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Single Umbilical Artery article January/February 2004 ⅐ Vol. 6 ⅐ No. 1 Single umbilical artery: What does it mean for the fetus? A case-control analysis of pathologically ascertained cases Sandra Prucka, MS1, Michele Clemens, MS1,2, Catherine Craven,† MD3, and Elizabeth McPherson, MD4 Purpose: To ascertain the frequency of chromosomal and other anomalies in fetuses with single umbilical artery. Methods: Placentas with single umbilical artery were identified from hospital pathology laboratory records. For each identified case, the next consecutive placenta with two umbilical arteries served as a control. Pathology records, maternal histories, and prenatal ultrasounds when available were reviewed for congenital anomalies, pregnancy complications, and maternal characteristics. When indicated, placental specimens, amniocytes, or neonatal bloods were karyotyped. Results: Single umbilical artery existed in 2.0% (97/4846) of pathological specimens. Fetuses with single umbilical artery had significantly more chromosomal (10.3% vs. 1.0%) and other congenital anomalies (27% vs. 8%). Conclusions: The high incidence of major chromosomal and congenital anomalies justifies detailed fetal ultrasonography, echocardiography, and amniocentesis for karyotype when single umbilical artery is discovered during routine ultrasound. Genet Med 2004:6(1):54–57. Key Words: single umbilical artery, chromosome anomalies, detailed ultrasound, karyotype, fetal echocardiography The umbilical cord forms between 13 and 38 days after con- fetuses who underwent prenatal ultrasound examination, 9% ception and normally serves as the conduit for two umbilical to 11% of aneuploid fetuses, and 0.5% to 2.5% of uncompli- arteries and one umbilical vein.1,2 In some cases only a single cated neonates. The reported incidence of SUA varies depend- umbilical artery (SUA) is present. Some report that this um- ing on the method used to identify its occurrence, being high- bilical abnormality can be observed as early as 13 weeks. How- est in abortuses and autopsies and relatively low on ultrasound ever, it is typically diagnosed in the third trimester.1,3 There are and in term neonates.1,6–8 Although there has been no evi- three theories to explain how a SUA may form during devel- dence supporting any genetic etiology or familial tendency of opment.1,4 The first is that a primary agenesis of one umbilical this condition, it is known that SUA occurs more frequently in artery results in a SUA. Another theory attributes the phenom- twin births (4.6%) versus singletons (1%).4,9 enon to a secondary atrophy or atresia of a previously normal The risk for congenital anomalies in infants with SUA also umbilical artery. A third theory describes a persistence of the depends on the method of ascertainment, being highest at au- original allantoic artery of the body stalk as an explanation for topsy, but cases diagnosed at ultrasound or at term delivery still SUA. Embryological considerations, as well as the detection of have an increased risk of anomalies compared to infants with occluded remnants of a second umbilical artery in some SUA two umbilical arteries. In the metaanalysis of Thummala et al.,8 fetuses, suggest that the second theory is the most likely nine autopsy-based studies show incidences of anomalies explanation.1,4,5 ranging from 25% to 81.8% with a mean of 61.4%, whereas 23 In a review of eight studies of SUA in the literature, Persutte studies based on screening of placentas or umbilical stumps of and Hobbins1 reported an incidence of SUA in 1.5% in spon- term neonates show anomalies ranging from 8.7% to 66.7% taneous abortuses, 7% of pregnancies that were terminated with a mean of 27%. Observed anomalies most often involve because of a serious malformation, 0.2% to 1.6% of euploid the urogenital, gastrointestinal cardiovascular, respiratory, and central nervous systems, as well as the face.9 Similar anom- alies have been noted on ultrasound among cases ascertained From the 1Department of Human Genetics, University of Pittsburgh Graduate School of 1,3 Public Health, Pittsburgh Pennsylvania; Departments of 2Genetics and 3Pathology, Magee- prenatally. We decided to use pathology as the means of Women’s Hospital, Pittsburgh, Pennsylvania; and 4Medical Genetics Services, Marshfield ascertainment because we felt it was more accurate than ultra- Clinic, Marshfield, Wisconsin. sound, despite recent advances with color imaging. Also we †Deceased. wanted data applicable to all stages of pregnancy, including the Dr. Elizabeth McPherson, Medical Genetics Services, Marshfield Clinic, 1000 North Oak second trimester when decisions about amniocentesis and Avenue 1A4, Marshfield, WI 54449. pregnancy intervention are being made. Therefore, we decided Received: July 30, 2003. to include all cases of pathologically confirmed SUA regardless Accepted: September 23, 2003. of gestational age and infant condition at delivery. We retro- DOI: 10.1097/01.GIM.0000105743.91723.B0 spectively reviewed the medical records, laboratory results, 54 Genetics IN Medicine Single umbilical artery and ultrasound of 2 years of SUA