ECHOGENIC (HYPERECHOGENIC) BOWEL

• Echogenic bowel is a well-defined, homogenous, hyperechogenic, lesion in the lower abdomen, which does not shadow (i.e. has no calcific areas), and usually resolves within a few weeks with no long term sequelae to the fetus (1,2).
• Fetal bowel is considered hyperechoic if it is as echogenic as the adjacent bone (more echogenic than fetal liver).
• Echogenic bowel in the third trimester is a relatively common finding with uncertain clinical significance
• Although initially considered a normal variant in second-trimester fetuses, it has been described as a prenatal marker for cystic fibrosis, chromosomal aneuploidy and numerous other pathologies.
• Prevalence = 0.2% to 1.8% (3).
• This finding can be diffuse or focal.
• Typically localized in the lower abdomen.
• Nyberg and associates 1993 (2):
• Hyperechoic bowel is present in 0.81% of all second trimester fetuses scanned, compared with 14.5% of fetuses with Down syndrome.
• Bernacerraf an co-workers (11):
• 0.6% incidence of hyperechoic bowel in the second trimester fetal population. Among 50 fetuses with hyperechoic bowel: 8(16%) were aneuploid (trisomy 21,6; Turners Syndrome,1; trisomy 13,1) and 8(16%) had severe IUGR
• 12.5% of all second trimester fetuses with Down syndrome had hyperechoic bowel.
• Hyperechogenic bowel therefore carried a 16-fold greater risk for Down syndrome.

ULTRASOUND

GRADING SYSTEM FOR ECHOGENIC BOWEL

Link to Ultrasound and Grading System for Echogenic Bowel

PATHO[HYSIOLOGY

The pathophysiology of increased bowel echogenicity is likely heterogeneous in nature. In most cases the increased echogenicity is thought to be due to:

· Abnormal, highly viscous meconium within the small bowel caused by obstruction (meconium ileus), poor bowel motility, or abnormal pancreatic enzymatic secretion (12).

· Alternatively, meconium peritonitis from a bowel perforation can cause subsequent bowel edema, which also makes the bowel appear echogenic (12) . If the meconium is confined to discrete sites of bowel perforation, the echogenicity appears as focal intra-abdominal calcifications (12) . Similar calcifications in the bowel have been associated with fetal infections, such as toxoplasmosis or cytomegalovirus (CMV), although the pathophysiology of this association is poorly understood.

· Focal areas of bowel echogenicity have also been attributed to areas of ischemia (12,13).

· Finally, bowel may appear echogenic because of the swallowing of blood, which is extremely echogenic (14).

CAUSES OF ECHOGENIC BOWEL

• Fetal aneuploidy especially Trisomy 21 and less frequently trisomy 18 or 13, Turner's syndrome and triploidy. The cause of echogenic bowel in aneuploidy is less clear. It is thought to be due to decreased bowel motility with increased water absorption from the meconium. There appears to be decreased microvillar enzymes activity in the amniotic fluid of aneuploid fetuses (2). The association of echogenic bowel with aneuploidy, particularly trisomy 21, has been demonstrated in several studies (15-18).
• A review of 11 published series of fetuses with echogenic bowel in which information was available about aneuploidy found that 11.8% had chromosomal abnormalities (12).
• The risk of aneuploidy in a fetus with echogenic bowel is highest in the presence of additional sonographic abnormalities;
• Echogenic bowel may be the only sonographically detected abnormality in an aneuploid fetus (18-20).
• The relative risk of Down syndrome for fetuses with hyperechoic bowel has been reported to be 5.5 times the a priori risk (21). This association has been postulated to be caused by poor bowel motility resulting in increased water absorption and thickened meconium (22).
• Cystic fibrosis associated with thick inspissated meconium (7-9). Meconium is more likely to be inspissated in the second trimester when the bowel lumen is narrow. This usually resolves as a result of enlarging small bowel and fetal swallowing of amniotic fluid. Echogenic bowel has been reported to be found on ultrasound in 50% to 78% of fetuses affected with CF (23,24).
• The association of echogenic bowel with fetuses affected with CF is thought to be caused by changes in the consistency of meconium in the small intestine as a result of abnormalities in pancreatic enzyme secretion. This can result in detectible sonographic findings, such as diffuse echogenic bowel, focal echogenic bowel with calcifications, a hyperechoic mass, or bowel dilation (12,24,25).
• These findings may appear as early as the second trimester (24,25).
• CF has been reported to affect 0.8% to 13.3% of fetuses with echogenic bowel (20, 26-29, 34), markedly higher than the rate of CF expected in a white population in which the carrier frequency is 1 in 25.
• As with any screening marker, echogenic bowel is most predictive of CF in populations at highest risk for CF. High-risk populations, however, are those that are most likely to be screened routinely for CF. There is some evidence that the detection of echogenic bowel in populations at low-risk for this disease does not increase the risk of CF when compared with the background risk.

