Single umbilical artery and risk of congenital malformation: population‐based study in Norway

Abstract

Objectives Single umbilical artery (SUA) is associated with congenital malformations in most organ systems, but reported findings have not been consistent. While it has been suggested that genetic and persisting environmental factors influence the development of SUA, it is not known whether there is an increased risk of recurrence in a subsequent pregnancy of the same woman. The aims of this study were to investigate the occurrence of, and risk factors for, SUA in Norway, to assess its association with congenital malformations and trisomies 13, 18 and 21 and to study the risk of recurrence of SUA in subsequent pregnancies. Methods This was a population‐based study of all (n = 918 933) singleton pregnancies of > 16 weeks' gestation recorded in the Medical Birth Registry of Norway from 1999 to 2014. To identify risk factors and congenital malformations associated with SUA, generalized estimating equations and logistic regression were used to calculate odds ratios (OR) with 95% CIs. ORs were also calculated for the recurrence of SUA in subsequent pregnancy. Results The occurrence of SUA in our population was 0.46% (4241/918 933). Parity ≥ 4, smoking, maternal pregestational diabetes, epilepsy, chronic hypertension, previous Cesarean delivery and conception by assisted reproductive technology increased the odds of having SUA. There was a particularly strong association between SUA and gastrointestinal atresia or stenosis in the neonate, with ORs of 25.8 (95% CI, 17.0–39.1) and 20.3 (95% CI, 13.4–30.9) for esophageal and anorectal atresia or stenosis, respectively, followed by an OR of 5.9 (95% CI, 1.9–18.5) for renal agenesis. SUA was associated with an up to 7–8 times increased risk of congenital heart defects. There was an association with microcephaly, congenital hydrocephalus and other congenital malformations of the brain and spinal cord. Diaphragmatic hernia, limb reductions and cleft lip or palate had a weaker association with SUA, with ORs ranging from 4.8 to 2.8. The associations with trisomy 18 and 13 were equally strong (OR 14.4 (95% CI, 9.3–22.4) and OR 13.6 (95% CI, 6.7–27.8), respectively), and the risk of trisomy 21 was doubled (OR 2.1 (95% CI, 1.2–3.6)). Pregnancies with SUA, with or without an associated malformation, had a 2‐fold increased risk for SUA in a subsequent pregnancy. Conclusions SUA is associated strongly with gastrointestinal atresia or stenosis, suggesting common developmental mechanisms. The increased risk of recurrence of SUA suggests that genetic and/or persisting environmental factors influence the risk. We found that SUA had equally strong associations with trisomies 13 and 18. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Isolated fetal neural tube defects associate with increased risk of placental pathology: evidence from the Collaborative Perinatal Project

“…While cases with anencephaly also had an increased risk of placental hypermaturity and terminal villi pathology, they had lower birthweight-to-placental size ratios than controls, which may be indicative of reduced placental efficiency 34 and may compromise maternal-fetal exchange 35 . These cases also had increased odds of having a single umbilical artery, which is consistent with reports of population-level associations between congenital anomalies of the brain and spinal cord and single umbilical artery 36 and is associated with low birthweight 37 . Together, these pathologies may have led to the lower birthweight and younger gestational age at birth we observed in cases with anencephaly in comparison to controls.…”

Isolated single umbilical artery and the risk of adverse perinatal outcome and third stage of labor complications: A population‐based study

“…Single umbilical artery (SUA) cords occurs in approximately 0.5-1% of singleton pregnancies 1,2 and is combined with congenital malformations in 11-30% of all cases. [1][2][3][4][5][6] Isolated single umbilical artery (iSUA) is the term used if no other malformation is observed.…”

Investigation of the risk factors of anorectal malformations

“…The most obvious finding was that 13 children (9.6%) in the case group had SUA, while no fetus in the control group had SUA. SUA, which occurs in approximately 0.46–5.9% of live births, is strongly associated with anorectal atresia or stenosis (Ebbing, Kessler, Moster, & Rasmussen, 2020). Some researchers have argued that the placental arteries and the hindgut might be jointly regulated by the same genes, and SUA may also disturb the hemodynamics of the embryo and cause corresponding malformations (Griffith, Wiley, & Sanders, 1992; Martínez‐Frías, Bermejo, Rodríguez‐Pinilla, & Prieto, 2008).…”