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True umbilical cord knot and obstetric outcome
International Journal of Gynecology and Obstetrics 122 (2013) 18–21
Contents lists available at SciVerse ScienceDirect
International Journal of Gynecology and Obstetrics journal homepage: www.elsevier.com/locate/ijgo
CLINICAL ARTICLE
True umbilical cord knot and obstetric outcome Sari Räisänen a,⁎, Leena Georgiadis a, b, Maija Harju a, b, Leea Keski-Nisula a, b, Seppo Heinonen a, b a b
Department of Obstetrics and Gynecology, Kuopio University Hospital, Kuopio, Finland University of Eastern Finland, Kuopio, Finland
a r t i c l e
i n f o
Article history: Received 6 December 2012 Received in revised form 12 February 2013 Accepted 7 March 2013 Keywords: Delivery Obstetrics Registries Risk factors Umbilical cord knot
a b s t r a c t Objective: To identify risk factors for true umbilical cord knot and to evaluate its association with fetal death, premature birth, low birth weight, small-for-gestational-age (SGA) infants, low Apgar score at 1 and 5 minutes, fetal venous pH of 7.15 or lower, and need for neonatal intensive care in singleton pregnancies. Methods: The total population of women who delivered at Kuopio University Hospital, Kuopio, Finland, between January 2000 and August 2012 was reviewed. Risk factors for umbilical cord knot and its association with adverse pregnancy outcome were evaluated separately among women with and without true cord knot via logistic regression analysis. Results: Overall, 340 (1.2%) of 27 537 singleton pregnancies were affected by umbilical cord knot, with increased incidence associated with advanced maternal age, multiparity, previous spontaneous abortion, polyhydramnios, and diabetes mellitus. Umbilical cord knot was associated with a 1.58-, 8.08-, 3.90-, 3.17-, 1.67-, and 2.00-fold increased risk of neonatal intensive care, fetal death, premature birth, SGA infants, and low Apgar score at 1 and 5 minutes, respectively. Conclusion: True umbilical cord knot is relatively common and is associated with increased incidence of SGA infants, premature birth, need for neonatal intensive care, and fetal death. © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction
2. Materials and methods
True umbilical cord knot is a relatively common complication that occurs in 0.3%–1.3% of all pregnancies [1–4]. The condition is associated with several maternal reproductive risk factors such as advanced maternal age, multiparity, obesity, previous spontaneous abortion, chronic hypertension, and gestational diabetes, in addition to various obstetric variables such as genetic amniocentesis, male fetus, polyhydramnios, long umbilical cord, and prolonged gestation. In several studies, it has been related to adverse pregnancy and delivery outcomes such as cord accidents (cord prolapse and nuchal cord [2,3]), fetal acidosis [4], low Apgar score at 1 minute [3], higher risk of cesarean delivery [2,3], and intrauterine fetal death [2–5]. The aim of the present study was to determine risk factors associated with true umbilical cord knot and to evaluate whether it was associated with adverse pregnancy outcomes among the total population of singleton births between January 2000 and August 2012 at a university hospital in Finland. A similar study using data for 1990 − 1999 from the same catchment area was conducted previously [3]; the present study also aimed to estimate whether the incidence of true knot and its association with adverse perinatal outcomes had changed over time.
The present hospital-based case–control study used retrospective data for January 1, 2000, to August 31, 2012, collected from the birth register at Kuopio University Hospital, Kuopio, Finland. The study also included information on maternal and neonatal birth characteristics and perinatal outcomes of all infants delivered after 22 gestational weeks or with a birth weight of at least 500 g during the study period. Background characteristics such as obstetric/gynecologic history and information on previous diseases and substance use (smoking and alcohol consumption) were obtained via paper questionnaire up to 2008 and via electronic questionnaire thereafter. Information was supplemented by midwives during prenatal visits and childbirth. Permission to use the data gathered from the birth register was granted by the Ethics Committee of Kuopio University Hospital. Written informed consent for the collection of information and its subsequent use in scientific research was provided by all pregnant women. The placenta and umbilical cord were checked clinically and measured (weight of placenta, and length and insertion of umbilical cord) by midwives after all vaginal and cesarean deliveries. Placenta previa and placental abruption were diagnosed clinically or on ultrasonography, as described elsewhere [6,7]. Gestational age was defined based on the date of the last menstrual period, and by ultrasound if there was a disparity of more than 3 days on the first-trimester measurement or 7 days on the second-trimester measurement. Assisted reproductive technology (ART) covered in vitro fertilization, intracytoplasmic sperm injection, frozen embryo replacement, and egg donation. Bleeding was defined as a patient who had been hospitalized for hemorrhage
⁎ Corresponding author at: Department of Obstetrics and Gynecology, Kuopio University Hospital, PO Box 1777, 70211 Kuopio, Finland. Tel.: + 358 503378258; fax: + 358 17172486. E-mail address: [email protected].fi (S. Räisänen).
