to CAH diagnosis. Symptoms of adrenal crisis are common within the first 10 days of life, and vomiting, severe hyponatremia, hyperkalemia, and clinical deterioration can rapidly develop.…”