• Loading...
    Contact Us

    Birth Defects Epidemiology & Surveillance
    Mail Code 1964
    P.O. Box 149347
    Austin, TX 78714-9347

    Phone: 512-776-7232
    Fax: 512-776-7330


    Email comments or questions

Birth Defects Risk Factor Series(2)

Loading...

NEW: Please take a moment to evaluate our birth defects risk factor series. Click here to take survey.

Click here for an Adobe PDF version of this document. (184KB PDF, Viewing Information)

Definition

A normal human conceptus possessed 46 chromosomes: 23 derived from the mother and and 23 from the father. Triploidy is a chromosomal abnormality where three complete sets of the haploid genome instead of the normal two sets are present within the conceptus. A triploid conceptus will possess 69 chromosomes. The most common triploid karyotypes and their distribution are presented in table 1. The low frequency of 69,XYY suggests that either the process by which this karyotype occurs is uncommon or the karyotype has lower survivability than the other karyotypes. Triploidy may occur with aneuploidies, resulting in complex karyotypes (e.g., karyotype 70,XXY,+21). Triploidy may also be found with mosaicism, where some of the cells in the body have a triploid chromosome complement and other cells in the body have a different chromosome complement, either normal diploid (e.g., karyotype 69,XXY/46,XX) or abnormal (e.g., karyotype 69,XXY/70,XXY,+21). Generally, triploidy is incompatible with life, and is associated with miscarriage and hydatidiform moles (Balakier 2002).

 Table 1. Distribution of triploidy cases represented by karyotype* in several studies

 

Study

 

69,XXX

 

69,XXY

 

69,XYY

 

Daniel 2001

 

42%

 

58%

 

0%

 

McFadden 2000

 

49%

 

49%

 

2%

 

Miny 1995

 

41%

 

59%

 

0%

 

Neuber 1993

 

41%

 

57%

 

2%

 

Ohno 1991

 

37%

 

63%

 

0%

 

Uchida 1985

 

43%

 

55%

 

2%

 

Jacobs 1982

 

31%

 

68%

 

1%

 

Niebuhr 1974

 

36%

 

60%

 

3%

*Includes mosaicisms and variations where another form of aneuploidy occurs along with the triploidy

Etiology

Triplody can occur in up to 2% of conceptuses; it is a common factor in first trimester spontaneous abortions (Brancati 2003). It can be recurrent, and maternally derived cases appear to live longer than paternally derived cases (Brancati 2003). Cases with diploid/triploid mosasicism also appear to have a longer survival time than triploidy cases (Forrester 2003). There are three different mechanisms that may produce triploidy:

1) nondisjunction in meiosis I or meiosis II of spermatogenesis (sperm formation), resulting in an extra set of paternal chromosomes (diandry)

2) nondisjunction in meiosis I or meiosis II of oogenesis (egg formation), resulting in an extra set of maternal chromosomes (digyny)

3) double fertilization of a normal egg, resulting in an extra set of paternal chromosomes (dispermy)

One investigation as reported that the “three relevant reproductive processes—meiosis and gametogenesis, fertilization, and early embryonic development are ‘remarkably imprecise’” (Hassold 1986, in Golubovsky 2003). As recent developments in reproductive science have unfolded, these mechanisms have been explored, and new information has been gathered.

It has been reported that mechanism 1 accounted for 23.6% of triploidy cases, mechanism 2 for 10%, and mechanism 3 for 66.4% (Jacobs 1978). As shown in table 2, a number of studies, particularly older studies, found that the majority of triploidy cases were of paternal origin (Daniel 2001, Redline1998, Uchida 1985, Jacobs 1982, Jacobs 1978, Kajii 1977) while more recent studies found the majority of triploidy cases to be of maternal origin (Baumer 2000, McFadden 2000, McFadden1993). Paternal origin for triploidy is higher at certain gestational ages while maternal origin for triploidy is higher at other gestational ages (McFadden 2000, Zaragoza 2000). Thus the wide variation in parental origin between the various studies may be due to the studies using cases derived from difference stages of fetal death.

Most cases of triploidy due to paternal origin result from dispermy (Baumer 2000, Zaragoza 2000, Kajii 1977). Several studies have reported that the majority (62-77%) of cases of triploidy of maternal origin result from nondisjunction in meiosis II (McFadden 2000, Zaragoza 2000, Jacobs 1982), although another investigation found the nondisjunction to be evenly distributed between meiosis I and meiosis II (Baumer 2000).