0020-7292/$ – see front matter © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijgo.2013.02.012
S. Räisänen et al. / International Journal of Gynecology and Obstetrics 122 (2013) 18–21
after 24 weeks of gestation. Pre-eclampsia was defined as gestational blood pressure of at least 140/90 mm Hg and at least 500 mg of protein in the urine over 24 hours. Gestational diabetes mellitus was defined by high blood glucose levels during pregnancy in an oral 75-g glucose tolerance test (fasting ≥4.8 mmol/L [until 2008] or ≥5.3 mmol/L [from 2009]; after 1 hour ≥10.0 mmol/L; and after 2 hours ≥8.6 mmol/L). Small for gestational age (SGA) was defined as a birth weight below the 10th percentile sex-specific population reference mean for gestational age. The presence of elevated liver enzymes was defined as described elsewhere [8]. Marital status was recorded as married, cohabiting, or single. Multiple pregnancies were excluded from the analysis. Differences between the women with umbilical cord knot and the control group (all other women with singleton pregnancies who delivered at the study hospital during the study period) were assessed using the χ 2 test for dichotomous variables and the Mann–Whitney U test for continuous variables. Reproductive risk factors for umbilical cord knot and its association with adverse pregnancy outcomes (need for neonatal intensive care, fetal death, premature birth [b37 gestational weeks], low birth weight [b 2500 g], SGA infant, Apgar score ≤6 at 1 and 5 minutes, and fetal venous pH ≤7.15) were defined separately for each outcome via logistic regression analysis. Possible independent variables were selected based on univariate analyses (P b 0.1). If a woman was affected by several adverse outcomes (e.g. SGA infants Table 1 Reproductive risk factors for umbilical cord knot among women with singleton pregnancies (n = 27 537).a Risk factors
Women with Control group umbilical cord (n = 27 197) knot (n = 340)
P value
Maternal age, y b18 18–34 ≥35 Parity Nulliparous Multiparous Pre-pregnancy BMI ≤24.9 25–29.9 30.0–34.9 ≥35.0 Spontaneous abortion 0 1 ≥2 Prior termination ≥7 deliveries Prior cesarean Prior fetal demise IUD use before pregnancy Infertility ART Gestational diabetes mellitus Maternal diabetes mellitus Placental abruption Pre-eclampsia Placenta previa Elevated liver enzymes Bleeding Oligohydramnios (AFI 0–5 cm) Polyhydramnios (AFI >25 cm) Anemia (Hb below 100 g/L) Smoking during pregnancy (>5 cigarettes per day) Alcohol consumption during pregnancy Married or cohabiting
30.7 ± 6.1 3 (0.9) 242 (71.2) 95 (27.9)
29.0 ± 5.6 177 (0.7) 22 242 (81.8) 4778 (17.6)
≤0.001 ≤0.001
95 (27.9) 245 (72.1)
11 248 (41.4) 15 949 (58.6)
197/326 (60.4) 86/326 (26.4) 27/326 (8.3) 16/326 (4.9)
17 171/25 894 (66.3) 5492/25 894 (21.2) 2184/25 894 (8.4) 1047/25 894 (4.0)
246 (72.4) 73 (21.5) 21 (6.2) 40 (11.8) 6 (1.8) 36 (10.6) 6/326 (1.8) 37 (10.9) 12 (3.5) 7/329 (2.1) 56 (16.5) 8 (2.4) 4 (1.2) 14 (4.1) 2 (0.6) 5 (1.5) 0/52 (0.0) 40 (11.8) 30 (8.8) 13 (3.8) 34/335 (10.1)
21 903 (80.5) 3943 (14.5) 1351 (5.0) 3286 (12.1) 247 (0.9) 2119 (7.8) 216/25 379 (0.9) 2109 (7.8) 1089 (4.0) 735/26 674 (2.8) 3726 (13.7) 234 (0.9) 178 (0.7) 1167 (4.3) 213 (0.8) 278 (1.0) 12/3849 (0.3) 3265 (12.0) 1277 (4.7) 745 (2.7) 2820/26 927 (10.5)
3/329 (0.9)
241/26 154 (0.9)
0.99
310 (91.2)
24 218 (89.0)
0.21
≤0.001
0.10
and premature birth), each was considered an independent outcome and the pregnancy was included in both categories. Differences were deemed to be significant if the P value was below 0.05. Data were analyzed using SPSS version 19.0 (IBM, Armonk, NY, USA). 3. Results Of the 27 537 women with singleton pregnancies who gave birth at Kuopio University Hospital during the study period, 340 (1.2%) experienced true umbilical cord knot. In univariate tests, these women were significantly older than those in the control group (P ≤ 0.001) (Table 1). They were also more frequently multiparous (P ≤ 0.001), had experienced more previous spontaneous abortions (P = 0.001), and more commonly used an intrauterine device (IUD) before pregnancy (P = 0.03) compared with women in the control group (Table 1). Furthermore, compared with women in the control group, significantly more women with umbilical cord knot had diabetes mellitus (P = 0.003) and polyhydramnios (P ≤ 0.001). However, after adjustment, only advanced maternal age (≥35 years), multiparity, previous spontaneous abortion, polyhydramnios, and diabetes mellitus were independent reproductive risk factors for umbilical cord knot (Table 2). Pregnancy and delivery characteristics were similar for women in the study and control groups, with the exceptions of mean umbilical cord length and fetal gender. Umbilical cords were significantly longer in cases of cord knot (mean, 76.3 ± 16.2 vs 59.4 ± 13.5 cm; P ≤ 0.001) and there was a higher proportion of male infants (61.5% vs 51.3%; P ≤ 0.001) compared with the control group (Table 3). After adjustment for confounding factors, umbilical cord knot was significantly associated with increased risk of several adverse perinatal and early neonatal outcomes. The adjusted odds of neonatal intensive care, intrauterine fetal death, premature birth, SGA infants, and low Apgar score at 1 and 5 minutes were, respectively, 1.58- 8.08-, 3.90-, 3.17-, 1.67-, and 2.00-fold higher among women with umbilical cord knot than among women in the control group (Table 4). Intrauterine fetal death was rare, occurring only in 81 of the 27 197 Table 2 Umbilical cord knot (n = 313) among women with singleton pregnancies (n = 24 456).a Characteristics
0.001
0.86 0.10 0.06 0.06 0.03 0.66 0.49 0.14 0.003 0.24 0.88 0.69 0.42 0.69 0.89 ≤0.001 0.23 0.85
Abbreviations: AFI, amniotic fluid index; ART, assisted reproductive technology; BMI, body mass index (calculated as weight in kilograms divided by the square of height in meters); Hb, hemoglobin; IUD, intrauterine device. a Values are given as mean ± SD or number (percentage) unless otherwise indicated.
