Birth weight discordancy in male-first and female-first pairs of unlike-sexed twins

We studied 153 consecutive twin pairs of unlike sex. Comparison of 71 male-female pairs with 82 female-male pairs showed similar mean twin birth weight and rate of discordance. However, males were significantly heavier (p less than 0.04) compared with females in the male-first but not in the female-first combination. The rate of female discordance was significantly higher compared with male discordance in both fetal sex combinations. It is concluded that females of unlike-sexed pairs are at greater risk to be growth discordant. Fetal sex, therefore, should be included as one of several factors that produce divergent twin growth.     

双色共变性荧光原位杂交产前诊断胎儿唐氏综合征

目的 探讨双色共变性荧光原位杂交用于非侵入性产前诊断胎儿唐氏综合征的可行性。方法 对11例孕妇外周血中的胎儿有核红细胞进行抗血型糖蛋白磁珠直接标记,再经磁激活细胞分选法富集,以Y和21号染色体专一探针对分离的胎儿有核红细胞行双色共变性荧光原位杂交,预测胎儿21号染色体倍性和性别,并用羊水染色体核型分析结果,验证预测准确性。结果 11例胎儿21号染色体倍性均正常,与羊水染色体核型分析结果相符。其中5例为男性胎儿,男性胎儿有核红细胞数量为9－65个,平均为25个,男性胎儿有核红细胞纯度为1．4％－18．8％;6例为女性胎儿,孕妇外周血中未见男性胎儿有核红细胞;性别预测结果与羊水染色体型分析结果一致。结论 双色共变性荧光原位杂交用于分析胎儿21号染色体倍性及性别,诊断胎儿唐氏综合征准确、可靠。     

Examination of fetal cells and cell-free fetal DNA in maternal blood for fetal gender determination

BACKGROUND: To assess applicability of noninvasive methods for prenatal sex determination, both intact fetal cells and cell-free DNA from maternal blood were studied. METHODS: Maternal peripheral blood samples were obtained from 41 women carrying chromosomally normal fetuses and from 3 women with aneuploid fetuses (47,XX,+18; 47,XY,+18 and 47,XY,+21) at 9-22 weeks of gestation. DNA was extracted from the plasma fraction and analyzed by the nested polymerase chain reaction (PCR) using Y chromosome specific primers. After fetal cells were enriched by MACS, fluorescence in situ hybridization (FISH) with chromosome X and Y specific probes was performed to detect XY cells. RESULTS: Although Y-chromosome-specific DNA was detected by PCR analysis in all maternal plasma samples with male fetuses, 26% women bearing female fetuses also gave positive results. By FISH analysis, XY cells were detected in not only 58% of women bearing male fetuses, but also 13% of their counterpoints with female fetuses. CONCLUSIONS: Our findings suggested that consistent results for fetal gender using PCR or FISH cannot be obtained with intact fetal cells and cell-free DNA present in maternal blood and plasma at 9-22 weeks of gestation, despite their apparent abundant presence.     

Fetal gender affects maternal serum total and placental alkaline phosphatase levels during pregnancy

OBJECTIVE: To analyze whether fetal gender affects total alkaline phosphatase (ALP) and placental ALP levels in normal pregnancy, and to determine the gestational age at which the difference occurs. METHODS: In this longitudinal study, serum total and placental ALP measurements were carried out in 30 normal pregnant women during different ranges of gestational weeks. Infant sex was recorded at the delivery for all women included in the study. Total and placental ALP levels were compared between pregnant women bearing female and male fetuses. RESULTS: At all gestational weeks studied, both total and placental ALP levels were higher in pregnant women carrying female fetuses than in male bearing pregnant women. Particularly, both total (260.9+/-110.2 versus 239.9+/-102.3; p=0.03) and placental (73.1+/-22.4 versus 61+/-18.2; p=0.04) ALP levels were significantly higher in the female group than in the male between 24 and 28 weeks, and the significant difference persisted between 32 and 36 weeks (p=0.02). CONCLUSIONS: Fetal gender seems to affect total and placental ALP levels in healthy pregnant women, particularly during the second and third trimester of pregnancy. Higher ALP levels in pregnant women with female fetuses than in those with male fetuses may suggest that knowledge of the fetal gender may be in particular importance for the studies using ALP as a marker for the prediction of variety of diseases and complications seen during pregnancy.     

