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Journal of Obstetrics and Gynaecology

ISSN: 0144-3615 (Print) 1364-6893 (Online) Journal homepage: https://www.tandfonline.com/loi/ijog20

The impact of nuchal cord on umbilical cord blood

gas analysis and ischaemia-modified albumin

levels in elective C-section

Aslı Yarcı Gursoy, Burcin Ozgu, Yasemin Tasci, Tuba Candar, Salim Erkaya &

Gamze Sinem Caglar

To cite this article: Aslı Yarcı Gursoy, Burcin Ozgu, Yasemin Tasci, Tuba Candar, Salim Erkaya & Gamze Sinem Caglar (2018) The impact of nuchal cord on umbilical cord blood gas analysis and ischaemia-modified albumin levels in elective C-section, Journal of Obstetrics and Gynaecology, 38:8, 1099-1103, DOI: 10.1080/01443615.2018.1454411

To link to this article: https://doi.org/10.1080/01443615.2018.1454411

Published online: 18 Jun 2018.

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ORIGINAL ARTICLE

The impact of nuchal cord on umbilical cord blood gas analysis and

ischaemia-modified albumin levels in elective C-section

Aslı Yarcı Gursoya, Burcin Ozgub, Yasemin Tascib, Tuba Candarc, Salim Erkayaband Gamze Sinem Caglara

a

Department of Obstetrics and Gynecology, Ufuk University Faculty of Medicine, Ankara, Turkey;bDepartment of Obstetrics and Gynecology, Zekai Tahir Burak Women’s Health Care and Research Hospital, Ankara, Turkey;c

Department of Biochemistry, Ufuk University Faculty of Medicine, Ankara, Turkey

ABSTRACT

This study was designed to evaluate umbilical cord ischaemia-modified albumin (IMA) levels and the cord blood gas parameters of foetuses with or without nuchal cords, at the time of elective C-section. The cross-sectional study population consisted of the patients who were admitted to the Tertiary Care Center between February and June 2015. Women with uncomplicated single term gestations between 37 and 40 completed weeks and scheduled for elective C-sections were included in the study. Fifty cases with a nuchal cord and 50 cases without a nuchal cord were recruited. Nuchal cord blood gas analysis and the IMA levels were evaluated. The IMA levels in umbilical artery of foetuses both in the study and control groups were similar (0.714 ± 0.150 vs. 0.689 ± 0.107 ABSU,p ¼ .340, respectively). The umbilical artery pH values of the study group were significantly lower than that in the control group (7.31 ± 0.04 vs. 7.32 ± 0.03, p ¼ .042; respectively). The results of the current study indicate that the nuchal cord has an impact on the foetal cord blood gas parameters to some extent before the initiation of labour. Fortunately, this impact does not end up with foetal tissue ischaemia, as confirmed by the IMA levels.

IMPACT STATEMENT

 What is already known on this subject? The impact of nuchal cord on perinatal outcomes has been the subject of research for many years. Although the accumulated data has pointed out some unfavourable perinatal effects, the heterogeneity of the study groups both including a vaginal deliv-ery and C-section and the inability to adjust the interfering factors ended up with some controver-sies. This is why there is not much known about the effects of the nuchal cord in women who are not in the labour process.

 What do the results of this study add? The current study aimed to exclude the interfering effects such as the active stage of labour. In this study, elective caesarean sections were selected as the study population to evaluate the effects of the nuchal cord on cord blood gas parameters and the IMA values. pH analysis in cord blood is used to detect hypoxia and the IMA is a new ischaemia marker. The results revealed that the in utero nuchal cord is associated with a significantly higher pCO2and lower pH values and similar IMA values.

 What are the implications of these findings for clinical practice and/or further research? The final outcome supports that the nuchal cord causes alterations in cord blood gas analysis but this does not reach critical levels. Therefore, the results show that there is no need to change clinical practice when the nuchal cord is detected by ultrasound in a term gestation.

