• 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 DEFECT RISK FACTOR SERIES: Atresia-Stenosis of the Small Intestine

Loading...

Click here for an Adobe PDF version of this document. (153KB PDF, Viewing Information)

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

DESCRIPTION

Defects of the small intestine include both atresia and stenosis. Atresia involves closure or disconnection of a portion or multiple portions of the small intestine while stenosis is a narrowing, webbing, or incomplete closure of a portion of the small intestine (Garza 2005). Small intestinal atresia/stenosis most frequently affects the duodenum (~50%), followed by the jejunum (~35%); the ileum (~15%) is least likely to be affected (Forrester 2004, Cragan 1993). This defect is usually diagnosed prenatally via ultrasound or shortly after delivery, as the intestinal blockage will cause abdominal distention, difficulty in feeding, and the bowel movements (Garza 2005).

Most cases of small intestinal atresia/stenosis do not occur with other birth defects; the exception to this is duodenal atresia/stenosis (Forrester 2004, Garne 2002, Haeusler 2002, Harris 1995, Cragan 1993, Camilla 1990). Approximately 50% of infants with duodenal atresia/stenosis have another anomaly, including cardiac, genitourinary, or anorectal defects, and annular pancreas (Garza 2005, Bianchi 2000). Duodenal atresia is also associated closely with trisomy 21; however, chromosomal abnormalities are not associated with the jejunum or ileum atresia/stenosis (Haeusler 2002, Torfs 1998, Kallen 1996, Harris 1995, Cragan 1993). A severe form of duodenal atresia/stenosis is described at “apple-peel” deformity. This name is derived from the appearance of the intestine as it spirals around the blood supply and resembles an apple peel (Yamanaka 2000).

EMBRYOLOGY

At approximately week 3 of gestation, the hepatobiliary system and pancreas are developing (Garza 2005). As these organs are forming, the duodenum is a solid structure. Between the 8 th to 10th weeks of gestation, a vacuolation process occurs whereby the duodenum becomes a hollow structure. Failure of the vacuolation process may result in duodenal atresia and stenosis (Sencan 2002). It has also been suggested that small intestinal atresia/stenosis may be due to vascular disruption during development (Werler 2003).

GENETIC FACTORS

Small intestinal atresia/stenosis has been reported to run in families (Gahukamble 2003, Gahukamble 2002). This defect has also been connected with deletions of chromosome 22q11 (most often associated with DiGeorge syndrome) and chromosome 12q24.3 (Doray 2002, Yamanaka 2000). Both of these chromosomes have been tentatively linked to digestive system development. Additionally, an as-yet unidentified portion of chromosome 2p23-p24 has also been suggested as a causal factor for this defect when it is associated with Feingold syndrome (van Bokhoven 2005). Further examination of the chromosome indicated that a microdeletion of the gene MYCN might also contribute to developmental disruption of the digestive system. MYCN is activated by Sonic Hedgehog (Shh) signaling; if a portion of the gene is missing, then Shh signaling is disrupted. This disruption has been shown to cause a variety of defects, including tracheo-esophogeal fistula and esophogeal atresia (van Bokhoven 2005).

Other studies indicate that fibroblastic growth factors (fgf) (signaling molecules that are involved in organogenesis) may contribute to small intestinal atresia/stenosis when they malfunction (Fairbanks 2004, Fairbanks 2003). An absence of specific fibroblastic growth factors or their receptors disrupts the signaling pathways; this disruption may cause several different defects. The authors suggest an autosomal recessive inheritance of this defect (Fairbanks 2004, Fairbanks 2003).

OUTCOME

Small intestinal atresia/stenosis has a variable outcome depending on the location and severity of the defect; the presence of additional defects and/or chromosomal abnormalities also contributes to the probability of survival (Garza 2005). Minor defects can be repaired surgically, and generally the prognosis is good (Garza 2005). However, repair of major defects including multiple intestinal atresias have not been as successful (Bilodeau 2004).