• Small bowel obstruction proximally (especially duodenal atresia) can produce hyperechogenic bowel by reducing the meconium fluid content (2,5).
• Hirschsprung's disease (increased frequency in fetuses with Down syndrome) could produce hyperechogenic bowel due to hypoperistalsis.
• Bowel atresia (6-8). Echogenic bowel is thought to be due to decreased amniotic fluid content of the meconium.
• Intra-amniotic hemorrhage (1,11). Echogenic bowel is probably due to swallowed blood products resulting in a hypercellular meconium, probably with small clots within the bowel lumen. This is thought to be caused by fetal swallowing of blood, which is very echogenic.
• One series found that 22% of fetuses with echogenic bowel had evidence of heme pigment in amniotic fluid (14).
• In another series, 3.1% of amniotic fluid was grossly contaminated with blood (29).
• Petrikovsky et al (30) examined 28 fetuses before and 12 hours after intrauterine transfusion, a procedure that commonly introduces blood into the amniotic cavity by postpuncture bleeding. Although none of the fetuses had echogenic bowel before intrauterine transfusion, 25% of these fetuses had evidence of bowel echogenicity within 12 hours of the bleeding episode and 18% still had evidence of echogenicity 2 weeks later (30).
• In general, pregnancies with evidence of intra-amniotic bleeding but without additional anomalies have a good prognosis (18).
• Oligohydramnios. Echogenic bowel is also thought to be due to decreased amniotic fluid content of meconium (2,5).
• IUGR - Most fetuses with IUGR do not have echogenic bowel. The suggested mechanism is bowel ischemia due to hemodynamic redistribution and subsequent mesenteric ischemia is therefore questionable. Intrauterine fetal growth restriction has been estimated to complicate 4% to 18% of pregnancies with echogenic bowel, even in the setting of a normal karyotype (12,19,20,25). The association of echogenic bowel with IUGR may be caused in part by ischemia from redistribution of blood flow away from the gut (3).
• The presence of IUGR or elevated maternal serum alpha-fetoprotein in the second trimester in association with echogenic bowel seems to be associated with a particularly poor fetal prognosis.
• In one series, all six fetuses with both echogenic bowel and elevated maternal serum alpha-fetoprotein were growth restricted: four died in utero, one of two live-born infants died during the neonatal period, and the single survivor developed necrotizing enterocolitis requiring surgery (31) . This poor prognosis has been confirmed in other studies (18).
• Poor perinatal outcome due to uteroplaental insufficiency, especially in cases in which the maternal serum alpha-fetoprotein concentration is elevated (2,5,6,9). As alpha-fetoprotein is a pure fetal product, cases with raised levels are likely to have experienced significant feto-maternal bleeding. This group may represent a subset of fetuses with severe placental damage.
• Other less common associations.
• Cytomegalovirus.
• Toxoplasmosis.
• Parvovirus.
Thalassemia – The high frequency of echogenic bowel in first and second trimester fetuses suggests bowel wall edema, due to severe anemia and hypoxia may be the cause (10).

The association of congenital infections with echogenic bowel has been reported to be from 0% to 10% (20).

· The most commonly detected infectious agent is CMV

· Simon-Bouy et al (29) prospectively checked maternal rubella, toxoplasmosis, and CMV serologies (IgG and IgM) in 682 cases of fetal echogenic bowel. When seroconversion was observed, CMV polymerase chain reaction testing was performed in amniotic fluid. Parvovirus B19 polymerase chain reaction was also performed in all cases.

