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Fused umbilical arteries near placental cord insertion
Fused umbilical arteries near placental cord insertion Toshio Fujikura, MD Tokyo, Japan OBJECTIVE: This study was undertaken to study the frequency and cause of fused umbilical arteries (FUAs). STUDY DESIGN: Umbilical cord on the placental side was carefully examined for FUAs by continuous interval sections. RESULTS: The frequency was 3.1% or 22 in 702 infants with the frequency in female infants of 4.1% being significantly higher than that in male infants of 2.0%. The mean distance of fused points was 2.3 ± 1.6 cm from placental cord insertion. Five of 22 cases showed both arterial fusion and division in the same umbilical cord. Marginal and velamentous insertions were significantly associated with FUAs. Gestational age, birth weight, and placental weight of 22 cases were within normal range. CONCLUSION: Single umbilical artery should be confirmed by 2 or 3 sections of umbilical cord because of the high frequency of FUA on the placental side. (Am J Obstet Gynecol 2003;188:765-7.)
Key words: Fused umbilical arteries
Fused umbilical arteries (FUAs) occurring near the placental cord insertion have been found under pathologic and sonographic examination.1-4 According to Fox2 and Benirschke and Kaufmann,1 diagnosis of single umbilical cord artery (SUA) should be confirmed by two or three sections of the umbilical cord. If the cord is sectioned close to the chorionic plate, FUA may be misdiagnosed as true SUA. The frequency of SUA varies from 0.2% to 1.1% and congenital malformations are found between 25% and 50% of the associated infants.1,2,5,6 The frequency of FUAs is still unknown by pathologic examination or prenatal sonographic diagnosis. Prenatal complications and congenital malformations are assumed to be rare with FUAs,3 but no consecutive study of FUAs has been performed. In this study, the frequencies of FUAs and SUA were studied by pathologic examination near the placental cord insertion. The associated abnormalities of umbilical cord and congenital malformations were also recorded. Material and methods A total of 702 placentas from single births at more than 20 weeks of gestation were consecutively collected at Sho Women’s Hospital during 1999 through 2000. Placentas with maternal complications such as toxemia and diabetes mellitus were included in this study. Data, including placental weight, birth weight, gestational age, fetal sex, From the Department of Pathology, Sho Women’s Hospital, Eiju General Hospital. Received for publication May 2, 2002; accepted November 5, 2002. Reprint requests: Toshio Fujikura, MD, 2-5-6 Hirakawa-cho, Chiyodaku, Tokyo 102-0093, Japan. E-mail: [email protected] © 2003, Mosby, Inc. All rights reserved. 0002-9378/2003 $30.00 + 0 doi:10.1067/mob.2003.165
and congenital malformations, were analyzed in relation to findings of the umbilical cord. Fresh placentas were fixed in 10% formalin for 3 to 4 days. After complete fixation, placental weight and marginal or velamentous insertion of umbilical cord were recorded after the removal of fetal membranes and umbilical cord. Umbilical cord on the placental side was cut at 4 to 5 mm intervals up to 10 cm and fused or single umbilical artery was detected by gross examination. Intervascular anastomosis was confirmed by several additional sections at the fused lesion (Figs 1 and 2). The mid portion and the fetal side of the umbilical cord were also examined, but continuous interval cross sections were not prepared in the rest of the umbilical cord beyond 10 cm. Histologic examination was conducted on fused or single umbilical cord and hematoxylin and eosin–stained sections were examined to confirm the findings at Eiju General Hospital. Table I lists the cases of FUAs and SUAs with gestational age, birth weight, fetal sex, placental weight, congenital malformations, and findings of the umbilical cord. Significant difference in frequencies was calculated by using χ2 tests. Results Frequency of FUAs was 3.1% or 22 in 702 infants with frequency by sex being 2.0% or 7 in 337 male infants and 4.1% or 15 in 365 female infants. The frequency was significantly higher in female than in male infants (P < .001). Marginal insertion was found in 18.1% or 4 in 22 cases of FUAs and 4.1% or 29 in 702 infants. The frequency of marginal insertion was 42.8% or 3 in 7 male infants and 6.6% or 1 in 15 female infants with FUAs. Marginal insertion was significantly associated with FUAs especially in male infants (P < .001). Velamentous inser765
766 Fujikura
March 2003 Am J Obstet Gynecol
Fig 1. FUAs (hematoxylin-eosin stain, original magnification 30). Two umbilical arteries are closely located in process of forming FUAs.
