Tohoku J. Exp. Med., 2007, 213, 291-295Cloacal-VATER Spectrum 291

Prenatal Diagnosis of Persistent Cloaca Associated with VATER (Vertebral Defects, Anal Atresia, Tracheo- Esophageal Fistula, and Renal Dysplasia)

1 1 1 1 MIKI MORI, KEIICHI MATSUBARA, EMIKO ABE, YUKO MATSUBARA, 1 1 1 1 TOMIHIRO KATAYAMA, TORU FUJIOKA, YASUKI KUSANAGI and MASAHARU ITO

1Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine, Toon, Japan

MORI, M., MATSUBARA, K., ABE, E., MATSUBARA, Y., KATAYAMA, T., FUJIOKA, T., KUSANAGI, Y. and ITO, M. Prenatal Diagnosis of Persistent Cloaca Associated with VATER (Vertebral Defects, Anal Atresia, Tracheo-Esophageal Fistula, and Renal Dysplasia). Tohoku J. Exp. Med., 2007, 213 (4), 291-295 ── The cloaca is a single canal from which the urinary, genital, and intestinal tracts arise around gestational weeks 5-6. Persistent cloaca can result from cystic mass formation within the pelvis, which is commonly associ- ation with multiple developmental defects. VATER association, which is a spectrum of anomalies, manifested by vertebral defects, anal atresia, tracheo-esophageal fi stula with esophageal atresia, and renal dysplasia, arises from abnormalities in mesodermal differen- tiation. Recently, both conditions have been proposed to represent a continuous spectrum of anomalies, but the pathophysiology concerning the continuity of the development and the clinical condition are still unclear. Since renal failure becomes a serious problem after birth, timely infant delivery is essential to avoid loss of renal function. We report a patient, in whom the overlap between these two conditions was identifi ed, and renal function was lost from one kidney. A polycystic mass was found in the fetal abdomen at 26 weeks of gestation. By ultrasonography, we detected a polycystic left kidney, a single umbilical artery, a ventricular septal defect, an esophageal atresia, ascites, an anal atresia, and a cys- tic mass with debris behind the bladder. The left kidney was non-functioning and the right kidney showed signs of hydronephrosis at 30 weeks of gestation. We measured the size and the blood fl ow of renal artery sequentially, and could deliver the fetus before the func- tion was lost from the right kidney. Our observations will help inform future patients where prompt intervention can help improve renal function and infant health. ──── persistent cloaca; prenatal diagnosis; renal function; ultrasonography; VATER association © 2007 Tohoku University Medical Press

