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Prognostic implications of fetal echogenic bowel
Prognostic implications of fetal echogenic
bowel
Robert Nathan Slotnick, Alfred Z Abuhamad
Introduction
Summary increased frequency of hyperechogenic on ultrasound has been reported in fetuses with bowel cystic fibrosis (CF) and trisomy-21. However, the diagnostic application of this observation has been hampered by the absence of a means of measuring
Background
An
echogenicity. Methods We devised
ultrasonic grading system in which quantified by linear gain reduction and echogenicity comparison with fetal iliac crest. From 7400 secondtrimester ultrasound referrals, 145 patients were identified as having a fetus with abnormally echogenic bowel. They were offered genetic counselling, parental and (if appropriate) CF carrier testing, and amniocentesis for karyotype and CF status if parents were informative. Follow-up was to 4 months of age. an
was
Findings Of 40 fetuses with mild increase in bowel sonodensity (grade 1), none had CF or aneuploidy. Of 81 patients identified with a moderate increase (grade 2), 2 had trisomy 21 and 2 had CF. And of 24 pregnancies with a pronounced increase (grade 3), 5 had CF and 6 had trisomy-21. Parental
CF
carrier and testing or has fetal CF status identify aneuploidy with a high positive ascertainment rate in fetuses echogenic bowel grades 2 and 3.
Interpretation
amniocentesis to
Several research groups have suggested a possible asociation between echogenic bowel on fetal sonography and the existence of fetal cystic fibrosis (CF) or aneuploidy, 1-5 but no systematic studies have been reported. So far, analyses have been subjective,6,7 because sonodensity could not be adequately quantified. If the associations are real they could provide useful pointers to diagnoses that are often missed. CF is the most common autosomal recessive disease affecting white populations.8 About 70% of cases are due to the AF 508 allele but genetic testing is complicated by the existence of about 400 other CF alleles and by differences between ethnic groups.9 Testing for fetal aneuploidy is one of the principal indications for prenatal diagnostic referral in the USA. The most frequent aneuploid state found in second trimester pregnancies is Down’s syndrome (trisomy-21), which has a live birth incidence of 1 in 700-800. With the introduction of biochemical screening, Down’s syndrome detection improved substantially, especially in women below the age of 35. Apart from echogenic bowel, ultrasonic markers of the condition include thickened nuchal fold, shortened bones, elongated iliac bones, and fetal pyelectasis. 10 We report here the quantification of fetal echogenic bowel identified in the early second trimester, together with the results of parental CF carrier analysis, karyotype studies and neonatal follow-up.
Methods
Division of Maternal Fetal Medicine, Department of Obstetrics Gynecology, Eastern Virginia Medical School, Norfolk, VA 23507, USA (R N Slotnick MD, A Z Abuhamad MD)
Correspondence to:
Dr Robert N Slotnick
and
From 7432 second trimester (12-24 weeks) obstetric ultrasound studies performed at our institution over 16 months, 145 singleton pregnancies were independently ascertained and identified as showing fetal echogenic bowel (FEB) at 16-20 weeks’ gestation. Those doing the ultrasound examination were unaware of the family history, previous pregnancy outcome, or current pregnancy abnormalities. In those pregnancies identified with FEB, sonodensity was quantified as follows. A contiguous view of the fetal abdomen including the brightest area of fetal bowel and the fetal iliac crest was generated. The ultrasonic overall time gain setting was reduced such that fetal bowel sonodensity could be compared with the density of fetal iliac crest. All studies were performed on one of two machines-an Acuson 128XP/10 OB (Mountain View, CA) or an ATL Ultramark 9/HDi (Bothell, WA) with curvilinear 3-5 or 5-0 MHz probes. Transvaginal studies were not included. Six different ultrasonographers were involved in the initial sonographic evaluations. Normal fetal bowel was arbitrarily assigned a score of 0. Sonodense fetal bowel which became unidentifiable before the loss of iliac crest image was assigned a score of 1. Sonodense fetal bowel whose image was lost at the same gain reduction as iliac crest was assigned a score of 2. Gain reduced images where iliac crest was lost before bowel image were awarded a score of 3 (figure). The scores were assigned by an ultrasonographer and confirmed by another ultrasonographer and a physician. Pedigree analysis and nondirective genetic counselling were offered to each patient/couple ascertained with FEB more than 0. Couples were also given access to parental carrier testing for CF
85
Table: Fetal
echogenic bowel: categories and
results
given cause for concern-in 4 because of recent vaginal bleeding, in 1 a serum alpha-fetoprotein (AFP) 2-5-3-0 multiples of the median (MoM), in 2 both vaginal bleeding and a raised AFP, and in 1 a positive rapid plasma reagin test. 21 couples accepted parental CF testing and 19 declined. No two-carrier partnerships were found. Amniocentesis was performed in 14 pregnancies, normal karyotypes being found in all. 26 couples declined had
Figure: Transverse sonographic image of fetal showing fetal echogenic bowel.