Maternal age has not been found to be associated with any of the three mechanisms by which triploidy occurs (Baumer 2000). One investigation observed that the XXX/XXY ratio changes from 1:2 to 2:1 and proportion of hydatidiform moles (triploidy of paternal origin) decreases with increasing maternal age, indicating that digyny is more important for older women and diandry more important for younger women (Neuber 1993).

One study identified no association between parental origin of the triploidy and phenotype (Kajii 1977). However, more recent studies reported paternal origin but not maternal origin to be associated with the hydatidiform mole phenotype of triploidy, although parental origin does not always result in hydatidiform mole (Zaragoza 2000, Redline 1998). Triploidy of maternal origin has also been associated with giant oocytes (Plachot 2003, Balakier 2002).

Table 2. Parental origin of the extra set of chromosomes in triploidy reported by various studies

 

Study

 

Maternal origin (%)

 

Paternal origin (%)

 

Daniel 2001

 

39%

 

61%

 

Baumer 2000

 

80%

 

20%

 

McFadden 2000

 

63%

 

37%

 

Redline 1998

 

34%

 

66%

 

Miny 1995

 

71%

 

29%

 

McFadden 1993

 

75%

 

25%

 

Uchida 1985

 

36%

 

64%

 

Jacobs 1982

 

33%

 

77%

 

Jacobs 1978

 

15%

 

85%

 

Kajii 1977

 

13%

 

88%

 Phenotype

There is wide variation in the clinical features associated with triploidy, ranging from a normal phenotype to multiple major birth defects. Cases of triploidy are grouped into two fetal and placental phenotypes that roughly correspond to the parental origin of the extra set of chromosomes (McFadden 1991):

Type I: well formed fetus with a normal or microcephalic head and a large placenta with cystic changes - associated with diandry

Type II: fetus with growth restriction and a large head and a small, noncystic placenta - associated with digyny

The professional literature has described the birth defects and other abnormalities associated with triploidy (Phillipp 2004, Sergi 2000, Doshi 1983, Wertelecki 1976). These anomalies include fetal growth restriction, partial hydatidiform mole (the placenta and fetus are partially comprised of vesicular villous structures resembling grapes), macrocephaly, hydrocephaly, holoprosencephaly, micrognathia, microphthalmia, bulbous nose, small mouth, malformed and low set ears, coloboma of the eye, cataracts, cleft lip and/or palate, syndactyly of the third and fourth digits of the hands or feet, simian crease of the hand, rocker bottom feet, ventricular septal defects, atrial septal defects, pulmonary hypoplasia, diaphragmatic hernia, intestinal malrotation, cystic kidney, adrenal hypoplasia, ovarian hypoplasia, and abnormal male genitalia (hypospadias, micropenis, undescended testicles). Neural tube defects may be found in 25% and abdominal wall defects in 10-18% of triploidy cases. Cases with diploid/triploid mosaicism tend to have a milder phenotype than completely triploid cases, but usually suffer from mental retardation (Daniel 2003, Tantravahi 1986).

Prenatal diagnosis

Triploidy may be prenatally diagnosed through cytogenetic analysis of cells obtained through such procedures as amniocentesis and chorionic villus sampling (Nagaishi 2004). Fetal nuchal translucency in the first trimester is frequently increased for fetuses with triploidy (Yaron 2004, Spencer 2000, Jauniaux 1997, Pandya 1995). Triploidy has been associated with elevated materal serum alpha fetoprotein (AFP) and total and beta-human chorionic gonadotropin (hCG) levels and low maternal serum pregnancy-assisted plasma protein-A (PAPP-A) levels in the first trimester (Yaron 2004, Spencer 2000, Jauniaux 1997). However, first-trimester nuchal translucency and maternal serum screening is not routinely performed in the United States. Triploidy has been associated with two distinct patterns of maternal serum AFP, hCG, and estriol levels in the second trimester (Benn 2000, Schmidt 1994, Canick 1993, Fejgin 1992, Mason 1992, Oyer 1992, Kohn 1991, Freeman 1989, Pircon 1989a, O’Brien 1988):

