First-trimester diagnosis of cystic hygroma—Course and outcome

First-trimester diagnosis of cystic hygroma-Course and outcome Rieteke M. van Zalen-Sprock, MD, John M.G. van Vugt, MD, PhD, and Herman P. van Geijn, MD, PhD Amsterdam, The Netherlands OBJECTIVE: We studied the outcomes of fetuses in whom cystic hygroma was diagnosed in the first trimester of pregnancy through the application of transvaginal ultrasonography. STUDY DESIGN: In the period 1990 to 1991 22 fetuses with cystic hygroma were found. All fetuses had karyotyping and a complete ultrasonographic search for associated anomalies. RESULTS: Aneuploidy was found in seven of 22 fetuses: four trisomy 21 , two trisomy 18, and one translocation. Monosomy X was absent in this series. In 15 of 22 cases there was a normal karyotype. In 10 of 15 euploid fetuses the small nonseptated hygroma resolved spontaneously. In four of 15 euploid fetuses other malformations were detected with ultrasonography (i.e., polycystic kidneys, coarctation of the aorta, bladder outlet obstruction, and fetal hydrops). CONCLUSION: Whenever a cystic hygroma is suspected in the antenatal period, even if of small size, a structured and detailed ultrasonographic examination and fetal karyotyping are recommended . (AM J OasTET GVNECOL 1992;167:94-8.)

Key words: Cystic hygroma, nuchal structures, transvaginal ultrasonography, first-trimester diagnosis, aneuploidy

High-frequency ultrasonography, especially through transvaginal application, allows early detection of fetal anomalies . Diagnosis in the first trimester of pregnancy has been reported for several fetal defects (e.g., gastroschisis, omphalocele, spina bifid a, and cystic hygroma) .'" Other anomalies such as omphalocele cannot always be definitely diagnosed in the first trimester of pregnancy. Protrusion of fetal intestines anterior to the abdominal wall may reRect normal physiologic herniation. 4 Although cystic hygromas are commonly found in first trimester abortuses,S the incidence at birth is rare (l/6000).' The introduction of transvaginal ultrasonography has dramatically increased the frequency of detection of first trimester cystic hygromas. Association of cystic hygromas with other structural defects and chromosomal abnormalities has been reported , although, on the other hand, regression of the hygroma has been observed with a good neonatal outcome.'. 6 This report describes the outcome of 22 fetuses with cystic hygroma diagnosed in the first trimester of pregnancy. From the Division of Maternal-Fetal M edicine and Prenatal Diagnosis, Department of Obstetrics and Gynecology, Free University H ospital. R eceivedforpublicalionJuly 11 , 1991 ; revised N ovember 11,1991 ; accepted December 30, 1991 . R epTint requests: M.M. van Zalen-Sprock, MD, Division of Maternal-Fetal Medicine and Prenatal Diagnosis, Department of Obslretrics and Gynecology, Free University Hospital, De Boelelaan 1117, Postbox 7057, 1007 MB Amsterdam, The N etherlands. 611136407

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Fig. 1. Longitudinal view of small nonseptated hygroma (arrows) in fetus with normal karyotype.

Subjects and methods Ultrasonographic scans were performed with a 5.0 or 7.5 MHz transvaginal sector scanner (Acuson 128, Mountain View, Calif.). In each case ultrasonographic examination was done for obstetric reasons such as pregnancy dating or vaginal blood loss. Cystic hygromas, which originated in the soft tissue with an intact skull and spinal column, were identified as single or multiloculated, fluid-filled cavities in the lateral or pos-

First-trimester diagnosis of cystic hygroma 95

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Table I. Outcome of fetuses with cystic hygromas Gestational age IO

12 wk 2 days 12 wk 3 days 13 13 13 13wk3days 13 wk 3 days 14 15 wk 2 days 12 wk 3 days 10 wk I day 13 wk 3 days 14 wk 3 days 15 wk 2 days 10 wk 5 days 12 wk 5 days 13 wk 5 days 15 wk 5 days 12 wk 5 days 15 wk 5 days 12 wk 6 days