DEMOGRAPHIC AND REPRODUCTIVE FACTORS

With respect to race/ethnicity, several studies have reported small intestinal atresia/stenosis to be more common in African-Americans than in whites (Harris 1995, Cragan 1993). One investigation observed no significant difference in risk of small intestinal atresia/stenosis in infants born to Vietnamese women compared to infants born to non-Hispanic white women in California (Shaw 2002). Another study found that rates for small intestinal atresia/stenosis were higher for Far East Asians than for Caucasians (Forrester 2004). Higher occurrence rates for this defect are not associated with mixed-race ancestry (Yang 2004).

One study failed to identify any secular trends in small intestinal atresia/stenosis over time (Forrester 2004, Cragan 1993). Another found no seasonal variation in intestinal atresia rates (Bound 1989).

Review of the literature failed to identify any studies that examined the relationship between small intestinal atresia/stenosis and geographic location. One investigation failed to identify any association between duodenal atresia or jejunoileal atresia and altitude (Castilla 1999).

The influence of maternal age on small intestinal atresia/stenosis risk has been variously reported to be U-shaped (Forrester 2004, Harris 1995) or higher for women who are less than 20 years of age (Francannet 1996), although one study failed to identify any association between maternal age and these defects (Cragan 1993).

No statistically significant relationship between these conditions and infant sex has been reported (Forrester 2004, Rittler 2004, Haeusler 2002, Harris 1995, Cragan 1993).

 

Risk for small intestinal atresia/stenosis increases with lower birth weight and lower gestational age (Rasmussen 2001, Martinez-Frias 2000, Cragan 1993, Mili 1991); however there does not appear to be an increased risk for this defect with large for gestational age infants (Lapunzina 2002). Small intestinal atresia has been associated with intrauterine growth retardation (Khoury 1988). One investigation reported no effect of parity on risk for these defects (Harris 1995). Small intestinal atresia/stenosis is more common among multiple gestation pregnancies (Martinez-Frias 2000, Mastroiacovo 1999, Francannet 1996, Harris 1995, Cragan 1994, Cragan 1993, Ramos-Arroyo 1991), although one study reported no association between plurality and small gut atresia (Kallen 1986).

One study identified higher risk of duodenal atresia with consanguinity (Martinez-Frias 2000), while another found no association between parental consanguinity and intestinal atresia (Rittler 2001). However, two more recent studies have indicated that inherited factors contribute to the etiology of this defect (Gahukamble 2003, Gahukamble 2002). Higher rates of small intestinal atresia/stenosis have been reported in a consanguineous Arab population even in the absence of teratogenic or environmental factors (Gahukamble 2002).

FACTORS IN LIFESTYLE OR ENVIRONMENT

Maternal education does not appear to affect risk for small intestinal atresia/stenosis (Martinez-Frias 2000). One investigation reported no association between parental farming occupation and pesticide exposure and risk of intestinal atresia (Kristensen 1997). Another investigation failed to identify any significant association between either duodenal atresia or jejunoileal atresia and proximity to various types of industry (Castilla 2000). An article that reviewed recent studies of paternal occupation and birth defects reported increased risk of small intestinal atresia and paternal occupation of motor vehicle operator (Chia 2002).

Maternal diabetes, hyperthyroidism, hypothyroidism, and other acute and chronic maternal diseases have not been associated with small intestinal atresia or duodenal atresia, although one study noted increased rates of esophageal/intestinal atresia with preexisting diabetes and gestational diabetes (Aberg 2001). Maternal infectious diseases have been suggested to increase risk for ileal atresia (Martinez-Frias 2000, Francannet 1996, Becerra 1990, Khoury 1989). One investigation reported no association between maternal fever, upper respiratory infection, or allergy and small intestinal atresia/stenosis (Werler 2002).