1) elevated AFP, elevated hCG, and low or normal estriol

2) low or normal AFP, low hCG, and low estriol

Second-trimester amniotic fluid AFP has been reported to be normal in the presence of triploidy except when there is also an open neural tube present (Freeman 1989). (See table 3 for a review of maternal serum marker levels and nuchal translucency in relation to triploidy.) However, second-trimester maternal serum screening in the United States does not systematically screen for triploidy. Moreover, one investigation found that the proportion of triploidy cases in a population at increased risk of Down syndrome as a result of maternal serum screening was not greater than expected for the general population (Ryall 2001). And fetuses with triploidy typically do not have a consistent pattern of abnormalities on prenatal ultrasound (Pircon 1989b). Thus cases of triploidy will frequently be prenatally diagnosed incidentally as a result of cytogenetic analysis for other reasons such as advanced maternal age.

maternal serum table

Prevalence and pregnancy outcome

Triploidy has been estimated to occur in 1-2% of all clinically recognized conceptions (Forrester 2003, Jacobs 1978). However, the majority of triploid conceptuses do not survive to term. It has been assessed that only one-third of triploidy conceptuses survive past 15 weeks gestation (Warburton 1994) and that for every triploidy conceptus that survives to term, approximately 1200 conceptuses result in fetal death (Doshi 1983). Triploidy has been reported in 1-13% of spontaneous abortions that were studied (Redline 1998, Ford 1996, Kalousek 1993, Neuber 1993, Ohno 1991, Shepard 1989). Triploidy is found in 8/10,000 chorionic villus samplings (Association of Clinical Cytogeneticists Working Party on Chorionic Villi in Prenatal Diagnosis 1994) and 4/10,000 amniocenteses (Horger 2001). The live birth rate for triploidy is 1/10,000 live births (Stoll 2001, Jacobs 1982, Jacobs 1974). As a result of prenatal diagnosis, a portion of triploidy fetuses will be electively terminated. An investigation in Europe reported an elective termination rate of 82% for triploidy (De Vigan 2001). One study reported 100% of fetuses prenatally diagnosed with triploidy were electively terminated (Horger 2001).

Mortality/survival

Triploidy is lethal, with no survivors reported beyond 10.5 months of age (Forrester 2003, Sherard 1986). Postnatal survivors usually have the type II phenotype with the extra chromosomes of maternal origin (Hasegawa 1999, Graham 1989). Infants with triploid/triploid mosaicism will have longer survival than infants with true triploidy (Tantravahi 1986).

Sex

The sex ratio of triploidy is linked to the distribution of sex chromosomes (table 1). Males account for 51-69% of triploidy cases (McFadden 2000, Miny 1995, Neuber 1993, Ohno 1991, Uchida 1985, Jacobs 1982).

Parental age

Neither maternal nor paternal age has been associated with triploidy risk (Ford 1996, Rochon 1990, Uchida 1985, Niebuhr 1974). However, as outlined in the Etiology section, maternal age does appear to be related to the type of triploidy (Neuber 1993).

Diabetes

One investigation found no association between maternal gestational diabetes and triploidy (Moore 2002).

Other

Animal studies have identified increased risk of triploidy with colchicine (an alkaloid used to treat gout), hypoxia, and heat shock (Niebuhr 1974). One study reported that 50% of mothers of triploidy conceptuses had preconceptional abdominal radiation exposure (Uchida 1985). Triploidy has also been potentially linked to delayed fertilization resulting from prolonged menstrual cycles or the cessation of oral contraceptives (Niebuhr 1974). Triploidy has been reported in conceptuses resulting from in vitro fertilization (Angell 1986, Ulmer 1985) and in conceptuses of women who have recurrent miscarriages (Carp 2001).