The cloaca is a single canal from which the plex anatomical abnormalities (Hendren 1992). urinary, genital, and intestinal tracts arise around Cloacal abnormalities are relatively rare with an gestational weeks 5-6. Developmental defects in overall incidence of 1 in 50,000 neonates (Pena septum formation lead to persistent cloaca, a con- 1989), and can be detected by prenatal ultraso- dition associated with a wide spectrum of com- nography as abnormalities in fetal ascites, cystic Received July 20, 2007; revision accepted for publication October 13, 2007. Correspondence: Keiichi Matsubara, Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan. e-mail: [email protected] 291 292 M. Mori et al. structures within the fetal pelvis including debris, hydronephrosis at 30 weeks gestation, which a poorly visualized fetal bladder, hydronephrosis, worsened during the course of pregnancy. The and reductions in amniotic fl uid (Warene et al. pelvic cyst size had increased to a volume of 9.8 2002). × 8.2 × 6.2 cm by 36 weeks gestation. VATER association (vertebral abnormality, Because the right hydronephrosis had wors- anal atresia, tracheo-esophageal fi stula with ened substantially, the baby was delivered at 36 esophageal atresia, and renal dysplasia) arises weeks of gestation by caesarean section. The from abnormalities in mesodermal differentiation infant weighed 2,414 g and measured 43 cm in and is defi ned a combination of three or more length at birth. Her Apgar scores were 6 at 1 min major malformations such as a vertebral abnor- and 9 at 5 min post-delivery. The infant was intu- mality, imperforate anus, esophageal atresia with bated because of dyspnea caused by abdominal tracheoesophageal fi stula, radial dysplasia, renal distension. Computed tomography confi rmed dysplasia, and vascular malformation (Quan and esophageal atresia with tracheoesophageal fi stula, Smith 1973; Barry and Auldist 1974). These con- right hydronephrosis (grade 2-3), a non-function- ditions result from dysmorphogenic events affect- ing left kidney, and persistent cloaca. Also, post- ing the craniocaudal region of the embryo. While natal ultrasonography confi rmed the presence of a VATER association is not life-threatening, renal VSD. failure is a common and severe complication of The tracheoesophageal fi stula was repaired this condition. Careful prenatal diagnosis using and a defunctioning transverse colostomy was ultrasonography and sequential observation of performed 12 hrs after birth. Approximately 140 renal function is important for ensuring infant ml of cloudy urine was drained by urethral cathe- health. ter, leading to disappearance of the pelvic cyst. Urethrocystography revealed a single perineal/ CLINICAL FINDINGS OF A PATIENT anal opening that drained into a common cloaca, A 27-year-old primigravid woman was as well as the lack an anus suggesting hydrocol- referred to our clinic for investigation of a poly- pos. Intestinal barium examination showed a rec- cystic left kidney detected within the fetus at 26 tal fi stula ending in the urogenital sinus with no weeks gestation. Ultrasonography (SSD-5500SV; vesicoureteric refl ux. Three weeks after delivery, ALOKA CO., Tokyo) revealed a polycystic left the baby was discharged. kidney, a single umbilical artery, a ventricular septal defect (VSD), an esophageal atresia, ascites DISCUSSION pooling with debris, an anal atresia, and a cystic During embryogenesis, urorectal septal for- mass measuring 3.5 × 2.6 × 1.5 cm, with debris mation occurs around the same time that VATER behind the bladder (Fig. 1). Amniocentesis was association develops. Axial mesodermal dyspla- performed, and the karyotype was normal (46XX). sia spectrum (AMDS) is thought to arise as a con- Viral infection screening was negative and there sequence of aberrant mesodermal migration dur- was no evidence of diabetes mellitus. At 29 ing early development, resulting in bronchial, weeks of gestation, ultrasonography revealed pulmonary, cardiovascular, gastrointestinal, renal, deformation of the thumb and polyhydramnion. urogenital and skeletal abnormalities (Russell et On the basis of all these characteristics, VATER al. 1981). Both cloacal malformation and VATER association was suspected. association are likely to be associated with The left kidney was suspected to be nonfunc- AMDS, as they are among the continuous spec- tioning since the renal arterial blood fl ow was sig- trum of AMDS anomalies (Henmi et al. 2000). nifi cantly reduced, and kidney size gradually Consistent with this hypothesis, Liu and Hutson decreased during the course of pregnancy. In (2000) showed in an adriamycin-induced rat contrast, the right kidney, which was normal dur- model of cloacal and urogenital anomalies, simi- ing the fi rst visit to our clinic, showed signs of larities to VATER association. Taken together, Cloacal-VATER Spectrum 293