Are amniotic fluid alpha-fetoprotein levels influenced by the gender in twin pairs?

OBJECTIVES: To examine the assumption that amniotic fluid alpha-fetoprotein (AFAFP) levels are different in female and male twin fetuses. DESIGN: Amniotic fluid levels of AFP in pregnancies with female and male fetuses in gender-concordant and gender-discordant twins were compared. A t test of p < 0.05 was considered significant. MATERIAL AND METHODS: Between 1995 and 1999, 332 genetic amniocenteses on twin pregnancies were performed at Meir Hospital, Kfar Saba, and Rambam Hospital, Haifa, Israel. One hundred and sixty-six were concordant for gender (84 females and 82 males) while 166 pairs differed in their gender. The amniotic fluid AFP levels of each sac were measured using fluorescent immunoassay methods by an AutoDELFIA machine. RESULTS: The mean levels of AFAFP were lower in female twins compared to their male counterparts in same-gender twins (p = 0.07), although the difference was quite small. Nevertheless, there was no such difference between AFAFP of male versus female fetuses in gender-discordant twins. CONCLUSIONS: The levels of AFAFP were higher in the male twins of gender-concordant twins in comparison to female twins. No such difference was found between female versus male fetuses in gender-disconcordant twins.     

Effect of Co-twin Fetal Sex on Fetal Anthropometry and Birth Time in Twin Pregnancies

ObjectiveThis study of twin deliveries aimed to examine the effect of fetal sex and fetal sex of the co-twin on fetal anthropometry and length of gestation.MethodsPregnancies were grouped as male/male, male/female, and female/female. Birth weight, head circumference, body length and delivery time of newborns were compared between unlike-sex and like-sex twin pregnancies.ResultsA total of 1028 pregnant women who met the inclusion criteria were enrolled in the study. Of these pregnancies, 32.6% (n = 335) were male/male, 33.4% (n = 343) were male/female, and 34.0% (n = 350) were female/female. The discordant (male/female) newborns had a higher total birth weight than concordant twins (P = 0.015). Compared with male newborns from male/female twin pregnancies, male newborns from male/male pregnancies were found to be 129 grams heavier, 0.7 cm longer, and had a 0.4 cm larger head circumference (P<0.001, P=0.023, and P = 0.039, respectively). Pregnancies with male/female fetuses had statistically significantly longer gestations than pregnancies with male/male and female/female fetuses (P = 0.003 and P = 0.004, respectively). The shortest mean gestation was observed in the male/male group. Male/male pregnancies had a 1.53 times higher risk of preterm delivery than male/female pregnancies and a 1.51 times higher risk than female/female pregnancies (OR 1.53; 95% CI 1.07–2.19 and OR 1.51; 95% CI 1.06–2.16, respectively).ConclusionsThis study suggests that, in twin pregnancies, birth weight, head circumference, and body length are affected by the sex of the co-twin. Male sex is associated with shorter gestation and male/male twin pregnancies are at higher risk for preterm labour.     

Different maternal serum hCG levels in pregnant women with female and male fetuses: does fetal hypophyseal--adrenal--gonadal axis play a role?