abdomen at 17
weeks
Bowel indicated by single arrow, iliac crest by curved homozygous for AF 508.
arrow.
Fetus
was
and to genetic amniocentesis, on the understanding that CF carrier testing would have a false-negative rate of 17%. Carrier testing was performed by the standard mutation and/or deletion analysis. (The procedure was confined to white couples of European extraction, since little is known of CF gene frequencies in other population groups.) 12, and later 17, different mutations/deletions were studied at both commercial and academic institutions. When both partners were identified as carriers, CF testing on the fetus was offered, the risk of procedure related miscarriage being quoted as 1 in 200. Neonatal follow-up was performed by chart review or by telephone, with special attention to prematurity, operative delivery, neonatal or infant hospital admissions, obvious anatomical defects, breathing difficulties, recurrent pulmonary infections, and parental appreciation of paediatric concerns. This project was presented to and approved by our departmental/divisional research committee. Patients were informed of the project’s experimental nature and its deviation from routine practice during their
genetic counselling
session.
Results Of the 145 fetuses with echogenic bowel 40 (27%) had grade 1, 81 (56%) had grade 2, and 24 (17%) had grade 3. In all but 2 cases the parents accepted genetic counselling and/or pedigree analysis. In 60 cases there
noteworthy family history of CF, but in only 5 was there an unambiguous history of a child born with CF, neonatal death, neonatal bowel obstruction, or neonatal meconium ileus or peritonitis. Prenatal diagnostic testing (parental CF carrier status, or amniocentesis for karyotype or fetal CF status or both) was done in 76 cases. In 10 cases parents declined the tests for reasons of cost. Follow-up to 4 months was completed in 83% of the total. was a
FEB 1 Of the 40 fetuses with FEB 1 (table), none showed abnormalities. Nor, on interview, were there any reasons to suspect increased risk of CF. In 8 cases the pregnancy 86
amniocentesis. Information on births and follow-up was available for all but 7 pregnancies. 2 women had had premature deliveries, and one of the infants had developed bronchopulmonary dysplasia. 6 women had given birth by caesarean section. In none of the 33 pregnancies for which we have information was the child born with CF or
karyotypic aneuploidy. FEB 2 FEB 2 was found in 81 pregnancies, and 79 patients were counselled. 2 women had an obstetric history suggestive of CF (neonatal death, neonatal bowel obstruction of unknown aetiology); and 1 patient was herself a CF homozygote (AF 508). In 14 women a raised AFP had been recorded (2-5-3-1 MoM). 24 couples were tested for parental CF carrier status. 4 couples had both partners heterozygous for the AF 508 deletion, and a homozygous affected fetus was found by amniocentesis in 2. Both CF pregnancies were carried to term. Altogether, amniocentesis was performed in 27 pregnancies and declined in 54. Trisomy 21 was diagnosed in 2 fetuses: one had a thickened nuchal fold on ultrasound, the other had no identifiable abnormality apart from the echogenic bowel. These pregnancies were carried to term. Neonatal and infant follow-up is available for 79 pregnancies. In 3 delivery was at less than 37 weeks; 15 patients gave birth by caesarean section. No abnormalities have been recorded, except in the 4 babies diagnosed antenatally as having CF or trisomy-21. FEB 3 24 pregnancies were scored FEB 3, and on counselling a familial risk was elicited in 2. One couple already had a child with CF, so the a-priori risk was 25%. Another woman had given birth two years before to a child with antenatal volvulus who had died from surgical complications two weeks after delivery; review of the pathology disclosed pancreatic duct inspissation and other
evidence of cystic fibrosis. 2