placental specimens at a large riculovertebral spectrum) (4), congenital heart disease (4), high-risk maternity center. VACTERL (Vertebral-anal-cardiac-tracheoesophageal fistula- renal-limb) (3), sirenomelia (2), anencephaly (2), limb-body PATIENTS AND METHODS wall defect (2), cleft lip/palate (2), hydrocephalus (1), cardiac rhabdomyoma (1), acardiac twin (1), renal (1), heterotaxy (1), Placentas with a SUA, as well as control placentas with a craniocerebellar-cardiac syndrome (1), and isolated short fe- 3-vessel cord, were obtained through examination of pathol- mur (with no craniofacial anomalies) (1). ogy records from the Pathology Department at Magee-Wom- In the control group, only one chromosome anomaly, a en’s Hospital in Pittsburgh, Pennsylvania during a 2-year pe- 92,XXYY/46,XY mosaic liveborn with developmental delay riod from 1998 to 2000. During the period of the study, there and minor dysmorphic features, was found. Congenital anom- were 21,861 deliveries at the institution of which 4,846 had alies observed in this group included renal (2), hydrocephalus placentas submitted to pathology. In all second and third tri- (2), thanatophoric dysplasia (1), gastroschisis (1), sacral agen- mester placentas and products of conception, the umbilical esis (1), and hypospadias (1). cord was examined as part of routine evaluation. All placentas A significant increase in combined chromosomal and con- with two vessel cords identified during the study period were genital anomalies occurred in cases versus controls, with included as cases, and for each, the next consecutive placenta 37.1% of the cases displaying major anomalies compared with with a 3-vessel cord served as the control. The women in the 9.3% of controls. Looking specifically at chromosomal anom- study, as well as their fetuses, were selected regardless of age, alies, we saw 10/97 (10.31%) of the SUAs with chromosomal ethnicity, or socioeconomic status. Pathology records were re- anomalies versus 1/97 (1.03%) of the controls with chromo- viewed to compare information on maternal complications, somal abnormalities. twinning, gestational age, birth weight, maternal age, and con- The maternal ages in cases and controls of our study popu- genital anomalies. Charts of the mothers were used as needed lation reflected the ages of patients in our high-risk maternity to verify data from the pathology report. In total, there were 97 setting, with a mean age of 29.06 years in cases and 29.30 years cases and 97 controls analyzed in this study. The pregnancy in controls. Looking at the maternal ages of our study popula- outcomes of cases and controls were recorded, and the number tion revealed that 26 (26.80%) of the cases and 26 (26.80%) of of anomalies in each category was tabulated. Not all women in the controls were 35 years of age or older. Of the 10 cases the case and control populations had an ultrasound performed observed to have a chromosomal condition, only 2 (20%) were during their pregnancy. However, all available ultrasound data over 35 years of age (Table 1). were reviewed. When clinically indicated, placental samples, Small for gestational age (SGA) was defined as below the 3rd amniocytes, or neonatal blood specimens were analyzed for percentile and large for gestational age (LGA) as above the 97th chromosomal abnormalities through standard karyotyping percentile on the charts of Usher and McLean.10 Using these procedures. criteria those born after 24 weeks, whose weights were avail- able, were analyzed. It was determined that 11/70 cases RESULTS (15.71%) and 12/80 controls (15.00%) were LGA, whereas 16/70 cases (22.86%) and 7/80 controls (8.75%) were SGA SUA occurred in 2.0% (97/4846) of the placentas submitted (Table 2). Twinning was observed in 8% of cases in compari- to pathology over this 2-year period. son to 5% of controls, whereas maternal nongestational diabe- Various chromosomal anomalies were observed in both the tes was seen in 8% of cases and 4% of controls. SUA and control groups (Table 1). In the SUA group, chromo- Ultrasound information was available on 62 of the SUA somal anomalies included 45,X (3), trisomy 13 (3), trisomy 18 mothers, of which 38 (61.3%) ultrasounds detected the SUA. (2), triploidy (1), and balanced de novo t(9;17) (1). Congenital Of the 36 SUA cases with anomalies, prenatal ultrasound data anomalies observed in this group included FAVS (Facioau- are only available on 31of the pregnancies. The five anomalies where no ultrasound data were available include one case of triploidy, one case of balanced t(9;17), one case of bilateral cleft Table 1 Chromosomal anomalies in cases and controls Cases Controls Table 2 Size for gestational age in cases and controls Chromosomal anomaly Observed Chromosomal anomaly Observed Cases Controls 45,X 3 92,XXYY/46,XY 1 Size for gestational age (n ϭ 70) (n ϭ 80) t test Trisomy 13 3 LGAa 11 (15.71%) 12 (15.00%) P ϭ 0.5786 Trisomy 18 2 AGAb 43 (61.43%) 61 (76.25%) P ϭ 0.1015 Triploidy 1 SGAc 16 (22.86%) 7 (8.75%) P ϭ 0.0013* Balanced t(9;17) 1 aLarge for gestational age; bappropriate for gestational age; csmall for gesta- tional age.
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