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Maternal age, y b18 18–34 ≥35 Parity Nulliparous Multiparous Pre-pregnancy BMI ≤24.9 25–29.9 30.0–34.9 ≥35.0 Spontaneous abortion 0 1 ≥2 ≥7 deliveries Prior cesarean Prior fetal demise IUD use before pregnancy Polyhydramnios (AFI >25) Maternal diabetes mellitus
Adjusted odds ratiob (95% confidence interval) 1.88 (0.46–7.72) 1 1.56 (1.21–2.02) 0.70 (0.53–0.91) 1 1 1.30 (1.00–1.69) 1.05 (0.74–1.47) —c 1 1.36 (1.03–1.80) 1.13 (0.71–1.79) 1.28 (0.55–2.96) 1.07 (0.74–1.54) 1.35 (0.55–3.34) 1.23 (0.86–1.76) 1.90 (1.30–2.79) 2.53 (1.22–5.22)
Abbreviations: AFI, amniotic fluid index; BMI, body mass index (calculated as weight in kilograms divided by the square of height in meters); IUD, intrauterine device. a Only cases for which all information was available were included. b Adjusted for maternal age, parity, pre-pregnancy BMI, spontaneous abortion, ≥7 deliveries, prior cesarean, prior fetal demise, IUD use before pregnancy, polyhydramnios, and maternal diabetes mellitus. c Could not be measured owing to small number of cases.
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S. Räisänen et al. / International Journal of Gynecology and Obstetrics 122 (2013) 18–21
Table 3 Pregnancy/delivery characteristics and delivery interventions.a Characteristic
Women with umbilical cord knot (n = 340)
Control group (n = 27 197)
Gestational age, wk ≤27 28–31 32–36 37–40 41–42 ≥43 Cesarean delivery No Elective Emergency Vacuum delivery Placental/fetal mass ratio, %b Umbilical cord length, cm Female Male Velamentous cord insertion Gender Female Male Birth weight, g
38.9 ± 2.6 4/338 (1.2) 7/338 (2.1) 18/338 (5.3) 234/338 (69.2) 75/338 (22.2) 0/338 (0.0)
39.2 ± 2.1 188/27 071 (0.7) 216/27 071 (0.8) 1208/27 071 (4.5) 19 509/27 071 (72.1) 5934/27 071 (21.9) 16/27 071 (0.1)
a b
Table 5 Delivery characteristics among stillborn infants (n = 81).a P value
0.07 0.11
0.36 277 (81.5) 26 (7.6) 37 (10.9) 22/245 (9.0) 18.8 ± 5.6 76.3 ± 16.2 75.2 ± 15.2 77.0 ± 16.8 4 (1.2)
22 911 (84.2) 1852 (6.8) 2434 (8.9) 1738/21 154 (8.2) 17.7 ± 6.0 59.4 ± 13.5 58.1 ± 13.3 60.5 ± 13.6 629 (2.3)
131 (38.5) 209 (61.5) 3518.4 ± 750.6
13 246/27 189 (48.7) 13 943/27 189 (51.3) 3479.6 ± 598.9
0.67 0.84 ≤0.001 ≤0.001 0.17 ≤0.001
0.34
Values are given as mean ± SD or number (percentage) unless otherwise indicated. Placental weight in grams divided by birth weight in grams × 100.
(0.3%) control pregnancies. Three (3.7%) of these infants had umbilical cord knots. There were no significant differences between stillborn infants with and without umbilical cord knot in terms of gestational age, mean umbilical cord length, cord insertion, gender, and occurrence of polyhydramnios (Table 5). 4. Discussion The incidence of true umbilical cord knot among women with singleton pregnancies (1.2%) corresponded well to results from previous general studies [2,4] and studies involving the same catchment area [3]. Changes in the study population from the earlier study [3] were minimal, except that the proportion of overweight women (body mass index [calculated as weight in kilograms divided by the square of height in meters] > 25) was up to 2-fold higher during the most recent study period. Furthermore, the proportions of women with advanced maternal age and those affected by placental abruption and polyhydramnios were slightly increased, whereas the percentages of women with maternal diabetes and pre-eclampsia were lower. After adjustment, advanced maternal age, multiparity, previous spontaneous abortion, polyhydramnios, and maternal diabetes mellitus were
Characteristic Gestational age, wk ≤27 28–31 32–36 37–40 41–42 ≥43 Umbilical cord length, cm Velamentous cord insertion Gender Female Male Polyhydramnios a
Umbilical cord knot (n = 3)
Control group (n = 78)
0 (0.0) 1 (33.3) 0 (0.0) 2 (66.7) 0 (0.0) 0 (0.0) 74.0 ± 49.3 0 (0.0)
32 (41.0) 5 (6.4) 15 (19.2) 23 (29.5) 3 (3.8) 0 (0.0) 51.7 ± 17.8 3 (3.8)
0 (0.0) 3 (100.0) 0 (0.0)
37/77 (48.1) 40/77 (51.9) 6 (7.7)
P value 0.20
0.52 0.72 0.10
0.63
Values are given as number (percentage) or mean ± SD unless otherwise indicated.