Karyotype

46,XY 46,XX 46,XY 46,XY 46,XY 46,XX 46,XY 46,XY 46,XX 46,XX 46,XX 46,XY 46,XY 46,XY 46,XX 47,XY,+21 47,XX,+21 47,XX,+21 47,XX,+21 47,XY,+ 18 47,XX,+ 18 45,X, - 15, + der(l5) + t(Y; 15)

+ + +

Associated anomalies

Outcome

+* +t

Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Noonan's syndrome Termination of pregnancy Termination of pregnancy Termination of pregnancy Termination of pregnancy Termination of pregnancy Termination of pregnancy Termination of pregnancy Termination of pregnancy Termination of pregnancy Termination of pregnancy Termination of pregnancy

+t +§

+ + +

+11

H

*Cardiac anomaly. tPolycystic kidneys. tUrethral stenosis with large bladder. §Hydrops. This patient had a previous child with a large cystic hygroma; an autosomal recessive type of cystic hygroma may be considered. IIOmphalocele and clubbed feet. ~Omphalocele.

terior cervical region. They all measured >3 mm in diameter and were either septated or nonseptated. 7 Whenever a cystic hygroma was suspected, a careful search for associated malformations was performed. 8- 1O Karyotype analysis was available from all patients through either chorionic villus (four transcervical, 16 transabdominal) or amniotic fluid (two) sampling. Autopsy was performed in all cases of elective abortion. In cases of small nonseptated cystic hygromas with a normal karyotype the patients had regular weekly ultrasonographic controls until the anatomic finding had resolved. An ultrasonographic examination was performed to detect or exclude additional (cardiac) anomalies at 16 to 18, 22 to 24, and 31 to 32 weeks of pregnancy. Results

The malformations were detected in all 22 cases between 10 and 16 weeks of gestation, as listed in Table 1. The mean gestational age at detection was 13.1 weeks (SD ± 1.6 weeks). Chromosome analysis was available from all 22 cases; seven fetuses (32%) had an abnormal and 15 fetuses (68%) a normal karyotype. In 10 of the euploid cases (67%) the posterior nonseptated hygromas could no longer be detected with ultrasonography after 16 weeks of gestation, and no signs of a distur-

bance in lymphatic drainage or other nuchal malformations such as webbed neck could be detected after birth (Fig. 1). Two of these fetuses had a single umbilical artery. Both infants were born at term and did not show any morphologic abnormality. In four euploid fetuses associated malformations were detected. One fetus had a cardiac anomaly, consisting of a small atrial and ventricular septal defect and a coarctation of the aorta, detected in the third trimester of pregnancy and confirmed after delivery. In this case the hygroma was partially absorbed. The ultrasonographic appearance changed during pregnancy from a translucent structure to a thick echogenic nuchal fold. The child was born with a webbed neck. Noonan's syndrome was considered, although the cardiac anomaly originally described with this single gene disorder consists of pulmonary stenosis. One pregnancy with a euploid fetus in which the hygroma had resolved showed later on severe oligohydramnios. At 22 weeks polycystic kidneys and absence of bladder filling were detected. The malformations in the third fetus consisted of bladder outlet obstruction and deformation of the legs. In the fourth case there was a serious progressive septated hygroma in the neck and axillary region in association with fetal hydrops. One pregnancy with a euploid fetus was terminated on the patient's request. Septation of the hygroma was found in six of 22

96

van Zalen-Sprock, van Vugt, and van Geijn

Fig. 2. Large sonolucent hygroma

July 1992 Am J Obstet Gynecol

(arrows)

in fetus with trisomy 18. C, Caput.

terior in the neck area (Fig. 2). In one case the malformation was lateral in the cervical region. Trisomy 21 was diagnosed (Fig. 3). All pregnancies with abnormal karyotypes (seven cases) were electively aborted as were four euploid pregnancies, three because of the associated anomalies and one because of serious mental instability in the mother. Autopsy results were available from all terminated pregnancies. The small nonseptated hygromas ultrasonographically detected in four of the seven aneuploid cases could not be identified by the pathologist at autopsy, probably due to lytic processes of the fetal material. The septated hygromas could all be identified by the pathologist at autopsy. Comment