Fetal gender has a significant effect on maternal and cord blood hCG levels, particularly during the last trimester of the pregnancy. However, the reason for this difference is obscure. The aim of the present study was to investigate whether term fetal hypophyseal - adrenal - gonadal axis differs between female and male fetuses thereby causing different hCG levels. The study consisted of 60 women with singleton pregnancies in the third trimester. Thirty-one pregnant women were carrying female fetuses, whereas 29 were carrying male. Human chorionic gonadotropin (hCG), estradiol, progesterone, testosterone, dehydro-epiandrosteron-sulfate (DHEAS), prolactin and growth hormone levels were measured in maternal serum and umbilical cord blood. In female bearing pregnancies maternal and cord blood hCG levels were significantly higher than in male bearing pregnancies (P<0.001). Maternal and cord blood estradiol, progesterone, testosterone, DHEAS, prolactin and growth hormone levels were not significantly different in either fetal gender. When all patients were considered as a group there were no correlations between fetal hCG levels and any of the measured hormones. Term fetal DHEAS, estrogen, progesterone, testosterone, growth hormone and prolactin levels do not contribute to different hCG levels between female and male fetuses. It is possible that fetal hypophyseal-adrenal gonadal axis does not play a central role as the cause of different hCG levels.     

Twin birth weight discordance and risk of preterm birth

OBJECTIVES: Our purpose was to determine whether birth weight discordance is a risk factor for preterm birth of twins, and to further characterize the relationships involved.Study Design: Maternally linked 1978-1990 Missouri birth certificates were used to analyze gestations resulting in live twins. We used contingency tables and multiple logistic regression. RESULTS: The degree of discordance correlated strongly with risk for live preterm birth but only for discordances >30% and preterm birth at <32 weeks' gestation. Among 9479 pregnancies with discordance <30%, 9.5% ended in birth at <32 weeks' gestation, versus 13.7% of 326 with discordance of 30% to 40% (P =.03) and versus 34.1% of 126 with discordance > or =40% (P <. 001). There were 42 preterm twin births at <32 weeks' gestation with discordances > or =40%. Of these, 51% were attributable to fetal growth restriction and 16% to large size for gestational age in one infant; in 72% the smaller twin was the second born, and in 86% the twins were like sex. The relative association between > or =40% discordance and preterm birth at <32 weeks' gestation was strengthened (final odds ratio, 9.54; P <.0001) in a multivariate model containing other risk factors for delivery at <32 weeks' gestation: black race, either twin small for gestational age, unmarried, teenage mother, number of male fetuses, like fetal sex, education <12 years, nulliparity, and cigarette smoking. CONCLUSIONS: Twin birth weight discordance has now clearly been demonstrated to be a risk factor for preterm birth. The effect was found particularly with discordances > or =40% before 32 weeks' gestation. Discordance was usually attributable to fetal growth restriction, most often in the second-born twin.     

Genetic analysis of the fetus using maternal blood

Circulating fetal DNA in maternal plasma and serum was first demonstrated by Lo et al. in 1997 and has become a useful tool for prenatal diagnosis less than five years later. There is more and more evidence that the trophoblastic cells act as the major source of this circulating fetal DNA. Contrary to fetal cells analysis in maternal blood which requires isolation and enrichment procedures, fetal DNA analysis is relatively easy to perform with the use of real-time PCR. Non-invasive fetal sex and fetal RHD genotype determination are, to date, the two main clinical indications. Those newly offered possibilities have changed the management of pregnant women who are carriers for X-linked genetic disorders; prenatal diagnosis by choriovillous sampling could only be performed for male fetuses avoiding an unnecessary risk of fetal loss for female fetuses. Moreover, fetal RHD genotyping by maternal blood analysis could be useful in RhD-negative women at risk of immunization in order to adapt prophylactic anti-D injection.     

Are there sex differences in Fetal Abdominal Subcutaneous Tissue (FAST) measurements?

Objective

To determine if Fetal Abdominal Subcutaneous Tissue (FAST) measurements using antenatal ultrasound differ between male and female fetuses.