significantly associated with an increased incidence of true umbilical cord knot. Advanced maternal age and previous spontaneous abortion are likely to be associated with multiparity but polyhydramnios and maternal diabetes mellitus are not affected by parity. Both gestational diabetes and diabetes mellitus are associated with an increased risk of polyhydramnios [9,10], which may explain the increased incidence of umbilical cord knot among women with diabetes mellitus in the present study. In the present study, there was a higher proportion of male fetuses and cords were, on average, 16.9 cm longer among infants with umbilical cord knot than in the control group—consistent with previous results from a study at Kuopio University Hospital [3]. These results might be explained by the significantly greater umbilical cord length among male, compared with female, infants with umbilical cord knot (77.0 ± 16.8 vs 75.2 ± 15.2 cm; P ≤ 0.001). A higher incidence of umbilical cord knot among male fetuses was also previously found in other studies [1,2,4] but the databases did not include information on length of cord. Furthermore, following on from studies of male predominance in pregnancies affected by gestational diabetes, it is also possible that some of the independent effects of diabetes on umbilical cord knots can be explained by fetal gender [1]. True umbilical cord knot was significantly associated with adverse pregnancy outcome; affected infants were more likely to have lower Apgar scores and be born preterm and SGA, and subsequently require more treatment after birth in a neonatal unit. However, the clinical significance of low Apgar scores is likely to be minor because fetal venous pH values were not affected by umbilical cord knot, consistent with a previous study from the same catchment area [3]. Furthermore, in another case–control study [11], umbilical artery gas values did not
Table 4 Perinatal and early neonatal outcomes among infants with umbilical cord knot and control group.a Outcome
Women with umbilical cord knot (n = 340)
Control group, (n = 27 197)
Unadjusted odds ratio (95% confidence interval)
Adjusted odds ratio (95% confidence interval)c
Need for neonatal intensive care Fetal death Premature birth (b37 weeks)b LBW (b2500 g) SGA (b90th percentile) Low 1-minute Apgar score (b7) Low 5-minute Apgar score (b7) Fetal venous pH b7.15 at birth
46 3/339 29/338 22 41 32 18 4/197
2489 (9.2) 81/27 178 (0.3) 1612/27 071 (6.0) 1288/27 194 (4.7) 2739/27 194 (10.1) 1465 (5.4) 734 (2.7) 393/14 837 (2.6)
1.55 2.99 1.48 1.39 1.22 1.83 2.02 0.76
1.58 8.08 3.90 1.52 3.17 1.67 2.00 0.95
(13.5) (0.9) (8.6) (6.5) (12.1) (9.4) (5.3) (2.0)
(1.14–2.13) (0.94–9.50) (1.01–2.18) (0.90–2.15) (0.88–1.70) (1.26–2.64) (1.25–3.26) (0.28–2.06)
(1.07–2.33)d (1.50–43.57)d (2.48–6.13)e (0.66–3.50) (2.18–4.62)e (1.10–2.54)d (1.13–3.54)d (0.34–2.61)
Abbreviations: LBW, low birth weight; SGA, small for gestational age. a Adjusted for umbilical cord knot, maternal age, parity, pre-pregnancy body mass index, spontaneous abortion, ≥7 deliveries, prior cesarean, prior fetal demise, intrauterine device use before pregnancy, maternal diabetes mellitus, polyhydramnios, gestational age, umbilical cord length, and gender. b Not adjusted for gestational age. c Only cases for which all information was available were included. d P ≤ 0.05. e P ≤ 0.001.
S. Räisänen et al. / International Journal of Gynecology and Obstetrics 122 (2013) 18–21
differ between infants with and without umbilical cord knot. However, a large retrospective observational study reported a significantly higher incidence of fetal acidosis (umbilical venous pH b 7.10) among infants with umbilical cord knot [4]. In the present study, a 3.2-fold higher risk of being born SGA indicated chronic uteroplacental insufficiency in infants affected by umbilical cord knot, although the mean birth weight (3518.4 ± 750.6 vs 3479.6 ± 598.9 g; P = 0.34) did not differ significantly between the study and the control groups. By contrast, a higher incidence of obesity and diabetes among affected pregnancies may have masked the negative effect of umbilical cord knot on fetal growth. Previous results have not shown a significant association between umbilical cord knot and fetal growth [2,3], but obesity and diabetes among the pregnant population have become more prevalent and the rates are still increasing [2,3]. Similarly, as in the present investigation, an increased risk of intrauterine fetal death associated with umbilical cord knot has been reported in previous studies [2–5]. Interestingly, umbilical cord knot was not associated with ART, placenta previa, or placental abruption. Moreover, its intrapartum clinical significance was minor, with no significant differences between the study and the control groups with regard to rates of cesarean delivery and vacuum extraction. The most important strength of the present study was that the data included the total population of women attending the same obstetric department between January 2000 and August 2012; thus, the likelihood of selection bias—which is inherent in multicenter studies— was decreased, while the validity of the results was increased. Furthermore, several clinical studies have validated the data used in the present study [6,7,12–14]. In conclusion, associations between adverse pregnancy outcomes and true umbilical cord knot indicate that the complication may impair fetal growth and wellbeing during pregnancy. During birth, however, its clinical significance seems to be minor. At present, little—if anything—can be done to prevent fetal death ascribable to the tightening of an umbilical cord knot because diagnosis using ultrasonography is challenging; however, the risk of death is still small [15,16]. Conflict of interest The authors have no conflicts of interest.