Fig. 3. Transverse scan through cervical spine (S), with lateral localized translucent cysts (arrows) in fetus with trisomy 21.

fetuses, whereas 16 of 22 were nonseptated. Three fetuses with a septated hygroma had aneuploidy and two fetuses had a normal karyotype but demonstrated associated anomalies. One fetus with a septated hygroma was euploid and had no associated malformations. Of the 16 cases with a nonseptated hygroma four were aneuploid (one with associated anomalies), two had associated anomalies with a normal karyotype, and 10 fetuses were euploid and showed no other malformations. In 21 of the 22 cases the hygroma was located pos-

Fetal cystic hygromas are congenital malformations of the lymphatic system manifested as single or multiloculated fluid-filled cavities in the neck region. The posterior or lateral position and cystic appearance are characteristic." The lymphatic vessels normally drain into two large sacs lateral to the jugular vein. 12 In case of a defect in the formation of the lymphatic vessels, the jugular sacs enlarge and lymph accumulates in tissues. The hygroma may regress and resolve if collateral routes develop or the jugular veins connect. 13.14 Larger hygromas are often divided by a midline septum in the nuchal region. Extension to the fetal skull may be present. This feature has to be differentiated from other craniocervical masses such as encephalocele or meningomyelocele, teratoma, hemangiomas, and familial nuchal bleb."·l7 Furthermore, one should be aware of diagnostic errors, i.e., a segment of the umbilical cord behind the neck, prominent fetal hair (later in pregnancy), an adjacent subchorionic cyst, or a part of the amnion not yet merged with the chorion in the first

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trimester. Cystic structures in the neck region have been described in various sizes. Cullen et al.' refer to nuchal blebs if the size is <3 mm. In that case the cystic structure is always nonseptated and disappears before the eleventh week. If a small cystic hygroma in the nuchal region has been detected there is also the possibility of a pseudomembrane, 18 especially when the suspected structure is not found in follow-up sonograms. Either the small cystic hygroma has absorbed or a dorsal specular reflection originating from the surface of the skin had been identified during the first examination. Larger hygromas have often been described as caused by Turner's syndrome. 19 Besides monosomy X, which is often associated with generalized edema and coarctation of the aorta, several other chromosomal disorders have been reported, such as trisomy 21, 18, and 13.'°·21 All these syndromes have a low recurrence risk. Other syndromes with a normal karyotype such as familial pterygium colli, Robert's syndrome, and Noonan's syndrome have been described with cystic hygromaY' 22. 23 The main features of Noonan's syndrome are very similar to monosomy X but are easily distinguished after birth facially, cytogenetically, and gonadally. Noonan's syndrome is often associated with hypertelorism, ptosis, dental malocclusion, lowset ears, broad nasal base, webbed neck, and low posterior hairline, and the affected children have normal ovaries 46,XX, or testis 46,XY. The associated congenital heart disease in Noonan's syndrome usually consists of pulmonary stenosis. This syndrome is caused by a single gene disorder and has a recurrence risk that may be much higher than in Turner's syndrome; it has a familial predilection and is probably transmitted in an autosomal dominant manner with incomplete penetrance. An extensive ultrasonographic examination is still the diagnostic choice in future pregnancies.'4 In the current series monosomy X was not diagnosed. Several authors describe 50% association of Turner's syndrome with cystic hygroma. It always concerned large septated cystic hygromas, often in combination with fetal hydrops. Transvaginal application and modern high-resolution equipment makes it possible to visualize smaller cystic hygromas early in pregnancy, structures often not detectable with abdominal ultrasonography. More embyros and fetuses will be identified with a cystic hygroma in the first trimester of pregnancy than before. Early detection enlarges the group with these findings drastically. Cytogenetic analysis on villus material obtained from retained abortions in the first trimester revealed an abnormal chromosome constitution in 77%.'5 The relative proportion of chromosome abnormalities in retained abortions is higher for trisomies (61 %) than for 4S,XO (7.5%).25 This eighttimes-higher proportion may explain the absence of a monosomy X in our series.