KEYWORDS

Cord blood; nuchal cord; ischaemia-modified albumin; elective; caesarean section; blood gas analysis

Introduction

Ischaemia-modified albumin (IMA) is the modified form of albumin generated as a result of oxidative stress following ischaemia, which causes changes in N-terminus (Bar-Or et al. 2001). IMA has been certified by the United States Food and Drug Administration (FDA) for use in cardiac pathologies as an early marker of ischaemia (Wu 2003). Besides, IMA has also been reported to increase in other ischaemic conditions, such as perinatal complications (Yarcı Gursoy et al. 2017). The levels of IMA in maternal and cord bloods have been the focus of research in pregnancies complicated with

intrauterine growth restriction (Guvendag Guven et al. 2013; Kiseli et al.2015); acute foetal distress (Caglar et al.2013) and with preeclampsia (Papageorghiou et al. 2008; Ustun et al. 2011). In the above-mentioned conditions diminished utero-placental perfusion and foetal oxygenation has been associ-ated with increased levels of IMA in cord blood. Likewise, umbilical cord blood flow, if partially or intermittently obstructed may result in decreased foetal oxygenation (Martin et al.2005).

The umbilical cord loops around the neck (nuchal cord) is a quite frequent situation, with an incidence ranging between CONTACTAslı Yarcı Gursoy asliyarci@gmail.com Department of Obstetrics and Gynecology, Ufuk University Faculty of Medicine, Mevlana Bulvarı (Konya Yolu) No.: 86–88, 06520 Balgat/Ankara, Turkey

ß 2018 Informa UK Limited, trading as Taylor & Francis Group

VOL. 38, NO. 8, 1099–1103

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15.8% and 30% in the late trimesters of pregnancy (Clapp et al. 1999; Assimakopoulos et al. 2005) and the clinical sig-nificance of this situation is controversial. Nearly six decades ago, Shui and Eastman (Shui and Eastman 1957) demon-strated for the first time in the literature that, the presence of a nuchal cord at a delivery did not increase the perinatal mortality, which was later supported by other authors (Clapp et al.1999; Qin et al.2000; Mastrobattista et al.2005; Sheiner et al.2006). On the other hand, in the 1990s, numerous stud-ies reported that a nuchal cord is associated with various problems in the first and second stages of labour and with adverse perinatal outcomes, such as the increased incidence of variable decelerations (Tejani et al. 1977), meconium-stained amniotic fluid (Jauniaux et al.1995), low Apgar scores (Larson et al. 1995; Clapp et al. 1999; Assimakopoulos et al. 2005), cerebral palsy (Clapp et al. 1999) and umbilical artery acidaemia (Hankins et al.1987).

Although, the clinical significance of such a frequent clin-ical condition still needs to be elucidated, the presence of the nuchal cord in labour and delivery has been associated with adverse neonatal outcomes. The recent data indicate that nuchal cords during labour and a vaginal delivery may cause decreased foetal perfusion (Martin et al.2005).

The effect of this clinical condition on foetal well-being has been evaluated previously with parameters such as Apgar scores (Clapp et al.1999; Assimakopoulos et al. 2005), a neonatal intensive care unit submission (Jauniaux et al. 1995), as well as cord blood gas analyses (Onderoglu et al. 2008). However, IMA, a new and potential ischaemia marker in perinatology, has never been used for evaluating the foetal well-being in foetuses with a nuchal cord. Moreover, the pre-vious studies concerning the effect of a nuchal cord on a cord blood gas analysis have included mostly heterogeneous populations of women delivering by either vaginal route or by a C-section. In order to exclude the possible interfering effect of the labour process in the presence of nuchal cord, this study is designed to evaluate umbilical cord IMA levels and cord blood gas analysis of foetuses with or without nuchal cords during an elective C-section.