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References [1] Aibar L, Puertas A, Valverde M, Carrillo MP, Montoya F. Fetal sex and perinatal outcomes. J Perinat Med 2012;40(3):271–6. [2] Hershkovitz R, Silberstein T, Sheiner E, Shoham-Vardi I, Holcberg G, Katz M, et al. Risk factors associated with true knots of the umbilical cord. Eur J Obstet Gynecol Reprod Biol 2001;98(1):36–9. [3] Airas U, Heinonen S. Clinical significance of true umbilical knots: a population-based analysis. Am J Perinatol 2002;19(3):127–32. [4] Joura EA, Zeisler H, Sator MO. Epidemiology and clinical value of true umbilical cord knots. Wien Klin Wochenschr 1998;110(6):232–5. [5] Oron T, Sheiner E, Shoham-Vardi I, Mazor M, Katz M, Hallak M. Risk factors for antepartum fetal death. J Reprod Med 2001;46(9):825–30. [6] Toivonen S, Heinonen S, Anttila M, Kosma VM, Saarikoski S. Reproductive risk factors, Doppler findings, and outcome of affected births in placental abruption: a population-based analysis. Am J Perinatol 2002;19(8):451–60. [7] Papinniemi M, Keski-Nisula L, Heinonen S. Placental ratio and risk of velamentous umbilical cord insertion are increased in women with placenta previa. Am J Perinatol 2007;24(6):353–7. [8] Heiskanen JT, Pirskanen MM, Hiltunen MJ, Mannermaa AJ, Punnonen KR, Heinonen ST. Insertion-deletion polymorphism in the gene for angiotensin-converting enzyme is associated with obstetric cholestasis but not with preeclampsia. Am J Obstet Gynecol 2001;185(3):600–3. [9] O'Sullivan EP, Avalos G, O'Reilly M, Dennedy MC, Gaffney G, Dunne F, et al. the prevalence and outcomes of gestational diabetes mellitus using new diagnostic criteria. Diabetologia 2011;54(7):1670–5. [10] Haram K, Thordarson H, Nedrebø BG, Reigstad H. Diabetes mellitus in pregnancy. Tidsskr Nor Laegeforen 1996;116(29):3452–8. [11] Maher JT, Conti JA. A comparison of umbilical cord blood gas values between newborns with and without true knots. Obstet Gynecol 1996;88(5):863–6. [12] Heinonen S, Ryynänen M, Kirkinen P, Saarikoski S. Perinatal diagnostic evaluation of velamentous umbilical cord insertion: clinical, Doppler, and ultrasonic findings. Obstet Gynecol 1996;87(1):112–7. [13] Raatikainen K, Huurinainen P, Heinonen S. Smoking in early gestation or through pregnancy: a decision crucial to pregnancy outcome. Prev Med 2007;44(1): 59–63. [14] Raatikainen K, Kuivasaari-Pirinen P, Hippeläinen M, Heinonen S. Comparison of the pregnancy outcomes of subfertile women after infertility treatment and in naturally conceived pregnancies. Hum Reprod 2012;27(4):1162–9. [15] Rodriguez N, Angarita AM, Casasbuenas A, Sarmiento A. Three-dimensional highdefinition flow imaging in prenatal diagnosis of a true umbilical cord knot. Ultrasound Obstet Gynecol 2012;39(2):245–6. [16] Scioscia M, Fornalè M, Bruni F, Peretti D, Trivella G. Four-dimensional and Doppler sonography in the diagnosis and surveillance of a true cord knot. J Clin Ultrasound 2011;39(3):157–9.
Contents lists available at SciVerse ScienceDirect
International Journal of Gynecology and Obstetrics journal homepage: www.elsevier.com/locate/ijgo
CLINICAL ARTICLE
True umbilical cord knot and obstetric outcome Sari Räisänen a,⁎, Leena Georgiadis a, b, Maija Harju a, b, Leea Keski-Nisula a, b, Seppo Heinonen a, b a b
Department of Obstetrics and Gynecology, Kuopio University Hospital, Kuopio, Finland University of Eastern Finland, Kuopio, Finland
a r t i c l e
i n f o
Article history: Received 6 December 2012 Received in revised form 12 February 2013 Accepted 7 March 2013 Keywords: Delivery Obstetrics Registries Risk factors Umbilical cord knot
a b s t r a c t Objective: To identify risk factors for true umbilical cord knot and to evaluate its association with fetal death, premature birth, low birth weight, small-for-gestational-age (SGA) infants, low Apgar score at 1 and 5 minutes, fetal venous pH of 7.15 or lower, and need for neonatal intensive care in singleton pregnancies. Methods: The total population of women who delivered at Kuopio University Hospital, Kuopio, Finland, between January 2000 and August 2012 was reviewed. Risk factors for umbilical cord knot and its association with adverse pregnancy outcome were evaluated separately among women with and without true cord knot via logistic regression analysis. Results: Overall, 340 (1.2%) of 27 537 singleton pregnancies were affected by umbilical cord knot, with increased incidence associated with advanced maternal age, multiparity, previous spontaneous abortion, polyhydramnios, and diabetes mellitus. Umbilical cord knot was associated with a 1.58-, 8.08-, 3.90-, 3.17-, 1.67-, and 2.00-fold increased risk of neonatal intensive care, fetal death, premature birth, SGA infants, and low Apgar score at 1 and 5 minutes, respectively. Conclusion: True umbilical cord knot is relatively common and is associated with increased incidence of SGA infants, premature birth, need for neonatal intensive care, and fetal death. © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction
2. Materials and methods
True umbilical cord knot is a relatively common complication that occurs in 0.3%–1.3% of all pregnancies [1–4]. The condition is associated with several maternal reproductive risk factors such as advanced maternal age, multiparity, obesity, previous spontaneous abortion, chronic hypertension, and gestational diabetes, in addition to various obstetric variables such as genetic amniocentesis, male fetus, polyhydramnios, long umbilical cord, and prolonged gestation. In several studies, it has been related to adverse pregnancy and delivery outcomes such as cord accidents (cord prolapse and nuchal cord [2,3]), fetal acidosis [4], low Apgar score at 1 minute [3], higher risk of cesarean delivery [2,3], and intrauterine fetal death [2–5]. The aim of the present study was to determine risk factors associated with true umbilical cord knot and to evaluate whether it was associated with adverse pregnancy outcomes among the total population of singleton births between January 2000 and August 2012 at a university hospital in Finland. A similar study using data for 1990 − 1999 from the same catchment area was conducted previously [3]; the present study also aimed to estimate whether the incidence of true knot and its association with adverse perinatal outcomes had changed over time.
The present hospital-based case–control study used retrospective data for January 1, 2000, to August 31, 2012, collected from the birth register at Kuopio University Hospital, Kuopio, Finland. The study also included information on maternal and neonatal birth characteristics and perinatal outcomes of all infants delivered after 22 gestational weeks or with a birth weight of at least 500 g during the study period. Background characteristics such as obstetric/gynecologic history and information on previous diseases and substance use (smoking and alcohol consumption) were obtained via paper questionnaire up to 2008 and via electronic questionnaire thereafter. Information was supplemented by midwives during prenatal visits and childbirth. Permission to use the data gathered from the birth register was granted by the Ethics Committee of Kuopio University Hospital. Written informed consent for the collection of information and its subsequent use in scientific research was provided by all pregnant women. The placenta and umbilical cord were checked clinically and measured (weight of placenta, and length and insertion of umbilical cord) by midwives after all vaginal and cesarean deliveries. Placenta previa and placental abruption were diagnosed clinically or on ultrasonography, as described elsewhere [6,7]. Gestational age was defined based on the date of the last menstrual period, and by ultrasound if there was a disparity of more than 3 days on the first-trimester measurement or 7 days on the second-trimester measurement. Assisted reproductive technology (ART) covered in vitro fertilization, intracytoplasmic sperm injection, frozen embryo replacement, and egg donation. Bleeding was defined as a patient who had been hospitalized for hemorrhage
⁎ Corresponding author at: Department of Obstetrics and Gynecology, Kuopio University Hospital, PO Box 1777, 70211 Kuopio, Finland. Tel.: + 358 503378258; fax: + 358 17172486. E-mail address: [email protected].fi (S. Räisänen).