Fig 2. FUAs (hematoxylin-eosin stain, original magnification 30). Two umbilical arteries fused together with narrow channel.
Table I. Placental and fetal findings of 24 cases with fused umbilical arteries or single umbilical artery Case No.
Gestational week
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
40 38 37 39 39 39 41 40 38 40 40 33 42 38 41 41 38 39 39 40 38 39 40 36
Birth weight (g) 3032 3026 2276 2622 3104 3520 3056 3196 2940 3714 3102 2094 3440 3160 3000 3350 3460 2800 3110 3550 3260 3160 2974 1190
Sex
Placental weight (g)
F F F M F F F F M F F F F M M F M F M M F F F M
510 450 390 360 440 630 610 550 420 420 370 350 520 470 540 520 500 490 340 430 660 450 450 200
tion was 4.5% or 1 in 22 cases of FUAs and 0.7% or 5 in 702 infants. Velamentous insertion was found in 5 male infants only. Velamentous insertion was also significantly associated with FUAs in male infants (P < .0001). The Table shows 22 cases of FUAs and 2 cases of SUAs with gestational age, birth weight, sex, placental weight, findings of the umbilical cord, and associated congenital malformations. Mean values of gestational age, birth weight, and placental weight in 22 cases of FUAs were 39.0 ± 1.8 weeks, 3089.6 ± 387.9 g, and 473.6 ± 89.5 g, respectively. Mean values of gestational age, birth weight, and placental weight in 337 male and 365 female infants
Findings of cord and fetal malformation Fuse at 5 cm (from placental cord insertion) Fuse at 1 cm Fuse at 3 cm Fuse at 1 cm Fuse at 1 cm and divide at 0.5 cm Fuse at 2.5 cm Fuse at 4.0 cm Fuse at 1.0 cm Fuse at 5.0 cm and divide at 4.0 cm, velamentous insertion Fuse at 2.0 cm Fuse at 0.8 cm Fuse at 1.0 cm Fuse at 5.0 cm Fuse at 6.0 cm, marginal insertion Fuse at 1.5 cm, marginal insertion Fuse at 0.9 cm, marginal insertion Fuse at 2.0 cm and divide at 1.0 cm Fuse at 2.5 cm and divide at 1.5 cm Fuse at 0.5 cm Fuse at 3.7 cm, marginal insertion Fuse at 1.5 cm and divide at 0.8 cm Fuse at 1.8 cm Single umbilical artery Single umbilical artery, velamentous insertion, cleft palate, cleft lip, cerebral malformation
were 38.9 ± 1.4 weeks and 39.2 ± 1.3 weeks, 3083.5 ± 387.7 g and 3037.3 ± 387.9 g, 494.6 ± 78.5 g and 490.5 ± 84.1 g, respectively. Although premature infants are present with FUAs in Table I, mean values of gestational age, birth weight, and placental weight in 22 cases of FUAs were within normal range. Mean distance of the fused points from the placental cord insertion was 2.3 ± 1.6 cm. In the Table, 5 of 22 cases show both arterial fusion and division in the same umbilical cord. The length of FUA varied from 0.5 cm to 1.0 cm in the 5 cases. There was no congenital malformation in 22 infants with FUAs. One infant with SUA was premature and had
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cleft palate, cleft lip, cerebral malformation, and velamentous insertion. The frequency of SUAs was 0.2% or 2 in 702 infants. Comment Single umbilical artery may result from primary aplasia or the consequence of atrophy of one artery.1 The cause of FUAs may be Hyrtl’s anastomosis of two umbilical arteries, which are considered to be a normal physiologic fusion.1 In this study, 5 of 22 FUAs showed both arterial fusion and division in the same umbilical cord. This finding seems to support that FUA is more likely caused by Hyrtl’s anastomosis, which shows fusion and division in the chorionic arteries.4 If FUAs could be considered as a type of SUA, arterial fusion (Hyrtl’s anastomosis) may be included in the cause along with aplasia and atrophy. FUAs were associated with marginal insertion (18.1% or 4 in 22 cases) and velamentous insertion (4.5% or 1 in 22 cases). Marginal and velamentous insertions are reported to occur in 6.8% and 1.1%, respectively, of the placentas in singletons1 and in 18% and 9.3%, respectively, among infants with SUAs.5 These abnormal insertions of the umbilical cord are found more in both FUAs and SUAs than in the control. The frequency of FUAs of 4.1% was higher in female than 2.0% in male infants. SUA occurs slightly more frequently in female than in male infants with a male/female ratio of 0.85:1.5 The frequency of SUA was low and 0.2% or 2 in 702 infants in this study. The low incidences of SUAs are reported among the Japanese (0.20%-0.48%).5 SUA is often accompanied by congenital malformations and low birth weight,1,2,5,6 but there was no evidence of fetal abnormalities with FUAs in this study. This suggests that SUA itself may not be a cause of congenital malformations and low birth weight. Sepulveda et al3 reported that one of five fetuses with FUAs was associated