Prenatal use of vasoconstrictive drugs, including cocaine, amphetamines, decongestants, and nicotine has been associated with intestinal atresia (Werler 2003, Hoyme 1990), although other studies have reported no association between fetal cocaine exposure and birth defects (Behnke 2001). One investigation found elevated rates of small intestinal atresia/stenosis/web with maternal use of pseudoephedrine and pseudoephedrine in combination with acetaminophen (Werler 2002). Thalidomide and hydantoin have been linked to increased risk of duodenal atresia (Jones 1988). One study reported a potential association between methylene blue used during amniocentesis and jejunal atresia (van der Pol 1992). Aspirin, phenylpropanolamine, ibuprofen, antihistamines, guaifenesin, dextromethorphan, vitamins, iron, other minerals, and ovulation induction have not been reported to increase risk of small intestinal atresia/stenosis (Werler 2002, Martinez-Frias 2000, Francannet 1996). Studies have reported no association between cephalosporin antibiotics, ampicillin, or the benzodiazepinesnitrazepam, medazepam, tofisopam, alprazolum, and clonazepam and intestinal atresia/stenosis (Eros 2002, Czeizel 2001a, Czeizel 2001b, Holmes 2001). Exposure to calcium channel blockers (Sorenson 2001), corticosteroids (Park-Wyllie 2000), marijuana (Fried 2000), chemotherapy (Cardonic 2004), and fluoxetine (Prozac™) (Chambers 1996) have not been found to be risk factors for small intestinal atresia/stenosis.

No association between maternal folic acid or multivitamin use and intestinal atresia has been reported (Botto 2004, Czeizel 1996). Furthermore, a study that examined co-trimoxazole, a combination of trimethoprim and sulfamethoxazole that is a folic acid antagonist, failed to find any association between the medication and atresia/stenosis of the small intestine (Czeizel 1990).

Living in proximity to a landfill sites and solid waste incinerators has not been found to be a risk factor for small intestinal atresia/stenosis (Cordier 2004, Harrison 2003).

PREVALENCE

The reported prevalence for small intestinal atresia/stenosis has shown variation between studies, ranging between 0.6 and 3.1 per 10,000 births for duodenal atresia/stenosis and 0.4 and 1.4 for other small intestinal atresia/stenosis (Table 1). Differences in prevalence may be due to differences in case inclusion criteria.

Table 1. Prevalence per 10,000 births of small intestinal atresia/stenosis

Reference

Location

Time period

Rate per 10,000 live births

Other* rate

Total rate

Texas DSHS 2005

Texas

1999-2002

 

 

3.1

Haeusler 2002

Europe

1996-1998

1.0

1.0

 

Martinez-Frias 2000

Spain

1976-1998

0.6

0.4

1.2

Martinez-Frias 2000

Latin America

1967-1996

0.6

0.5

1.2

Torfs 1998

California , USA

1983-1993

2.3

 

3.9

Stoll 1996

France

1979-1987

 

 

3.0

Harris 1995

France

1976-1990

0.7

0.8

 

Harris 1995

Sweden

1973-1990

1.1

0.5

 

Harris 1995

California , USA

1983-1990

1.0

0.9

 

Papp 1995

Hungary

1988-1990

2.0

 

 

Cragan 1993

Georgia , USA

1968-1989

1.4

1.4

2.8

Castilla 1990

Central and South America

1982-1986

0.7

0.6

 

*Other small intestinal atresia/stenosis

REFERENCES

Aberg A, Westbom L, Kallen B. Congenital malformations among infants whose mothers had gestational diabetes or preexisting diabetes. Early Hum Dev 2001;61:85-95.

Becerra JE, Khoury MJ, Cordero JF, Erickson JD. Diabetes mellitus during pregnancy and the risks for specific birth defects: a population-based case-control study. Pediatrics 1990;85:1-9.

Behnke M, Eyler FD, Garvan CW, Wobie K. The search for congenital malformations in newborns with fetal cocaine exposure. Pediatrics 2001;107:e74.

Bianchi DW, Crombleholme TM, D'Alton ME. Duodenal atresia. In: Fetology: Diagnosis and Management of the Fetal Patient. New York: McGraw-Hill, 2000; pp. 523-529.

Bilodeau A, Prasil P, Cloutier R, Laframboise R, Meguerditchian A, Roy G, Leclerc S, Peloquin J. Hereditary multiple intestinal atresia: thirty years later. Journal of Pediatric Surgery, Vol. 39, No. 5, 2004.