Materials and methods

The cross-sectional study was conducted in a Tertiary Care Center between February and June, 2015. The study was approved by the Ethical Committee and an informed consent was taken from the participants. Women with uncomplicated single term gestations between 37 and 40 completed weeks and scheduled for elective C-section either due to a repeat C-section or foetal malpresentation were offered to partici-pate in the study. Among the participants who were found to have at least one nuchal cord around the foetal neck dur-ing C-section constituted the study group and the others who were found not to have a nuchal cord were recruited for the control group. The gestational age was determined according to the ultrasonographic examination performed between the 11th and 14th weeks of gestation. Pregnant women, with chronic hypertension, preeclampsia, intrauterine growth restriction, pregestational or gestational diabetes mel-litus, who are smokers, whose maternal age is <18 and >35,

who have placental insertion abnormalities, preterm deliveries (<37 weeks), maternal chronic diseases with or without any medication supplementation and who were having emer-gency caesarean sections due to uterine contractions were excluded.

Data of 100 women, 50 in study and 50 in control group, were included in the analysis. Maternal venous blood samples for IMA measurements were collected in the theatre room just before any intervention. The umbilical artery blood sam-ples, both for blood gas analysis and IMA, were collected from the umbilical artery just after the delivery of the foetus. The blood gas analysis was evaluated just at the theatre room by Radiometer ABL 800 Basic (Radiometer, Copenhagen, Denmark). The blood samples in plain tubes taken for IMA analysis were centrifuged within one hour after their collection and serums were separated and stored at 80C. All the samples of maternal and cord blood were analysed in a single run. The IMA concentrations were ana-lysed by measuring the complex, composed of dithiothreitol and cobalt (Sigma AldrichVR

, St Louis, MO) and unbound to albumin by the colourimetric method in a spectrophotom-eter. The analyses in the spectrophotometer (Human HumalyzerVR

2000, Wiesbaden, Germany) were performed at 470 nm for the detection of the absorbance of the specimens, and the results were given in absorbance units (ABSU).

Statistical analyses

The statistical analysis was performed with IBM SPSS for Windows Version 21.0 software. Numerical variables were expressed as the mean ± standard deviation or median [min.–max.] as appropriate. The categorical variables were presented as numbers and percentages. Normality of the con-tinuous variables was tested by the Shapiro Wilks test. The Levene test was used to show the homogeneity of the var-iances. The Independent samplest test or the Mann–Whitney U test was used to determine the difference between the two independent groups according to the parametric test assumptions. More than two independent groups were com-pared by one-way ANOVA or by use of the Kruskal Wallis test, as appropriate. The categorical variables were compared by the Chi square or the Fisher exact test. A p value of <.05 was considered as statistically significant.

Results

The demographic variables including the age, gravidity, par-ity, body mass index, biochemical parameters and the com-plete blood count parameters were similar between the two groups (Table 1). IMA levels in maternal blood and umbilical artery of the foetuses were similar between the study and control groups (p ¼ .745 and p ¼ .340, respectively). None of the foetuses suffered from foetal umbilical artery acidaemia, which is defined as a pH value <7.0 by Task Force on Neonatal Encephalopathy (ACOG 2014). The umbilical artery pH values of the study group were significantly lower than the control group (p ¼ .042) whereas the pCO2 levels were significantly higher in study group compared to the controls 1100 A. Y. GURSOY ET AL.

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(p ¼ .005). The base deficit and pO2 values were similar between the two groups (p > .05). In the study group 31 (62%) of the foetuses had one nuchal loop, whereas 19 (38%) foetuses had more than one loop (13 foetuses had two and six foetuses had three loops). Regarding the number of nuchal loops, pH values, base deficits and umbilical cord IMA levels were not different between the cases with one or more than one nuchal loop and controls (Table 2).

Discussion

The results of this study show that the existence of a nuchal cord is associated with lower cord blood pH levels, which do

not go beyond the accepted clinically significant values. Moreover, the foetuses with or without a nuchal cord demon-strated similar cord blood IMA levels. This is the first study evaluating the IMA levels in foetuses with a nuchal cord delivered by an elective C-section. The current data supports that, although a nuchal cord has an effect on cord blood gas parameters to some extent, the parameters remain in the normal range, so were clinically negligible for this study. Besides, the absence of significant difference between IMA values between study and control groups supports these outcomes.

