Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Open Access

Peer-reviewed

Research Article

Umbilical cord characteristics and their association with adverse pregnancy outcomes: A systematic review and meta-analysis

  • Dexter J. L. Hayes ,

    Roles Conceptualization, Data curation, Formal analysis, Methodology, Writing – original draft, Writing – review & editing

    dexter.hayes@manchester.ac.uk

    Affiliation Tommy’s Stillbirth Research Centre, University of Manchester, Manchester, United Kingdom

    ⨯
  • Jane Warland,

    Roles Data curation, Writing – review & editing

    Affiliation University of South Australia, Adelaide, Australia

    ⨯
  • Mana M. Parast,

    Roles Data curation, Writing – review & editing

    Affiliation University of California, San Diego, CL, United States of America

    ⨯
  • Robert W. Bendon,

    Roles Data curation, Writing – review & editing

    Affiliation Retired from Norton Children’s Hospital, Louisville, Kentucky, United States of America

    ⨯
  • Junichi Hasegawa,

    Roles Data curation, Writing – review & editing

    Affiliation St Marianna University School of Medicine, Kawasaki, Japan

    ⨯
  • Julia Banks,

    Roles Data curation

    Affiliation Tommy’s Stillbirth Research Centre, University of Manchester, Manchester, United Kingdom

    ⨯
  • Laura Clapham,

    Roles Data curation

    Affiliation Tommy’s Stillbirth Research Centre, University of Manchester, Manchester, United Kingdom

    ⨯
  • Alexander E. P. Heazell

    Roles Conceptualization, Methodology, Writing – original draft, Writing – review & editing

    Affiliation Tommy’s Stillbirth Research Centre, University of Manchester, Manchester, United Kingdom

    ⨯

Abstract

Objective

Current data on the role of the umbilical cord in pregnancy complications are conflicting; estimates of the proportion of stillbirths due to cord problems range from 3.4 to 26.7%. A systematic review and meta-analysis were undertaken to determine which umbilical cord abnormalities are associated with stillbirth and related adverse pregnancy outcomes.

Methods

MEDLINE, EMBASE, CINAHL and Google Scholar were searched from 1960 to present day. Reference lists of included studies and grey literature were also searched. Cohort, cross-sectional, or case-control studies of singleton pregnancies after 20 weeks’ gestation that reported the frequency of umbilical cord characteristics or cord abnormalities and their relationship to stillbirth or other adverse outcomes were included. Quality of included studies was assessed using NIH quality assessment tools. Analyses were performed in STATA.

Results

This review included 145 studies. Nuchal cords were present in 22% of births (95% CI 19, 25); multiple loops of cord were present in 4% (95% CI 3, 5) and true knots of the cord in 1% (95% CI 0, 1) of births. There was no evidence for an association between stillbirth and any nuchal cord (OR 1.11, 95% CI 0.62, 1.98). Comparing multiple loops of nuchal cord to single loops or no loop gave an OR of 2.36 (95% CI 0.99, 5.62). We were not able to look at the effect of tight or loose nuchal loops. The likelihood of stillbirth was significantly higher with a true cord knot (OR 4.65, 95% CI 2.09, 10.37).

Conclusions

True umbilical cord knots are associated with increased risk of stillbirth; the incidence of stillbirth is higher with multiple nuchal loops compared to single nuchal cords. No studies reported the combined effects of multiple umbilical cord abnormalities. Our analyses suggest specific avenues for future research.

Citation: Hayes DJL, Warland J, Parast MM, Bendon RW, Hasegawa J, Banks J, et al. (2020) Umbilical cord characteristics and their association with adverse pregnancy outcomes: A systematic review and meta-analysis. PLoS ONE 15(9): e0239630. https://doi.org/10.1371/journal.pone.0239630

Editor: Kelli K. Ryckman, Univesity of Iowa, UNITED STATES

Received: June 8, 2020; Accepted: September 9, 2020; Published: September 24, 2020

Copyright: © 2020 Hayes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: We are grateful to the STAR Legacy Foundation for providing financial support for this study. The funder had no role in study design, data collection and analyses, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Umbilical cord abnormalities (UCA) usually describe situations where fetal blood flow is reduced or interrupted due to altered structure or function of the umbilical cord. UCA are associated with adverse pregnancy outcomes including stillbirth, birth asphyxia and emergency Caesarean birth. However, estimates of the contribution of UCA to these outcomes vary; for example between 3.4% to 20% of stillbirths are reported to be caused by UCA [1]. Some of the variation may be due to the use of different classification systems for stillbirth, not all of which include UCA as a cause of death.

Of the possible reported UCA, nuchal cord, where the umbilical cord is wound at least once around the fetal neck [2], has been the subject of the most studies; its incidence increases throughout gestation, peaking at birth [3, 4]. While there are reports of nuchal cord in individual cases of stillbirth [5], data from larger studies are conflicting, with some finding significant associations [5, 6] and others reporting no effect of nuchal cord on stillbirth [7, 8]. Other UCA, including true knots and cord prolapse are rarer, but are also linked to adverse outcomes; cohort studies have demonstrated associations between true knots and perinatal death and between cord prolapse and low Apgar scores [9, 10]. In addition, an excessive or reduced number of coils of blood vessels within the cord has also been associated with various adverse outcomes [11]. UCAs can also present in combination, for example true knots may occur more in longer cords which are also more prone to entanglement [12, 13], complicating the appreciation of the significance of individual abnormalities.

Variation in published results may be due to differences in study design, mode of detection (at birth or antenatal ultrasound), definitions of abnormalities, and lack of information about characteristics such as the number of loops of nuchal cord [14], tightness of cord loops or knots [15], or duration of UCA. To address these uncertainties and to better understand the association between UCA and adverse pregnancy outcomes we undertook a systematic review and meta-analysis of observational studies to describe the normal characteristics of human umbilical cord, the incidence of UCA in singleton pregnancies, and to determine the association between UCA and adverse pregnancy outcomes. We also aimed to understand potential sources of variation between studies.

Materials and methods

The review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on the 4th of October 2018 (CRD420180099049). The systematic review and meta-analysis were conducted according to the PRISMA guideline [16].

Eligibility criteria, information sources, search strategy

Cohort or cross-sectional studies that reported normal characteristics of umbilical cord or the incidence of abnormalities were included in this review. Cohort studies that reported the incidence of UCA and their relation to adverse pregnancy outcomes or case control studies that compared pregnancies with and without UCA, or that looked at the incidence of UCA in adverse outcomes were also included. Inclusion criteria were studies of singleton pregnancies after 20 weeks of gestation, without congenital abnormalities, conducted in hospital settings (secondary or tertiary centres). Studies reporting UCA in multiple pregnancies were excluded as cord entanglement is a specific complication of monoamniotic twins. Studies of vasa praevia were not included as there is a recent systematic review [17]. All other umbilical cord abnormalities were considered for inclusion in this review.

Literature searches were conducted in MEDLINE, EMBASE, CINAHL and Google Scholar to identify relevant papers published since 1960. In addition, references from articles found, conference proceedings, and bibliographies from review articles and book chapters were examined for appropriate references. Searches were initially performed in May 2018 and updated on 1st December 2019. Example search strategies for the association between cord abnormalities and adverse pregnancy outcomes can be seen in Appendix A.

Outcomes of interest

The primary outcome for this review was stillbirth or intrauterine fetal death (IUFD), defined as death of a baby before birth and after 20 weeks' gestation (although the definitions employed in studies were anticipated to vary according to geographical location). Secondary outcomes studied were: neonatal intensive care unit (NICU) admission, preterm birth (<37 weeks’ gestation), small-for-gestational-age (birthweight <10th centile or as defined by study), low birth weight at term (<2500g), low Apgar score (<7 at 1 minute and 5 minutes) and frequency of caesarean birth. These outcomes were selected because they reflect a proposed pathway through which UCA can lead to fetal death either acutely antenatally or intrapartum, or, if the UCA were present chronically, cause fetal vascular malperfusion leading to small for gestational age infants or sufficient intrapartum compromise [18], subsequent intervention in labour (Caesarean section), low Apgar score, and/or NICU admission (Fig 1). We anticipated that a positive association would be more compelling if it was associated with a number of these related outcomes.

thumbnail
Download:
Fig 1. Proposed pathway for potential effects of chronic and acute UCA.

https://doi.org/10.1371/journal.pone.0239630.g001

Study selection and data extraction

Titles and abstracts were reviewed by two authors (from DH, JB, LC, AH) to identify relevant studies and full text papers were obtained. Data were extracted by two authors using a pre-piloted data extraction form (from DH, JW, RB, MP, JB, LC, AH); disagreements were resolved by consultation with a third author. Studies not published in English were translated where possible. When full text was not available for a study its authors were contacted, abstracts were not included if all necessary information was not present.

Assessment of risk of bias

Quality of included studies was assessed using the NIH quality assessment tool for observational cohort and cross-sectional studies and the NIH quality assessment tool for case control studies [19]; quality of studies was judged to be good, fair, or poor. This was tailored to best suit our review question, piloted on five studies, then assessed for all included studies by two authors as described above. Studies where data on diagnostic accuracy of antenatal ultrasound could be extracted were additionally assessed using QUADAS-2 [20], which rates risk of bias and concerns regarding applicability as high, low, or unclear.