with unilateral renal agenesis with a subsequent diagnosis of Hallermann-Streiff syndrome. In their study, the area in which two umbilical arteries joined to form a single distal umbilical artery about 12 to 18 cm from the placental cord insertion was found in three cases. The maximal distance of FUAs from the placental cord insertion was 6 cm in this study and so the cause of FUAs could be different from their study. In relation to this study, supernumerary umbilical vessels related to vascular division were examined by the same method near the placental cord insertion. The frequency of supernumerary umbilical vessels was 24.8% or 96 in 387 cases. Mean distance of the divided points from the placental cord insertion was 1.2 ± 0.4 cm in the divided veins and 1.4 ± 0.5 cm in the divided arteries. The high frequencies of supernumerary umbilical vessels and FUAs indicate that normal vascular division and fusion that occur in the chorionic plate start in the umbilical cord near the placental cord insertion. It is important to note that both arterial fusion and division coexisted in 5 cases of 22 FUAs. REFERENCES
1. Benirschke K, Kaufmann P. Pathology of the human placenta. 4th ed. New York: Springer-Verlag; 2000. p. 341-2, 355, 363-6. 2. Fox H. Pathology of the placenta. 2nd ed. London: WB Saunders; 1997. p. 421-5. 3. Sepulveda W, Dezerega V, Carstens E, Gutierrez J. Fused umbilical arteries: prenatal sonographic diagnosis and clinical significance. J Ultrasound Med 2001;20:59-62. 4. Ullberg U, Sandstedt B, Lingman, G. Hyrtl’s anastomosis, the only connection between the two umbilical arteries: a study in full term placentas from AGA infants with normal umbilical artery blood flow. Acta Obstet Gynecol Scand 2001;80:1-6. 5. Heifetz SA. Single umbilical artery: a statistical analysis of 237 autopsy cases and review of literature. Perspect Pediatr Pathol 1984;8:345-78. 6. Froehlich LA, Fujikura T. Significance of a single umbilical artery: report from the collaborative study of cerebral palsy. Am J Obstet Gynecol 1966;94:274-9.
Key words: Fused umbilical arteries
Fused umbilical arteries (FUAs) occurring near the placental cord insertion have been found under pathologic and sonographic examination.1-4 According to Fox2 and Benirschke and Kaufmann,1 diagnosis of single umbilical cord artery (SUA) should be confirmed by two or three sections of the umbilical cord. If the cord is sectioned close to the chorionic plate, FUA may be misdiagnosed as true SUA. The frequency of SUA varies from 0.2% to 1.1% and congenital malformations are found between 25% and 50% of the associated infants.1,2,5,6 The frequency of FUAs is still unknown by pathologic examination or prenatal sonographic diagnosis. Prenatal complications and congenital malformations are assumed to be rare with FUAs,3 but no consecutive study of FUAs has been performed. In this study, the frequencies of FUAs and SUA were studied by pathologic examination near the placental cord insertion. The associated abnormalities of umbilical cord and congenital malformations were also recorded. Material and methods A total of 702 placentas from single births at more than 20 weeks of gestation were consecutively collected at Sho Women’s Hospital during 1999 through 2000. Placentas with maternal complications such as toxemia and diabetes mellitus were included in this study. Data, including placental weight, birth weight, gestational age, fetal sex, From the Department of Pathology, Sho Women’s Hospital, Eiju General Hospital. Received for publication May 2, 2002; accepted November 5, 2002. Reprint requests: Toshio Fujikura, MD, 2-5-6 Hirakawa-cho, Chiyodaku, Tokyo 102-0093, Japan. E-mail: [email protected] © 2003, Mosby, Inc. All rights reserved. 0002-9378/2003 $30.00 + 0 doi:10.1067/mob.2003.165