Study design

Women who had an ultrasound examination for fetal growth between 20 and 40 weeks gestation were studied. Women with diabetes mellitus were excluded. The fetal anterior abdominal subcutaneous tissue was measured on the anterior abdominal wall in millimetres anterior to the margins of the ribs, using magnification at the level of the abdominal circumference. The fetal sex was recorded after delivery.

Results

A total of 557 fetuses were measured, 290 male and 267 female. The FAST measurements increased with gestational age. The FAST increased at the same rate for both male and female fetuses and at any given week there was no sex difference.

Conclusions

The increased fat composition in females reported after birth was not found in abdominal wall subcutaneous fat measurements using ultrasound during pregnancy. Antenatal centile charts for FAST do not need to be based on sex.     

Prenatal diagnosis of female monozygotic twins discordant for Turner syndrome: implications for prenatal genetic counselling

We describe a set of monozygotic (MZ) female twins, one of whom presented with a typical Turner syndrome (TS) phenotype and the other a normal female phenotype. Prenatal fetal ultrasonographic examination showed a monochorial diamniotic pregnancy with a hygroma colli and growth delay in Twin A and no anomalies in Twin B. Karyotypic analysis performed on fetal blood samples demonstrated a 46,XX/45,X (23/2) mosaicism in Twin A and a normal 46,XX chromosome constitution in Twin B. At birth, Twin A presented with a typical TS and Twin B had a normal female phenotype. Postnatal cytogenetic investigation of blood lymphocytes showed the same 46,XX/45,X mosaicism in both twins: 46,XX/45,X (40/7) in Twin A and 46,XX/45,X (40/5) in Twin B. Further investigations at the age of 10 months showed in Twin A a 46,XX/45,X (98/2) mosaicism in lymphocytes and 100% of 45,X (50 analysed cells) in fibroblasts, and in Twin B a normal 46,XX (100 analysed cells) chromosome constitution in lymphocytes but a mild 46,XX/45,X (78/2) mosaicism in fibroblasts. Monozygosity was confirmed by molecular analysis. To our knowledge, this is the first report of prenatal diagnosis of MZ female twins discordant for TS. Review of reported sets of MZ female twins (eight cases) or triplets (one case) discordant for TS shows, as in the present case, that the phenotype correlates better with the chromosomal distribution of mosaicism in fibroblasts than in lymphocytes. In the blood of MZ twins chimerism may modify the initial allocation of the mosaicism. These results suggest that, in cases of prenatal diagnosis of MZ female twins discordant for TS, the phenotype of each twin would be better predicted from karyotype analysis of cells from amniotic fluid than from fetal blood.     

Detection of Y chromosome-specific DNA in the plasma and urine of pregnant women using nested polymerase chain reaction

The present study was undertaken to evaluate a nested polymerase chain reaction (PCR) for detection of Y chromosome-specific fetal DNA in maternal plasma and urine of pregnant women during different gestational stages. DNA isolated from plasma and urine samples of 80 pregnant women (between 7 and 40 weeks' gestation) underwent amplification for Y chromosome-specific 198 bp DNA by nested PCR. The postpartum analysis of fetal gender showed that 55 women carried male and 25 female fetuses. Among the 55 women bearing male fetuses, Y chromosome-specific signals were detected in 53 (96%) plasma and 21 (38%) urine samples. Moreover, out of 25 women bearing female fetuses, 3 (12%) and 1 (4%) women had Y chromosome-specific signal in plasma and urine, respectively. Analysis of results with respect to gestational age revealed that there was no significant difference in the detection of Y chromosome-specific DNA between different trimesters in maternal plasma of women bearing male fetuses. These results showed that fetus-specific DNA was detected with high sensitivity (96%) and specificity (88%) in the maternal plasma by nested PCR, and therefore the method could be useful as a non-invasive procedure for fetal sex determination and prenatal diagnosis.     