Botto LD, Olney RS, Erickson JD. Vitamin supplements and the risk for congenital anomalies other than neural tube defects. American Journal of Medical Genetics Part C (Semin. Med. Genet.), Vol. 125C, 2004.

Bound JP, Harvey PW, Francis BJ. Seasonal prevalence of major congenital malformations in the Fylde of Lancashire 1957-1981. J Epidemiol Community Health 1989;43:330-342.

Cardonic E, Iacobucci A. Use of chemotherapy during human pregnancy. Lancet, Vol. 5, May 2004.

Castilla EE, Campana H, Camelo JS. Economic activity and congenital anomalies: an ecologic study in Argentina. Environ Health Perspect 2000;108:193-197.

Castilla EE, Lopez-Camelo JS, Campana H. Altitude as a risk factor for congenital anomalies. Am J Med Genet 1999;86:9-14.

Castilla EE, Lopez-Camelo JS. The surveillance of birth defects in South America: I. The search for time clusters: epidemics. In: Advances in Mutagenesis Research. Springer-Verlag, New York. 1990 pp. 191-210.

Chambers CD, Johnson KA, Dick LM, Felix RJ, Jones KL. Birth outcomes in pregnant women taking fluoxetine. New England Journal of Medicine, Vol. 335, No. 14, 1996.

Chia SE, Shi LM. Review of recent epidemiological studies on paternal occupations and birth defects. Occup Environ Med. 2002;59:149-155.

Cordier S, Chevrier C, Robert-Gnansia E, Lorente C, Brula C, Hours M. Risk of congenital anomalies in the vicinity of municipal solid waste incinerators. Occup Environ Med, Vol. 61, 2004.

Cragan JD, Martin ML, Waters GD, Khoury MJ. Increased risk of small intestinal atresia among twins in the United States. Arch Pediatr Adolesc Med 1994;148:733-739.

Cragan JD, Martin ML, Moore Ca, Khoury MJ. Descriptive epidemiology of small intestine atresia, Atlanta, Georgia. Teratology 1993;48:441-450.

Czeizel A. A case-control analysis of the teratogenic effects of co-trimoxazole. Reprod Toxicol 1990;4:305-313.

Czeizel AE, Toth M, Rockenbauer M. Population-based case control study of folic acid supplementation during pregnancy. Teratology 1996;53:345-351.

Czeizel AE, Rockenbauer M, Sorensen HT, Olsen J. Use of cephalosporins during pregnancy and in the presence of congenital abnormalities: a population-based, case-control study. Am J Obstet Gynecol 2001a;184:1289-1296.

Czeizel AE, Rockenbauer M, Sorensen HT, Olsen J. A population-based case-control teratologic study of ampicillin treatment during pregnancy. Am J Obstet Gynecol 2001b;185:140-147.

Doray B, Becmeur F, Girard-Lemaire F, Schluth C, Flori E. Esophageal and duodenal atresia in a girl with 12q24.3-qtr deletion. Clinical Genetics, Vol. 61, 2002.

Eros E, Czeizel AE, Rockenbauer M, Sorensen HT, Olsen J. A population-based case-control teratologic study of nitrazepam, medazepam, tofisopam, alprazolum and clonazepam treatment during pregnancy. Eur J Obstet Gynecol Reprod Biol 2002;101:147-154.

Fairbanks TJ, Kanard R, Del Moral PM, Sala FG, De Langhe S, Warburton D, Anderson KD, Bellusci S, Burns RC. Fibroblast growth factor receptor 2 IIIb invalidation—a potential cause of familial duodenal atresia. Journal of Pediatric Surgery, Vol. 39, No. 6, 2003.

Fairbanks TJ, Kanard RC, De Langhe SP, Sala FG, Del Moral PM, Warburton D, Anderson KD, Bellusci S, Burns RC. A genetic mechanism for cecal atresia: the role of the Fgf10 signaling pathway. Journal of Surgical Research, Vol. 120, 2004.

Forrester MB , Merz RD. Population-based study of small intestinal atresia and stenosis, Hawaii, 1986-2000. Public Health, Vol. 118, 2004.