and congenital malformations, were analyzed in relation to findings of the umbilical cord. Fresh placentas were fixed in 10% formalin for 3 to 4 days. After complete fixation, placental weight and marginal or velamentous insertion of umbilical cord were recorded after the removal of fetal membranes and umbilical cord. Umbilical cord on the placental side was cut at 4 to 5 mm intervals up to 10 cm and fused or single umbilical artery was detected by gross examination. Intervascular anastomosis was confirmed by several additional sections at the fused lesion (Figs 1 and 2). The mid portion and the fetal side of the umbilical cord were also examined, but continuous interval cross sections were not prepared in the rest of the umbilical cord beyond 10 cm. Histologic examination was conducted on fused or single umbilical cord and hematoxylin and eosin–stained sections were examined to confirm the findings at Eiju General Hospital. Table I lists the cases of FUAs and SUAs with gestational age, birth weight, fetal sex, placental weight, congenital malformations, and findings of the umbilical cord. Significant difference in frequencies was calculated by using χ2 tests. Results Frequency of FUAs was 3.1% or 22 in 702 infants with frequency by sex being 2.0% or 7 in 337 male infants and 4.1% or 15 in 365 female infants. The frequency was significantly higher in female than in male infants (P < .001). Marginal insertion was found in 18.1% or 4 in 22 cases of FUAs and 4.1% or 29 in 702 infants. The frequency of marginal insertion was 42.8% or 3 in 7 male infants and 6.6% or 1 in 15 female infants with FUAs. Marginal insertion was significantly associated with FUAs especially in male infants (P < .001). Velamentous inser765
766 Fujikura
March 2003 Am J Obstet Gynecol
Fig 1. FUAs (hematoxylin-eosin stain, original magnification 30). Two umbilical arteries are closely located in process of forming FUAs.
Fig 2. FUAs (hematoxylin-eosin stain, original magnification 30). Two umbilical arteries fused together with narrow channel.
Table I. Placental and fetal findings of 24 cases with fused umbilical arteries or single umbilical artery Case No.
Gestational week
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
40 38 37 39 39 39 41 40 38 40 40 33 42 38 41 41 38 39 39 40 38 39 40 36
Birth weight (g) 3032 3026 2276 2622 3104 3520 3056 3196 2940 3714 3102 2094 3440 3160 3000 3350 3460 2800 3110 3550 3260 3160 2974 1190
Sex
Placental weight (g)
F F F M F F F F M F F F F M M F M F M M F F F M
510 450 390 360 440 630 610 550 420 420 370 350 520 470 540 520 500 490 340 430 660 450 450 200
tion was 4.5% or 1 in 22 cases of FUAs and 0.7% or 5 in 702 infants. Velamentous insertion was found in 5 male infants only. Velamentous insertion was also significantly associated with FUAs in male infants (P < .0001). The Table shows 22 cases of FUAs and 2 cases of SUAs with gestational age, birth weight, sex, placental weight, findings of the umbilical cord, and associated congenital malformations. Mean values of gestational age, birth weight, and placental weight in 22 cases of FUAs were 39.0 ± 1.8 weeks, 3089.6 ± 387.9 g, and 473.6 ± 89.5 g, respectively. Mean values of gestational age, birth weight, and placental weight in 337 male and 365 female infants
Findings of cord and fetal malformation Fuse at 5 cm (from placental cord insertion) Fuse at 1 cm Fuse at 3 cm Fuse at 1 cm Fuse at 1 cm and divide at 0.5 cm Fuse at 2.5 cm Fuse at 4.0 cm Fuse at 1.0 cm Fuse at 5.0 cm and divide at 4.0 cm, velamentous insertion Fuse at 2.0 cm Fuse at 0.8 cm Fuse at 1.0 cm Fuse at 5.0 cm Fuse at 6.0 cm, marginal insertion Fuse at 1.5 cm, marginal insertion Fuse at 0.9 cm, marginal insertion Fuse at 2.0 cm and divide at 1.0 cm Fuse at 2.5 cm and divide at 1.5 cm Fuse at 0.5 cm Fuse at 3.7 cm, marginal insertion Fuse at 1.5 cm and divide at 0.8 cm Fuse at 1.8 cm Single umbilical artery Single umbilical artery, velamentous insertion, cleft palate, cleft lip, cerebral malformation
were 38.9 ± 1.4 weeks and 39.2 ± 1.3 weeks, 3083.5 ± 387.7 g and 3037.3 ± 387.9 g, 494.6 ± 78.5 g and 490.5 ± 84.1 g, respectively. Although premature infants are present with FUAs in Table I, mean values of gestational age, birth weight, and placental weight in 22 cases of FUAs were within normal range. Mean distance of the fused points from the placental cord insertion was 2.3 ± 1.6 cm. In the Table, 5 of 22 cases show both arterial fusion and division in the same umbilical cord. The length of FUA varied from 0.5 cm to 1.0 cm in the 5 cases. There was no congenital malformation in 22 infants with FUAs. One infant with SUA was premature and had