0020-7292/$ – see front matter © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijgo.2013.02.012
S. Räisänen et al. / International Journal of Gynecology and Obstetrics 122 (2013) 18–21
after 24 weeks of gestation. Pre-eclampsia was defined as gestational blood pressure of at least 140/90 mm Hg and at least 500 mg of protein in the urine over 24 hours. Gestational diabetes mellitus was defined by high blood glucose levels during pregnancy in an oral 75-g glucose tolerance test (fasting ≥4.8 mmol/L [until 2008] or ≥5.3 mmol/L [from 2009]; after 1 hour ≥10.0 mmol/L; and after 2 hours ≥8.6 mmol/L). Small for gestational age (SGA) was defined as a birth weight below the 10th percentile sex-specific population reference mean for gestational age. The presence of elevated liver enzymes was defined as described elsewhere [8]. Marital status was recorded as married, cohabiting, or single. Multiple pregnancies were excluded from the analysis. Differences between the women with umbilical cord knot and the control group (all other women with singleton pregnancies who delivered at the study hospital during the study period) were assessed using the χ 2 test for dichotomous variables and the Mann–Whitney U test for continuous variables. Reproductive risk factors for umbilical cord knot and its association with adverse pregnancy outcomes (need for neonatal intensive care, fetal death, premature birth [b37 gestational weeks], low birth weight [b 2500 g], SGA infant, Apgar score ≤6 at 1 and 5 minutes, and fetal venous pH ≤7.15) were defined separately for each outcome via logistic regression analysis. Possible independent variables were selected based on univariate analyses (P b 0.1). If a woman was affected by several adverse outcomes (e.g. SGA infants Table 1 Reproductive risk factors for umbilical cord knot among women with singleton pregnancies (n = 27 537).a Risk factors
Women with Control group umbilical cord (n = 27 197) knot (n = 340)
P value
Maternal age, y b18 18–34 ≥35 Parity Nulliparous Multiparous Pre-pregnancy BMI ≤24.9 25–29.9 30.0–34.9 ≥35.0 Spontaneous abortion 0 1 ≥2 Prior termination ≥7 deliveries Prior cesarean Prior fetal demise IUD use before pregnancy Infertility ART Gestational diabetes mellitus Maternal diabetes mellitus Placental abruption Pre-eclampsia Placenta previa Elevated liver enzymes Bleeding Oligohydramnios (AFI 0–5 cm) Polyhydramnios (AFI >25 cm) Anemia (Hb below 100 g/L) Smoking during pregnancy (>5 cigarettes per day) Alcohol consumption during pregnancy Married or cohabiting
30.7 ± 6.1 3 (0.9) 242 (71.2) 95 (27.9)
29.0 ± 5.6 177 (0.7) 22 242 (81.8) 4778 (17.6)
≤0.001 ≤0.001
95 (27.9) 245 (72.1)
11 248 (41.4) 15 949 (58.6)
197/326 (60.4) 86/326 (26.4) 27/326 (8.3) 16/326 (4.9)
17 171/25 894 (66.3) 5492/25 894 (21.2) 2184/25 894 (8.4) 1047/25 894 (4.0)
246 (72.4) 73 (21.5) 21 (6.2) 40 (11.8) 6 (1.8) 36 (10.6) 6/326 (1.8) 37 (10.9) 12 (3.5) 7/329 (2.1) 56 (16.5) 8 (2.4) 4 (1.2) 14 (4.1) 2 (0.6) 5 (1.5) 0/52 (0.0) 40 (11.8) 30 (8.8) 13 (3.8) 34/335 (10.1)
21 903 (80.5) 3943 (14.5) 1351 (5.0) 3286 (12.1) 247 (0.9) 2119 (7.8) 216/25 379 (0.9) 2109 (7.8) 1089 (4.0) 735/26 674 (2.8) 3726 (13.7) 234 (0.9) 178 (0.7) 1167 (4.3) 213 (0.8) 278 (1.0) 12/3849 (0.3) 3265 (12.0) 1277 (4.7) 745 (2.7) 2820/26 927 (10.5)
3/329 (0.9)
241/26 154 (0.9)
0.99
310 (91.2)
24 218 (89.0)
0.21
≤0.001
0.10
and premature birth), each was considered an independent outcome and the pregnancy was included in both categories. Differences were deemed to be significant if the P value was below 0.05. Data were analyzed using SPSS version 19.0 (IBM, Armonk, NY, USA). 3. Results Of the 27 537 women with singleton pregnancies who gave birth at Kuopio University Hospital during the study period, 340 (1.2%) experienced true umbilical cord knot. In univariate tests, these women were significantly older than those in the control group (P ≤ 0.001) (Table 1). They were also more frequently multiparous (P ≤ 0.001), had experienced more previous spontaneous abortions (P = 0.001), and more commonly used an intrauterine device (IUD) before pregnancy (P = 0.03) compared with women in the control group (Table 1). Furthermore, compared with women in the control group, significantly more women with umbilical cord knot had diabetes mellitus (P = 0.003) and polyhydramnios (P ≤ 0.001). However, after adjustment, only advanced maternal age (≥35 years), multiparity, previous spontaneous abortion, polyhydramnios, and diabetes mellitus were independent reproductive risk factors for umbilical cord knot (Table 2). Pregnancy and delivery characteristics were similar for women in the study and control groups, with the exceptions of mean umbilical cord length and fetal gender. Umbilical cords were significantly longer in cases of cord knot (mean, 76.3 ± 16.2 vs 59.4 ± 13.5 cm; P ≤ 0.001) and there was a higher proportion of male infants (61.5% vs 51.3%; P ≤ 0.001) compared with the control group (Table 3). After adjustment for confounding factors, umbilical cord knot was significantly associated with increased risk of several adverse perinatal and early neonatal outcomes. The adjusted odds of neonatal intensive care, intrauterine fetal death, premature birth, SGA infants, and low Apgar score at 1 and 5 minutes were, respectively, 1.58- 8.08-, 3.90-, 3.17-, 1.67-, and 2.00-fold higher among women with umbilical cord knot than among women in the control group (Table 4). Intrauterine fetal death was rare, occurring only in 81 of the 27 197 Table 2 Umbilical cord knot (n = 313) among women with singleton pregnancies (n = 24 456).a Characteristics
0.001
0.86 0.10 0.06 0.06 0.03 0.66 0.49 0.14 0.003 0.24 0.88 0.69 0.42 0.69 0.89 ≤0.001 0.23 0.85
Abbreviations: AFI, amniotic fluid index; ART, assisted reproductive technology; BMI, body mass index (calculated as weight in kilograms divided by the square of height in meters); Hb, hemoglobin; IUD, intrauterine device. a Values are given as mean ± SD or number (percentage) unless otherwise indicated.