Data synthesis

Analyses were performed using STATA version 15 [21]. Random effects meta-analysis was performed in anticipation of heterogeneity between studies due to study design. I2, derived from Cochran’s chi-squared statistic Q, was calculated to describe the percentage of variability in effect estimates that is due to heterogeneity. Heterogeneity was classified as low (I2 = 0–40%), moderate (I2 = 41–60%), substantial (I2 = 61–80%), or considerable (I2 = 81–100%) [22]. Subgroup analyses were performed to investigate heterogeneity where appropriate and funnel plots were created to test for sample size effects.

Incidences of UCA were calculated using the command metaprop [23]. The relationship between presence of UCA and adverse outcome was investigated using the command metan [24]. Planned subgroup analyses were performed to examine the effects of different forms of UCA such as number of loops of cord and whether the cord could be unwound at birth. Although not originally an aim of this study, we also found papers that allowed us to calculate the diagnostic accuracy of ultrasound for detecting UCA. The STATA command metandi [25] was used to calculate the summary sensitivity and specificity from these studies and to produce an HSROC curve.

Results

Study selection and study characteristics

After screening of 2,755 abstracts, 275 full text manuscripts were assessed and 145 studies met the inclusion criteria for this review (Fig 2). Two authors [26, 27] provided further information about their studies when contacted. Key characteristics of included studies are presented in Table 1.

thumbnail
Download:
Fig 2. PRISMA diagram.

https://doi.org/10.1371/journal.pone.0239630.g002

thumbnail
Download:
Table 1. Characteristics of included studies.

https://doi.org/10.1371/journal.pone.0239630.t001

Risk of bias of included studies

Quality of included studies was mostly judged to be fair: 35 studies were judged to be good and 7 poor, with the remaining 103 studies judged as fair quality using the NIH quality assessment tools. Most studies had issues with at least one of the following criteria: providing sample size justifications; measuring different levels of exposures, for example the number of loops of nuchal cord; defining exposure or outcome measures, such as the definitions of UCA or gestational age at birth or blinding of exposure and outcome assessors.

Synthesis of results

Results are presented in four sections: normal characteristics of umbilical cord, incidence of UCA, diagnostic accuracy of ultrasound, and associations between UCA and adverse pregnancy outcomes.

Normal characteristics of umbilical cord.

The average cord length at birth was found to be 56.0±11.1cm, using data from 39 studies of 94,849 pregnancies. Studies used a range of definitions, but if a study presented data for several different gestational age periods, then the one closest to term was used for this analysis. The average cord length at birth at 39 weeks’ gestation was 55.6±12.4cm, using data from 11 studies of 13,263 pregnancies; this was chosen as it was the gestational age reported by the most studies. The mean umbilical coiling index at birth, defined as the complete number of vascular coils divided by the cord’s length in centimetres [28], was 0.24±0.10 coils/cm using data from 21 studies of 8,315 pregnancies.

Incidence of UCA.

Nuchal cord. The incidence of any nuchal cord at birth, determined from data from 57 studies of 830,624 pregnancies, was 22% (95% CI 19, 24). Nuchal loops combined with other entanglements were included in this analysis. Heterogeneity was considerable, I2 99.92% (p<0.001). When the number of nuchal loops were recorded (data that could be extracted only as ‘multiple’ and not as the exact number of loops were not included), incidences were: 1 loop 16% (95% CI 13, 19); 2 loops 3% (95% CI 2, 4) 3 loops 1% (95% CI 0, 1); 4 or 5 loops <1%. 32 studies of 89,455 pregnancies presented data for at least a single loop of cord. Loose nuchal loops were more frequent than tight loops, with a summary frequency of 10% (95% CI 4, 18) compared to 5% (95% CI 4, 7; data from 230,729 pregnancies from 10 studies).

The incidence of nuchal cord detected by ultrasound scan at any gestational age was 28% (95% CI 21, 36; I2 97.67%; data from 13 studies of 4,107 pregnancies). Case control studies were not included in this analysis.

It was not possible to calculate the incidence of other entanglements due to variation in study definitions and outcomes.

Cord prolapse. Incidence of cord prolapse was calculated from 21 studies of 11,057,165 pregnancies; the overall incidence was 0.17%.

True knots. Overall, the incidence of true knots at birth was 1% (0, 1). Heterogeneity was considerable(I2 98.52%, p<0.001); data from 27 studies of 1,289,679 births. Only one paper [29] recorded the incidence of multiple knots; 14 were found from 22,012 births (0.06%).

Abnormal coiling. Twenty-one studies reported the frequency of abnormal coiling, but the incidences of hypercoiling and hypocoiling were not calculated as they were generally defined using the 90th and 10th centiles respectively.

It is important to note, however, that the actual measurements used to define these centiles differed between studies depending on the populations.

Abnormal length. The incidence of abnormal cord length could not be recorded due to wide variation in study definitions. Definitions of a long cord ranged from >59.0cm to >95.0cm, and definitions of a short cord ranged from <35.0cm to <50cm.

Diagnostic accuracy of ultrasound.

Nuchal cord. We identified 12 papers which reported the diagnostic accuracy of ultrasound scanning for predicting nuchal cord at birth, these are described in the characteristics of included studies table (Table 1). For this element, a positive index test result was any nuchal cord suspected antenatally using ultrasound and the reference standard was the presence of a nuchal cord at birth. Results were combined for ultrasound screening at any gestation; four studies [7, 30–32] performed screening immediately prior to induction or during labour and in all but two studies all measurements were performed after 36 weeks [33, 34].

QUADAS-2 was used to quantify the risk of bias and applicability concerns for each included study. Most papers were at low or unclear risk of bias for all domains. Akkaya et al. [30] was judged to be at high risk of bias for patient selection and index test domains, while Gonzalez-Quintero et al. [34] was judged to be at high risk of bias for patient selection; these were both case control studies. Studies were all low or unclear risk of bias for applicability concerns. Only one study [32] was judged to be low risk for all domains. Six studies blinded reference standard results[3, 4, 32, 35–37] all but one of these [36] also blinded index test results. All other studies did not state whether blinding took place.

Summary sensitivity for ultrasound at all gestations was 80.5 (95% CI 66.3, 89.6), summary specificity 86.6 (95% CI 80.0, 91.2). However, there was considerable variation in sensitivity of individual studies ranging from 29.0 to 96.8%, with specificities ranging from 57.0% to 96.6%. The positive likelihood ratio (LR+) was 6.01 and the negative likelihood ratio (LR-) was 0.17. Sensitivities and specificities from each study were used to produce an HSROC plot (Fig 3); the diagnostic odds ratio (DOR) for ultrasound scanning at all gestations was 26.6 (95% CI 9.46, 74.7). There did not appear to be a linear relationship between accuracy and gestational age although for studies where ultrasound scanning was performed in early labour the sensitivity values were higher, ranging from 90.2 to 96.8%.

thumbnail
Download:
Fig 3. HSROC plot for the diagnostic accuracy of antenatal ultrasound to predict nuchal cord at birth.

https://doi.org/10.1371/journal.pone.0239630.g003

True knots. The accuracy of ultrasound for the detection of true knots at birth could not be analysed due to a lack of available study data.

Associations between UCA and adverse pregnancy outcomes.

Nuchal cord and stillbirth. When data for any nuchal cord at birth were pooled, no statistically significant association was detected between presence of any nuchal cord and stillbirth (OR 1.11; 95% CI 0.62, 1.98). Heterogeneity was moderate (I2 44.4%, p = 0.055). As no association was detected for a single loop of nuchal cord versus controls (OR 0.87; 95% CI 0.56, 1.35), data were combined for an analysis comparing multiple loops to combined data for no loop and a single loop. This resulted in an OR of 2.36 (95% CI 0.99, 5.62; p = 0.053) for multiple loops of nuchal cord (Fig 4). Heterogeneity for this analysis was low (I2 7.0%, p = 0.372). Comparing multiple loops to no loops, excluding single loops from the analysis, resulted in an OR of 1.91 (95% CI 0.90, 4.06). Heterogeneity was again low (I2 0.0, p = 0.623). 123 stillbirths from 40,114 pregnancies were included in the pooled analysis. There was no evidence of small study effects (Harbord’s test, p = 0.137).

thumbnail
Download:
Fig 4. The association between nuchal cord loops and the likelihood of stillbirth.

https://doi.org/10.1371/journal.pone.0239630.g004

Three studies presented data for the relationship between nuchal cord detected by ultrasound at any gestation and stillbirth, no statistically significant association was detected (OR 0.72; 95% CI 0.17, 3.05). Heterogeneity for this analysis was low (I2 = 25.8%, p = 0.260). Data from this analysis were obtained from 1955 pregnancies, 24 of which were stillbirths.

