The progression of salt‐wasting and the body weight change during the first 2 weeks of life in classical 21‐hydroxylase deficiency patients

Abstract

BackgroundOne of the major purposes of newborn screening for 21‐hydroxylase deficiency (21OHD) is preventing life‐threatening adrenal crisis. However, the details of adrenal crisis in newborns are not precisely documented.AimWe aimed to clarify the clinical details of salt‐wasting in newborn 21OHD patients.MethodsBased on the follow‐up survey of the screening in Tokyo from 1989 to 2017, we retrospectively analysed the conditions of classical 21OHD neonates before the initiation of therapy.ResultsOne hundred classical 21OHD patients (55 male, 45 female) were analysed. The age at the first hospital visit was 0–20 days with sex difference (male: 9.0 ± 3.5 days; female: 6.2 ± 3.9 days). Thirty‐seven (37.4%) patients exhibited severe salt‐wasting (SSW), that is, Na < 130 mEq/L, K > 7 mEq/L or Na/K ratio < 20; except for one case, SSW developed in or after the second week of life. The serum concentrations of Na, K and Na/K were linearly correlated with age in days (R2 = .38, .25, and .34 respectively), suggesting that the risk of SSW increases linearly without a threshold. The age at which the regression lines reached Na < 130 mEq/L, K > 7 mEq/L and Na/K < 20 was approximately coincided, 11.1, 12.3 and 11.2 days, respectively. All SSW patients exhibited decreased body weight from birth in their second week of life.ConclusionOur data revealed that the risk of developing SSW increases during the second week of life without a threshold, and for preventing SSW, early intervention, ideally during first week of life, is desirable. An increased body weight in the second week of life indicates the absence of SSW.

Thirty-Year Lessons from the Newborn Screening for Congenital Adrenal Hyperplasia (CAH) in Japan

“…Neonates with 17αOHP levels more than the retest cutoff value are retested. When the 17αOHP levels are higher than the retest cutoff value two-three times, the screening is considered positive (Figure 2) [4,5,[11][12][13]. In some female patients, blood sampling for the screening is performed ahead of schedule due to atypical genitalia, which is one of the major clinical symptoms in female neonates with 21OHD and is frequently recognized at birth.…”

“…Furthermore, even in cases of 21OHD, the possibility of developing severe salt wasting, such as hyponatremia (<130 mEq/L) or hyperkalemia (>7 mEq/L), is extremely low without loss of body weight (Figure 4). Contrary to body weight change, the relevance of predicting severe salt wasting based on the 17αOHP level is extremely low because the 17αOHP level is not associated with Na or K levels [13]. Although the findings of body weight change in patients cannot be the direct criteria for the CAH screening protocol, they may assist in some individual cases, e.g., for triaging Although the findings of body weight change in patients cannot be the direct criteria for the CAH screening protocol, they may assist in some individual cases, e.g., for triaging a neonate with a positive result who is living in a region with limited access to a pediatric endocrinologist or in which there is no CAH screening.…”

“…Neonates with 17αOHP levels more than the retest cutoff value are retested. When the 17αOHP levels are higher than the retest cutoff value two–three times, the screening is considered positive ( Figure 2 ) [ 4 , 5 , 11 , 12 , 13 ].…”

“…For the quality control of the screening, most screening laboratories perform follow-up surveys of the patients who were referred to hospitals. In the surveys, clinical information of the patients, including confirmed diagnosis, is collected from the pediatric endocrinologists at the hospitals [ 13 ].…”

Challenges in Assessing the Cost-Effectiveness of Newborn Screening: The Example of Congenital Adrenal Hyperplasia

“…Such crises typically occur in the second or third week of life, sometimes prior to the reporting of screening results. Rapid collection, transport, and processing of specimens and rapid reporting of markedly abnormal results can allow for early onset of treatment prior to the emergence of severe symptoms and can reduce the need for, or length of, neonatal hospitalizations [ 36 ]. In one pilot screening study, six unscreened males with SW-CAH were all hospitalized with adrenal or SW crises, compared with none of five screened males with SW-CAH [ 37 ]; another study found 0/17 and 10/40 frequencies of hospitalization in screened and unscreened infants with CAH [ 17 ].…”