To-date, lower umbilical artery pH values in the presence of a nuchal cord has been reported by numerous authors (Hankins et al. 1987; Larson et al. 1995; Onderoglu et al. 2008; Bernad et al.2012; Narang et al.2014). However, many of the previous studies included heterogeneous groups of women who delivered by vaginal route, by an elective C-sec-tion or an emergency C-secC-sec-tion, revealing inconsistent results, although, the cord blood pH values at delivery might be affected by the dynamics of the labour. Moreover, the unfavourable factors (e.g. meconium-stained amniotic fluid, operative delivery) associated with the lower pH values com-plicating the delivery have been reported to be more fre-quently observed in foetuses with a nuchal cord (Stembera and Horska 1972; Hankins et al. 1987; Larson et al. 1995; Assimakopoulos et al.2005; Onderoglu et al.2008; Nkwabong and Fomulu 2011). Therefore, in order to discriminate the impact of nuchal cord per se on the cord blood IMA levels, women who delivered by an elective C–section were recruited in this study. In this group of pregnant women, the pH values of the cord blood have been shown to be signifi-cantly lower, but still remaining in the normal range. Whether this result has any clinical significance is questionable.

IMA has been reported to increase as soon as the ischae-mic insult starts and stays high, throughout the reversible cel-lular damage phase (Gaze 2009). Besides, IMA is an end product of an oxidative stress lacking tissue specificity (Gaze 2009) and proposed to be generated by hypoxia, acidosis, energy-dependent membrane distruption and exposure to free iron and copper (Bar-Or et al. 2000; Roy et al. 2006; Sbarouni et al. 2011), also reported to be affected by the albumin, lactate and blood glucose levels (Dominguez-Rodriguez and Abreu-Gonzalez 2010). Strenuous physical exercise, tourniquet application during surgery and arterial clamping during revascularisation procedures are the previ-ously reported clinical conditions correlated with increased IMA levels (Apple et al. 2002; Refaai et al. 2006). Likewise, a partial or intermittent obstruction of umbilical blood flow in an intrauterine period might be associated with elevated IMA levels. But, there is no certain data about this issue. From this aspect, in our study, an intrauterine nuchal cord seems not to end up with a foetal tissue ischaemia reflected by IMA levels, before the initiation of the labour.

Depending on population-based studies, the routine screen-ing for nuchal cord is not recommended (Clapp et al. 2003; Mastrobattista et al. 2005; Sheiner et al. 2006). In addition, an early detection might lead to unnecessary anxiety in patients and the healthcare professionals (Sherer and Manning 1999). Table 2. Comparison of maternal and foetal IMA values and cord blood gas

parameters in control, nuchal cord with one or more loops. Control group (n ¼ 50) Nuchal cord (1 Loop) (n ¼ 31) Nuchal cord (>1 Loop) (n ¼ 19) p Maternal IMA 0.710 ± 0.137 0.701 ± 0.143 0.701 ± 0.139 .948 (ABSU) Umbilical artery 0.689 ± 0.107 0.704 ± 0.168 0.729 ± 0.115 .512 IMA (ABSU) pH 7.32 ± 0.03 7.31 ± 0.04 7.31 ± 0.03 .128 Base deficit 3.35 3.05 3.40 .760 (mmol/L) [0.80–11.40] [0.20–11.00] [0.10–10.80] pCO2(mmHg) 42.5 ± 5.3 45.4 ± 5.6 45.6 ± 4.7 .026a pO2(mmHg) 21.8 ± 5.0 21.8 ± 5.0 21.5 ± 4.6 .091

MA: ischaemia-modified albumin; ABSU: absorbance unit.

aControl group is significantly different than both study groups (1 Loop and

>1 Loop).