Francannet C, Robert E. Etude epidemiologique des atresias intestinales: Registre Centre-Est 1976-1992. J Gynecol Obstet Biol Reprod ( Paris) 1996;25:485-494.

Fried, P. The consequences of marijuanta use during pregnancy: a review of the human literature. In Women and Cannabis: Medicine, Science, and Sociology, Haworth Integrative Healing Press.

Garne E, Rasmussen L, Husby S. Gastrointestinal malformations in Funen County, Denmark - epidemiology, associated malformations, surgery and mortality. Eur J Pediatr Surg 2002;12:101-106.

Gahukamble DB, Adnan ARM, Al-Gadi M. Distal foregut atresias in consecutive siblings and twins in the same family. Pediatr Surg Int, Vol. 19, 2003.

Gahukamble DB, Adnan ARM, Al-Gadi M. Atresias of the gastrointestinal tract in an inbred, previously unstudied population. Pediatr Surg Int, Vol. 18, 2002.

Garza JJ, Jaksic T. Intestinal atresia, stenosis, and webs. Web reference, http://emedicine.medscape.com/article/940615-overview. Accessed August 4, 2005.

Haeusler MC, Berghold A, Stoll C, Barisic I, Clementi M. Prenatal ultrasonographic detection of gastrointestinal obstruction: results from 18 European congenital anomaly registries. Prenat Diagn 2002;22:616-623.

Harris J, Kallen B, Robert E. Descriptive epidemiology of alimentary tract atresia. Teratology 1995;52:15-29.

Harrison RM. Hazardous waste landfill sites and congenital anomalies. Occup Environ Med, Vol. 60, 2003.

Holmes LB, Harvey EA, Coull BA, Huntington KB, Khoshbin S, Hayes AM, Ryan LM. The teratogenicity of anticonvulsant drugs. New England Journal of Medicine, Vol. 334, 2001.

Hoyme HE, Jones KL, Dixon SD, Jewett T, Hanson JW, Robinson LK, Msall ME, Allanson JE. Prenatal cocaine exposure and fetal vascular disruption. Pediatrics 1990;85:743-747.

Jones KL. Smith's Recognizable Patterns of Human Malformation. WB Saunders, Philadelphia, 1988, p.755.

Kallen B, Mastroiacovo P, Robert E. Major congenital malformations in Down syndrome. Am J Med Genet 1996;65:160-166.

Kallen B. Congenital malformations in twins: a population study. Acta Genet Med Gemellol (Roma) 1986;35:167-178.

Khoury MJ, Becerra JE, d'Almada PJ. Maternal thyroid disease and risk of birth defects in offspring: a population-based case-control study. Paediatr Perinat Epidemiol 1989;3:402-420.

Khoury MJ, Erickson JD, Cordero JF, McCarthy BJ. Congenital malformations and intrauterine growth retardation: a population study. Pediatrics 1988;82:83-90.

Kristensen P, Irgens LM, Andersen A, Bye AS, Sundheim L. Birth defects among offspring of Norwegian farmers, 1967-1991.Epidemiology 1997;8:537-544.

Lapunzina P, Camelo JSL, Rittler M, Castilla EE. Risks of congenital anomalies in larger for gestational age infants. Journal of Pediatrics, Vol. 140, No. 2, 2002.

Martinez-Frias ML, Castilla EE, Bermejo E, Prieto L, Orioli IM. Isolated small intestinal atresias in Latin America and Spain: Epidemiological analysis. Am J Med Genet 2000;93:355-359.

Mastroiacovo P, Castilla EE, Arpino C, Botting B, Cocchi G, Goujard J, Marinacci C, Merlob P, Metneki J, Mutchinick O, Ritvanen A, Rosano A. Congenital malformations in twins: an international study. Am J Med Genet 1999;83:117-124.

Mili F, Edmonds LD, Khoury MJ, McClearn AB. Prevalence of birth defects among low-birth-weight infants. A population study. Am J Dis Child 1991;145:1313-1318.

