Birth Defects Res A Clin Mol Teratol. 2015 Sep;103(9):787-93.
Multicenter investigation of lifestyle-related diseases and visceral disorders in thalidomide embryopathy at around 50 years of age.
- 1Division of Medical Check-up, Department of General Medicine, National Center for Global Health and Medicine, Tokyo, Japan.
- 2Department of Clinical Study and Informatics Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan.
- 3General Internal Medicine, National Center for Global Health and Medicine, Tokyo, Japan.
BACKGROUND: In utero exposure to thalidomide causes a wide range of birth defects, including phocomelia, hearing loss and visceral disorders, known as thalidomide embryopathy (TE). Fifty years after the first report of TE, we conducted the first cross-sectional multicenter study to investigate the development of lifestyle-related diseases and identify risk factors for visceral disorders in subjects with TE.
METHODS: Seventy-six cases with TE (31 men, 45 women) underwent medical examinations between 2011 and 2014 to determine the types of TE-related anomalies (limbs, auditory organs, or visceral organs) and lifestyle-related diseases present. Logistic multiple regression analyses, adjusted for gender and age, were conducted between TE and lifestyle-related diseases and to evaluate association between block vertebra and gallbladder aplasia.
RESULTS: Fatty liver (FL), nonalcoholic FL disease and dyslipidemia were detected in 52.6%, 35.0%, and 23.7% of subjects, respectively, with higher incidences among men. Dyslipidemia was detected in 40.0% of subjects with FL and was significantly associated with FL (odds ratio = 8.86; p = 0.008). Block vertebrae were detected in 44.4% of subjects with gallbladder aplasia, and this association was significant (odds ratio = 9.96; p = 0.006).
CONCLUSION: Subjects with TE have also a risk for lifestyle-related disease as well as the general Japanese population. In addition, cervical spine radiography and magnetic resonance imaging are recommended to assess block vertebrae in subjects with TE with gallbladder aplasia who develop shoulder pain.
KEYWORDS: block vertebra; gallbladder aplasia; lifestyle-related disease; thalidomide embryopathy; visceral disorders
Fifty years after the first report of thalidomide embryopathy (TE), we conducted the first cross-sectional multicenter study to investigate the development of lifestyle-related diseases and identify risk factors for visceral disorders in subjects with TE. We conducted a multicenter survey in Japan from 2011 to 2014 by the National Center for Global Health and Medicine, Teikyo University School of Medicine and National Hospital Organization, Kyoto Medical Center. A total of 76 adults [31 men and 45 women] with TE were included in this study. Mean age was 50.2±1.2 years old.
The subjects with TE were divided into three groups: the limb group (which contained subjects with abnormalities of the limbs), the auditory organ group (which contained subjects with hearing loss ) and the mixed group (which contained subjects with both limb and auditory abnormalities). The limb group accounts for 75% of the defects, with the remaining 25% being the auditory organ group and the mixed group.
The frequency of lifestyle-related diseases among male and female subjects is shown in Figure 1. Blue bar shows males, red bar shows females, and green line shows all subjects. Hypertension (46.7% of all subjects) ,fatty liver (FL) (52.6% of all subjects) and nonalcoholic fatty liver disease (NAFLD) (35.0% of all subjects) were the most common health issues encountered in these subjects. Approximately 15-25% of subjects had central obesity, dyslipidemia, hyperuricemia and hyperglycemia were also major concerns for subjects with TE. In this study, only men developed MS. These data demonstrated that men were at a higher risk than women for the development of almost all lifestyle-related diseases, including MS. Estrogen suppresses visceral fat accumulation and increases subcutaneous fat accumulation (1). Therefore, gender-specific characteristics appear to play a major role in the development of MS, and there may be an association between sex hormones and MS.
Dyslipidemia was detected in 40.0% of subjects with FL and 71.4% of subjects with NAFLD (Figure 2). NAFLD is no longer considered a primary liver disease, but rather a component of MS, insulin resistance and lifestyle-related diseases. All cases of TE with FL confirmed by abdominal ultrasonography, which is a painless examination, should be monitored for the development of lifestyle-related diseases, such as dyslipidemia and metabolic syndrome.
Specifically hyperuricemia and dyslipidemia are risk factors for arteriosclerosis and renal dysfunction. It is important for TE subjects to detect them at an early stage. It is difficult to introduce hemodialysis among TE. So it is important for TE to protect renal function. If hyperuricemia and dyslipidemia are detected, early therapy, which includes diet therapy, is also important.
Gallbladder development begins gestational week 4, and block vertebra (BV) is believed to be caused by blood flow obstruction from gestational week 3 to 8. Our study showed BV was significantly associated with gallbladder aplasia. Therefore, if subjects with TE with gallbladder aplasia develop shoulder stiffness and/or pain, cervical spine X-ray and MRI are recommended to investigate the presence of BV.
Importance of the study:
First, subjects with TE also have a risk of lifestyle-related diseases. Dyslipidemia was significantly associated with FL. All cases of TE with FL confirmed by abdominal ultrasonography should be monitored for the development of lifestyle-related diseases, such as dyslipidemia and metabolic syndrome.
Second, in addition, cervical spine radiography and MRI are recommended to assess BV in subjects with TE with gallbladder aplasia who develop shoulder pain.
(1)Yoshida S, Inadera H, Ishikawa Y, et al. (1991) Endocrine disorders and body fat distribution. Int J Obes 15 Suppl 2:37-40 )
Acknowledgements: This study was funded by a Grant-in-Aid for Research on Regulatory Science of Pharmaceuticals and Medical Devices (grant no.: H23-Iyaku-Shitei-023) from the Ministry of Health, Labour and Welfare of Japan, and in part by Grants-in-Aid for Research from the National Center for Global Health and Medicine (grant no.: 26A-201).
Tomoko Shiga, PhD.
Department of General Medicine, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo 162-8655, Japan email@example.com