DOI 10.1515/crpm-2012-0044 Case Rep. Perinat. Med. 2012; 1(1-2): 87–90

Genevi è ve Donata Koolhaas * , Martine Helene Hollander and Harry Molendijk A case of a four-vessel umbilical cord: don ’ t stop counting at three!

Abstract: There are various numerical abnormalities of We present a case in which a four-vessel umbilical umbilical cord vessels known in the literature, the single cord was found, which appeared to contain two arteries umbilical artery being the most prevalent. A four-vessel and two veins. Although a literature search demonstrated umbilical cord is found less frequently, and moreover, that this is not a rare event (1:526) [ 17 ], it appears to be is less well-known in daily practice. A persistent right little known among both obstetricians/sonographers and umbilical vein, however, can be associated with poten- pediatricians. tially serious congenital defects. A case of a four-vessel umbilical cord containing two arteries and two veins is presented. The literature on this subject reports both a dif- ferentiation between the two variants, intrahepatic and Case report extrahepatic, which can be distinguished during antena- tal ultrasound screening, and a possible association with A 26-year-old primigravida was referred to our hospital by congenital abnormalities, some of which can carry sub- her primary caregiver at 41 weeks and 3 days because of stantial morbidity and mortality. Although the incidence decreased fetal movements and oligohydramnios. Labor of a four-vessel umbilical cord is low, its presence should was induced, and she had a spontaneous vaginal delivery. be considered both during routine antenatal ultrasound Even though the labor was complicated by meconium- screening and on physical examination of any neonate. stained amniotic fluid, a baby boy was born in good con- dition: Apgar scores 8 and 9 after 1 and 5 min, respectively, Keywords: Cord; umbilical; vascular abnormality. birth weight of 4420 g, and umbilical cord blood gas with a pH 7.13 and base excess of − 12.5 mmol/L. The presence of meconium-stained amniotic fluid constitutes, in our hos- *Corresponding author: Genevi è ve Donata Koolhaas, Department of pital, a reason for postnatal examination by the pediatric Paediatrics, Isala Clinics, Dokter van Heesweg 2, 8025 AB Zwolle, The Netherlands, Tel.: + 3138427382/ + 31652601089 , faculty. The examination showed no dysmorphic signs E-mail: [email protected] or other abnormalities during cardiopulmonary auscul- Martine Helene Hollander: Department of Obstetrics and tation. However, the umbilical cord seemed to contain Gynaecology, Isala Clinics, Zwolle, The Netherlands four vessels, two of which were obviously arteries and Harry Molendijk: Department of Neonatology, Isala Clinics, Zwolle, two appeared to be veins ( Figure 1 ). The routine 20-week The Netherlands ultrasound scan had revealed no abnormalities. However, our guidelines state a screening for two arteries and one vein, in which case an extra vein can be overlooked. This Introduction finding was consequently reported during handover the next morning, but elicited a certain amount of surprise During the first full physical investigation of any neonate, and disbelief. Apparently, our pediatric faculty (includ- close inspection of the umbilical cord is of paramount ing neonatal specialists) was unfamiliar with this entity. importance. This examination should include the pres- We conducted a review of the literature on the subject. ence of meconium staining, which can indicate the sever- This yielded a substantial number of publications in ity and duration of intrauterine fetal distress, the degree of which we found that some of the defects associated with coiling and fragility of the cord, the number of umbilical a four- vessel umbilical cord can be of a potentially serious vessels present, hematomas, and the quantity of Whar- nature. Therefore, we decided to recall the infant, who ton ’ s jelly, aberrations in either of which may give rise to had already been discharged, to our neonatal outpatient a suspicion of further (congenital) pathology. The single department for further evaluation on day 4 of postnatal life. umbilical artery is the best known numerical vessel abnor- Apart from age-appropriate weight loss and minor mality [ 2 , 12 ]. Therefore, most investigators are inclined to jaundice, the neonate had been well. Physical examina- stop counting once three have been identified. tion again showed no abnormalities. Special attention 88 Koolhaas et al., A case of a four-vessel umbilical cord

