J Clin Pathol 1989;42:931-934

Calcification of umbilical artery: two distinct lesionsT Y KHONG,* S A DILLY

From the *Department ofPaediatric Pathology, John Radcliffe Hospital, Oxford, and the Department ofHistopathology, St George's Hospital Medical School, London

SUMMARY The clinical and pathological features of five cases of calcification of umbilical cordvessels were reviewed. Two distinct lesions were identified: calcification could produce either sclerosisof the wall or obliteration of the lumen. In three cases there was calcification within the media andadventitia of the umbilical arteries, with extension into Wharton's jelly in one case. The pathogenesisof this pattern of calcification-the sclerotic variant-is unclear but the findings of inflammation inthe umbilical cord and its vessels, membranes, and decidua suggest intrauterine infection. In twocases there was complete calcification of umbilical arterial lumina resulting in total obliteration. Thefindings of fetal vessels in the chorionic plate with medial calcification in one of these two cases raisesthe possibility ofthrombosis within the umbilical cord vessels as a cause, but the latter was not found.One infant from each group was liveborn. Both had shown signs of fetal distress in utero anddelivered prematurely. The other three pregnancies resulted in macerated stillbirth preterm.

Calcification of umbilical cord vessels is rare.'Previous reports have described clinical and patho-logical features associated with calcification of thevessel wall,'" but the paucity of reports suggest that itis an exceedingly rare occurrence. We report threefurther cases of umbilical vessel wall calcification andtwo cases of complete calcification of the umbilicalarterial lumen, the latter phenomenon not previouslyreported.

Accepted for publication 20 April 1989

Case reports and pathological findings

The clinical data are shown in table 1 and a summaryof the pathological findings in table 2. The strikingfeature in cases 1 and 2 was the complete calcificationof umbilical arterial lumina resulting in total oblitera-tion (fig 1). This is different from that seen in cases 3, 4,

and 5 where the calcification was within the media andadventitia of the umbilical arteries (fig 2). Calcifica-tion ofthe vessel wall affected only one vessel in cases 3and 5 but affected all three vessels in the umbilical cord

Table 1 Clinical data

Case GestationalNo Age Gravidity Ethnic origin Maternal history age Delivery Outcome

1 24 G2Pl Occidental Angioneurotic oedema, 35 Caesarean Livebom male,urticaria, section for 1480 gpolyarthropathy fetal distressDiagnosed as "lupus-like" treated withprednisolone andazathioprine

2 19 Gl Occidental Skin irritation and rash 34 Induced labour Maceratedat 28 weeks gestation for intra- female, 940 g

uterine death3 43 GI Oriental Premature labour 32 Caesarean Liveborn male,

section for 1350 gfetal distress

4 22 G2PO + 1 Occidental - 25 Induced labour Macerated male,for intra- 619 guterine death

5 21 G2PO + I Occidental 32 Induced labour Maceratedfor intra- female, 1650 guterine death

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932 Khong, DillyTable 2 Pathologicalfindings

Necropsy

Not relevant

Permission refused; externally loss offingers and toes due to amnioticrupture syndrome

Not relevant (umbilical arterycatheter passed easily into pretermneonate)

Maceration changes

Maceration changes

Placenta

292 g, 20% infarction

460 g, cord twisted round partiallydetached amniotic epithelium

393 g

186 g, oedematous cord withnarrowing at fetal insertion

360 g, umbilical cord showed markedcircumferential fibrosis andcalcification around all 3 vessels

Histology

Complete calcification of umbilicalarterial lumen

Thrombosis of fetal vessels in chorionicplate with medial calcification

Complete calcification of umbilicalarterial lumen

Endarteritis with medial and adventitialproliferation and coarse calcificationof one umbilical artery; finecalcification around the other twovessels

Mild chorioamnionitis and acutedecidualitis present

Endarteritis with fine calcification ofadventitia of both umbilical arteriesand umbilical vein

Funisitis and chorioamnionitis alsopresent

Vasculitis and thrombosis of fetalvessels in chorionic plate withcalcification of some of the contents

Funisitis and vasculitis withcalcification of part of the adventitiaof one umbilical artery with extensioninto Wharton's jelly

..._.~ ~ ~ ~ ~ ~

~ S

peeoc:.o

cacfcto; .)

Fig 2 Case 3: calcification ofmedia and adventitia of

umbilical arteries and vein. (Haemawtoxylin and eosin.)

Case No

1

2

3

4

5

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Umbilical arterial calcification

A.

Fig 3 Case S:fine calcification ofumbilical artery withdense calcification in Wharton 'sjelly. (Haematoxylin andeosin.)

of case 4. Calcification was seen in Wharton's jelly incase 5 (fig 3). Thrombosis of fetal vessels in thechorionic plate with either calcification ofthe media orthe contents was seen in cases 2 and 5 (fig 4). Gramstains did not show the presence of organisms.

Discussion

Because placentas are examined on a semi-selectivebasis the exact prevalence of calcification of umbilicalcord vessels is not known. We believe, however, thatthe condition is rare as these five cases were foundfrom archival material over a 13 year period (1975-1988) in Oxford and over a five year period (1983-1988) at St George's Hospital, London.