Nuchal cord and other adverse outcomes. Results from analyses of the relationships between nuchal cord and all secondary adverse outcomes are shown in Table 2. Analyses could not be performed for the association between nuchal cord detected using ultrasound and Apgar scores <7 at 5 minutes, NICU admission, small-for-gestational age, or preterm birth, or for the association between nuchal cord at birth and preterm birth.

thumbnail
Download:
Table 2. Analyses of the relationship between nuchal cord and adverse outcomes.

https://doi.org/10.1371/journal.pone.0239630.t002

A single loop of nuchal cord at birth was only associated with a 1 minute Apgar score <7 whereas multiple loops of cord were associated with increased likelihood of caesarean section and Apgar scores <7 at both one and five minutes. Tight loops of nuchal cord but not loose loops were associated with low Apgar scores.

We found no evidence for an association between nuchal cords at birth and NICU admission. Overall heterogeneity was substantial at 66.8% (p<0.01); this was due to considerable heterogeneity in the data from multiple loops (I2 88.5%, p = 0.00), whereas heterogeneity in the data for single loops was low (I2 30.5%, p = 0.22). However, the likelihood of NICU admission with a tight nuchal cord at birth was twice as high as with no nuchal cord, although this was not statistically significant.

No included studies specified nuchal cord as an indication for birth; if a study presented emergency caesarean section or caesarean section for fetal distress separately, then these data were used instead of the overall rate. However, caesarean section was significantly more likely in pregnancies with nuchal cord detected via ultrasound (OR 1.64; 95% CI 1.07, 2.51) Heterogeneity was low (I2 33.5%, p = 0.211).

No significant relationship between nuchal cord and birth weight <2500g (OR 0.66; 95% CI 0.50, 1.35), or fetal growth restriction or small for gestational age infants (OR 1.41; 95% CI 0.90, 2.21) was identified. Studies of fetal growth restriction and small for gestational age were combined as they used a wide range of definitions [8, 38–45].

Sensitivity analyses for nuchal cord papers. No studies that were rated poor by quality assessment presented data for nuchal cord and its relationship to adverse outcome so planned sensitivity analyses were not performed.

True knots and stillbirth. The likelihood of stillbirth was significantly higher in pregnancies with a true knot in the umbilical cord at birth than in those without, with an OR of 3.96 (95% CI 1.85, 8.47; 7 studies of 930,314 births) (Fig 5) Heterogeneity was moderate (I2 60%, p<0.05).

thumbnail
Download:
Fig 5. The association between true knots and the likelihood of stillbirth.

https://doi.org/10.1371/journal.pone.0239630.g005

True knots and other adverse outcomes. Results from these analyses are presented in Table 3. Statistically significant associations with modest effect sizes were found between true cord knots at birth and all of our secondary outcomes except for caesarean section.We were not able to look at the association between true knots at birth and low Apgar scores at 1 minute. No evidence of small study effects was seen for our main outcome of stillbirths in studies of true knots; Egger’s test gave a p value of 0.27 (Fig 6).

thumbnail
Download:
Fig 6. Funnel plot for studies included in the analysis of the relationship between nuchal cord and stillbirth.

https://doi.org/10.1371/journal.pone.0239630.g006

thumbnail
Download:
Table 3. Analyses of the relationship between true knots and adverse outcomes.

https://doi.org/10.1371/journal.pone.0239630.t003

Abnormal coiling and intrauterine fetal death. We were unable to perform meta-analysis to analyse the relationship between abnormal coiling of the umbilical cord and stillbirth

Abnormal coiling and other adverse outcomes. Outcome data are shown in Table 4. For all coiling analyses the hypo- or hypercoiled group was compared to the group with normal coiling only. The only exception is a study of hypocoiling by Strong, Finberg & Mattox [46] where the control group was all cords with an umbilical coiling index (UCI) above the 10th centile (so would also have included hypercoiled cords). Analyses were also performed combining all thresholds for hypo- and hypercoiling as in most cases variation was minimal; for UCI at birth the range of thresholds classed as hypocoiling was from <0.6 to <0.17 UCI, with one outlier [47] using <0.26 UCI. For hypercoiling the range was >0.26 to >0.48 UCI. Some studies stated that they used <10th and <90th centile thresholds but did not specify the actual measurements to which these corresponded. Studies that measured UCI antenatally were not analysed with studies that measured coiling at birth; definitions for hypo- and hypercoiling from these studies also tended to differ, potentially due to the gestation at measurement.

thumbnail
Download:
Table 4. Analyses of the relationship between abnormal coiling and adverse outcomes.

https://doi.org/10.1371/journal.pone.0239630.t004

Apgar score <7 at 1 minute was measured with UCI at birth by three studies [48–50] and antenatal UCI by another [51]. One study defined a low Apgar score at 1 minute as below 4 [52] and another combined all poor Apgar scores [47]. These studies were not included in this analysis. Thresholds for diagnosis of hyper- or hypocoiled cords are displayed on the forest plots and did not appear to lead to any variation in the effect sizes between studies. Sensitivity analyses were also performed for the SGA/FGR analyses based on whether a definition for this outcome was provided by the study, but no effect was seen. For hypercoiling the OR was reduced once studies with unclear definitions were removed but there was still a statistically significant association with SGA.

Abnormal cord length and adverse outcomes. We did not perform any analyses of the relationship between abnormal cord length and adverse outcomes due to variation in study definitions, as described earlier.

Cord prolapse and adverse outcomes. We were unable to perform meta-analysis to investigate the relationship between cord prolapse and any of our outcomes of interest due to a lack of available data.

A summary of normal cord characteristics, UCA incidences, diagnostic accuracy data, and associations between UCA and stillbirth is provided in Table 5.

thumbnail
Download:
Table 5. Summary of results.

https://doi.org/10.1371/journal.pone.0239630.t005

Discussion

Our systematic review was able to combine a large amount of data to determine the normal characteristics of umbilical cord and report the frequency of abnormalities. Some cord abnormalities are common, for example nuchal cord was found in 22% of births (95% CI 19–24), whereas true knots and cord prolapse are less common (1% and 0.1% of births respectively). The definition of some abnormalities e.g. UCI were consistent between studies but others, such as the length of cord were heterogeneous, due to the thresholds applied to define abnormality which often overlapped with the normal ranges (e.g. pooled mean cord length 56.0±11cm, “long cord” defined as >59cm). Estimates of frequency also varied by gestation studied.

We selected stillbirth as our primary outcome, and identified secondary outcomes to reflect diagnosis of fetal compromise that was not sufficiently severe to cause fetal death or represent intervention that prevented it. None of the abnormalities studied showed a significant association with all outcomes and the observed odds ratios were in the range of 1 to 5. This review found the diagnostic accuracy of antenatal or antepartum ultrasound to identify cord abnormalities was modest; the diagnosis of nuchal cord was most accurate when performed in early labour (all studies had sensitivity >90% and specificity >83%). This may be because its incidence is highest at term and there is less time for fetal movements to affect whether the cord is around the fetal neck or not [36, 53]. There are insufficient data to determine whether other abnormalities of the umbilical cord can be reliably detected by antenatal ultrasound.

Strengths and limitations

This systematic review was strengthened by being conducted according to a pre-specified protocol by an international multidisciplinary review team to maximise the inclusion of relevant data. Up to 270,973 births were included in the meta-analyses giving robust estimates of effect size. However, this review is limited by variation in the definitions used to define both UCA and the associated outcomes, which restricted the number of analyses that can be reliably performed. We were also not able to identify any unpublished data suitable for inclusion, meaning that some of our effect sizes may be overstated due to publication bias.

Our proposed pathway for the differential effects of chronic vs. acute UCA is also limited in that we could mostly report evidence of UCA at birth without knowing how long it had been present, and could not address temporal variation (i.e. whether nuchal cord had been intermittently present). Due to the nature of our included studies we were also unable to distinguish between events that occurred antepartum vs. intrapartum or acute vs. chronic effects, nor could we look at the effects of combinations of UCA, which could affect the likelihood of adverse outcomes, for example shorter cords may lead to tighter nuchal cords and knots when they are present while longer cords may be more prone to entanglements (studies have shown the average cord length to be higher in cases with nuchal cord) [54]. Limb and body entanglements were also not recorded by the majority of studies.

Quality assessment showed that recording of UCA needs to be far more stringent, especially in nuchal cords; number of loops, tightness (which is unlikely to be a true dichotomous variable [55] and also may change during labour so tightness at birth may not reflect tightness antenatally) [56], and type of nuchal cord (A or B, indicating whether the cord is in a locked pattern or can easily be unwound) [57] should all be recorded along with whether other entanglements were present. Classification of stillbirth also requires improvement so that umbilical cord pathology is accurately recorded. Early classification systems such as the Wigglesworth classification did not include umbilical cord complications as a cause of perinatal death. Even when modern classification systems are applied, there is variation in recording of umbilical cord complications resulting in the estimated incidence of cord complications varying from 3.4% to 20%. A recent detailed analysis using the INCODE system suggested 19% of stillbirths are due to cord accident [58]. Variation in reporting of umbilical cord pathology would be reduced by a core outcome set for studies examining the association between UCA and adverse outcome.

