Hypospadias in sons of women exposed to diethylstilbestrol in utero: a cohort study

被引:191
作者
Klip, H
Verloop, J
van Gool, JD
Koster, META
Burger, CW
van Leeuwen, FE
机构
[1] Netherlands Canc Inst, Dept Epidemiol, NL-1066 CX Amsterdam, Netherlands
[2] Univ Med Ctr Utrecht, Paediat Renal Ctr, Utrecht, Netherlands
[3] Univ Rotterdam Hosp, Dept Obstet & Gynaecol, Rotterdam, Netherlands
关键词
D O I
10.1016/S0140-6736(02)08152-7
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Transgenerational effects of diethylstilbestrol (DES) have been reported in animals, but effects in human beings are unknown. Alerted by two case reports, we aimed to establish the risk of hypospadias in the sons of women who were exposed to DES in utero. Methods We did a cohort study of all sons of a Dutch cohort of 16 284 women with a diagnosis of fertility problems. We used a mailed questionnaire assessing late effects of fertility treatment to identify boys with hypospadias. We compared the prevalence rate of hypospadias between boys with and without maternal DES exposure in utero. Findings 16 284 mothers (response rate 67%) reported 8934 sons. The mothers of 205 boys reported DES exposure in utero. Four of these children were reported to have hypospadias. In the remaining 8729 children, only eight cases of hypospadias were reported (prevalence ratio 21.3 [95% Cl 6.5-70.1]). All cases of hypospadias were medically confirmed. Maternal age or fertility treatment did not affect the risk of hypospadias. Children conceived after assisted reproductive techniques such as in-vitro fertilisation were not at increased risk of hypospadias compared with children conceived naturally (1.8, 0.6-5.7). Interpretation Our findings suggest an increased risk of hypospadias in the sons of women exposed to DES in utero. Although the absolute risk of this anomaly is small, this transgenerational effect of DES warrants additional studies.
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页码:1102 / 1107
页数:6
相关论文
共 30 条
[1]   CURRENT CONCEPTS - MATERNAL PROGESTINS AS A POSSIBLE CAUSE OF HYPOSPADIAS [J].
AARSKOG, D .
NEW ENGLAND JOURNAL OF MEDICINE, 1979, 300 (02) :75-78
[2]   Is the incidence of hypospadias increasing? Analysis of Finnish hospital discharge data 1970-1994 [J].
Aho, M ;
Koivisto, AM ;
Tammela, TLJ ;
Auvinen, A .
ENVIRONMENTAL HEALTH PERSPECTIVES, 2000, 108 (05) :463-465
[3]   Risk factor patterns for cryptorchidism and hypospadias [J].
Akre, O ;
Lipworth, L ;
Cnattingius, S ;
Sparén, P ;
Ekbom, A .
EPIDEMIOLOGY, 1999, 10 (04) :364-369
[4]   Hypospadias and urethral development [J].
Baskin, LS .
JOURNAL OF UROLOGY, 2000, 163 (03) :951-956
[5]   Deliveries and children born after in-vitro fertilisation in Sweden 1982-95:: a retrospective cohort study [J].
Bergh, T ;
Ericson, A ;
Hillensjö, T ;
Nygren, KG ;
Wennerholm, UB .
LANCET, 1999, 354 (9190) :1579-1585
[6]  
Canning D A, 1999, J Urol, V161, P366
[7]   Rise in prevalence of hypospadias [J].
Dolk, H .
LANCET, 1998, 351 (9105) :770-770
[8]  
DRISCOLL SG, 1980, OBSTET GYNECOL, V56, P537
[9]   ASSOCIATION OF DIETHYLSTILBESTROL EXPOSURE INUTERO WITH CRYPTORCHIDISM, TESTICULAR HYPOPLASIA AND SEMEN ABNORMALITIES [J].
GILL, WB ;
SCHUMACHER, GFB ;
BIBBO, M ;
STRAUS, FH ;
SCHOENBERG, HW .
JOURNAL OF UROLOGY, 1979, 122 (01) :36-39
[10]   DIETHYLSTILBESTROL REVISITED - A REVIEW OF THE LONG-TERM HEALTH-EFFECTS [J].
GIUSTI, RM ;
IWAMOTO, K ;
HATCH, EE .
ANNALS OF INTERNAL MEDICINE, 1995, 122 (10) :778-788