women
had had
a
raised AFP
(2-5-3-0 MoM). In 6 pregnancies
revealed ultrasound studies abnormalities other than echogenic bowel. 4 fetuses had either cystic hygroma or increased nuchal thickness (>6 mm). 2 patients had oligohydramnios. CF carrier testing was done in 13 of the 24 parental pairs and 3 double-carrier couples were identified, two pairs with AF 508 deletions and one pair with AF 508 and R 117. Each of these 3 pregnancies was shown by amniocentesis to be affected by CF. A total of 12 women had amniocentesis (12 declined) and 5 fetuses proved to have trisomy-21. 3 of the 5 aneuploid fetuses in the amniocentesis had associated sonographic group abnormalities-nuchal thickening, oligohydramnios, or both. Pregnancy and neonatal follow-up information is available for 22 of the 24 patients in the FEB 3 group. Of the 12 couples declining parental CF carrier testing and amniocentesis, 2 had infants with cystic fibrosis (diagnosed by sweat test) and 1 had a fetal death in the second trimister with proven trisomy-21 (this fetus had been noted to have a large cystic hygroma at 17 weeks). All 5 trisomy 21 pregnancies with FEB 3 were either lost or terminated.
Follow-up
might be the biophysical correlate of bowel sonographic echogenicity? Several groups have argued that intraluminal content (eg, meconium) provides the "sonodensity", but proof remains unestablished. It seems just as reasonable that bowel echogenicity in the second trimester might result from inspissated secretion within What
the bowel wall. Each
of increased second trimester bowel echogenicity, even those cases of CF, showed a subsequent decrease in FEB grade. This change might represent release of inspissated material into bowel lumen. Pathological confirmation on fetal post-mortem specimens would be instructive. Two reports’3,’ have suggested an association between increased fetal bowel and intra-amniotic echogenicity cytomegalovirus infection. Viral cultures on stored amniotic fluid specimens from our series of patients are now being prepared for study. As a result of the findings reported here, we now offer genetic counselling, parental carrier testing, and amniocentesis for karyotype to patients in whom a fetus with FEB 2 or 3 is identified in the middle trimester. If carrier studies are informative for both partners, then amniocyte DNA studies can then be initiated. References 1 Dicke JM, Crane JP. Sonographically detected hyperechoic fetal bowel: significance and implications for pregnancy management. Obstet 2
When CF was diagnosed antenatally, paediatricians were consulted. All these pregnancies were carried to term. In one, meconium peritonitis was suspected from ultrasound appearances in the third trimester. All have done well, requiring only short hospital admissions for pulmonary infections; the compound heterozygote (AF 508/R 117) in this group has required only pancreatic enzyme
3
4
5
supplements. 35 of the FEB 2 and 3 pregnancies were sonographically re-examined at 22-26 weeks, 4-6 weeks after the initial study. In every case, including 4 with CF, the score was
lower.
Discussion
perception of risk for a genetic or obstetric diagnosis depends in large part on the evaluator. As a rule, the condition will not be diagnosed until it is thought of. In both trisomy-21 and CF, ultrasound observations can usefully stimulate further investigations. Because the human eye is notoriously unreliable in evaluating echogenicity,8 several investigators have compared density perceptions between tissues"’" or have devised mathematical models for quantifying sonodensity.12 In our study we employed an independent internal sonographic standard (the fetal iliac crest) as a simpler and more reproduceable method that would allow interpatient comparisons. A weakness of the paper is that we did not formally study interobserver variation, though informally there was little disagreement between observers.