Calcification of umbilical cord vessels can take oneof two forms producing obliteration on the one handand sclerosis on the other. deSa distinguished betweencalcification of umbilical cord vessels and sclerosingfunisitis or constrictive sclerosis ofWharton's jelly.' Inthe former, there is calcification of the cord vessel wallwhile in the latter there is often calcification of anattenuated and sclerosed Wharton's jelly. Our thirdand fourth cases showed calcification predominantly

Fig 4 Case 2: calcification ofthrombus and media ofchorionic plate artery. (Haematoxylin and eosin.)

in the adventitia while our fifth case showed calcifica-tion within Wharton's jelly as well as within the wall ofthe blood vessels; it is our contention that it is difficultto ascertain the primary site ofcalcification. This is notsurprising as the adventitia merges imperceptibly withthe surrounding Wharton's jelly' and Wharton's jellyhas been likened to the adventitia of the umbilicalarteries.6 It would seem more appropriate to classifythese as sclerosing calcification in contrast to theobliterative lesion seen in cases 1 and 2. Blancsuggested that calcified umbilical cord vessels were dueto intrauterine viral infections7 while deSa thoughtthat sclerosing funisitis was a response to any infec-tion.' In none of our cases, however, was thereevidence of villitis or viral inclusions, but the findingsof decidualitis (case 3), funisitis (cases 4 and 5),chorioamnionitis (cases 3 and 4) and endarteritis orvasculitis (cases 3, 4, and 5) suggest intrauterineinfection. Bacteriological studies on the mothers werenegative. Sclerosing calcification of umbilical vesselshas been found in association with fetal hydropsfollowing fetomaterial haemorrhage,' Salla disease,'fetal renal calcification,4 normal liveborn infants'3and macerated stillbirths. ' 4

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934Complete calcification of the umbilical artery lumen

as seen in our first two cases has not hitherto beendescribed. Its pathogenesis is unclear but the finding offocal calcification of thrombus of the major vessels inthe chorionic plate in case 2, similar to those describedby Benirschke and Driscoll,8 suggests that it may be adegenerative phenomenon, as a result of dystrophiccalcification of a thrombus more proximally. Perrinand Kahn-Vander Bel presented a case in which therewas focal calcification of a laminated thrombus in anumbilical cord vessel4 while Heifetz had a case of"vascular mural calcification" in his series ofumbilicalcord thrombosis, although the extent of calcificationwas not illustrated.9 Thrombosis ofumbilical vessels israre,5 9 10 and a thrombus was not found in theumbilical cords of cases 1 or 2.These cases are different to the condition referred to

variably as idiopathic arterial calcification" or infan-tile arterial calcification'2 where generalised arterialcalcification, including coronary and renal arteries,with or without intimal proliferation, have beendescribed. In that condition, some were stillbirths butmost were infants and in none has calcification of theumbilical arteries been described. Furthermore, in ourcases 4 and 5 where necropsy was performed, systemiccalcification was not seen.Whatever the pathogenesis of calcification of

umbilical cord vessels, there seem to be two relativelydistinctive patterns, either calcification leading tocomplete obliteration ofthe arterial lumen or calcifica-tion ofthe arterial wall with or without involvement ofWharton's jelly. A possible cause for the first isthrombosis and, for the second, infection.

We thank the clinicians Mr D H Barlow, J M Pearce,J H Hughes, S C Simmons for their permission toreport these cases, Dr J W Keeling for helpful

Khong, Dilly

discussions, and MrG Richardson and Miss H Mellorfor photographic assistance.

References

I deSa DJ. Diseases of the umbilical cord. In: Perrin EVDK, ed.Pathology of the Placenta. New York: Churchill Livingstone,1984:128-33.

2 Rust W. Seltsame veraderungen an den Nabelschnurgefassen.Arch Gynak 1937;165:58-62.

3 Walz W. Uber das odem der Nabelschnur. Zentralbl Gynak1947;69:144-5.

4 Perrin EVD, Kahn-Vander Bel J. Degeneration and calcificationof the umbilical cord. Obstet Gynecol 1965;26:371-6.

5 Kohler HG. Pathology ofthe umbilical cord and fetal membranes.In: Fox H, ed. Haines and Taylor obstetrical andgynaecologicalpathology. Edinburgh: Churchill Livingstone, 1987:1079-116.

6 Zawisch C. Die Wharton'sche sulze und die Gefasse des Nabel-stranges. Zeitsch Zellforsch 1955;42:94-133, cited by Kohler.5

7 Blanc WA. The future of antepartum morphologic studies. In:Adamsons K, ed. Diagnosis and treatment offetal disorders.New York: Springer-Verlag, 1968:20.

8 Benirschke K, Driscoll SG. The pathology of the human placenta.New York: Springer-Verlag, 1967:83.

9 Heifetz SA. Thrombosis of the umbilical cord: analysis of 52 casesand literature review. Pediatr Pathol 1988;8:37-54.

10 Fox H. Pathology of the Placenta. Eastbourne: WB Saunders,1978:445.

11 Ivemark BI, Lagergren C, Ljungqvist A. Generalized arterialcalcification associated with hydramnios in two stillborninfants. Acta Paediatr 1962;(Suppl 135):103-10.

12 Van Dyck M, Proesmans W, Van Hollebeke E, Marchal G,Moerman Ph. Idiopathic infantile arterial calcification withcardiac, renal and central nervous system involvement. Eur JPediatr 1989;148:374-7.

Requests for reprints to: Dr T Y Khong, Department ofPaediatric Pathology, John Radcliffe Hospital, OxfordOX3 9DU, England.

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