REFERENCES

  • Angell RR, Templeton AA, Aitken RJ. Chromosome studies in human in vitro fertilization. Hum Genet 1986;72:333-339.
  • Association of Clinical Cytogeneticists Working Party on Chorionic Villi in Prenatal Diagnosis. Cytogenetic analysis of chorionic villi for prenatal diagnosis: an ACC collaborative study of U.K. data. Prenat Diagn 1994;14:363-379.
  • Balakier H, Bouman D, Sojeki A, Librach C, Squire JA. Morphological and cytogenetic analysis of human giant oocytes and giant embryos. Human Reproduction 2002;17:9:2394-2401.
  • Baumer A, Balmer D, Binkert F, Schinzel A. Parental origin and mechanisms of formation of triploidy: a study of 25 cases. Eur J Hum Genet 2000;8:911-917.
  • Benn PA, Gainey A, Ingardia CJ, Rodis JF, Egan JF. Second trimester maternal serum analytes in triploid pregnancies: correlation with phenotype and sex chromosome complement. Prenat Diagn 2001;21:680-686.
  • Brancati F, Mingarelli R, Dallapiccola B. Recurrent tripoloidy of maternal origin. European Journal of Human Genetics. 2003:11:972-974.
  • Canick JA, Saller DN. Maternal serum screening for aneuploidy and open fetal defects. Obstet Gynecol Clin North Am 1993;20:443-454.
  • Carp H, Toder V, Aviram A, Daniely M, Mashiach S, Barkai G. Karyotype of the abortus in recurrent miscarriage. Fertil Steril 2001;75:678-682.
  • Daniel A, Wu Z, Bennetts B, Slater H, Osborn R, Jackson J, Pupko V, Nelson J, Watson G, Cooke-Yarborough C, Loo C. Karyotype, phenotype and parental origin in 19 cases of triploidy. Prenat Diagn 2001;21:1034-1048.
  • Daniel A, Wu Z, Darmanian A, Collins F, Jackson J. Three different origins of triploid/diploid mosaics. Prenatal Diagnosis 2003:23:529-534.
  • De Vigan C, Baena N, Cariati E, Clementi M, Stoll C; EUROSCAN Working Group. Contribution of ultrasonographic examination to the prenatal detection of chromosomal abnormalities in 19 centres across Europe. Ann Genet 2001;44:209-217.
  • Doshi N, Surti U, Szulman AE. Morphologic anomalies in triploid liveborn fetuses. Hum Pathol 1983;14:716-723.
  • Fejgin M, Amiel A, Goldberger S, Barnes I, Zer T, Kohn G. Placental insufficiency as a possible cause of low maternal serum human chorionic gonadotropin and low maternal serum unconjugated estriol levels in triploidy. Am J Obstet Gynecol 1992;167:766-767.
  • Ford JH, Wilkin HZ, Thomas P, McCarthy C. A 13-year cytogenetic study of spontaneous abortion: clinical applications of testing. Aust N Z J Obstet Gynaecol 1996;36:314-318.
  • Forrester MB , Merz RD. Pregnancy outcome and prenatal diagnosis of sex chromosome abnormalities in Hawaii, 1986-1999. American Journal of Medical Genetics 2003:119A:305-310.
  • Forrester MB , Merz RD. Epidemiology of triploidy in a population-based birth defects registry, Hawaii, 1986-1999. American Journal of Medical Genetics 2003:119A:319-323.
  • Freeman SB, Priest JH, MacMahon WC, Fernhoff PM, Elsas LJ. Prenatal ascertainment of triploidy by maternal serum alpha-fetoprotein screening. Prenat Diagn 1989;9:339-347.
  • Graham JM Jr, Rawnsley EF, Simmons GM, Wurster-Hill DH, Park JP, Marin-Padilla M, Crow HC. Triploidy: pregnancy complications and clinical findings in seven cases. Prenat Diagn 1989;9:409-419.
  • Hasegawa T, Harada N, Ikeda K, Ishii T, Hokuto I, Kasai K, Tanaka M, Fukuzawa R, Niikawa N, Matsuo N. Digynic triploid infant surviving for 46 days. Am J Med Genet 1999;87:306-310.
  • Horger EO, Finch H, Vincent VA. A single physician's experience with four thousand six hundred genetic amniocenteses. Am J Obstet Gynecol 2001;185:279-288.
  • Jacobs PA, Melville M, Ratcliffe S, Keay AJ, Syme J. A cytogenetic survey of 11,680 newborn infants. Ann Hum Genet 1974;37:359-376.
  • Jacobs PA, Angell RR, Buchanan IM, Hassold TJ, Matsuyama AM, Manuel B. The origin of human triploids. Ann Hum Genet 1978;42:49-57.