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Maternal age, y b18 18–34 ≥35 Parity Nulliparous Multiparous Pre-pregnancy BMI ≤24.9 25–29.9 30.0–34.9 ≥35.0 Spontaneous abortion 0 1 ≥2 ≥7 deliveries Prior cesarean Prior fetal demise IUD use before pregnancy Polyhydramnios (AFI >25) Maternal diabetes mellitus
Adjusted odds ratiob (95% confidence interval) 1.88 (0.46–7.72) 1 1.56 (1.21–2.02) 0.70 (0.53–0.91) 1 1 1.30 (1.00–1.69) 1.05 (0.74–1.47) —c 1 1.36 (1.03–1.80) 1.13 (0.71–1.79) 1.28 (0.55–2.96) 1.07 (0.74–1.54) 1.35 (0.55–3.34) 1.23 (0.86–1.76) 1.90 (1.30–2.79) 2.53 (1.22–5.22)
Abbreviations: AFI, amniotic fluid index; BMI, body mass index (calculated as weight in kilograms divided by the square of height in meters); IUD, intrauterine device. a Only cases for which all information was available were included. b Adjusted for maternal age, parity, pre-pregnancy BMI, spontaneous abortion, ≥7 deliveries, prior cesarean, prior fetal demise, IUD use before pregnancy, polyhydramnios, and maternal diabetes mellitus. c Could not be measured owing to small number of cases.
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Table 3 Pregnancy/delivery characteristics and delivery interventions.a Characteristic
Women with umbilical cord knot (n = 340)
Control group (n = 27 197)
Gestational age, wk ≤27 28–31 32–36 37–40 41–42 ≥43 Cesarean delivery No Elective Emergency Vacuum delivery Placental/fetal mass ratio, %b Umbilical cord length, cm Female Male Velamentous cord insertion Gender Female Male Birth weight, g
38.9 ± 2.6 4/338 (1.2) 7/338 (2.1) 18/338 (5.3) 234/338 (69.2) 75/338 (22.2) 0/338 (0.0)
39.2 ± 2.1 188/27 071 (0.7) 216/27 071 (0.8) 1208/27 071 (4.5) 19 509/27 071 (72.1) 5934/27 071 (21.9) 16/27 071 (0.1)
a b
Table 5 Delivery characteristics among stillborn infants (n = 81).a P value
0.07 0.11
0.36 277 (81.5) 26 (7.6) 37 (10.9) 22/245 (9.0) 18.8 ± 5.6 76.3 ± 16.2 75.2 ± 15.2 77.0 ± 16.8 4 (1.2)
22 911 (84.2) 1852 (6.8) 2434 (8.9) 1738/21 154 (8.2) 17.7 ± 6.0 59.4 ± 13.5 58.1 ± 13.3 60.5 ± 13.6 629 (2.3)
131 (38.5) 209 (61.5) 3518.4 ± 750.6
13 246/27 189 (48.7) 13 943/27 189 (51.3) 3479.6 ± 598.9
0.67 0.84 ≤0.001 ≤0.001 0.17 ≤0.001
0.34
Values are given as mean ± SD or number (percentage) unless otherwise indicated. Placental weight in grams divided by birth weight in grams × 100.
(0.3%) control pregnancies. Three (3.7%) of these infants had umbilical cord knots. There were no significant differences between stillborn infants with and without umbilical cord knot in terms of gestational age, mean umbilical cord length, cord insertion, gender, and occurrence of polyhydramnios (Table 5). 4. Discussion The incidence of true umbilical cord knot among women with singleton pregnancies (1.2%) corresponded well to results from previous general studies [2,4] and studies involving the same catchment area [3]. Changes in the study population from the earlier study [3] were minimal, except that the proportion of overweight women (body mass index [calculated as weight in kilograms divided by the square of height in meters] > 25) was up to 2-fold higher during the most recent study period. Furthermore, the proportions of women with advanced maternal age and those affected by placental abruption and polyhydramnios were slightly increased, whereas the percentages of women with maternal diabetes and pre-eclampsia were lower. After adjustment, advanced maternal age, multiparity, previous spontaneous abortion, polyhydramnios, and maternal diabetes mellitus were
Characteristic Gestational age, wk ≤27 28–31 32–36 37–40 41–42 ≥43 Umbilical cord length, cm Velamentous cord insertion Gender Female Male Polyhydramnios a
Umbilical cord knot (n = 3)
Control group (n = 78)
0 (0.0) 1 (33.3) 0 (0.0) 2 (66.7) 0 (0.0) 0 (0.0) 74.0 ± 49.3 0 (0.0)
32 (41.0) 5 (6.4) 15 (19.2) 23 (29.5) 3 (3.8) 0 (0.0) 51.7 ± 17.8 3 (3.8)
0 (0.0) 3 (100.0) 0 (0.0)
37/77 (48.1) 40/77 (51.9) 6 (7.7)
P value 0.20
0.52 0.72 0.10
0.63
Values are given as number (percentage) or mean ± SD unless otherwise indicated.