Clinical implications

Our data demonstrate that UCA are associated with adverse perinatal outcomes. The broadest range of associations with stillbirth and associated adverse outcomes were seen for true knots, following by coiling abnormalities then nuchal cord, whereas the strongest effect sizes were for tight nuchal cords. Robust information about the diagnostic accuracy for UCA is only available for nuchal cords, in this case the pooled sensitivity and specificity of antenatal ultrasound was 80.5% and 86.6% respectively. Nuchal cords were only associated with adverse outcomes when either multiple or tight loops were present. On the basis of this information identifying an isolated nuchal cord antenatally is unlikely to prevent adverse outcome, but may increase intervention. However, combining identification of nuchal cord and abnormal umbilical artery flow increases the likelihood of intrapartum compromise [7, 59]. Further test-accuracy studies are needed, but must be appropriately blinded to prevent intervention altering the outcome.

We hypothesised that umbilical cord abnormalities act via a common pathway of restricting blood flow to the fetus which may be acute or chronic (Fig 1). Thus, we expected to see associations with stillbirth and the secondary outcomes investigated in this meta-analysis. Given the comparatively modest effect size of the relationship between UCA and the outcomes studied here, we conclude that all stillbirths and adverse perinatal outcomes should be thoroughly investigated, even when UCA are present at birth to determine whether a) histopathological changes consistent with UCA are present, including lesions of fetal vascular malperfusion [42], and b) to exclude other possible causes, in order that a robust link may be made between the outcome and antecedent cord complications. In the context of stillbirth, the triple risk model proposes that fetal deaths can result from a combination of fetal stressors, maternal factors, and placental or fetal vulnerability [60]. Applying this model, UCA is a fetal stressor, where stillbirths occur with combinations of risk factors such as reduced placental perfusion, and maternal factors such as maternal obesity, or maternal sleep position. Further studies are also needed to understand the biological mechanisms underpinning UCA and adverse outcomes. For some, such as tight loops of cord or a true knot, this may be from direct occlusion, whereas in hyper- or hypo-coiled cords this may reflect haemodynamic consequences or developmental abnormalities. Larger datasets applying consistent thresholds for abnormalities are required to accurately determine the relationship of UCA to adverse perinatal outcomes.

Conclusion

This systematic review and meta-analysis has demonstrated links between UCA and several adverse pregnancy outcomes, although not all analyses were adequately powered and some comparisons were restricted by the methodologies of the original studies. Further studies are needed to allow robust clinical recommendations on the management of UCA to be made. These should make use of the information presented about normal cord characteristics to inform thresholds for abnormalities and examine multiple UCA and a range of adverse perinatal outcomes. Ideally, UCA should also be recorded antenatally in blinded studies so that prognostic accuracy can be calculated. Until such data are available, clinicians should be cautious about assigning causality of an adverse outcome based on an isolated observation of UCA.