  • Jacobs PA, Szulman AE, Funkhouser J, Matsuura JS, Wilson CC. Human triploidy: relationship between parental origin of the additional haploid complement and development of partial hydatidiform mole. Ann Hum Genet 1982;46:223-231.
  • Jauniaux E, Brown R, Snijders RJ, Noble P, Nicolaides KH. Early prenatal diagnosis of triploidy. Am J Obstet Gynecol 1997;176:550-554.
  • Kajii T, Niikawa N. Origin of triploidy and tetraploidy in man: 11 cases with chromosome markers. Cytogenet Cell Genet 1977;18:109-125.
  • Kalousek DK, Pantzar T, Tsai M, Paradice B. Early spontaneous abortion: morphologic and karyotypic findings in 3,912 cases. Birth Defects Orig Artic Ser 1993;29:53-61.
  • Kohn G, Zamir R, Zer T, Amiel A, Fejgin M. Significance of very low maternal serum human chorionic gonadotropin in prenatal diagnosis of triploidy. Prenat Diagn 1991;11:277.
  • Mason G, Linton G, Cuckle H, Holding S. Low maternal serum human chorionic gonadotrophin and unconjugated oestriol in a triploidy pregnancy. Prenat Diagn 1992;12:545-547.
  • McFadden DE , Kalousek DK. Two different phenotypes of fetuses with chromosomal triploidy: correlation with parental origin of the extra haploid set. Am J Med Genet 1991;38:535-538.
  • McFadden DE , Kwong LC, Yam IY, Langlois S. Parental origin of triploidy in human fetuses: evidence for genomic imprinting. Hum Genet 1993;92:465-469.
  • McFadden DE , Langlois S. Parental and meiotic origin of triploidy in the embryonic and fetal periods. Clin Genet 2000;58:192-200.
  • Miny P, Koppers B, Dworniczak B, Bogdanova N, Holzgreve W, Tercanli S, Basaran S, Rehder H, Exeler R, Horst J. Parental origin of the extra haploid chromosome set in triploidies diagnosed prenatally. Am J Med Genet 1995;57:102-106.
  • Moore LL, Bradlee ML, Singer MR, Rothman KJ, Milunsky A. Chromosomal anomalies among the offspring of women with gestational diabetes. Am J Epidemiol. 2002;155:719-724.
  • Nagaishi M, Yamomoto T, Iinuma K, Shimomura K, Berend SA, Knops J. Chromosome abnormalities identified in 347 spontaneous abortions collected in Japan. J Obstet Gynaecol Res 2004:30:3:237-241.
  • Neuber M, Rehder H, Zuther C, Lettau R, Schwinger E. Polyploidies in abortion material decrease with maternal age. Hum Genet 1993;91:563-566.
  • Niebuhr E. Triploidy in man. Cytogenetical and clinical aspects. Humangenetik 1974;21:103-125.
  • O'Brien WF, Knuppel RA, Kousseff B, Sternlicht D, Nichols P. Elevated maternal serum alpha-fetoprotein in triploidy. Obstet Gynecol 1988;71:994-995.
  • Ohno M, Maeda T, Matsunobu A. A cytogenetic study of spontaneous abortions with direct analysis of chorionic villi. Obstet Gynecol 1991;77:394-398.
  • Oyer CE, Canick JA. Maternal serum hCG levels in triploidy: variability and need to consider molar tissue. Prenat Diagn 1992;12:627-629.
  • Pandya PP, Kondylios A, Hilbert L, Snijders RJ, Nicolaides KH. Chromosomal defects and outcome in 1015 fetuses with increased nuchal translucency. Ultrasound Obstet Gynecol 1995;5:15-19.
  • Pircon RA, Towers CV, Porto M, Gocke SE, Garite TJ. Maternal serum alpha-fetoprotein and fetal triploidy. Prenat Diagn 1989a;9:701-707.
  • Pircon RA, Porto M, Towers CV, Crade M, Gocke SE. Ultrasound findings in pregnancies complicated by fetal triploidy. J Ultrasound Med 1989b;8:507-511.
  • Pircon RA, Towers CV, Porto M, Gocke SE, Garite TJ. Maternal serum alpha-fetoprotein and fetal triploidy. Prenat Diagn 1989a;9:701-707.
  • Phillipp T, Grillenberger K, Separovic ER, Philipp K, Kalousek DK. Effects of triploidy on early human development. Prenatal Diagnosis 2004:24:276-281.
  • Plachot M. Genetic analysis of the oocyte—a review. Placenta 2003:24:s66-s69.
  • Redline RW, Hassold T, Zaragoza MV. Prevalence of the partial molar phenotype in triploidy of maternal and paternal origin. Hum Pathol 1998;29:505-511.