Fig. 1. Prenatal ultrasound image of the fetus at 26 weeks of gestation. Gastrointestinal and urogenital abnormalities were found. a) imperforate anus (arrow) behind the vagina (V), b) ascites, c) pelvic cystic mass (C) with debris behind the bladder (B), d) polycystic left kidney. Also shown are ex- planatory drawings. 294 M. Mori et al. our patient could be diagnosed as a combination diagnosed failure of the left kidney. During the of an intermediate form of the cloacal-VATER fi rst visit to our outpatient, the size and morpholo- spectrum, although details of the internal genitalia gy of the right kidney, as well as arterial blood were unclear. Prenatal diagnosis of this spectrum fl ow, appeared normal. However, right kidney by ultrasonography is important and could reveal became polycystic and the size increased during cardiac anomalies, imperforate anus, as well as pregnancy. While determining the appropriate vertebral anomalies. Esophageal atresia with tra- time for infant delivery can be diffi cult, when cheoesophageal fi stula is diffi cult to diagnose pre- fetal renal failure is predicted and the estimated nataly. However, magnetic resonance imaging fetal body weight is suffi cient to support survival (MRI) may be used to detect these anomalies outside of uterus, early delivery is essential. In (Goldberg et al. 2006). Pelvic cysts and debris addition, measurement of the amount of urine are typical features of persistent cloaca, and ultra- production and the Creatinine concentration in the sonography and MRI can be used to diagnose amnion are effective methods for monitoring fetal persistent cloaca. renal function. Functional studies of the bowel, genital, and Early diagnosis and treatment can lead to urinary tracts have been scarce historically. near normal urogenital and digestive function. If However, recent technological advances have hydronephrosis exists, hydrocolpos must be ruled improved the ease with which these results can be out before performing an ureterostomy or a neph- collected from most patients (Hendren 1992). rostomy, as the hydrocolpos may interfere with Cloacal malformation and VATER association ureter drainage. Since failure to accurately detect lead to elevated risk of neurovesical damage, and these abnormalities can lead to serious complica- renal failure is the most serious problem. Renal tions, fetuses with persistent cloaca with multiple failure can result from persistent cloaca and anomalies should be examined by careful prenatal VATER association by at least two mechanisms. screening to prepare for prompt surgery after First, unilateral renal agenesis, which occurs in birth. approximately 20% of patients with cloacal mal- formations (Brock and Pena 1992), may induce References poor renal function when the opposite renal unit Appignani, B.A., Jaramillo, D., Barnes, P.D. & Poussaint, T.Y. exhibits refl ux or obstruction (Hendren 1998; Liu (1994) Dysraphic myelodysplasias associated with uro- and Hutson 2000). However, some patients diag- genital and anorectal anomalies: prevalence and types seen with MR imaging. Am. J. Roentgenol., 163, 1199-1203. nosed as unilateral renal agenesis after birth might Barry, J. & Auldist, A. (1974) The Vater association: One end have gone undetected before birth. Secondly, a of a spectrum of anomalies. Am. J. Dis. Child., 128, 769-771. long common cloacal channel leads to urine Brock, W. & Pena, A. (1992) Cloacal abnormalities and imper- drainage and accumulation in the vagina, causing forate anus. In: Clinical Pediatric Urology, 3rd ed., edited hydrocolpos and bladder dysfunction (Appignani by P. Kelalis, L. King & A. Belman, W.B. Saunders, Phila- delphia, PA, 920-942. et al. 1994; Shimada et al. 2005). Goldberg, S., Ringertz, H. & Barth, R.A. (2006) Prenatal diag- Urine escapes from the hydrocolpos via fal- nosis of horseshoe lung and esophageal atresia. Pediatr. Radiol., 36, 983-986. lopian tubes into the abdominal cavity leading to Hendren, W. (1992) Cloacal malformations: experience with ascites pooling. Later, chronic infl ammation 105 cases. J. Pediatr. Surg., 27, 890-901. caused by urine and meconium accumulation Hendren, W. (1998) Cloacal malformations. In: Campbell’s Urology, 7th ed., edited by P. Walsh, A. Retik, E. Vaughan blocks the fallopian tubes increasing hydrocolpos, & A. Wein, W.B. Saunders, Philadelphia, PA, 1991-2018. as in our patient. In these patients, the infant Henmi, N., Okubo, S., Kasahara, T., Okugawa, T., Yamazaki, H., Harada, W. & Uchiyama, M. (2000) A case of esophageal should be delivered before function is lost from atresia with tracheoesophageal fi stula, imperforate anus, both kidneys. persistent cloaca, incomplete fusion of the labium and Here, we measured renal arterial blood fl ow chronic renal failure due to urethral obstruction. Pediatr. Int., 42, 585-588. and renal size by ultrasonography. On the basis Liu, M.-P. & Hutson, J. (2000) Cloacal and urogenital malfor- of kidney size and renal arterial blood fl ow, we mations in adriamycin-exposed rat fetuses. B. J. U. Inter- Cloacal-VATER Spectrum 295

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