· A total of 19 viral infections were diagnosed, which represented 2.8% of fetuses: 15 (2.2%) CMV and 4 (0.6%) parvovirus.

· In 11 of the fetuses with CMV, echogenic bowel was the only sonographic abnormality noted.

· All four of the fetuses with parvovirus had associated abnormalities. It is unclear how a viral infection results in the echogenic appearance of the bowel. It may be caused by direct intestinal damage from inflammation or meconium peritonitis or indirectly by ascites, anemia, or growth restriction (12,32).

OUTCOME

Outcome of 682 cases of echogenic bowel
Outcome	N (%)	Termination of pregnancy (N)	IU Fetal Demise (N)	Neonatal death (N)
Normal healthy newborn	447 (65.5)	—	—	—
Chromosomal abnormality	29 (4.3)	21	2	0
Trisomy 21	17 (2.5)	15	1	0
Other	12 (1.8)	6	1	0
Severe	7 (1)	6	1	0
Less severe(a)	5 (0.7)	0	0	0
Cystic fibrosis	21 (3.1)	16	0	0
Infectious diseases	19 (2.8)	12	1	0
Cytomegalovirus	15 (2.2)	12	1	0
Parvovirus	4 (0.6)	0	0	0
Toxoplasmosis	0 (0)	—	—	—
Rubella	0 (0)	—	—	—
Intrauterine Growth Restriction	28 (4.1)	0	2	0
Intra-amniotic bleeding	21 (3.1)	NS	NS	NS
Unexplained IUFD	13 (1.9)	—	13	—
Associated structural abnormalities	47 (6.9)	17	2	3
Gastrointestinal abnormalities	20 (2.9)	3	1	0
Multiple visceral abnormalities	12 (1.8)	4	1	1
Cardiac abnormalities	5 (0.7)	2	0	1
Other	10 (1.5)	8	0	1
(a) - Less severe includes Klinefelter syndrome, Robertsonian translocation, and mosaic trisomy X.
Simon-Bouy B, Satre V, Ferec C, Malinge MC, Girodon E, Denamur E, et al. Hyperechogenic fetal bowel: a large French Collaborative Study of 682 cases. Am J Med Genet 2003;121A(3):209–13.
The largest series in the literature is a prospective collaborative series of 680 cases of fetuses with echogenic bowel referred for prenatal diagnosis . In the above series: · hyperechoic bowel was observed in 0.1% of second-trimester ultrasounds. · Chromosome abnormalities were observed in 29 (4.3%) cases, of which 24 (3.5%) were severe, including 17 (2.5%) of which were Down syndrome. · In 11 (65%) of the cases with Down syndrome, echogenic bowel was the only sonographic abnormality noted. · The risk of a severe chromosomal abnormality (including Down syndrome) when echogenic bowel was isolated or seen in conjunction with other abnormalities was 1.6% and 1.9%, respectively.

Table of Echogenic Bowel and Pregnancy Outcome
Ref	GA (wks)	Poor perinatal outcome (%)	Chromosomal defects (%)	Cystic fibrosis(%)	Infection(%)	IUGR (%)*	Perinatal death(%)**
1	15-34	40	3	13	0	21	14
2	15-24	47	25	0	1	18	8
3	14-24	42	16	0	0	19	12
4	15-21	34	6	0	6	13	17
5	14-34	39	4	1	4	7	13
6	16-20	14	6	5	0	0	0
7	14-23	46	6	3	6	7	8
8	16-22	28	5	5	0	11	11
9	15-23	29	11	0	10	7	8
* Excluding chromosomally abnormal fetuses. ** Excluding chromosomally abnormal fetuses and terminations.

It is still controversial whether isolated echogenic bowel justifies invasive testing irrespective of whether associated findings are present. Strocher and co-workers (9) found the prevalence of chromosome defects is at least five-fold higher than that expected on the basis of maternal age. They suggest that even for a 20-year old with a background prevalence of 1:1295 for trisomy 21, the adjusted risk is 1:260.

· One analysis of nine studies found that 34% of fetuses with echogenic bowel have a poor perinatal outcome, however the most important prognostic factor is whether or not there are associated fetal abnormalities (20).