References

  1. 1. The Stillbirth Collaborative Research Network Writing Group. Causes of death among stillbirths. JAMA. 2011;306: 2459–68. pmid:22166605
  2. 2. Crawford J. Cord Round the Neck. Acta Paediatr. 1962;51: 594–603. pmid:14023723
  3. 3. Clapp JF, Stepanchak W, Hashimoto K, Ehrenberg H, Lopez B. The natural history of antenatal nuchal cords. Am J Obstet Gynecol. 2003;189: 488–93. pmid:14520223
  4. 4. Lal N, Deka D, Mittal S. Does the nuchal cord persist? An ultrasound and color-Doppler-based prospective study. J Obstet Gynaecol Res. 2008;34: 314–317. pmid:18686343
  5. 5. Collins J. The human umbilical cord. RCOG Press. 2000.
    • 6. Adinma JIB. Effect of cord entanglement on pregnancy outcome. Int J Gynecol Obstet. 1990;32: 15–18.
    • 7. Abdallah A, Eldorf A, Sallam S, Ahmed S, Shawky M, Nawara M, et al. Nuchal cord: impact of umbilical artery Doppler indices on intrapartum and neonatal outcomes: a prospective cohort study. J Matern Neonatal Med. 2018; 1–12. pmid:29635952
    • 8. Onderoğlu LS, Dursun P, Durukan T. Perinatal features and umbilical cord blood gases in newborns complicated with nuchal cord. Turk J Pediatr. 50: 466–70. Available: http://www.ncbi.nlm.nih.gov/pubmed/19102052 pmid:19102052
    • 9. Linde LE, Rasmussen S, Kessler J, Ebbing C. Extreme umbilical cord lengths, cord knot and entanglement: Risk factors and risk of adverse outcomes, a population-based study. Räisänen SH, editor. PLoS One. 2018;13: e0194814. pmid:29584790
    • 10. Gabbay-Benziv R, Maman M, Wiznitzer A, Linder N, Yogev Y. Umbilical cord prolapse during delivery–risk factors and pregnancy outcome: a single center experience. J Matern Neonatal Med. 2014;27: 14–17. pmid:23617536
    • 11. Pergialiotis V, Kotrogianni P, Koutaki D, Christopoulos-Timogiannakis E, Papantoniou N, Daskalakis G. Umbilical cord coiling index for the prediction of adverse pregnancy outcomes: a meta-analysis and sequential analysis. J Matern Neonatal Med. 2019; 1–8. pmid:30870055
    • 12. Narang Y, Vaid NB, Jain S, Suneja A, Guleria K, Faridi MMA, et al. Is nuchal cord justified as a cause of obstetrician anxiety? Arch Gynecol Obstet. 2014;289: 795–801. pmid:24190695
    • 13. Nkwabong E, Ndoumbe Mballo J, Dohbit JS. Risk factors for nuchal cord entanglement at delivery. Int J Gynecol Obstet. 2018;141: 108–112. pmid:29215708
    • 14. Larson JD, Rayburn WF, Crosby S, Thurnau GR. Multiple nuchal cord entanglements and intrapartum complications. Am J Obstet Gynecol. 1995;173: 1228–31. Available: http://www.ncbi.nlm.nih.gov/pubmed/7485326 pmid:7485326
    • 15. Singh G, Sidhu K. Nuchal Cord: A retrospective analysis. Med J Armed Forces India. 2008;64: 237–240. pmid:27408155
    • 16. Moher D, Liberati A, Tetzlaff J, Altman DG. Guidelines and Guidance Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. [cited 15 May 2019]. pmid:19621072
    • 17. Ruiter L, Kok N, Limpens J, Derks J, de Graaf I, Mol B, et al. Incidence of and risk indicators for vasa praevia: a systematic review. BJOG An Int J Obstet Gynaecol. 2016;123: 1278–1287. pmid:26694639
    • 18. Khong TY, Mooney EE, Ariel I, Balmus NCM, Boyd TK, Brundler M-A, et al. Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement. Arch Pathol Lab Med. 2016;140: 698–713. pmid:27223167
    • 19. NIH. Study Quality Assessment Tools. [cited 10 Sep 2019]. Available: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools
      • 20. Whiting P, Rutjes A, Westwood M, Mallett S, Deeks J, Reitsma J, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;18: 529–36.
      • 21. StataCorp. Stata Statistical Software. College Station, TX: StataCorp LLC; 2017.
        • 22. Higgins J, Thomas J, Chandler J, Cumpston M, Li T, Page M, et al. Cochrane Handbook for Systematic Reviews of Interventions. John Wiley & Sons; 2019.
          • 23. Nyaga VN, Arbyn M, Aerts M. Metaprop: a Stata command to perform meta-analysis of binomial data. Arch Public Heal. 2014;72: 39. pmid:25810908
          • 24. Harris RJ, Deeks JJ, Altman DG, Bradburn MJ, Harbord RM, Sterne JAC. Metan: Fixed- and Random-Effects Meta-Analysis. Stata J Promot Commun Stat Stata. 2008;8: 3–28.
          • 25. Harbord RM, Whiting P. Metandi: Meta-analysis of Diagnostic Accuracy Using Hierarchical Logistic Regression. Stata J Promot Commun Stat Stata. 2009;9: 211–229.
          • 26. Yamamoto Y, Aoki S, Oba MS, Seki K, Hirahara F. Relationship Between Short Umbilical Cord Length and Adverse Pregnancy Outcomes. Fetal Pediatr Pathol. 2016;35: 81–87. pmid:26735975
          • 27. Tamrakar SR. Incidence of nuchal cord, mode of delivery and perinatal outcome: a notable experience in Dhulikhel Hospital—Kathmandu University Hospital. Nepal Med Coll J. 2013;15: 40–5. Available: http://www.ncbi.nlm.nih.gov/pubmed/24592793 pmid:24592793
          • 28. Strong TH, Jarles DL, Vega JS, Feldman DB. The umbilical coiling index. Am J Obstet Gynecol. 1994;170: 29–32. pmid:8296839
          • 29. Sørnes T. Umbilical cord knots. Acta Obstet Gynecol Scand. 2000;79: 157–9. Available: http://www.ncbi.nlm.nih.gov/pubmed/10716294 pmid:10716294
          • 30. Akkaya H, Büke B, Pekcan MK, Şahin K, Uysal G, Yeğin GF, et al. Nuchal cord: is it really the silent risk of pregnancy? J Matern Fetal Neonatal Med. 2017;30: 1730–1733. pmid:27585242
          • 31. Peregrine E, O’Brien P, Jauniaux E. Ultrasound detection of nuchal cord prior to labor induction and the risk of cesarean section: Editorial comment. Obstet Gynecol Surv. 2005;60: 506–507. http://dx.doi.org/10.1097/01.ogx.0000172319.27668.34
          • 32. Qin Y, Wang CC, Lau TK, Rogers MS. Color ultrasonography: a useful technique in the identification of nuchal cord during labor. Ultrasound Obstet Gynecol. 2000;15: 413–7. pmid:10976484
          • 33. Aksoy U. Prenatal color Doppler sonographic evaluation of nuchal encirclement by the umbilical cord. J Clin Ultrasound. 31: 473–7. pmid:14595737
          • 34. González-Quintero VH, Tolaymat L, Muller AC, Izquierdo L, O’Sullivan MJ, Martin D. Outcomes of pregnancies with sonographically detected nuchal cords remote from delivery. J Ultrasound Med. 2004;23: 43–7. Available: http://www.ncbi.nlm.nih.gov/pubmed/14756352 pmid:14756352
          • 35. Assimakopoulos E, Zafrakas M, Garmiris P, Goulis DG, Athanasiadis AP, Dragoumis K, et al. Nuchal cord detected by ultrasound at term is associated with mode of delivery and perinatal outcome. Eur J Obstet Gynecol Reprod Biol. 2005;123: 188–92. pmid:15941615
          • 36. Hanaoka U, Yanagihara T, Tanaka H, Hata T. Comparison of three-dimensional, two-dimensional and color Doppler ultrasound in predicting the presence of a nuchal cord at birth. Ultrasound Obstet Gynecol. 2002;19: 471–4. pmid:11982980
          • 37. Peregrine E, O’Brien P, Jauniaux E. Ultrasound detection of nuchal cord prior to labor induction and the risk of Cesarean section. Ultrasound Obstet Gynecol. 2005;25: 160–4. pmid:15543520
          • 38. Carey JC, Rayburn WE. Nuchal cord encirclernents and birth weight. J Reprod Med. 2003;48: 460–462. Available: http://www.ncbi.nlm.nih.gov/pubmed/12856519 pmid:12856519
          • 39. Dhar KK, Ray SN, Dhall GI. Significance of nuchal cord. J Indian Med Assoc. 1995;93: 451–3. Available: http://www.ncbi.nlm.nih.gov/pubmed/8773129 pmid:8773129
          • 40. Ghosh GS, Gudmundsson S. Nuchal cord in post-term pregnancy—relationship to suspected intrapartum fetal distress indicating operative intervention. J Perinat Med. 2008;36: 142–4. pmid:18211253
          • 41. Miser WF. Outcome of infants born with nuchal cords. J Fam Pract. 1992;34: 441–5. Available: http://www.ncbi.nlm.nih.gov/pubmed/1556538 pmid:1556538
          • 42. Tantbirojn P, Saleemuddin A, Sirois K, Crum CP, Boyd TK, Tworoger S, et al. Gross abnormalities of the umbilical cord: related placental histology and clinical significance. Placenta. 2009;30: 1083–8. pmid:19853300
          • 43. Vintzileos AM, Egan JFX, Rodis JF, Campbell WA, Wolf EJ, Balducci J. Obstetrical factors associated with nuchal cord in a high-risk population. J Matern Neonatal Med. 1992;1: 196–201.
          • 44. Wang L, Kuromaki K, Kawabe A, Kikugawa A, Matsunaga S, Takagi A. Nuchal cord complication in male small for gestational age increases fetal distress risk during labor. Taiwan J Obstet Gynecol. 2016. pmid:27590384
          • 45. Vasa R, Dimitrov R, Patel S. Nuchal cord at delivery and perinatal outcomes: Single-center retrospective study, with emphasis on fetal acid-base balance. Pediatr Neonatol. 2018. pmid:29581058
          • 46. Strong TH, Finberg HJ, Mattox JH. Antepartum diagnosis of noncoiled umbilical cords. Am J Obstet Gynecol. 1994;170: 1729–31. pmid:8203433
          • 47. Mittal A, Nanda S, Sen J. Antenatal umbilical coiling index as a predictor of perinatal outcome. Arch Gynecol Obstet. 2015;291: 763–768. pmid:25209352
          • 48. Ma’ayeh M, McClennen E, Chamchad D, Geary M, Brest N, Gerson A. Hypercoiling of the umbilical cord in uncomplicated singleton pregnancies. J Perinat Med. 2017;46: 593–598. Available: https://www.degruyter.com/view/j/jpme.ahead-of-print/jpm-2017-0034/jpm-2017-0034.xml
