Trisomy 18: Changes in sex ratio during intrauterine life

Among live-births generally more males are born than females. In Switzerland sex ratio of healthy newbornswas 1.04 (male to female: 37,340 to 35,742) in 2004 [Bundesamt für Statistik, 2005]. Considering the higher prenatal loss rate of males, Huether [1990] extrapolated a sex ratio at conception for whites of approximately 1.15. Trisomy 18 is a multiple malformation syndrome; many of the live-born children die during the first days of life. For fetuses with trisomy 18 diagnosed at amniocentesis (usually at about 16–20 gestational weeks), Hook et al. [1983] calculated a fetal survival coefficient of 0.32. Hook et al. [1989] further observed spontaneous fetal death in 81.8% (9 of 11) of males and 58.3% (7 of 12) of females. Distinctly more females than males are born alive [FergusonSmith, 1962; Weber, 1967; Taylor, 1968; Goldstein and Nielson, 1988; Root and Carey, 1994]. Huether et al. [1996] reported a substantial loss of males with trisomy 18 during the second half of fetal development. They reported a prenatal sex ratio of 0.9 for trisomy 18 before and after 16 weeks of gestation and of 0.69 at birth. Not only are more males lost during pregnancy, but also the survival after birth for males seems to be significantly shorter than that of females [Weber, 1967; Van Dyke and Allen, 1990; Root and Carey, 1994; Rasmussen et al., 2003; Niedrist et al., 2006]. Since most of the first trimester pregnancies with trisomy 18 are terminated after prenatal diagnosis, we know little about what would have been the spontaneous outcome for the different sexes. In order to get all available information about the change of the sex ratio in pregnancies with trisomy 18, we collected data about the sex distribution at the timeof cytogenetic diagnosis. In this study, we included not only the prenatally examined cases but also the postnatally detected cases (spontaneous abortions, stillborns, and live-borns) in whom the gestational age at birth was known in order not to miss sex differences in the third trimester of pregnancy. We collected data on 352 cases with trisomy 18 from two cytogenetic laboratories in Zurich between January 1964 and May 2003. Part of this study has already been published elsewhere [Niedrist et al., 2006]. For the present study the information about the time of gestation is based on the data given by the referring doctors on the application form and the information about the karyotype on the cytogenetic laboratory results. The time of the chorionic villus sampling or amniocentesis in our study was decided by the referring doctors and we collected the data retrospectively. Cases of mosaic trisomy 18 were excluded. In prenatal cases we registered the gestational age at the time of the first cytogenetic examination. If there has been no prenatal intervention, we used, in liveor stillborn children, the gestational age at delivery. For statistical analysis we used SPSS version 13 [2000–2006]. Approval by an ethics committee or Institutional Review Board was not required by the authors’ institution for the present study. In 320 cases of trisomy 18 the week of gestation at the time of cytogenetic intervention and the sex were known (Fig. 1). In 194 cases the cytogenetic diagnosis was obtained prenatally (94 males, 100 females) and in 126 cases (41 males, 85 females) the diagnosis was performed postnatally. In 32 cases either the week of gestation at diagnosis/birth or the