The prenatal genetic ultrasonogram has been used extensively in evaluating the risk of aneuploidy. Incorporation of soft ultrasonographic markers of aneuploidy, such as renal pyelectasis, echogenic bowel, echogenic intracardiac focus, choroid plexus cyst, and thickening of the nuchal fold has decreased the need for amniocentesis in high-risk populations without compromising screening efficacy.1 Several studies have evaluated the association of fetal gender and the distribution of these markers.2–10 Pyelectasis was the only ultrasonographic marker that demonstrated a gender difference, with a male-to-female ratio of approximately 2:1.5–14 The association of pyelectasis with aneuploidy is well established. Nevertheless, it is speculated that in the majority of male fetuses the presence of pyelectasis represents either a normal physiologic variant or occurs secondary to anatomic abnormalities such as a posterior urethral valve. Consequently, some investigators have hypothesized that the presence of pyelectasis in a female fetus is indicative of a greater risk of aneuploidy.8,9 Chudleigh et al8 concluded that “there was a trend toward higher prevalence of aneuploidy in female fetuses with mild pyelectasis.” A similar conclusion was reached by Nicolaides et al,9 suggesting increased aneuploidy risk in female fetuses with pyelectasis. Recently, Wax et al10 confirmed the observation that pyelectasis demonstrates an increased prevalence in male fetuses. However, the study population was too small for the authors to draw conclusions regarding the association of pyelectasis, fetal gender, and aneuploidy. Therefore, the purpose of the present study was to evaluate the prevalence of major chromosomal trisomies in male and female fetuses with pyelectasis.
MATERIALS AND METHODS
The database comprised all amniocentesis specimens processed in the Genzyme Genetics Orange, California and Santa Fe, New Mexico laboratories between 1995 and 2004. Pertinent information was entered into a computerized database that included the indication for testing, maternal age, and the karyotype. Gender was uniformly determined by karyotype analysis. The study population consisted of all amniocentesis specimens obtained after an ultrasonographic finding of pyelectasis (whether it was an isolated finding or in combination with other markers) that had either a normal karyotype or a major trisomy such as trisomy 13, trisomy 18, or trisomy 21. Multifetal pregnancies were excluded.
The prevalence of a major trisomy in male and female fetuses with pyelectasis was compared with the use of binomial distribution. Continuous variables were compared with the use of unpaired Student t tests. P values less than .05 were considered statistically significant. Statistical analysis was performed with the True Epistat 5.3 software package (Epistat Services Inc, Richardson, TX).
The study received an “exempt review” status from the Institutional Review Board.
A total of 760,495 second-trimester amniocentesis specimens were available for analysis. Fetal pyelectasis was reported in 690 cases (0.09%). Eleven male fetuses and 8 female fetuses were excluded from further analysis secondary to abnormal karyotypes other than trisomy 13, 18, or 21. Six hundred seventy-one (n = 671) cases of renal pyelectasis were eligible for analysis: 457 (68.1%) were male fetuses, and 214 (31.9%) were female fetuses. Three hundred twenty (n = 320) cases had isolated pyelectasis: 220 (68.8%) were male fetuses, and 100 (31.2%) were female fetuses. Pyelectasis occurring with other abnormalities (nonisolated) was observed in 351 fetuses: 237 (67.5%) male fetuses and 114 (32.5%) female fetuses. Maternal age for male and female fetuses with pyelectasis was 29.5 ± 6.1 and 29.4 ± 6.3 years, respectively (P = .78). The gender distribution within the study population is presented in Table 1.
The male predominance, with a male-to-female ratio of 2.14:1 (457 compared with 214) was statistically significant (P < .001). Likewise, a statistically significant male predominance with a male-to-female ratio of 2.2:1 and 2.08:1 was detected in the groups of isolated and the nonisolated pyelectasis, respectively (P < .001).
A major trisomy was detected in 26 male fetuses (5.7%): 18 cases of trisomy 21, 2 cases of trisomy 18, and 6 cases of trisomy 13. Nine female fetuses had a trisomy (4.2%): 6 cases of trisomy 21 and 3 cases of trisomy 13. There was no significant difference in the overall prevalence of major trisomies between male and female fetuses with pyelectasis (P = .14). Among the fetuses with isolated pyelectasis, 3 male fetuses (1.4%) and none of the female fetuses (0%) had a major trisomy (P = .25). In the subgroup of fetuses with nonisolated pyelectasis, 23 male fetuses (9.7%) and 9 female fetuses (7.9%) had a major trisomy (P = .11). The distribution of major trisomies within the study population is presented in Table 2.
The male-to-female ratio of 2.14:1 in our population is similar to the ratio previously reported by other investigators.4,8,10 In addition, our results indicate that the association between pyelectasis and major trisomies is unlikely to be gender dependent.
Benacerraf and associates5 were the first to investigate gender-specific ultrasonographic markers in fetuses with trisomy 21. Their study population included only 15 fetuses with pyelectasis. They did not find a significant difference in the prevalence of pyelectasis between male and female fetuses. Hence, they concluded that “criteria for evaluation of ultrasonographic markers for the identification of second-trimester fetuses with Down syndrome should be the same in male and female fetuses.” Our results, based on a much larger study population, support Benacerraf’s conclusions. Recently, Wax et al10 conducted a study to determine the association of ultrasonographic markers with fetal gender. Pyelectasis was the only marker to demonstrate a male predominance. Their study population included only 3 fetuses with a major trisomy complicated with pyelectasis. The hypothesis that pyelectasis carries a higher aneuploidy risk in female fetuses could not be properly assessed, because the number of cases of pyelectasis and aneuploidy was too small.
Our study differs from several previous studies that evaluated the effect of gender on the risk of aneuploidy in fetuses with pyelectasis. In previous studies a karyotype analysis was not routinely performed, and chromosomal abnormalities were largely derived from pediatric reports. In contrast, we used a well-documented, large database of 760,495 amniocentesis specimens. In addition, our determination of fetal gender is based on the amniocentesis data, whereas other studies relied on less accurate information such as prenatal ultrasonographic evaluation or retrospective, postpartum data collection.
Similar to most previous studies on this topic, our study has limitations that are mainly the result of its retrospective design. The study population is based on fetuses with an ultrasonographic diagnosis of pyelectasis who underwent amniocentesis. The initial ultrasonographic evaluation that detected pyelectasis was performed by multiple providers in multiple centers. However, fetal pyelectasis is the most common anomaly identified on prenatal ultrasonography, which makes its detection and assessment relatively simple. In addition, despite the relatively large study population (N = 671), a power analysis indicates that a study population of at least 18,760 fetuses would be necessary to draw a definitive conclusion regarding the effect of fetal gender in fetuses with pyelectasis on the risk of major trisomies.
In summary, we believe that it is reasonable to assume that the prevalence of trisomy 13, 18, or 21 among fetuses with pyelectasis is unlikely to be dependent on fetal gender. Therefore, we suggest that counseling patients with regard to the genetic implications of fetal pyelectasis should be gender independent.
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