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Volume 188, Number 3 Am J Obstet Gynecol
cleft palate, cleft lip, cerebral malformation, and velamentous insertion. The frequency of SUAs was 0.2% or 2 in 702 infants. Comment Single umbilical artery may result from primary aplasia or the consequence of atrophy of one artery.1 The cause of FUAs may be Hyrtl’s anastomosis of two umbilical arteries, which are considered to be a normal physiologic fusion.1 In this study, 5 of 22 FUAs showed both arterial fusion and division in the same umbilical cord. This finding seems to support that FUA is more likely caused by Hyrtl’s anastomosis, which shows fusion and division in the chorionic arteries.4 If FUAs could be considered as a type of SUA, arterial fusion (Hyrtl’s anastomosis) may be included in the cause along with aplasia and atrophy. FUAs were associated with marginal insertion (18.1% or 4 in 22 cases) and velamentous insertion (4.5% or 1 in 22 cases). Marginal and velamentous insertions are reported to occur in 6.8% and 1.1%, respectively, of the placentas in singletons1 and in 18% and 9.3%, respectively, among infants with SUAs.5 These abnormal insertions of the umbilical cord are found more in both FUAs and SUAs than in the control. The frequency of FUAs of 4.1% was higher in female than 2.0% in male infants. SUA occurs slightly more frequently in female than in male infants with a male/female ratio of 0.85:1.5 The frequency of SUA was low and 0.2% or 2 in 702 infants in this study. The low incidences of SUAs are reported among the Japanese (0.20%-0.48%).5 SUA is often accompanied by congenital malformations and low birth weight,1,2,5,6 but there was no evidence of fetal abnormalities with FUAs in this study. This suggests that SUA itself may not be a cause of congenital malformations and low birth weight. Sepulveda et al3 reported that one of five fetuses with FUAs was associated
with unilateral renal agenesis with a subsequent diagnosis of Hallermann-Streiff syndrome. In their study, the area in which two umbilical arteries joined to form a single distal umbilical artery about 12 to 18 cm from the placental cord insertion was found in three cases. The maximal distance of FUAs from the placental cord insertion was 6 cm in this study and so the cause of FUAs could be different from their study. In relation to this study, supernumerary umbilical vessels related to vascular division were examined by the same method near the placental cord insertion. The frequency of supernumerary umbilical vessels was 24.8% or 96 in 387 cases. Mean distance of the divided points from the placental cord insertion was 1.2 ± 0.4 cm in the divided veins and 1.4 ± 0.5 cm in the divided arteries. The high frequencies of supernumerary umbilical vessels and FUAs indicate that normal vascular division and fusion that occur in the chorionic plate start in the umbilical cord near the placental cord insertion. It is important to note that both arterial fusion and division coexisted in 5 cases of 22 FUAs. REFERENCES
1. Benirschke K, Kaufmann P. Pathology of the human placenta. 4th ed. New York: Springer-Verlag; 2000. p. 341-2, 355, 363-6. 2. Fox H. Pathology of the placenta. 2nd ed. London: WB Saunders; 1997. p. 421-5. 3. Sepulveda W, Dezerega V, Carstens E, Gutierrez J. Fused umbilical arteries: prenatal sonographic diagnosis and clinical significance. J Ultrasound Med 2001;20:59-62. 4. Ullberg U, Sandstedt B, Lingman, G. Hyrtl’s anastomosis, the only connection between the two umbilical arteries: a study in full term placentas from AGA infants with normal umbilical artery blood flow. Acta Obstet Gynecol Scand 2001;80:1-6. 5. Heifetz SA. Single umbilical artery: a statistical analysis of 237 autopsy cases and review of literature. Perspect Pediatr Pathol 1984;8:345-78. 6. Froehlich LA, Fujikura T. Significance of a single umbilical artery: report from the collaborative study of cerebral palsy. Am J Obstet Gynecol 1966;94:274-9.