Papp Z, Toth-Pal E, Papp C, Toth Z, Szabo M, Veress L, Torok O. Impact of prenatal mid-trimester screening on the prevalence of fetal structural anomalies: a prospective epidemiological study. Ultrasound Obstet Gynecol 1995;6:320-326.

Park-Wyllie L, Mazzotta P, Pastuszac A, Moretti ME, Beique L, Hunnisett L, Friesen MH, Jacobson S, Kasapinovic S, Chang D, Diav-Citrin O, Chitayat D, Nulman I, Einarson TR, Koren G. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology, Vol. 62, 2000.

Ramos-Arroyo MA. Birth defects in twins: study in a Spanish population. Acta Genet Med Gemellol (Roma) 1991;40:337-344.

Rasmussen SA, Moore CA, Paulozzi LJ, Rhodenhiser EP. Risk for birth defects among premature infants: A population-based study. J Pediatr 2001;138:668-673.

Rittler M, Liascovich R, Lopez-Camelo J, Castilla EE. Parental consanguinity in specific types of congenital anomalies. Am J Med Genet 2001;102:36-43.

Rittler M, Lopez-Camelo J, Castilla EE. Sex ratio and associated risk factors for 50 congenital anomaly types: lues for causal heterogeneity. Birth Defects Research (Part A), Vol. 70, 2004.

Sencan A, Mir E, Gunsar C, Akcora B. Symptomatic annular pancreas in newborns. Med Sci Monit 2002;8:CR434-CR437.

Shaw GM, Carmichael SL, Nelson V. Congenital malformations in offspring of Vietnamese women in California, 1985-97. Teratology 2002;65:121-124.

Sorenson HT, Czeizel AE, Rockenbauer M, Steffensen FH, Olsen J. The risk of limb deficiencies and other congenital abnormalities in children exposed in utero to calcium channel blockers. Acta Obstet Gynecol Scand, Vol. 80, 2001.

Stoll C, Alembik Y, Dott B, Roth MP. Evaluation of prenatal diagnosis of congenital gastro-intestinal atresias. Eur J Epidemiol 1996;12:611-616.

Texas Department of State Health Services. Texas birth defects registry report of birth defects among 1999-2002 deliveries. 2005.

Torfs CP, Christianson RE. Anomalies in Down syndrome individuals in a large population-based registry. Am J Med Genet 1998;77:431-438.

Van Bokhoven H, Celli J, van Reeuwijk J, Rinne T, Glaudemans B, van Beusekom E, Rieu P, Newbury-Ecob RA, Chiang C, Brunner HG. MYCN haploinsufficiency is associated with reduced brain size and intestinal atresias in Feingold syndrome. Nature Genetics, Vol. 37, No. 5, 2005.

van der Pol JG, Wolf H, Boer K, Treffers PE, Leschot NJ, Hey HA, Vos A. Jejunal atresia related to the use of methylene blue in genetic amniocentesis in twins. Br J Obstet Gynaecol 1992;99:141-143.

Werler MM, Sheehan JE, Mitchell AA. Association of vasoconstrictive exposures with risks of gastroschisis and small intestinal atresia. Epidemiology, Vol. 14, 2003.

Werler MM, Sheehan JE, Mitchell AA. Maternal medication use and risks of gastroschisis and small intestinal atresia. Am J Epidemiol 2002;155:26-31.

Yamanaka S, Tanaka Y, Kawataki M, Ijiri R, Imaizumi K, Kurahasi H. Chromosome 22q11 deletion complicated by dissecting pulmonary arterial aneurysm and jujunal atresia in an infant. Arch Pathol Lab Med, Vol. 124, 2000.

Yang J, Carmichael SL, Kaidarova Z, Shaw GM. Risks of selected congenital malformations among offspring of mixed race-ethnicity. Birth Defects Research (Part A): Clinical and Molecular Teratology, Vol. 70, 2004.

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.

Document E58-10957  Revised November 2005

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

Return to Birth Defects Risk Factor Page

Document E58-10957B                    Revised November 2005

Birth Defects Epidemiology and Surveillance Home Page

Last updated November 20, 2013