Two arteries

Schematic overview

Two veins

Figure 1 Umbilical cord (reproduced with permission of the parents). was paid to the existence of a cardiac murmur suggestive what we now know as extrahepatic PRUV [10 , 11 ]. Initial of congenital defects. In addition, a screening ultrasound reports mention a high prevalence of associated abnor- examination was performed to rule out congenital defects malities [5 , 9 , 13 ]; however, in recent years, a less serious of the heart, liver, and kidneys. At that time, intra-abdom- picture has emerged [ 16 ]. Prenatal diagnosis is possible inal umbilical vessels were not seen, probably because and of importance, as PRUV is associated in the literature umbilical vessels were obliterated in the transitional with a wide range of congenital defects of varying severity phase of the circulation, so a differentiation between the [1 , 3 , 6 , 8 , 14 , 16 , 17 ] (Table 1 ), some of which could cause intrahepatic and extrahepatic variant could not be made. significant morbidity and even mortality if not discovered The child was discharged from specialist care and referred and treated in a timely fashion. back to the primary health-care provider. When more than the usual three vessels are found to be present on either ultrasound or postnatal examina- tion, the extra lumen can be a vein (PRUV), an artery, or Discussion a remnant of the omphalomesenteric or allantoic duct [ 3 ]. Of these, PRUV is the most prevalent. The 5-week embryo has a right and a left umbilical vein On prenatal ultrasound, two types of PRUV can be dis- as well as two umbilical arteries. Between the gestational tinguished: the intrahepatic and the extrahepatic type. The ages of 6 and 7 weeks, the right umbilical vein normally intrahepatic type (75– 95%) is the most common variant [6 , becomes obliterated [15 ] and the left vein and both arter- 8 ] and is not usually associated with other abnormalities ies remain to form the umbilical cord [16 ]. In some cases, [1 , 17 ]. In this variant, the aberrant right umbilical vein this obliteration does not take place and both left and connects to the right portal branch and from there to the right umbilical veins persist, leading to a four-vessel ductus venosus. There are two sonographic clues that umbilical cord. A persistent right umbilical vein (PRUV) point in this direction: the portal vein curves toward the is believed to be associated with first-trimester folic acid stomach in a transverse section of the abdomen, and the deficiency, specific teratogens such as retinoic acid, and fetal gallbladder is located medially to the umbilical vein early obstruction of the left umbilical vein from external [ 14 , 17 ]. In the extrahepatic type, the right umbilical vein pressure or occlusion [ 9 ]. drains directly into the systemic circulation. This type is In 1826, Mende reported a case of an abnormal route of associated with absence of the ductus venosus or the left the umbilical vein entering the right atrium, suggestive for umbilical vein (in which case only three umbilical vessels Koolhaas et al., A case of a four-vessel umbilical cord 89

Our search of the literature yielded several studies Cardiovascular (60.3%) Musculoskeletal (7.7%) –ASD –Short limbs describing an incidence for PRUV of 0.2 – 0.4% [ 4 , 7 ]. The –VSD –Hemivertebrae largest of these prospectively evaluated 8950 low-risk –Patent foramen ovale –Caudal regression patients who were seen for routine second-trimester ultra- –Interrupted IVC sound [17 ]. The sonographers were specifically instructed –Mono-atrium Renal (15.4%) and trained to screen for PRUV. They found an incidence –Persistent left SVC –Dysplastic kidney –Heart block –Pelvic kidney of 1:526, whereby 23% of these fetuses were found to have –Aortic stenosis –Multicystic kidney additional malformations. Another study retrospectively –Total venous connection anomaly – Unilateral or bilateral analyzed 39 neonates with PRUV and found that in 7.9% of renal agenesis the cases where other malformations were present, karyo- –Fallot tetralogy typing showed aneuploidy [ 16 ]. –Mitral atresia Cerebral (15.4%) –Double outlet right ventricle –Hydrocephalus –Aortic coarctation –Corpus callosum agenesis –Transposition of the great arteries –Plexus cyst –Truncus arteriosus Conclusion –Dextrocardia Other –Hypertrophic cardiomyopathy –Hypospadias A four-vessel cord, most often caused by a persistent right –Ectopia cordis –Retrognatia umbilical vein, is not an extremely rare occurrence but –Hypoplasia of one pulmonary artery –VACTERL –Single umbilical artery is often overlooked during routine ultrasound because –Struma the sonographer is unaware of this possibility. Further- Gastrointestinal (12.8%) –Hydrops/thick NT more, physical examination of the neonate by midwives –Abdominal visceral situs inversus –Four finger line or medical doctors is frequently limited to searching for –Heterotaxia syndrome –Polysplenia/asplenia three umbilical vessels. The extrahepatic variant of PRUV –Ascites –Facial clefts can be associated with numerous, sometimes serious, –Bifid liver –Trisomy 18 –Diaphragmatic hernia –Turner syndrome congenital abnormalities and, if found, warrants careful further evaluation. This could include karyotyping. Table 1 PRUV-associated abnormalities [1 , 3 , 6 , 8 , 14 , 16 , 17 ]. When, as in our case, the diagnosis of PRUV is made ASD = atrial septum defect, VSD = ventricular septum defect, postnatally, a systematic physical examination should be IVC = inferior vena cava, SVC = superior vena cava. performed by qualified staff with extra attention being paid to the possibility of congenital heart defects. are present) and can be associated with a variety of other In conclusion, regarding the umbilical cord, we rec- congenital abnormalities [ 1 ]. ommend both antenatally and postnatally, don ’ t stop Postnatal diagnosis is usually made during cannula- counting at three! tion of the umbilical cord for the purpose of neonatal treat- ment, in which case the catheter intended for an umbilical artery ends up in the extra umbilical vein [6 ]. Received June 11, 2012. Accepted October 19, 2012.