· The prognosis seems to be particularly poor in the setting of early IUGR and elevated maternal serum alpha-fetoprotein. Fetuses with echogenic bowel as an isolated finding seem to have a much better prognosis. This is because in most cases the finding of isolated echogenic bowel is associated with a normal fetus.

· One study, which examined 175 fetuses in 171 pregnancies complicated by isolated echogenic bowel, found that only 6.3% of fetuses were affected with CF (five fetuses), aneuploidy (five fetuses), and CMV (one fetus) (34).

· In a larger series, 447 (65.5%) of 682 cases of echogenic bowel resulted in the birth of a normal healthy newborn (see previous table) . In the normal fetus, the finding of echogenic bowel usually resolves over a period of weeks with no adverse sequelae (33). Despite this, there does seem to be an increased risk of unexplained intrauterine fetal demise in fetuses with unexplained echogenic bowel, with a rate of 1.9% reported in one series (29).

REFERENCES

1. Dickie LM, Crane JP. Sonographically detected hyperechoic fetal bowel: significance and implications for pregnancy management. Obstet Gynecol 1992;80:778-782

2. Nyberg DA, Dubinsky T, Resta RG et.al. Echogenic fetal bowel during the second trimester: clinical importance. Radiology 1993;188:527-531

3. Bromley B, Doubilet P, Frigoletto FD et.al. Is fetal hyperechogenic bowel on fetal sonogram an indication for amniocentesis. Obstet Gynecol 1994;83:647-651.

4. Hill LM, Fries J, Hecker J et.al Second trimester echogenic small bowel: an increased risk for adverse perinatal outcome. Prenata Diagn 1994;14:845-850.

5. Muller F, Dommergues M, Aubry MC et.al. Hyperechogenic fetal bowel: an Ultrasonographic marker for adverse fetal and neonatal outcome. Am J Obstet Gynecol 1995;173:508-513.

6. Slotnick RN, Abuhamed AZ. Prognostic implications of fetal echogenic bowel. Lancet 1996;347:85-87.

7. Yaron Y, Hassan S, Geva E et.al. Evaluation of fetal echogenic bowel in the second trimester. Fetal Diagn Ther 1999;14:176-180.

8. Ghose I, Mason GC, Martinez D et.al. Hyperechogenic fetal bowel: a prospective analysis of sixty consecutive cases. Br J Obstet Gynaecol 2000;107:426-429.

9. Strocker AM, Snijders RJ, Carlson DE et.al. Fetal echogenic bowel:parameters to be considered in differential diagnosis. Ultrasound Obstet Gynecol 2000;16:519-523.

10. Lam YH, Tang MHY, Lee CP et.al. Echogenic bowel in fetuses with homozygous alpha thalassemia –1 in the first and second trimesters. Ultrasound Obstet Gynecol 1999;14:180-182.

11. Benacerraf BR. The second trimester fetus with Down syndrome detection using sonographic features. Ultrasound Obstet Gynecol 1996;7:147-150.

12. Eddleman KA, Stone JL, Berkowitz RL. Fetal echogenic bowel: the bottom line. Contemporary Ob/Gyn 1998;43:53-69.  

13. Achiron R, Mazkereth R, Orvieto R, Kuint J, Lipitz S, Rotstein Z. Echogenic bowel in intrauterine growth restriction fetuses: does this jeopardize the gut? Obstet Gynecol 2002;100:120-5.  

14. Sepulveda W, Reid R, Nicolaidis P, Prendiville O, Chapman RS, Fisk NM. Second-trimester echogenic bowel and intraamniotic bleeding: association between fetal bowel echogenicity and amniotic fluid spectrophotometry at 410 nm. Am J Obstet Gynecol 1996;174:839-42.  

15. Nyberg DA, Resta RG, Mahony BS, Dubinsky T, Luthy DA, Hickok DE, et al. Fetal hyperechogenic bowel and Down's syndrome. Ultrasound Obstet Gynecol 1993;3:330-3.  

16. Bahado-Singh R, Morotti R, Copel JA, Mahoney MJ. Hyperechoic fetal bowel: the perinatal consequences. Prenat Diagn 1994;14:981-7.  