First-trimester diagnosis of cystic hygroma 97

Not all pregnant women have an ultrasonographic examination in the first or early second trimester of pregnancy. A cystic hygroma may have resolved if the sonogram is made in the second or third trimester. It is possible that some cases of Down syndrome obvious at birth could have been diagnosed early in pregnancy if the nuchal region had been inspected ultrasonographically in the first trimester. Hygromas can also be associated with trisomy 18 or 13, but the majority of these cases will be detected by ultrasonography either in the first trimester or later in pregnancy because of associated anomalies. In most of these cases the diagnosis can be suspected prenatally and confirmed by chromosome analysis. In conclusion, the following recommendations can be made. A close look at the nuchal region should be part of every thorough investigation for congenital anomalies, especially in the first trimester. The finding-even if of limited size-has to be followed by a detailed ultrasonographic examination, and fetal karyotyping should be offered.? In case of euploidy and a resolving cystic hygroma, or if the aspect of the hygroma changes during pregnancy, a close look for cardiac anomalies is advisable. We thank Nico Leschot, MD, PhD, Institute of Anthropogenetics, University of Amsterdam, for the chromosome analysis done at his institute; Hans van der Harten, MD, PhD, Department of Pathology, Free University Amsterdam, for the autopsy results; and Veronique Karsdorp, MD, Marianne Cortenraad, MD, Sacha Amitai, and Joke van der Ouderaa for their contributions in the ultrasonographic examinations. REFERENCES

1. Guzman ER. Early prenatal diagnosis of gastroschisis with transvaginal ultrasonography. AM J OBSTET GYNECOL 1990; 162: 1253-4. 2. Rottem S, Bronshtein M. Transvaginal sonographic diagnosis of congenital anomalies between 9 weeks and 16 weeks, menstrual age. JCU 1990;18:307-14. 3. Cullen MT, Gabrielli S, Green JJ, et al. Diagnosis and significance of cystic hygroma in the first trimester. Prenat Diagn 1990;10:643-51. 4. Timor-Tritsch IE, Warren WB, Peisner DB, Pirrone E. First trimester midgut herniation: a high frequency transvaginal sonographic study. AM J OBSTET GYNECOL 1989;161:831-3. 5. Byrne J, Blanc WA, Warburton D, Wigger J. The significance of cystic hygroma in fetuses. Hum Pathol 1984;15:61-7. 6. Bernstein HS, Filly RA, Goldberg JD, Golbus MS. Prognosis of fetuses with a cystic hygroma. Pre nat Diagn 1991; II :349-55. 7. Bronshtein M, Rottem S, Yoffe N, Blumenfeld Z. First trimester and early second trimester diagnosis of nuchal cystic hygroma by transvaginal sonography: diverse prognosis of the septated from the nonseptated lesion. AM J OBSTET GYNECOL 1989;161:78-82. 8. Van Zalen-Sprock MM, van Vugt JMG, Karsdorp VHM, Maas R, van Geijn HP. Ultrasound diagnosis of fetal abnormalities and cytogenetical evaluation. Prenat Diagn 1991; 11 :655-60. 9. Palmer CG, Miles JH, Howard-Peebles PN, Magenis RE,

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Patil S, Friedman ]M. Fetal karyotype following ascertainment of fetal anomalies by ultrasound. Prenat Diagn 1987;7:551-5. Rizzo N, Pittalis MC, Pilu G, Orsini LF, Perolo A, Bovicelli L. Prenatal karyotyping in malformed fetuses. Pre nat Diagn 1990;10:17-23. Chervenak FA, Isaacson G, Blakemore K], et a1. Fetal cystic hygroma, cause and natural history. N Engl] Med 1983;309:822-5. Moore KL. The developing human. ed 3. Philadelphia. WB Saunders, 1982:339-41. Chodirker BN, Harman CR, Greenberg CR. Spontaneous resolution of a cystic hygroma in a fetus with Turner syndrome. Prenat Diagn 1988;8:291-6. Baccichetti C, Lenzini E, Suma V, Benini F, Marini A. Spontaneous resolution of cystic hygroma in a 46,XX normal female. Prenat Diagn 1990;10:399-403. Watson W], Thorp ]M, Seeds ]W. Familial cystic hygroma with normal karyotype. Prenat Diagn 1990;10:37-40. Grundy H, Glasmann A, Burlbaw], Walton S, Danner C, Doan L. Hemangioma presenting as a cystic mass in the fetal neck.] Ultrasound Med 1985;4: 147-50. Pearce ]M, Griffin D, Campbell S. The differential prenatal diagnosis of cystic hygromata and encephalocele by ultrasound examination. ]CU 1985; 13:317-20.