case
6
7
8
The
9
10
11 12
13
14
Gynecol 1992; 80: 778-82. Nyberg DA, Dubinsky T, Resta RG, Mahony BS, Hickock DE, Luthy DA. Echogenic fetal bowel in the second trimester: clinical importance. Radiology 1993; 188: 527-31. Sciosca Al, Pretorius DH, Budorick NE, Cahill TC, Axelrod F, Leopold GR. Second trimester echogenic bowel and chromosomal abnormalities. Am J Obstet Gynecol 1992 167: 889-94. Caspi B, Elchalal M, Lancet M, Chamke J. Prenatal diagnosis of cystic fibrosis: ultrasonographic appearance of meconium ileus in the fetus. Prenat Diagn 1988; 8: 379-82. Chalubinski K, Deutinger J, Bernaschek G. Meconium peritonitis: extrusion of meconium and different sonographical appearance in relation to the stage of the disease. Prenat Diagn 1992; 12: 631-36. Caspi B, Blickstein I, Appelman Z. The accuracy of the assessment of normal fetal intestinal echogenicity. Electro-optical densitometry versus the ultrasonographer’s eye. Gynecol Obstet Invest 1992; 33: 26. Blickstein I, Goldman R. The relation between different system gain settings and the accuracy of densitometric assessment of echogenicity. J Ultrasound Med 1994; 13: 675-78. Boat T, Welsh M, Beaudet AL. Cystic fibrosis. In: Scriver C, Beaudet AL, Sly W, Valle D, eds. The metabolic basis of inherited disease. New York: McGraw-Hill, 1989: 2649-60. Beaudet AL, Kazazaian HJ Jr, Bowman JE. Statements from the National Institutes of Health Workshop on Population screening for the Cystic Fibrosis Gene. N Engl J Med 1990; 323: 70-71 Nyberg DA, Resta RG, Luthy DA, Hickock DE, Mahony BS, Hirsch JH. Prenatal sonographic findings of Down syndrome: review of 95 cases. Obstet Gynecol 1990; 76: 370-77. Platt JF, Rubin JM, Bowerman RA, et al. The inability to detect kidney disease on the basis of echogenicity. AJR 1988; 151: 317. Blickstein I. Quantitative assessment of sonographic image echogenicity by transmission densitometry: fetal liver model. J Ultrasound Med 1993; 12: 567-71. Forouzan I. Fetal abdominal echogenic mass: an early sign of intrauterine cytomegalovirus infection. Obstet Gynecol 1992; 80: 535-37. Weiner CP, Grose CF, Naides SJ. Diagnosis of fetal infection in the patient with an ultrasonographically detected abnormality but a negative clinical history. Am J Obstet Gynecol 1993; 68: 6-11.
87
bowel
Robert Nathan Slotnick, Alfred Z Abuhamad
Introduction
Summary increased frequency of hyperechogenic on ultrasound has been reported in fetuses with bowel cystic fibrosis (CF) and trisomy-21. However, the diagnostic application of this observation has been hampered by the absence of a means of measuring
Background
An
echogenicity. Methods We devised
ultrasonic grading system in which quantified by linear gain reduction and echogenicity comparison with fetal iliac crest. From 7400 secondtrimester ultrasound referrals, 145 patients were identified as having a fetus with abnormally echogenic bowel. They were offered genetic counselling, parental and (if appropriate) CF carrier testing, and amniocentesis for karyotype and CF status if parents were informative. Follow-up was to 4 months of age. an
was
Findings Of 40 fetuses with mild increase in bowel sonodensity (grade 1), none had CF or aneuploidy. Of 81 patients identified with a moderate increase (grade 2), 2 had trisomy 21 and 2 had CF. And of 24 pregnancies with a pronounced increase (grade 3), 5 had CF and 6 had trisomy-21. Parental
CF
carrier and testing or has fetal CF status identify aneuploidy with a high positive ascertainment rate in fetuses echogenic bowel grades 2 and 3.
Interpretation
amniocentesis to
Several research groups have suggested a possible asociation between echogenic bowel on fetal sonography and the existence of fetal cystic fibrosis (CF) or aneuploidy, 1-5 but no systematic studies have been reported. So far, analyses have been subjective,6,7 because sonodensity could not be adequately quantified. If the associations are real they could provide useful pointers to diagnoses that are often missed. CF is the most common autosomal recessive disease affecting white populations.8 About 70% of cases are due to the AF 508 allele but genetic testing is complicated by the existence of about 400 other CF alleles and by differences between ethnic groups.9 Testing for fetal aneuploidy is one of the principal indications for prenatal diagnostic referral in the USA. The most frequent aneuploid state found in second trimester pregnancies is Down’s syndrome (trisomy-21), which has a live birth incidence of 1 in 700-800. With the introduction of biochemical screening, Down’s syndrome detection improved substantially, especially in women below the age of 35. Apart from echogenic bowel, ultrasonic markers of the condition include thickened nuchal fold, shortened bones, elongated iliac bones, and fetal pyelectasis. 10 We report here the quantification of fetal echogenic bowel identified in the early second trimester, together with the results of parental CF carrier analysis, karyotype studies and neonatal follow-up.