Prenatal diagnosis in monozygotic twins with Down syndrome who had different phenotypes

We report the case of monozygotic (MZ) male twin fetuses with different Down syndrome (DS) phenotypes. Prenatal fetal sonography showed a bichorial biamniotic pregnancy with increased nuchal translucency in twin A and a cervical cystic hygroma and heart defect in twin B. Cytogenetic analysis performed after double amniocentesis showed free and homogeneous trisomy 21 in both twins. Monozygosity was confirmed by molecular analysis. The pregnancy was terminated at 17 weeks of gestation (WG). Postmortem analysis confirmed the phenotypic discordance. To our knowledge, this is the first reported prenatal diagnosis of MZ male twins with different Down syndrome phenotypes but identical karyotypes. We discuss the mechanisms involved in phenotypic discordance of monozygotic twins and particularly the role of environmental factors.     

Impact of maternal cigarette smoking on fetal growth and body composition

OBJECTIVE: The aim of this study was to determine the impact of maternal cigarette smoking on the fetal accretion of fat and lean body mass. We hypothesized that maternal smoking would result in a reduction in the deposition of lean body mass. STUDY DESIGN: Longitudinal ultrasonographic examinations on 65 singleton fetuses without anomalies of smoking mothers were compared with 36 singleton fetuses without anomalies of nonsmoking mothers. A total of 214 ultrasonographic examinations were performed between 27 and 37 weeks' gestation. All subjects underwent at least 2 ultrasonographic examinations separated by 4 weeks. We compared the slopes of the growth curves for individual morphometric parameters including head circumference, femur length, abdominal circumference, thigh muscle area, thigh fat area, estimated fetal weight and percentage of thigh fat between groups. Analysis was performed with a repeated measures analysis of covariance. Potential covariates included prepregnancy body mass index (in kilograms per square meter), weight gain during pregnancy, maternal age, parity, and fetal sex recorded at birth. Demographic variables are expressed as mean +/- SD; fetal measurements are expressed as mean +/- SE. Both t tests and chi(2) analyses were used to compare groups with respect to demographic variables. P <.05 was accepted for significance. RESULTS: There were no significant differences between groups in maternal prepregnancy weight, maternal height, maternal prepregnancy body mass index, weight gain in pregnancy, parity, or fetal sex. Smokers were younger than nonsmokers (smokers, 23.7 +/- 6.0 years; nonsmokers, 31.8 +/- 6. 0 years; P <.0001), and neonatal weight was reduced among smokers (smokers, 3269 +/- 507 g; nonsmokers, 3519 +/- 411 g; P <.01). There were no differences in the growth rates of head circumference (P =. 79) and femur length (P =.67). Growth rates of abdominal circumference (smokers, 9.0 +/- 0.3 mm/wk; nonsmokers, 10.3 +/- 0.5 mm/wk; P =.01), estimated fetal weight (smokers, 171 +/- 5.4 g/wk; nonsmokers, 193 +/- 8.0 g/wk; P =.008), and muscle area (smokers, 64. 1 +/- 3.8 mm(2)/wk; nonsmokers, 76.4 +/- 5.6 mm(2)/wk; P =.03) were significantly reduced among smokers. There was a reduction in the rate of fat deposition in the thighs of fetuses of smoking mothers (smokers, 38.7 +/- 3.7 mm(2)/wk; nonsmokers, 54.6 +/- 5.4 mm(2)/wk; P =.004); however there was no absolute difference in the amount of fat measured in the thigh between 33 and 37 weeks' gestation. CONCLUSION: We detected reduced fetal growth that selectively affected abdominal circumference and peripheral muscle mass while not affecting head circumference and femur length in fetuses of smoking mothers. The effect of cigarette smoking on fetal fat deposition was less clear. Cigarette smoking appears to have a selective effect within lean body mass compartments, with affected compartments including peripheral fetal muscle. The findings of a reduction in abdominal circumference growth compared with control subjects in combination with no difference in subcutaneous fat content beyond 33 weeks' gestation are potentially explained by a reduction in fetal liver size that may result from maternal smoking.     

