Bleeding complications other than ICH may be more extensive, and the presentation of FNAIT may have a greater spectrum than previously described. A high index of suspicion on the possible diagnosis of FNAIT with any bleeding complication in a fetus or neonate may enable adequate diagnostics, adequate treatment, and appropriate follow-up in future pregnancies, as is especially relevant for FNAIT.

The number of children undergoing hematopoietic stem cell transplantation (HSCT) for nonmalignant diseases has increased in recent years. Endocrine complications are common after HSCT for malignant diseases, while little is known about long-term prevalence and risk factors in children transplanted for nonmalignant diseases. We retrospectively evaluated gonadal function, near adult height and thyroid function in 197 survivors of pediatric HSCT for hemoglobinopathies (n = 66), inborn errors of immunity/ metabolism (n = 74) and bone marrow failure disorders (n = 57); median follow-up was 6.2 years (range 3.0-10.5). Gonadal dysfunction occurred in 55% of (post)pubertal females, was still present at last assessment in 43% and was more common after busulfan-than treosulfan-based conditioning (HR 10.6, CI 2.2-52.7; adjusted for HSCT indication). Gonadal dysfunction occurred in 39% of (post)pubertal males, was still present at last assessment in 32% and was less common in those who were prepubertal compared to (post)pubertal at HSCT (HR 0.11; CI 0.05-0.21). Near adult height was more than 2 SDS below mean parental height in 21% of males and 8% of females. Hypothyroidism occurred in 16% of patients; 4% received thyroxin treatment. In conclusion, endocrine complications, especially gonadal dysfunction, are common after pediatric HSCT for nonmalignant conditions. In females, treosulfan seems less gonadotoxic than busulfan. Careful long-term endocrine follow-up is indicated.

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Endocrine complications are amongst the most frequent late effects after pediatric hematopoietic stem cell transplantation (HSCT) for malignant diseases. Little is known about the prevalence and risk factors of endocrine complications in children transplanted for nonmalignant diseases. This retrospective study included 134 males and 63 females transplanted for a non-malignant disease between 1997 and 2018 with at least 2 years of follow up. Endocrine late effects and growth were evaluated. Gonadal dysfunction was defined as transient or permanent elevation of gonadotropins or hypogonadotropic hypogonadism. Median age at HSCT was 5.7 years (IQR 2.8-11.3) and median follow-up was 6.2 years (IQR 3.0-10.4). Underlying diseases were inborn errors of immunity (n=74), hemoglobinopathies (n=66) and bone marrow failure (n=57). The majority of patients had received busulfan-based conditioning (46%) or treosulfan-based conditioning (34%). Gonadal dysfunction occurred in 24/44 (post)pubertal female patients (55%) and was permanent in 19/44 (43%). 22/44 received hormonal substitution, which could be discontinued in 7. In females who received busulfan-based conditioning 16/17 (94%) developed gonadal dysfunction compared to 5/15 (33%) patients with treosulfan-based conditioning; the odds ratio for permanent gonadal dysfunction was 18.7 (3.61-135, p=0.001). Gonadal dysfunction occurred in 28/66 (post)pubertal male patients (42%) and was permanent in 23/66 (35%). 6/66 received hormonal substitution, which could be discontinued in 1. Gonadal dysfunction was more common in males (post)pubertal at HSCT, 14/21 (67%), compared to those prepubertal at HSCT, 14/45 (31%), p=0.014. 3/15 treated with a treosulfan-based regimen (20%) developed gonadal dysfunction, all transient, versus 19/39 with a busulfan-based regimen (49%), with 2 transient. 29/187 patients developed hypothyroidism (16%), 7 patients received thyroxine treatment (4%). All patients with persistent primary hypothyroidism (n=6) had positive TPO-antibodies. 17 patients received growth hormone treatment and were excluded from analysis. In patients without growth hormone treatment near adult height (NAH) was -1.2 SDS (median, IQR -2.0- -0.3) below mean parental height (MPH) in males and -0.4 SDS (median, IQR -1.6-0.3) in females. NAH below -2 SDS was seen in 13/43 males (30%) and 2/36 females (6%). The majority of these patients already had a height below -2 SDS before HSCT (73%). In conclusion, this study on late endocrine effects after HSCT in children with nonmalignant diseases indicates frequent gonadal dysfunction, present in 55% of females and 42% of males. In this cohort, risk of gonadal dysfunction in females was higher after busulfan-based conditioning than treosulfan-based conditioning. Careful long-term endocrine follow-up is indicated.