Methods
Division of Maternal Fetal Medicine, Department of Obstetrics Gynecology, Eastern Virginia Medical School, Norfolk, VA 23507, USA (R N Slotnick MD, A Z Abuhamad MD)
Correspondence to:
Dr Robert N Slotnick
and
From 7432 second trimester (12-24 weeks) obstetric ultrasound studies performed at our institution over 16 months, 145 singleton pregnancies were independently ascertained and identified as showing fetal echogenic bowel (FEB) at 16-20 weeks’ gestation. Those doing the ultrasound examination were unaware of the family history, previous pregnancy outcome, or current pregnancy abnormalities. In those pregnancies identified with FEB, sonodensity was quantified as follows. A contiguous view of the fetal abdomen including the brightest area of fetal bowel and the fetal iliac crest was generated. The ultrasonic overall time gain setting was reduced such that fetal bowel sonodensity could be compared with the density of fetal iliac crest. All studies were performed on one of two machines-an Acuson 128XP/10 OB (Mountain View, CA) or an ATL Ultramark 9/HDi (Bothell, WA) with curvilinear 3-5 or 5-0 MHz probes. Transvaginal studies were not included. Six different ultrasonographers were involved in the initial sonographic evaluations. Normal fetal bowel was arbitrarily assigned a score of 0. Sonodense fetal bowel which became unidentifiable before the loss of iliac crest image was assigned a score of 1. Sonodense fetal bowel whose image was lost at the same gain reduction as iliac crest was assigned a score of 2. Gain reduced images where iliac crest was lost before bowel image were awarded a score of 3 (figure). The scores were assigned by an ultrasonographer and confirmed by another ultrasonographer and a physician. Pedigree analysis and nondirective genetic counselling were offered to each patient/couple ascertained with FEB more than 0. Couples were also given access to parental carrier testing for CF
85
Table: Fetal
echogenic bowel: categories and
results
given cause for concern-in 4 because of recent vaginal bleeding, in 1 a serum alpha-fetoprotein (AFP) 2-5-3-0 multiples of the median (MoM), in 2 both vaginal bleeding and a raised AFP, and in 1 a positive rapid plasma reagin test. 21 couples accepted parental CF testing and 19 declined. No two-carrier partnerships were found. Amniocentesis was performed in 14 pregnancies, normal karyotypes being found in all. 26 couples declined had
Figure: Transverse sonographic image of fetal showing fetal echogenic bowel.
abdomen at 17
weeks
Bowel indicated by single arrow, iliac crest by curved homozygous for AF 508.
arrow.
Fetus
was
and to genetic amniocentesis, on the understanding that CF carrier testing would have a false-negative rate of 17%. Carrier testing was performed by the standard mutation and/or deletion analysis. (The procedure was confined to white couples of European extraction, since little is known of CF gene frequencies in other population groups.) 12, and later 17, different mutations/deletions were studied at both commercial and academic institutions. When both partners were identified as carriers, CF testing on the fetus was offered, the risk of procedure related miscarriage being quoted as 1 in 200. Neonatal follow-up was performed by chart review or by telephone, with special attention to prematurity, operative delivery, neonatal or infant hospital admissions, obvious anatomical defects, breathing difficulties, recurrent pulmonary infections, and parental appreciation of paediatric concerns. This project was presented to and approved by our departmental/divisional research committee. Patients were informed of the project’s experimental nature and its deviation from routine practice during their
genetic counselling
session.