  • Rochon L, Vekemans MJ. Triploidy arising from a first meiotic non-disjunction in a mother carrying a reciprocal translocation. J Med Genet 1990;27:724-726.
  • Ryall RG, Callen D, Cocciolone R, Duvnjak A, Esca R, Frantzis N, Gjerde EM, Haan EA, Hocking T, Sutherland G, Thomas DW, Webb F. Karyotypes found in the population declared at increased risk of Down syndrome following maternal serum screening. Prenat Diagn 2001;21:553-557.
  • Schmidt D, Shaffer LG, McCaskill C, Rose E, Greenberg F. Very low maternal serum chorionic gonadotropin levels in association with fetal triploidy. Am J Obstet Gynecol 1994;170:77-80.
  • Sergi C, Schiesser M, Adam S, Otto HF. Analysis of the spectrum of malformations in human fetuses of the second and third trimester of pregnancy with human triploidy. Pathologica 2000;92:257-263.
  • Shepard TH, Fantel AG, Fitzsimmons J. Congenital defect rates among spontaneous abortuses: twenty years of monitoring. Teratology 1989;39:325-331.
  • Sherard J, Bean C, Bove B, DelDuca V Jr, Esterly KL, Karcsh HJ, Munshi G, Reamer JF, Suazo G, Wilmoth D, Dahlke MB, Weiss C, Borgaonkar DS. Long survival in a 69,XXY triploid male. Am J Med Genet 1986;25:307-312.
  • Spencer K, Liao AW, Skentou H, Cicero S, Nicolaides KH. Screening for triploidy by fetal nuchal translucency and maternal serum free beta-hCG and PAPP-A at 10-14 weeks of gestation. Prenat Diagn 2000;20:495-499.
  • Stoll C, Tenconi R, Clementi M. Detection of congenital anomalies by fetal ultrasonographic examination across Europe. Community Genet 2001;4:225-232.
  • Tantravahi U, Bianchi DW, Haley C, Destrempes MM, Ricker AT, Korf BR, Latt SA. Use of Y chromosome specific probes to detect low level sex chromosome mosaicism. Clin Genet 1986;29:445-448.
  • Uchida IA , Freeman VC. Triploidy and chromosomes. Am J Obstet Gynecol 1985;151:65-69.
  • Ulmer R, Rehder H, Trotnow S, Kniewald A, Kniewald T, Pfeiffer RA. Triploid embryo after in vitro fertilization. Arch Gynecol 1985;237:101-107.
  • Warburton D, Stein Z, Kline J, Susser M. Chromosome abnormalities in spontaneous abortion: data from the New York City study. In: Hook EB, Porter HJ, eds. Reproductive loss. New York: Academic Press 1994:261-287.
  • Wertelecki W, Graham JM, Sergovich FR. The clinical syndrome of triploidy. Obstet Gynecol 1976;47:69-76.
  • Yaron Y, Ochshorn Y, Tsabari S, Shira AB. First-trimester nuchal translucency and maternal serum free β-hCG and PAPP-A can detect triploidy and determine the parental origin. Prenatal Diagnosis 2004:24:445-450.
  • Zaragoza MV, Surti U, Redline RW, Millie E, Chakravarti A, Hassold TJ. Parental origin and phenotype of triploidy in spontaneous abortions: predominance of diandry and association with the partial hydatidiform mole. Am J Hum Genet 2000;66:1807-1820.
 

Please Note: The primary purpose of this report is to provide background necessary for conducting cluster investigations. It summarizes literature about risk factors associated with this defect. The strengths and limitations of each reference were not critically examined prior to inclusion in this report. Consumers and professionals using this information are advised to consult the references given for more in-depth information. 

This report is for information purposes only and is not intended to diagnose, cure, mitigate, treat, or prevent disease or other conditions and is not intended to provide a determination or assessment of the state of health. Individuals affected by this condition should consult their physician and when appropriate, seek genetic counseling.


For more information:

Birth Defects Epidemiology and Surveillance
Texas Department of State Health Services
1100 W. 49th Street, Austin, Texas 78756
512-776-7232 Fax 512-776-7330

Document E58-10957F                    Revised May 2005

Return to Birth Defects Risk Factor Page

Last updated February 10, 2012