First trimester fetal sex determination in maternal serum using real-time PCR

OBJECTIVE: Fetal sex prediction can be achieved using PCR targeted at the SRY gene by analyzing cell-free fetal DNA in maternal serum. Unfortunately, the results reported to date, show lack of sensitivity, especially in the first trimester of pregnancy. Therefore, determination of fetal sex by maternal serum analysis can not replace caryotype analysis following chorionic villus sampling. PATIENTS AND METHODS: A new highly sensitive real-time PCR was developed to detect a SRY gene sequence in maternal serum. Analysis was performed on 121 pregnant women during their first trimester of pregnancy (mean gestational age: 11.8 weeks). Among them, 61 had at least one previous male-bearing pregnancy. Results were compared to fetal sex. RESULTS: SRY PCR analysis of maternal serum was in complete concordance with fetal sex. Among the 121 pregnant women, 61 were bearing a male fetus and 60 a female fetus No false negative results were observed. Furthermore, no false positive results results occurred although 27 women carried female fetus during the current pregnancy, had at least one previous male-bearing pregnancy. DISCUSSION AND CONCLUSION: This study demonstrates that a reliable, non-invasive sex determination can be achieved by PCR analysis of maternal serum during the first trimester of pregnancy. This non-invasive approach for fetal sex prediction should have great implications in the management of pregnant women carriers of an X-linked genetic disorder. Prenatal diagnosis is thus performed for male fetuses only, avoiding invasive procedures and the risk of fetal loss for female fetuses.     

A comparison of maternal age, sex ratio and associated major anomalies among fetal trisomy 18 cases with different cell division of error

OBJECTIVES: To compare the maternal age, sex ratio, and associated major anomalies among fetal trisomy 18 cases with different cell division of error. METHODS: Thirty-one consecutive cases of fetal trisomy 18 detected perinatally during a period of 6 years were studied. Among these, 18 were 47,XY,+18, and 13 were 47,XX,+18. The average gestational age at diagnosis was 19.7 +/- 4.6 weeks, and the maternal age at diagnosis was 34.5 +/- 5.8 years. DNA polymorphism analysis was applied to determine the parental origin, stage of non-disjunctional error and recombination. RESULTS: Twenty-eight cases were of maternal origin. Among these, 20 had major anomalies, 17 had meiosis II (MII) errors, 10 had meiosis I (MI) errors, and one had a postzygotic mitotic (PZM) or non-crossover MII error. Three cases were of paternal origin. Among these, two had major anomalies, two had MI errors, and one had a PZM or non-crossover MII error. For the 17 cases with maternal MII errors, the average maternal age was 34.5 +/- 6.6 years. Of these cases, 12 had major anomalies, 13 were male, and 4 were female, giving a male:female sex ratio of 3.25:1. For the 10 cases with maternal MI errors, the average maternal age was 34.8 +/- 5.7 years. Of these cases, seven had major anomalies, three were male, and seven were female, giving a male:female sex ratio of 0.429:1. CONCLUSION: In trisomy 18, there is a male preponderance in the fetuses caused by maternal MII errors and a female preponderance in the fetuses caused by maternal MI errors. No significant difference was noted in maternal age or in associated major anomalies between the two groups of maternal MII errors and maternal MI errors. No significant difference was noted in associated major anomalies between the maternal and paternal cases.     