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18. Hertzberg BS, Bowie ]D, Carroll BS, Killam AP, Ruiz P. Normal sonographic appearance of the fetal neck late in the first trimester: the pseudomembrane. Radiology 1989; 171 :427-9. 19. Exalto N, van Zalen RM, van Brandenburg]A. Early prenatal diagnosis of cystic hygroma by real-time ultrasound. ]CU 1985;13:655-8. 20. Redford DHA, McNay MA, Ferguson-Smith ME, ]amieson ME. Aneuploidy and cystic hygroma detectable by ultrasound. Prenat Diagn 1984;4:377-82. 21. Benacerraf BR, Miller WA, Frigoletto FD ] r. Sonographic detection of fetuses with trisomies 13 and 18: accuracy and limitations. AM] OBSTET GYNECOL 1988;158:404-9. 22. Graham ]D, Stephens TD, Shepard TH. Nuchal cystic hygroma in a fetus with presumed Roberts' syndrome. Am] Med Gen 1983;15:163-7. 23. Zarabi M, Mieckowski GC, Mazer J. Cystic hygroma associated with Noonan's syndrome. ]CU 1983; 11 :398-400. 24. Noonan ]A, Ehmke DA. Associated noncardiac malformations in children with congenital heart disease. Pediatrics 1963;63:468-9. 25. Guerneri S, Bettio D, Simoni G, Brambati B, Lanzani A, Fraccaro M. Prevalence and distribution of chromosome abnormalities in a sample of first trimester internal abortions. Hum Reprod 1987;2:735-9.

Baking powder pica mimicking preeclampsia John R. Barton, MD,. Caroline A. Riely, MD: and Baha M. Sibai, MD" Memphis, Tennessee We report a case of baking powder pica during pregnancy that was associated with maternal hypertension, hypokalemia, and elevated liver function tests. After discontinuation of baking powder ingestion and correction of electrolyte abnormalities, the blood pressure and the liver function tests normalized. (AM J CasTET GVNECOL 1992;167:98-9.)

Key words: Pica, preeclampsia. pregnancy Pica is an eating disorder manifested by the abnormal desire to ingest substances not generally considered for normal consumption. Previous investigations of the association of pica and toxemia of pregnancy noted a significant correlation with geophagia but not amylophagia. 1 Presented is a report of a woman who, while consuming large quantities of baking powder during

From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology: and the Department of Medicine,! University of Tennessee, Memphis. Received for publication January 13,1992; accepted February 18,

1992. Reprint requests: John B. Barton, MD, Antenatal Diagnostic Division, Central Baptist Hospital, 1740 Nicholasville Road, Lexington, KY 40503. 611 /37254

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her pregnancy, developed hypertension, hypokalemia, and elevated liver function tests.

Case report A 23-year-old black woman, gravida 3, para 2, was seen at 19.5 weeks' gestation with a 3-day history of headaches, dizziness, nausea, and vomiting. Blood pressure was 144/90 mm Hg with a first-trimester blood pressure of 110/50 mm Hg. Laboratory data included serum aspartate aminotransferase 144 U 1L. lactic dehydrogenase 359 U fL, platelet count 226,000Imm', hematocrit 21.8%, and serum potassium 3.1 mEq/L. A urine drug screen was negative. During hospitalization, after transfusion of packed red blood cells for anemia and correction of hypokalemia, the blood pressure and liver function tests normalized. The patient was discharged home, but on a return clinic