17. Bromley B, Doubilet P, Frigoletto FD, Krauss C, Estroff JA, Benacerraf BR. Is fetal hyperechoic bowel on second-trimester sonogram an indication for amniocentesis? Obstet Gynecol 1994;83:647-51.  

18. Strocker AM, Snijders RJ, Carlson DE, Greene N, Gregory KD, Walla CA, et al. Fetal echogenic bowel: parameters to be considered in differential diagnosis. Ultrasound Obstet Gynecol 2000;16:519-23.  

19. Simon-Bouy B, Muller F. French Collaborative Group. Hyperechogenic fetal bowel and Down syndrome: results of a French collaborative study based on 680 prospective cases. Prenat Diagn 2002;22:189-92.  

20. Sepulveda W, Sebire NJ. Fetal echogenic bowel: a complex scenario. Ultrasound Obstet Gynecol 2000;16:510-4.  

21. Shipp TD, Benacerraf BR. Second trimester ultrasound screening for chromosomal abnormalities. Prenat Diagn 2002;22:296-307.  

22. Nyberg DA, Dubinsky T, Resta RG, Mahony BS, Hickok DE, Luthy DA. Echogenic fetal bowel during the second trimester: clinical importance. Radiology 1993;188:527-31.  

23. Hill LM. Ultrasound of fetal gastrointestinal tract. In: CallenPW, editors. Ultrasonography in obstetrics and gynecology Philadelphia: WB Saunders; 2000. p. 457-87.

24. Boue A, Muller F, Nezelof C, Oury JF, Duchatel F, Dumez Y, et al. Prenatal diagnosis in 200 pregnancies with a 1-in-4 risk of cystic fibrosis. Hum Genet 1986;74:288-97.  

25. Muller F, Aubry MC, Gasser B, Duchatel F, Boue J, Boue A. Prenatal diagnosis of cystic fibrosis. II. Meconium ileus in affected fetuses. Prenat Diagn 1985;5:109-17.  

26. Berlin BM, Norton ME, Sugarman EA, Tsipis JE, Allitto BA. Cystic fibrosis and chromosome abnormalities associated with echogenic fetal bowel. Obstet Gynecol 1999;94:135-8.  

27. Muller F, Dommergues M, Simon-Buoy B, Ferec C, Oury JF, Autry MC, et al. Cystic fibrosis screening: a fetus with hyperechogenic bowel may be the index case. J Med Genet 1998;35:657-60.  

28. Dicke JM, Crane JP. Sonographically detected hyperechoic fetal bowel: significance and implications for pregnancy management. Obstet Gynecol 1992;80:778-82.  

29. Simon-Bouy B, Satre V, Ferec C, Malinge MC, Girodon E, Denamur E, et al. Hyperechogenic fetal bowel: a large French collaborative study of 682 cases. Am J Med Genet 2003;121A:209-13.  

30. Petrikovsky B, Smith-Levitin M, Holsten N. Intra-amniotic bleeding and fetal echogenic bowel. Obstet Gynecol 1999;93:684-6.  

31. Achiron R, Seidman DS, Horowitz A, Mashiach S, Goldman B, Lipitz S. Hyperechogenic fetal bowel and elevated serum alpha-fetoprotein: a poor fetal prognosis. Obstet Gynecol 1996;88:368-71.  

32. Chasen S.T. Fetal echogenic bowel. In: UpToDate, version 11.2. Wellesley, MA; 2003. [28]. Achiron R, Seidman DS, Horowitz A, Mashiach S, Goldman B, Lipitz S. Hyperechogenic fetal bowel and elevated serum alpha-fetoprotein: a poor fetal prognosis. Obstet Gynecol 1996;88:368-71.  

33. Stipoljev F, Sertic J, Kos M, Miskovic B, Obrad-Sabljak R, Stavljenic-Rukavina A, et al. Incidence of chromosomopathies and cystic fibrosis mutations in second trimester fetuses with isolated hyperechoic bowel. J Matern Fetal Neonatal Med 1999;8:44-7.  

34. Al-Kouatly HB, Chasen ST, Streltzoff J, Chervenak FA. The clinical significance of fetal echogenic bowel. Am J Obstet Gynecol 2001;185:1035-8.