          • 49. Chholak D, Gupta P, Khajotia S. Study to evaluate association of umbilical cord index and perinatal outcome. Int J Reprod Contraception, Obstet Gynecol. 2017;6: 408–412.
          • 50. Ercal T, Lacin S, Altunyurt S, Saygili U, Cinar O, Mumcu A. Umbilical coiling index: is it a marker for the foetus at risk? Br J Clin Pract. 1996;50: 254–6. Available: http://www.ncbi.nlm.nih.gov/pubmed/8794602 pmid:8794602
          • 51. Jo Y, Jang D, Lee G. The sonographic umbilical cord coiling in late second trimester of gestation and perinatal outcomes. Int J Med Sci. 2011;8: 594–598. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198255/ pmid:22022212
          • 52. Devaru D, Thusoo M. Umbilical Coiling Index & the Perinatal Outcome. J Obstet Gynecol India. 2012;62: 43–46. pmid:23372289
          • 53. Jauniaux E, Ramsay B, Peellaerts C, Scholler Y. Perinatal features of pregnancies complicated by nuchal cord. Am J Perinatol. 1995;12: 255–8. pmid:7575829
          • 54. Balkawade NU, Shinde MA. Study of Length of Umbilical Cord and Fetal Outcome: A Study of 1,000 Deliveries. J Obstet Gynecol India. 2012;62: 520–525. pmid:24082551
          • 55. Henry E, Andres RL, Christensen RD. Neonatal outcomes following a tight nuchal cord. J Perinatol. 2013;33: 231–4. pmid:22699359
          • 56. Collins JH. Tight nuchal cord morbidity and mortality. Am J Obstet Gynecol. 1999;180: 251. Available: http://www.ncbi.nlm.nih.gov/pubmed/9914613 pmid:9914613
          • 57. Collins JH. Nuchal cord type A and type B. Am J Obs Gynecol. 1997;177: 94.
          • 58. Hammad IA, Blue NR, Allshouse AA, Silver RM, Gibbins KJ, Page JM, et al. Umbilical Cord Abnormalities and Stillbirth. Obstet Gynecol. 2020; 1. pmid:32028503
          • 59. Zhao F, Geng Q, Kong F, Ning Y. Quantitative analysis of tightness of Nuchal cord and its relationship with Fetal intrauterine distress. Int J Clin Exp Med. 2015;8: 17507–17514. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694241/ pmid:26770341
          • 60. Warland J, Mitchell EA. A triple risk model for unexplained late stillbirth. BMC Pregnancy Childbirth. 2014;14: 142. pmid:24731396
          • 61. Adesina KT, Ogunlaja OO, Aboyeji AP, Olarinoye OA, Adeniran AS, Fawole AA, et al. Umbilical cord parameters in Ilorin: correlates and foetal outcome. East Afr Med J. 2014;91: 274–80. Available: http://www.ncbi.nlm.nih.gov/pubmed/26862652 pmid:26862652
          • 62. Adesina KT, Ogunlaja OA, Olarinoye AO, Aboyeji AP, Akande HJ, Fawole AA, et al. An observation of umbilical coiling index in a low risk population in Nigeria. J Perinat Med. 2018;46. pmid:28915121
          • 63. Agboola A. Correlates of human umbilical cord length. Int J Gynaecol Obs. 1978/01/01. 1978;16: 238–239.
          • 64. Aibar L, Puertas A, Valverde M, Carrillo MP, Montoya F. Fetal sex and perinatal outcomes. J Perinat Med. 2012;40: 271–6. pmid:22505506
          • 65. Airas U, Heinonen S. Clinical significance of true umbilical knots: a population-based analysis. Am J Perinatol. 2002;19: 127–32. pmid:12012287
          • 66. Algreisi F, Brown R, Shrim A, Albasri SF, Shamarani H. Effect of long and short umbilical cord on perinatal outcome. Int J Reprod Contraception, Obstet Gynecol. 2016;5: 4228–4231. Available: http://www.ijrcog.org/index.php/ijrcog/article/view/27
          • 67. Alnakash A, Ali E. Effect of Nuchal Cord on Mode of Delivery and Perinatal Outcome. Iraqi Postgrad Med J. 2018 [cited 13 Sep 2018]. Available: https://www.iasj.net/iasj?func=article&aId=147764
          • 68. Assimakopoulos E, Zafrakas M, Garmiris P, Goulis DG, Athanasiadis AP, Dragoumis K, et al. Nuchal cord detected by ultrasound at term is associated with mode of delivery and perinatal outcome. Eur J Obstet Gynecol Reprod Biol. 2005;123: 188–92. pmid:15941615
          • 69. Aviram A, Ashwal E, Hiersch L, Hadar E, Wiznitzer A, Yogev Y. Decreased perception of fetal movements at term among nulliparous women E old complaint, new insights? Am J Obstet Gynecol. 2015;212: S80. http://dx.doi.org/10.1016/j.ajog.2014.10.171
          • 70. Balsak D, Erol O, Töz E, Tahaoǧlu AE, Toǧrul C, Eser A, et al. Perinatal outcomes of sonographically detected nuchal cord in southeastern Turkey. Clin Exp Obstet Gynecol. 2017;44: 395–397. pmid:29949280
          • 71. Bärtling TH, Klöck FK, Bräcker HP, Claeys J. Characteristic changes of the pre-ejection period of the human fetal heart during umbilical cord complications. J Perinat Med. 1980;8: 183–94. Available: http://www.ncbi.nlm.nih.gov/pubmed/7431191 pmid:7431191
          • 72. Begum A, Sultana H, Hasan R, Ahmed M. a Clinical Study of Fetal Outcome in Cases of Nuchal Cord. JAFMC Bangladesh. 2011;7: 25–27. Available: https://www.banglajol.info/index.php/JAFMC/article/view/8622
          • 73. Behbehani S, Patenaude V, Abenhaim HA. Maternal Risk Factors and Outcomes of Umbilical Cord Prolapse: A Population-Based Study. J Obs Gynaecol Can. 2016/02/14. 2016;38: 23–28. pmid:26872752
          • 74. Bernad ES, Craina M, Tudor A, Bernad SI. Perinatal outcome associated with nuchal umbilical cord. Clin Exp Obstet Gynecol. 2012;39: 494–7. Available: http://www.ncbi.nlm.nih.gov/pubmed/23444751 pmid:23444751
          • 75. Bjoro K Jr., Bjøro K. Gross pathology of the placenta in intrauterine growth retardation. Ann Chir Gynaecol. 1981/01/01. 1981;70: 316–322. Available: http://www.ncbi.nlm.nih.gov/pubmed/7337404 pmid:7337404
          • 76. Blickstein I, Shoham-Schwartz Z, Lancet M. Predisposing factors in the formation of true knots of the umbilical cord—analysis of morphometric and perinatal data. Int J Gynaecol Obstet. 1987;25: 395–8. Available: http://www.ncbi.nlm.nih.gov/pubmed/2889634 pmid:2889634
          • 77. Bohîlțea RE, Turcan N, Cîrstoiu M. Prenatal ultrasound diagnosis and pregnancy outcome of umbilical cord knot—debate regarding ethical aspects of a series of cases. J Med Life. 2016;9: 297–301. Available: http://www.ncbi.nlm.nih.gov/pubmed/27974939 pmid:27974939
          • 78. Brant HA, Lewis B V. Prolapse of the umbilical cord. Lancet (London, England). 1966;2: 1443–5. Available: http://www.ncbi.nlm.nih.gov/pubmed/4163444
          • 79. Carey JC, Rayburn WF. Nuchal cord encirclements and risk of stillbirth. Int J Gynaecol Obstet. 2000;69: 173–4. Available: http://www.ncbi.nlm.nih.gov/pubmed/10802092 pmid:10802092
          • 80. Carter E, Chu C, Thompson Z, … MT-J of, 2018 undefined. True knot at the time of delivery: electronic fetal monitoring characteristics and neonatal outcomes. nature.com. Available: https://www.nature.com/articles/s41372-018-0250-4
            • 81. Caspi E, Lotan Y, Schreyer P. Prolapse of the cord: reduction of perinatal mortality by bladder instillation and cesarean section. Isr J Med Sci. 1983;19: 541–5. Available: http://www.ncbi.nlm.nih.gov/pubmed/6862862 pmid:6862862
            • 82. Chaurasia BD. Single umbilical artery with caudal defects in human fetuses. Teratology. 1974;9: 287–97. pmid:4857608
            • 83. Chitra T, Sushanth YS. Umbilical coiling index as a marker of perinatal outcome: an analytical study. Obs Gynecol Int. 2012;2012: 213689. pmid:22496697
            • 84. Clapp JF, Stepanchak W, Hashimoto K, Ehrenberg H, Lopez B. The natural history of antenatal nuchal cords. Am J Obstet Gynecol. 2003;189: 488–93. Available: http://www.ncbi.nlm.nih.gov/pubmed/14520223 pmid:14520223
            • 85. D’Antona D, Aldrich CJ, Spencer JA, Delpy D, Reynolds EO, Wyatt JS. Effect of nuchal cord on fetal cerebral haemodynamics and oxygenation measured by near infrared spectroscopy during labour. Eur J Obstet Gynecol Reprod Biol. 1995;59: 205–9. Available: http://www.ncbi.nlm.nih.gov/pubmed/7657017 pmid:7657017
            • 86. de Laat MWM, Franx A, Bots ML, Visser GHA, Nikkels PGJ. Umbilical Coiling Index in Normal and Complicated Pregnancies. Obstet Gynecol. 2006;107: 1049–1055. pmid:16648410
            • 87. Degani S, Lewinsky RM, Berger H, Spiegel D. Sonographic estimation of umbilical coiling index and correlation with Doppler flow characteristics. Obstet Gynecol. 1995;86: 990–3. Available: http://www.ncbi.nlm.nih.gov/pubmed/7501354 pmid:7501354
            • 88. Degani S, Leibovich Z, Shapiro I, Gonen R, Ohel G. Early second-trimester low umbilical coiling index predicts small-for-gestational-age fetuses. J Ultrasound Med. 2001;20: 1183–1188. pmid:11758023
            • 89. Dilbaz B, Ozturkoglu E, Dilbaz S, Ozturk N, Sivaslioglu AA, Haberal A. Risk factors and perinatal outcomes associated with umbilical cord prolapse. Arch Gynecol Obstet. 2006;274: 104–7. pmid:16538441
            • 90. Buyukkayaci Duman N, Topuz S, Bostanci MO, Gorkem U, Yuksel Kocak D, Togrul C, et al. The effects of umbilical cord entanglement upon labor management and fetal health: retrospective case control study. J Matern Neonatal Med. 2018;31: 656–660. pmid:28282778