significantly associated with an increased incidence of true umbilical cord knot. Advanced maternal age and previous spontaneous abortion are likely to be associated with multiparity but polyhydramnios and maternal diabetes mellitus are not affected by parity. Both gestational diabetes and diabetes mellitus are associated with an increased risk of polyhydramnios [9,10], which may explain the increased incidence of umbilical cord knot among women with diabetes mellitus in the present study. In the present study, there was a higher proportion of male fetuses and cords were, on average, 16.9 cm longer among infants with umbilical cord knot than in the control group—consistent with previous results from a study at Kuopio University Hospital [3]. These results might be explained by the significantly greater umbilical cord length among male, compared with female, infants with umbilical cord knot (77.0 ± 16.8 vs 75.2 ± 15.2 cm; P ≤ 0.001). A higher incidence of umbilical cord knot among male fetuses was also previously found in other studies [1,2,4] but the databases did not include information on length of cord. Furthermore, following on from studies of male predominance in pregnancies affected by gestational diabetes, it is also possible that some of the independent effects of diabetes on umbilical cord knots can be explained by fetal gender [1]. True umbilical cord knot was significantly associated with adverse pregnancy outcome; affected infants were more likely to have lower Apgar scores and be born preterm and SGA, and subsequently require more treatment after birth in a neonatal unit. However, the clinical significance of low Apgar scores is likely to be minor because fetal venous pH values were not affected by umbilical cord knot, consistent with a previous study from the same catchment area [3]. Furthermore, in another case–control study [11], umbilical artery gas values did not
Table 4 Perinatal and early neonatal outcomes among infants with umbilical cord knot and control group.a Outcome
Women with umbilical cord knot (n = 340)
Control group, (n = 27 197)
Unadjusted odds ratio (95% confidence interval)
Adjusted odds ratio (95% confidence interval)c
Need for neonatal intensive care Fetal death Premature birth (b37 weeks)b LBW (b2500 g) SGA (b90th percentile) Low 1-minute Apgar score (b7) Low 5-minute Apgar score (b7) Fetal venous pH b7.15 at birth
46 3/339 29/338 22 41 32 18 4/197
2489 (9.2) 81/27 178 (0.3) 1612/27 071 (6.0) 1288/27 194 (4.7) 2739/27 194 (10.1) 1465 (5.4) 734 (2.7) 393/14 837 (2.6)
1.55 2.99 1.48 1.39 1.22 1.83 2.02 0.76
1.58 8.08 3.90 1.52 3.17 1.67 2.00 0.95
(13.5) (0.9) (8.6) (6.5) (12.1) (9.4) (5.3) (2.0)
(1.14–2.13) (0.94–9.50) (1.01–2.18) (0.90–2.15) (0.88–1.70) (1.26–2.64) (1.25–3.26) (0.28–2.06)
(1.07–2.33)d (1.50–43.57)d (2.48–6.13)e (0.66–3.50) (2.18–4.62)e (1.10–2.54)d (1.13–3.54)d (0.34–2.61)
Abbreviations: LBW, low birth weight; SGA, small for gestational age. a Adjusted for umbilical cord knot, maternal age, parity, pre-pregnancy body mass index, spontaneous abortion, ≥7 deliveries, prior cesarean, prior fetal demise, intrauterine device use before pregnancy, maternal diabetes mellitus, polyhydramnios, gestational age, umbilical cord length, and gender. b Not adjusted for gestational age. c Only cases for which all information was available were included. d P ≤ 0.05. e P ≤ 0.001.
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differ between infants with and without umbilical cord knot. However, a large retrospective observational study reported a significantly higher incidence of fetal acidosis (umbilical venous pH b 7.10) among infants with umbilical cord knot [4]. In the present study, a 3.2-fold higher risk of being born SGA indicated chronic uteroplacental insufficiency in infants affected by umbilical cord knot, although the mean birth weight (3518.4 ± 750.6 vs 3479.6 ± 598.9 g; P = 0.34) did not differ significantly between the study and the control groups. By contrast, a higher incidence of obesity and diabetes among affected pregnancies may have masked the negative effect of umbilical cord knot on fetal growth. Previous results have not shown a significant association between umbilical cord knot and fetal growth [2,3], but obesity and diabetes among the pregnant population have become more prevalent and the rates are still increasing [2,3]. Similarly, as in the present investigation, an increased risk of intrauterine fetal death associated with umbilical cord knot has been reported in previous studies [2–5]. Interestingly, umbilical cord knot was not associated with ART, placenta previa, or placental abruption. Moreover, its intrapartum clinical significance was minor, with no significant differences between the study and the control groups with regard to rates of cesarean delivery and vacuum extraction. The most important strength of the present study was that the data included the total population of women attending the same obstetric department between January 2000 and August 2012; thus, the likelihood of selection bias—which is inherent in multicenter studies— was decreased, while the validity of the results was increased. Furthermore, several clinical studies have validated the data used in the present study [6,7,12–14]. In conclusion, associations between adverse pregnancy outcomes and true umbilical cord knot indicate that the complication may impair fetal growth and wellbeing during pregnancy. During birth, however, its clinical significance seems to be minor. At present, little—if anything—can be done to prevent fetal death ascribable to the tightening of an umbilical cord knot because diagnosis using ultrasonography is challenging; however, the risk of death is still small [15,16]. Conflict of interest The authors have no conflicts of interest.
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