Results Of the 145 fetuses with echogenic bowel 40 (27%) had grade 1, 81 (56%) had grade 2, and 24 (17%) had grade 3. In all but 2 cases the parents accepted genetic counselling and/or pedigree analysis. In 60 cases there
noteworthy family history of CF, but in only 5 was there an unambiguous history of a child born with CF, neonatal death, neonatal bowel obstruction, or neonatal meconium ileus or peritonitis. Prenatal diagnostic testing (parental CF carrier status, or amniocentesis for karyotype or fetal CF status or both) was done in 76 cases. In 10 cases parents declined the tests for reasons of cost. Follow-up to 4 months was completed in 83% of the total. was a
FEB 1 Of the 40 fetuses with FEB 1 (table), none showed abnormalities. Nor, on interview, were there any reasons to suspect increased risk of CF. In 8 cases the pregnancy 86
amniocentesis. Information on births and follow-up was available for all but 7 pregnancies. 2 women had had premature deliveries, and one of the infants had developed bronchopulmonary dysplasia. 6 women had given birth by caesarean section. In none of the 33 pregnancies for which we have information was the child born with CF or
karyotypic aneuploidy. FEB 2 FEB 2 was found in 81 pregnancies, and 79 patients were counselled. 2 women had an obstetric history suggestive of CF (neonatal death, neonatal bowel obstruction of unknown aetiology); and 1 patient was herself a CF homozygote (AF 508). In 14 women a raised AFP had been recorded (2-5-3-1 MoM). 24 couples were tested for parental CF carrier status. 4 couples had both partners heterozygous for the AF 508 deletion, and a homozygous affected fetus was found by amniocentesis in 2. Both CF pregnancies were carried to term. Altogether, amniocentesis was performed in 27 pregnancies and declined in 54. Trisomy 21 was diagnosed in 2 fetuses: one had a thickened nuchal fold on ultrasound, the other had no identifiable abnormality apart from the echogenic bowel. These pregnancies were carried to term. Neonatal and infant follow-up is available for 79 pregnancies. In 3 delivery was at less than 37 weeks; 15 patients gave birth by caesarean section. No abnormalities have been recorded, except in the 4 babies diagnosed antenatally as having CF or trisomy-21. FEB 3 24 pregnancies were scored FEB 3, and on counselling a familial risk was elicited in 2. One couple already had a child with CF, so the a-priori risk was 25%. Another woman had given birth two years before to a child with antenatal volvulus who had died from surgical complications two weeks after delivery; review of the pathology disclosed pancreatic duct inspissation and other
evidence of cystic fibrosis. 2
women
had had
a
raised AFP
(2-5-3-0 MoM). In 6 pregnancies
revealed ultrasound studies abnormalities other than echogenic bowel. 4 fetuses had either cystic hygroma or increased nuchal thickness (>6 mm). 2 patients had oligohydramnios. CF carrier testing was done in 13 of the 24 parental pairs and 3 double-carrier couples were identified, two pairs with AF 508 deletions and one pair with AF 508 and R 117. Each of these 3 pregnancies was shown by amniocentesis to be affected by CF. A total of 12 women had amniocentesis (12 declined) and 5 fetuses proved to have trisomy-21. 3 of the 5 aneuploid fetuses in the amniocentesis had associated sonographic group abnormalities-nuchal thickening, oligohydramnios, or both. Pregnancy and neonatal follow-up information is available for 22 of the 24 patients in the FEB 3 group. Of the 12 couples declining parental CF carrier testing and amniocentesis, 2 had infants with cystic fibrosis (diagnosed by sweat test) and 1 had a fetal death in the second trimister with proven trisomy-21 (this fetus had been noted to have a large cystic hygroma at 17 weeks). All 5 trisomy 21 pregnancies with FEB 3 were either lost or terminated.