            • 91. El Behery MM, Nouh AA, Alanwar AM, Diab AE. Effect of umbilical vein blood flow on perinatal outcome of fetuses with lean and/or hypo-coiled umbilical cord. Arch Gynecol Obstet. 2011;283: 53–8. pmid:19898858
            • 92. Enakpene CA, Omigbodun AO, Arowojolu AO. Perinatal mortality following umbilical cord prolapse. Int J Gynaecol Obstet. 2006;95: 44–5. pmid:16828093
            • 93. Ercal T, Lacin S, Altunyurt S, Saygili U, Cinar O, Mumcu A. Umbilical coiling index: is it a marker for the foetus at risk? Br J Clin Pr. 1996/07/01. 1996;50: 254–256.
            • 94. Ernst LM, Minturn L, Huang MH, Curry E, Su EJ. Gross patterns of umbilical cord coiling: correlations with placental histology and stillbirth. Placenta. 2013/05/07. 2013;34: 583–588. pmid:23642640
            • 95. Ertuğrul S, Gün I, Müngen E, Muhçu M, Kılıç S, Atay V. Evaluation of neonatal outcomes in elective repeat cesarean delivery at term according to weeks of gestation. J Obstet Gynaecol Res. 2013;39: 105–12. pmid:22889289
            • 96. Ezimokhai M, Rizk DE, Thomas L. Maternal risk factors for abnormal vascular coiling of the umbilical cord. Am J Perinatol. 2000;17: 441–5. pmid:11142396
            • 97. Gabbay-Benziv R, Maman M, Wiznitzer A, Linder N, Yogev Y. Umbilical cord prolapse during delivery–risk factors and pregnancy outcome: a single center experience. J Matern Neonatal Med. 2014;27: 14–17. pmid:23617536
            • 98. Gaikwad P, Patole K. Umbilical coiling index and perinatal outcome. MVP Journal of Medical Sciences 2016;3(2):118–121.
            • 99. Georgiadis L, Keski-Nisula L, Harju M, Raisanen S, Georgiadis S, Hannila ML, et al. Umbilical cord length in singleton gestations: a Finnish population-based retrospective register study. Placenta. 2014/02/25. 2014;35: 275–280. pmid:24560495
            • 100. Ghezzi F, Raio L, Di Naro E, Franchi M, Brühwiler H, D’Addario V, et al. First-trimester sonographic umbilical cord diameter and the growth of the human embryo. Ultrasound Obstet Gynecol. 2001;18: 348–51. pmid:11778994
            • 101. Gibbons C, O’Herlihy C, Murphy J. Umbilical cord prolapse—changing patterns and improved outcomes: a retrospective cohort study. BJOG An Int J Obstet Gynaecol. 2014;121: 1705–1708. pmid:24931454
            • 102. Gupta A, Kakkar T, Pathania H, Singh V. Impact of Nuchal Cord on Intrapartum Complications, Mode of Delivery and Perinatal Outcome. J Evol Med Dent Sci. 2018;7.
            • 103. Guzikowski W, Kowalczyk D, Więcek J. Diagnosis of true umbilical cord knot. Arch Med Sci. 2014;10: 91–5. pmid:24701220
            • 104. Hanaoka U, Yanagihara T, Tanaka H, Hata T. Comparison of three-dimensional, two-dimensional and color Doppler ultrasound in predicting the presence of a nuchal cord at birth. Ultrasound Obstet Gynecol. 2002;19: 471–4. pmid:11982980
            • 105. Hashimoto K, Clapp JF. The effect of nuchal cord on amniotic fluid and cord blood erythropoietin at delivery. J Soc Gynecol Investig. 2003;10: 406–11. Available: http://www.ncbi.nlm.nih.gov/pubmed/14519481 pmid:14519481
            • 106. Hehir MP, Hartigan L, Mahony R. Perinatal death associated with umbilical cord prolapse. J Perinat Med. 2017;45. pmid:27831923
            • 107. 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 Obs Gynecol Reprod Biol. 2001/08/23. 2001;98: 36–39.
            • 108. Jauniaux E, Ramsay B, Peellaerts C, Scholler Y. Perinatal features of pregnancies complicated by nuchal cord. Am J Perinatol. 1995;12: 255–8. pmid:7575829
            • 109. Jaya DS, Kumar NS, Bai LS. Anthropometric indices, cord length and placental weight in newborns. Indian Pediatr. 1995/11/01. 1995;32: 1183–1188. pmid:8772867
            • 110. Jessop FA, Lees CC, Pathak S, Hook CE, Sebire NJ. Umbilical cord coiling: clinical outcomes in an unselected population and systematic review. Virchows Arch. 2014;464: 105–112. pmid:24259031
            • 111. Joshi K, Saxena R, Bhat M, Lomrod Y, Verma K. Incidence of Cord around the Neck and Its Effects on Labour and Neonatal Outcome. Adv Hum Biol. 2017;7: 15–18.
            • 112. Kahana B, Sheiner E, Levy A, Lazer S, Mazor M. Umbilical cord prolapse and perinatal outcomes. Int J Gynaecol Obstet. 2004;84: 127–32. pmid:14871514
            • 113. Namli Kalem M, Kalem Z, Akgun N, Yuce E, Aktas H. The Journal of Maternal-Fetal & Neonatal Medicine Investigation of possible maternal and fetal factors which affect umbilical coiling index. [cited 8 Jan 2020]. pmid:29065736
            • 114. Kashanian M, Akbarian A, Kouhpayehzadeh J. The umbilical coiling index and adverse perinatal outcome. Int J Gynecol Obstet. 2006;95: 8–13. pmid:16860802
            • 115. Katsura D, Takahashi Y, Shimizu T, Watanbe Y, Iwagaki S, Murakami T, et al. Prenatal measurement of umbilical cord length using magnetic resonance imaging. Eur J Obstet Gynecol Reprod Biol. 2018;231: 142–146. Available: https://www.sciencedirect.com/science/article/pii/S0301211518310522 pmid:30388608
            • 116. Kesrouani A, Daher A, Maoula A, Attieh E, Richa S. Impact of a prenatally diagnosed nuchal cord on obstetrical outcome in an unselected population. J Matern Fetal Neonatal Med. 2017;30: 434–436. pmid:27049480
            • 117. Kobayashi N, Aoki S, Oba MS, Takahashi T, Hirahara F. Effect of Umbilical Cord Entanglement and Position on Pregnancy Outcomes. Obstet Gynecol Int. 2015;2015: 342065. pmid:26240566
            • 118. Kong CW, Lee DHY, Chan LW, To WWK. Impact of nuchal cord on fetal outcomes, mode of delivery, and management: a questionnaire survey of pregnant women. Hong Kong Med J = Xianggang yi xue za zhi. 2015;21: 143–8. pmid:25756276
            • 119. LaMonica GE, Wilson ML, Fullilove AM, Rayburn WE. Minimum cord length that allows spontaneous vaginal delivery. J Reprod Med. 2008;53: 217–9. Available: http://www.ncbi.nlm.nih.gov/pubmed/18441729 pmid:18441729
            • 120. Larson JD, Rayburn WF, Crosby S, Thurnau GR. Multiple nuchal cord entanglements and intrapartum complications. Am J Obs Gynecol. 1995/10/01. 1995;173: 1228–1231.
            • 121. Larson JD, Rayburn WF, Harlan VL. Nuchal cord entanglements and gestational age. Am J Perinatol. 1997;14: 555–7. pmid:9394166
            • 122. Lipitz S, Seidman DS, Gale R, Stevenson DK, Alcalay M, Menczer J, et al. Is fetal growth affected by cord entanglement? J Perinatol. 1993;13: 385–8. Available: http://www.ncbi.nlm.nih.gov/pubmed/8263624 pmid:8263624
            • 123. Lolis D, Stefos T, Ziakas G, Sotiriadis A. Birth characteristics of 5,278 pregnancies. J Matern Neonatal Med. 1998;7: 32–35.
            • 124. Machin GA, Ackerman J, Gilbert-Barness E. Abnormal umbilical cord coiling is associated with adverse perinatal outcomes. Pediatr Dev Pathol. 2000;3: 462–471. pmid:10890931
            • 125. Malpas P. Length of the Human Umbilical Cord at Term. Br Med J. 1964;1: 673–674. pmid:14096463
            • 126. Mariya T, Fujibe Y, Shinkai S, Sugita N, Suzuki M, Endo T, et al. Multiple part umbilical cord entanglement and neonatal outcomes. Taiwan J Obstet Gynecol. 2018;57: 672–676. pmid:30342649
            • 127. Mastrobattista JM, Hollier LM, Yeomans ER, Ramin SM, Day M-C, Sosa A, et al. Effects of nuchal cord on birthweight and immediate neonatal outcomes. Am J Perinatol. 2005;22: 83–5. pmid:15731986
            • 128. Markov D, Milanova K, Dimitrov A, Marinov B, Nikolov A, Ivanov S. [Nuchal cord between 37 and 42 completed weeks of gestation—diagnosis and prognostic value]. Akush Ginekol (Sofiia). 2007;46: 3–10. Available: http://www.ncbi.nlm.nih.gov/pubmed/18335605
            • 129. McLennan H, Price E, Urbanska M, Craig N, Fraser M. Umbilical cord knots and encirclements. Aust N Z J Obstet Gynaecol. 1988;28: 116–119. Available: http://www.ncbi.nlm.nih.gov/pubmed/3228405 pmid:3228405
            • 130. Naeye RL. Umbilical cord length: clinical significance. J Pediatr. 1985;107: 278–81. Available: http://www.ncbi.nlm.nih.gov/pubmed/4020556 pmid:4020556
            • 131. Najafi L, Khamseh ME, Kashanian M, Younesi L, Abedini A, Valojerdi AE, et al. Antenatal umbilical coiling index in gestational diabetes mellitus and non-gestational diabetes pregnancy. Taiwan J Obstet Gynecol. 2018;57: 487–492. pmid:30122566
            • 132. Ndolo JM, Vinayak S, Silaba MO, Stones W. Antenatal umbilical coiling index and newborn outcomes: cohort study. NcbiNlmNihGov. 2017;7: 21. https://dx.doi.org/10.4103/jcis.JCIS_111_16
            • 133. Nnatu S. Length of human umbilical cord in african population. J Natl Med Assoc. 1960;83: 33–36. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627007/pdf/jnma00879-0041.pdf
            • 134. Ogueh O, Al-Tarkait A, Vallerand D, Rouah F, Morin L, Benjamin A, et al. Obstetrical factors related to nuchal cord. Acta Obstet Gynecol Scand. 2006;85: 810–4. pmid:16817078
            • 135. Ohno Y, Terauchi M, Tamakoshi K. Perinatal outcomes of abnormal umbilical coiling according to a modified umbilical coiling index. J Obstet Gynaecol Res. 2016;42: 1457–1463. pmid:27527823