Chromosomal abnormalities in fetuses with ultrasonographically detected neural tube defects

We analyzed the karyotype of fetuses with ultrasonographically detected neural tube defects (NTDs). In our study, we included a total of 194 fetuses with NTDs. We analyzed the type of NTD, the karyotype, maternal age, fetal gestational age at diagnosis, and fetal sex. Of the 194 fetuses with NTDs, 87 were anencephalic and 107 had other, nonanencephalic, NTDs. A total of 12 fetuses were shown to have chromosomal abnormalities. Three of 87 anencephalic fetuses (3.45%) had chromosomal abnormalities. The sex ratio for anencephalic fetuses was 65.5% : 34.5% for female and male fetuses. Nine of 107 fetuses with other NTDs (8.41%) had chromosomal abnormalities. Seven fetuses had isolated NTDs and a further seven fetuses had additional ultrasonographic anomalies. Two of the latter had abnormal karyotypes. The sex ratio of all other NTD cases was 67.3% : 32.7% for female and male fetuses. The high number of chromosomal abnormalities justifies prenatal karyotyping in all fetuses with ultrasonographically diagnosed NTDs.     

Fetoscopy and fetal blood sampling in the management of a twin pregnancy with 45,X/46,XX amniotic fluid cell mosaicism and a suspected fluid sampling error

A 37 year-old woman with a twin pregnancy underwent amniocentesis to exclude fetal chromosome abnormality. The results indicated that both fetuses were mosaics, with 45,X and 46,XX, cell lines. Since it was suspected from the ultrasound scan that the twins were dizygotic, the result was questioned. Fetoscopy and fetal blood sampling were performed and karyotyping the fetal lymphocytes confirmed that one twin was indeed a mosaic, 45,X/46,XX, but the other had a normal male chromosome complement. The pregnancy resulted in the birth of a phenotypically normal girl, in whom the 45,X/46,XX mosaicism was confirmed, and a normal boy.     

142例胎儿唇腭裂的超声诊断与遗传因素分析

目的探讨胎儿唇腭裂的影像学特征与遗传基础。方法142例病例均接受产前超声系统检查,经过两级医生检查及会诊做出最终诊断。同时收集活产胎儿的胎儿脐带或引产胎儿的大腿肌肉组织,进行全基因组测序(whole genome sequening,WGS),以发现染色体数目异常和拷贝数异常(copy number variations,CNVs)。结果142例孕妇年龄分布为21~41岁,孕周为12~35周。142例胎儿中,男性94例,女性48例,男女比例为1∶0.51。根据唇腭裂的类型,单纯唇裂有84/142例(59.15%),唇裂合并其他系统畸形情况有31/142例(21.83%)。单纯唇腭裂有14/142例(9.86%),唇腭裂合并其他系统畸形情况有13/142例(9.15%)。9.2%(13/142)的胎儿有染色体数目异常,8.4%(12/142)的胎儿检出了致病性CNV。结论对CNVs的检测可以增加胎儿腭裂的遗传检测诊断率,在临床中应重视检测致病性CNVs。     

First-trimester fetal sex determination in maternal serum using real-time PCR.

Fetal sex prediction can be achieved using PCR targeted at the SRY gene by analysing cell-free fetal DNA in maternal serum. Unfortunately, the results reported to date show a lack of sensitivity, especially during the first trimester of pregnancy. Therefore, determination of fetal sex by maternal serum analysis could not replace karyotype analysis following chorionic villus sampling. A new highly sensitive real-time PCR was developed to detect an SRY gene sequence in maternal serum. Analysis was performed on 121 pregnant women during the first trimester of pregnancy (mean gestational age: 11.8 weeks). Among them, 51 had at least one previous male-bearing pregnancy. Results were compared with fetal sex. SRY PCR analysis of maternal serum was in complete concordance with fetal sex. Among the 121 pregnant women, 61 were bearing a male fetus and 60 a female fetus. No false-negative results were observed. Furthermore, no false-positive results occurred, even though 27 women carrying a female fetus during the current pregnancy had at least one previous male-bearing pregnancy. This study demonstrates that a reliable, non-invasive sex determination can be achieved by PCR analysis of maternal serum during the first trimester of pregnancy. This non-invasive approach for fetal sex prediction should have great implications in the management of pregnant women who are carriers of an X-linked genetic disorder. Prenatal diagnosis might thus be performed for male fetuses only, avoiding invasive procedures and the risk of the loss of female fetuses.