Ultrasound Obstet Gynecol. 2019 May 27. doi: 10.1002/uog.20359. [Epub ahead of print]
Single umbilical artery and risk of congenital malformations: a population-based study in Norway.
Single umbilical artery is associated to congenitalmalformations in most organ systems, but the pattern has not been consistent. Genetic and persisting environmental factors have been suggested to influence the development of single umbilical artery, but if there is an increased risk of single umbilical artery in a subsequent pregnancy of the same woman is not known. Whether there is an effect of the sex of the fetus on the risk of single umbilical artery and associated malformations is unclear. Most studies of single umbilical artery and malformations are based on pathology reports or hospital based series which may be affected by selection bias, warranting population-based studies.
To investigate the occurrence, risk factors, associated malformations and trisomy 13, 18 and 21 in pregnancies with single umbilical artery cords in Norway, and to study the risk of recurrence of SUA in subsequent pregnancies.
This was a population-based study of all singleton pregnancies with gestational age >16 weeks using data from the Medical Birth Registry of Norway from 1999-2014 (n=918 933). Odds ratios (OR) with 95% confidence intervals (CI) were calculated for single umbilical artery and for malformations associated with single umbilical artery using Generalized Estimating Equations and logistic regression. We also calculated odds ratio for recurrence of single umbilical artery in a subsequent pregnancy in the same woman.
The occurrence of single umbilical artery in our population was 0.46 % (4241/918 933). Parity 4+, smoking, maternal diabetes, epilepsy, chronic hypertension, a previous caesarean delivery, and pregnancies conceived by assisted reproductive technology increased the risk of single umbilical artery. There was an especially strong association of single umbilical artery to gastro-intestinal atresia in the neonate, with an OR 25.8 -20.33 (95%CI 17.0-39.1, and 13.4-30.9, esophageal and anorectal atresia or stenosis, respectively), followed by renal agenesis OR 5.9 (95%CI 1.9-18.5). Single umbilical artery was associated with up to 7-8 times increased risk of congenital heart defects. Diaphragmatic hernia, limb reductions, cleft lip or palate had a weaker association with ORs ranging from 4.8-2.8. The association to trisomy 18 and 13 was equally strong (OR 14.4, (95%CI 9.3-22.4) and OR 13 (95%CI 6.7-27.8), respectively), and the risk of trisomy 21 doubled (OR 2.1 (95%CI 1.2-3.6)). Women who carried a fetus with single umbilical artery (with or without malformations) in one pregnancy had doubled and higher risk of single umbilical artery in the subsequent pregnancy.
Single umbilical artery was strongly associated with gastro intestinal atresia, suggesting common developmental mechanisms. The increased risk of recurrence of single umbilical artery and malformations suggests that genetic and or persisting environmental factors influence the risks. We found that SUA had an equally strong association to trisomy 13 and 18. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Intestinal atresia; Malformations; Recurrence; Single umbilical artery; Trisomy; Umbilical cordPMID: 31132166 DOI: 10.1002/uog.20359