            • 136. Olaya-C M, Bernal JE. Clinical associations to abnormal umbilical cord length in Latin American newborns. J Neonatal Perinatal Med. 2015;8: 251–256. pmid:26485559
            • 137. Osak R, Webster KM, Bocking AD, Campbell MK, Richardson BS. Nuchal cord evident at birth impacts on fetal size relative to that of the placenta. Early Hum Dev. 1997;49: 193–202. Available: http://www.ncbi.nlm.nih.gov/pubmed/9378081 pmid:9378081
            • 138. Pathak S, Hook E, Hackett G, Murdoch E, Sebire NJ, Jessop F, et al. Cord coiling, umbilical cord insertion and placental shape in an unselected cohort delivering at term: relationship with common obstetric outcomes. Placenta. 2010/09/14. 2010;31: 963–968. pmid:20832856
            • 139. Patil N, Kulkarni S, Lohitaswa R. Umbilical cord coiling index and perinatal outcome. Journal of Clinical and Diagnostic Research. 2013;7(8):1675–1677. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782929/ pmid:24086872
            • 140. Peng HQ, Levitin-Smith M, Rochelson B, Kahn E. Umbilical cord stricture and overcoiling are common causes of fetal demise. Pediatr Dev Pathol. 2006;9: 14–19. pmid:16808633
            • 141. Poljak B, Banovic I, Vidovic-Filipovic S, Gabric Z, Juric-Vitanovic A. [Prenatal diagnosis of coiling of the umbilical cord around the neck and its effect on early neonatal prognosis]. Lijec Vjesn. 1989/08/01. 1989;111: 260–262. pmid:2682110
            • 142. Purola E, Schreck-Purola I. Looping of the umbilical cord around the foetal neck. Ann Paediatr Fenn. 1968;14: 43–6. Available: http://www.ncbi.nlm.nih.gov/pubmed/5706792 pmid:5706792
            • 143. Räisänen S, Georgiadis L, Harju M, Keski-Nisula L, Heinonen S. True umbilical cord knot and obstetric outcome. Int J Gynecol Obstet. 2013;122: 18–21. pmid:23523334
            • 144. Rana J, Ebert GA, Kappy KA. Adverse perinatal outcome in patients with an abnormal umbilical coiling index. Obstet Gynecol. 1995;85: 573–7. pmid:7898836
            • 145. Rayburn WF, Beynen A, Brinkman DL. Umbilical cord length and intrapartum complications. Obstet Gynecol. 1981;57: 450–2. Available: http://www.ncbi.nlm.nih.gov/pubmed/7243092 pmid:7243092
            • 146. Rogers MS, Ip YW, Qin Y, Rogers SM, Sahota D. Relationship between umbilical cord morphology and nuchal cord entanglement. Acta Obstet Gynecol Scand. 2003;82: 32–7. Available: http://www.ncbi.nlm.nih.gov/pubmed/12580837 pmid:12580837
            • 147. Romero Gutiérrez G, Estrada Razo S, Chávez Curiel A, Ponce Ponce de León AL. [Color Doppler flowmetry values in fetuses with nuchal cord encirclement]. Ginecol Obstet Mex. 2000;68: 401–7. Available: http://www.ncbi.nlm.nih.gov/pubmed/11138400 pmid:11138400
            • 148. Sahoo K, Mahajan A, Shaha P, Kshirsagar N. Evaluation of umbilical coiling index as a predictor of pregnancy outcome. IJHSR. 2015;5: 92–100. Available: http://www.ijhsr.org/IJHSR_Vol.5_Issue.3_March2015/15.pdf
            • 149. Salge AKM, Reis MR, Siqueira KM, Castral TC, Guimarães JV, Castro EC da C. Associação entre as características macroscópicas do cordão umbilical, gestação de alto risco e repercussões neonatais. Rev da Esc Enferm da USP. 2018;51. pmid:29412226
            • 150. Schäffer L, Burkhardt T, Zimmermann R, Kurmanavicius J. Nuchal cords in term and postterm deliveries—Do we need to know? Obstet Gynecol. 2005;106: 23–28. pmid:15994613
            • 151. Sharma B, Bhardwaj N, Gupta S, Gupta PK, Verma A, Malviya K. Association of Umbilical Coiling Index by Colour Doppler Ultrasonography at 18–22 Weeks of Gestation and Perinatal Outcome. J Obstet Gynecol India. 2012;62: 650–654. pmid:24293842
            • 152. Sheiner E, Abramowicz JS, Levy A, Silberstein T, Mazor M, Hershkovitz R. Nuchal cord is not associated with adverse perinatal outcome. Arch Gynecol Obstet. 2006;274: 81–3. pmid:16374604
            • 153. Shiva Kumar H. Study of length of umbilical cord and fetal outcome: a study of 1000 deliveries. Int J Reprod Contraception, Obstet Gynecol. 2017;6: 3770.
            • 154. Shrestha NS, Singh N. Nuchal cord and perinatal outcome. Kathmandu Univ Med J (KUMJ). 2007;5: 360–3. Available: http://www.ncbi.nlm.nih.gov/pubmed/18604054
            • 155. Sinnathuray TA. Cord round the neck. An evaluation of its significance. Singapore Med J. 1965;6: 213–8. Available: http://www.ncbi.nlm.nih.gov/pubmed/5899274 pmid:5899274
            • 156. Sørnes T, Bakke T. Uterine size, parity and umbilical cord length. Acta Obstet Gynecol Scand. 1989;68: 439–41. Available: http://www.ncbi.nlm.nih.gov/pubmed/2520789 pmid:2520789
            • 157. Sørnes T. Umbilical cord encirclements and fetal growth restriction. Obstet Gynecol. 1995;86: 725–8. pmid:7566836
            • 158. Sørnes T. Umbilical cord knots. Acta Obstet Gynecol Scand. 2000;79: 157–9. Available: http://www.ncbi.nlm.nih.gov/pubmed/10716294 pmid:10716294
            • 159. Stanek J. Association of coexisting morphological umbilical cord abnormality and clinical cord compromise with hypoxic and thrombotic placental histology. Virchows Arch. 2016/03/18. 2016;468: 723–732. pmid:26983702
            • 160. Stefos T, Sotiriadis A, Vasilios D, Tsirkas P, Korkontzelos I, Avgoustatos F, et al. Umbilical cord length and parity—the Greek experience. Eur J Obstet Gynecol Reprod Biol. 2003;107: 41–4. Available: http://www.ncbi.nlm.nih.gov/pubmed/12593892 pmid:12593892
            • 161. Strong TH, Manriquez-Gilpin MP, Gilpin BG. Umbilical vascular coiling and nuchal entanglement. J Matern Neonatal Med. 1996;5: 359–361.
            • 162. Suzuki S, Hiraizumi Y, Miyake H. Influence of umbilical cord abnormalities (velamentous/marginal cord insertion and nuchal cord) on the perinatal outcomes of the second twin after vaginal delivery of the first twin. J Perinat Med. 2011;39: 745–8. pmid:21812754
            • 163. Tamrakar S. Incidence of nuchal cord, mode of delivery and perinatal outcome: A notable experience in Dhulikel Hospital—Kathmandu University Hospital. Nepal Med Coll J. 2013;15: 40–45. pmid:24592793
            • 164. Tantbirojn P, Saleemuddin A, Sirois K, Crum CP, Boyd TK, Tworoger S, et al. Gross abnormalities of the umbilical cord: related placental histology and clinical significance. Placenta. 2009;30: 1083–1088. pmid:19853300
            • 165. Tapasvi I, Tapasvi C, Grover S, Bhambri M, Bhalla S. To identify the relationship between umbilical cord length and birth weight, amniotic fluid index, perinatal outcome in term pregnancies—study in a tertiary care hospital of North India. Indian J Basic Appl Med Res. 2017;6: 569–577. Available: http://ijbamr.com/pdf/September 2017 569–577 AA.pdf.pdf
            • 166. Tripathy . Umbilical Coiling Index and Its Relationship with Perinatal Outcomes. Indian J Neonatal Med Res. 2014;2: 1–4.
            • 167. Uygur D, Kis S, Tuncer R, Ozcan FS, Erkaya S. Risk factors and infant outcomes associated with umbilical cord prolapse. Int J Gynaecol Obs. 2002/08/15. 2002;78: 127–130.
            • 168. van Dijk CC, Franx A, de Laat MWM, Bruinse HW, Visser GHA, Nikkels PGJ, et al. The umbilical coiling index in normal pregnancy. J Matern Neonatal Med. 2002;11: 280–3. pmid:12375686
            • 169. Walker CW, Pye BG. The length of the human umbilical cord: a statistical report. Br Med J. 1960/02/20. 1960;1: 546–548. pmid:13842494
            • 170. Walla T, Rothschild MA, Schmolling JC, Banaschak S. Umbilical cord entanglement’s frequency and its impact on the newborn. Int J Legal Med. 2018;132: 747–752. pmid:29170816
            • 171. Wasswa EW, Nakubulwa S, Mutyaba T. Fetal demise and associated factors following umbilical cord prolapse in Mulago hospital, Uganda: a retrospective study. Reprod Health. 2014;11: 12. pmid:24485199
            • 172. Weiner E, Fainstein N, Schreiber L, Sagiv R, Bar J, Kovo M. The association between umbilical cord abnormalities and the development of non-reassuring fetal heart rate leading to emergent cesarean deliveries. J Perinatol. 2015/08/21. 2015;35: 919–923. pmid:26291780
            • 173. Winch GC, Claman AD. Prolapse of the cord. Can Med Assoc J. 1961;84: 1369–73. Available: http://www.ncbi.nlm.nih.gov/pubmed/13785757 pmid:13785757
            • 174. Wu JF, Chang SY, Hsu TY, Hsieh CH, Kung FT, Hwang FR, et al. Multivariate analyses of the relationship between umbilical cord length and obstetric outcome. Chang yi xue za zhi. 1996;19: 247–52. Available: http://www.ncbi.nlm.nih.gov/pubmed/8921643
            • 175. Yadav B., Kurdukar D., Darade R., Mahada N. Correlation of Umbilical Cord Length and Foetal Outcome. J Evol Med Dent Sci. 2013;2: 412–417. Available: http://www.jemds.com/data_pdf/BBYadav-CORRELATION OF UMBILICAL CORD.pdf
            • 176. Zahoor F, Minhas Z, Zaki A. Perinatal outcome of nuchal cord. 2013;27: 174–178. Available: https://www.scopus.com/record/display.uri?eid=2-s2.0-84875035194&origin=inward&txGid=160f3b40a56fd0a0bfce78f5906a9ded