References

[1] Blazer S, Zimmer EZ, Bronshtein M. Persistent intrahepatic right [5] Jeanty P. Persistent right umbilical vein: an ominous prenatal umbilical vein in the fetus: a benign anatomic variant. Obstet finding? Radiology. 1990;177:735– 8. Gynecol. 2000;95:433 – 6. [6] Karatza A, Tsamandas A, Varvarigou A, Davlouros P, Pavlou [2] Boom de ML, Kist-vanHolthe JE, Sramek A, Lardenoye SWJ, V, Mantagos S. Supernumerary umbilical vein in a hydropic Walther FJ, Lopriore E. Is screening for renal anomalies neonate with hypertrophic cardiomyopathy. Fetal Pediatr warranted in neonates with isolated single umbilical artery? Pathol. 2011;30:173 – 6. Neonatology. 2010;97:225 – 7. [7] Kirsch CFE, Feldstein VA, Goldstein RB, Filly RA. Persistent [3] Heredia F, Jeanty P. Umbilical cord anomalies. Available at: intrahepatic right umbilical vein: a prenatal sonographic series http://www.thefetus.net. Accessed June 2012. without associated anomalies. J Ultrasound Med. 1996;15:371– 4. [4] Hill LM, Mills A, Peterson C, Boyles D. Persistent right umbilical [8] Lai WW. Prenatal diagnosis of abnormal persistence of the right vein: sonographic detection and subsequent neonatal outcome. or left umbilical vein: report of 4 cases and literature review. Obstet Gynecol. 1994;84:923 – 5. J Am Soc Echocardiogr. 1998;11:905 – 9. 90 Koolhaas et al., A case of a four-vessel umbilical cord

[9] Manohar S. Persistent right umbilical vein. Available at: www. [14] Suchet IB. Persistent right umbilical vein and abnormal thefetus.net. Accessed June 2012. extrahepactic connections. Available at: http://www. [10] Mende LJC. Beobachtungen und Bemerkungen aus der fetalultrasound.com/online/text/34-024.htm. Accessed June Geburtsh ü lfe und gerichtlichen Medizin, nebst fortlaufenden 2012. Nachrichten ü ber die Ereignisse in der Kö niglichen Entbindungs- [15] Theander G, Karlsson S. Persistent right umbilical vein. Acta Anstalt in G ö ttingen. Zeitschrift f ü r die Geburtsh ü lfe in ihrer Radiol. 1978;19:268 – 74. Beziehung auf die gerichtlichen Medicin. 1826 [16] Weichert J, Hartge D, Germer U, Axt-Fliedner R, Gembruch U. [11] Monie I. Umbilical vein entering the right atrium: comments Persistent right umbilical vein: a prenatal condition worth on a previously reported human case. Teratology. 1971;4: mentioning? Ultrasound Obstet Gynecol. 2011;37:543 – 8. 461 – 3. [17] Wolman I, Gull I, Fait G, Amster R, Kupferminc MJ, Lessing JB, [12] Parilla BV, Tamura RK, MacGregor SN, Geibel LJ, Sabbangha RE. et al. Persistent right umbilical vein: incidence and The clinical significance of a single umbilical artery as an significance. Ultrasound Obstet Gynecol. 2002;19:562– 4. isolated finding on prenatal ultrasound. Obstet Gynecol. 1995; 85:570 – 2. [13] Shen O, Tadmor OP, Yagel S. Prenatal diagnosis of persistent The authors stated that there are no conflicts of interest regarding right umbilical vein. Ultrasound Obstet Gynecol. 1996;8:31 – 3. the publication of this article.