Follow-up
might be the biophysical correlate of bowel sonographic echogenicity? Several groups have argued that intraluminal content (eg, meconium) provides the "sonodensity", but proof remains unestablished. It seems just as reasonable that bowel echogenicity in the second trimester might result from inspissated secretion within What
the bowel wall. Each
of increased second trimester bowel echogenicity, even those cases of CF, showed a subsequent decrease in FEB grade. This change might represent release of inspissated material into bowel lumen. Pathological confirmation on fetal post-mortem specimens would be instructive. Two reports’3,’ have suggested an association between increased fetal bowel and intra-amniotic echogenicity cytomegalovirus infection. Viral cultures on stored amniotic fluid specimens from our series of patients are now being prepared for study. As a result of the findings reported here, we now offer genetic counselling, parental carrier testing, and amniocentesis for karyotype to patients in whom a fetus with FEB 2 or 3 is identified in the middle trimester. If carrier studies are informative for both partners, then amniocyte DNA studies can then be initiated. References 1 Dicke JM, Crane JP. Sonographically detected hyperechoic fetal bowel: significance and implications for pregnancy management. Obstet 2
When CF was diagnosed antenatally, paediatricians were consulted. All these pregnancies were carried to term. In one, meconium peritonitis was suspected from ultrasound appearances in the third trimester. All have done well, requiring only short hospital admissions for pulmonary infections; the compound heterozygote (AF 508/R 117) in this group has required only pancreatic enzyme
3
4
5
supplements. 35 of the FEB 2 and 3 pregnancies were sonographically re-examined at 22-26 weeks, 4-6 weeks after the initial study. In every case, including 4 with CF, the score was
lower.
Discussion
perception of risk for a genetic or obstetric diagnosis depends in large part on the evaluator. As a rule, the condition will not be diagnosed until it is thought of. In both trisomy-21 and CF, ultrasound observations can usefully stimulate further investigations. Because the human eye is notoriously unreliable in evaluating echogenicity,8 several investigators have compared density perceptions between tissues"’" or have devised mathematical models for quantifying sonodensity.12 In our study we employed an independent internal sonographic standard (the fetal iliac crest) as a simpler and more reproduceable method that would allow interpatient comparisons. A weakness of the paper is that we did not formally study interobserver variation, though informally there was little disagreement between observers.
case
6
7
8
The
9
10
11 12
13
14
Gynecol 1992; 80: 778-82. Nyberg DA, Dubinsky T, Resta RG, Mahony BS, Hickock DE, Luthy DA. Echogenic fetal bowel in the second trimester: clinical importance. Radiology 1993; 188: 527-31. Sciosca Al, Pretorius DH, Budorick NE, Cahill TC, Axelrod F, Leopold GR. Second trimester echogenic bowel and chromosomal abnormalities. Am J Obstet Gynecol 1992 167: 889-94. Caspi B, Elchalal M, Lancet M, Chamke J. Prenatal diagnosis of cystic fibrosis: ultrasonographic appearance of meconium ileus in the fetus. Prenat Diagn 1988; 8: 379-82. Chalubinski K, Deutinger J, Bernaschek G. Meconium peritonitis: extrusion of meconium and different sonographical appearance in relation to the stage of the disease. Prenat Diagn 1992; 12: 631-36. Caspi B, Blickstein I, Appelman Z. The accuracy of the assessment of normal fetal intestinal echogenicity. Electro-optical densitometry versus the ultrasonographer’s eye. Gynecol Obstet Invest 1992; 33: 26. Blickstein I, Goldman R. The relation between different system gain settings and the accuracy of densitometric assessment of echogenicity. J Ultrasound Med 1994; 13: 675-78. Boat T, Welsh M, Beaudet AL. Cystic fibrosis. In: Scriver C, Beaudet AL, Sly W, Valle D, eds. The metabolic basis of inherited disease. New York: McGraw-Hill, 1989: 2649-60. Beaudet AL, Kazazaian HJ Jr, Bowman JE. Statements from the National Institutes of Health Workshop on Population screening for the Cystic Fibrosis Gene. N Engl J Med 1990; 323: 70-71 Nyberg DA, Resta RG, Luthy DA, Hickock DE, Mahony BS, Hirsch JH. Prenatal sonographic findings of Down syndrome: review of 95 cases. Obstet Gynecol 1990; 76: 370-77. Platt JF, Rubin JM, Bowerman RA, et al. The inability to detect kidney disease on the basis of echogenicity. AJR 1988; 151: 317. Blickstein I. Quantitative assessment of sonographic image echogenicity by transmission densitometry: fetal liver model. J Ultrasound Med 1993; 12: 567-71. Forouzan I. Fetal abdominal echogenic mass: an early sign of intrauterine cytomegalovirus infection. Obstet Gynecol 1992; 80: 535-37. Weiner CP, Grose CF, Naides SJ. Diagnosis of fetal infection in the patient with an ultrasonographically detected abnormality but a negative clinical history. Am J Obstet Gynecol 1993; 68: 6-11.
87