Table 1. Demographic parameters and laboratory values of groups. Study group

(n ¼ 50)

Control group (n ¼ 50) p Maternal age (years) 28.6 ± 4.8 27.9 ± 5.2 .499

Gravidity 2 [1–4] 2 [1–9] .488 Parity 1 [0–2] 1 [0–4] .899 Abortus 0 [0–1] 0 [0–2] .688 Children 1 [0–2] 1 [0–4] .726 BMI (Kg/m2) 30.6 ± 3.2 30.4 ± 3.3 .766 WBC (/mL) 11,376 ± 1838 11,264 ± 1945 .768 Hb (g/dL) 11.8 ± 1.4 11.6 ± 1.5 .434 Plt (/mL) 203,380 ± 55,942 191,780 ± 42,280 .245 Gestational day at birth 274 [271–290] 274 [267–280] .074

AST (U/L) 19 [9–56] 20[9–34] .318 ALT (U/L) 16 [5–67] 18 [7–34] .477 BUN (mg/dL) 14 [9–25] 14 [8–24] .429 Foetal gender (F/M) 28/22 (56%/44%) 30/19 (61.2%/38.8%) .746 Indication for caesarean section

Previous C/S 46 (92%) 44 (88%) .135

Abnormal foetal presentation 4 (8%) 6 (12%)

Foetal birthweight (g) 3265.6 ± 343.3 3348.8 ± 358.1 .239 Apgar score 1-min 9 [7–9] 9 [8–9] .406 Apgar score 5-min 10 [9–10] 10 [10–10] .317 Maternal IMA (ABSU) 0.701 ± 0.140 0.710 ± 0.137 .745 Umbilical artery IMA 0.714 ± 0.150 0.689 ± 0.107 .340 (ABSU)

pH 7.31 ± 0.04 7.32 ± 0.03 .042

Base deficit (mmol/L) 3.10 [0.10–11.00] 3.35 [0.80–11.40] .986 pCO2(mmHg) 45.6 ± 5.2 42.5 ± 5.3 .005

pO2(mmHg) 20.3 ± 4.3 21.8 ± 5.0 .112

BMI: body mass index; WBC: white blood count; Hb: haemoglobin; Plt: platelet; AST: aspartate aminotransferase; ALT: alanine aminotransferase; BUN: blood urea nitrogen; IMA: ischaemia-modified alb€umin; ABSU: absorbance unit. p<.05.

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Also, the detection of nuchal cord is not an absolute medical indication for a C-section on its own (National Collaborating Centre for Women's and Children's Health (UK)2011). However, with increasing concern about the medico-legal issues in obstetrics, a shift from the more severe to the milder and wider indications for C-section has appeared (Gao et al. 2013). Reports from different regions of the world claim that, the rate of C-section associated with the nuchal cord ranges between 11.1 and 35% (Sheiner et al. 2006; Onderoglu et al. 2008; Nkwabong and Fomulu 2011) being one of the common indi-cations for a caesarean delivery for perceived safety reasons (Nkwabong and Fomulu 2011). The factors associated with adverse neonatal outcomes correlated with a nuchal cord are the tightness of the cord (had to be cut for the progression of delivery), the number of loops and the time of persistence of nuchal cord (Clapp et al.1999).

Even if the lack of data about the tightness of the loops and the time of persistence of nuchal cord are the limitations of this study, detection of these parameters is almost impos-sible in routine practice. Another limitation of the study might be the absence of the data regarding albumin levels in the maternal and cord blood samples since the albumin level is one of the mostly known interfering factors with the IMA lev-els. This is because IMA is a fraction of the albumin affected by ischaemia, its levels have been shown to be negatively cor-related with the albumin levels when it is in normal range (10–49 g/L) but should be evaluated cautiously when the albu-min levels are extremely low (< 3.4 g/L) (Gaze et al. 2006; Lippi et al.2007; Gafsou et al.2010; D’souza et al.2014).

In conclusion, this study indicates that, a nuchal cord has an impact on the foetal cord blood gas parameters to some degree before the initiation of the labour process. Fortunately, this impact does not end up with foetal tissue ischaemia which was evaluated by the cord blood IMA levels. As this is the first study concerning this issue, further studies are needed to relieve the ‘anxiety of the obstetricians’ (Narang et al. 2014) and decrease the unnecessary interven-tions undertaken before the active stages of labour.

Disclosure statement

The authors report no conflicts of interest.

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Şekil

Table 2. Comparison of maternal and foetal IMA values and cord blood gas parameters in control, nuchal cord with one or more loops.

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No- dülden alınan deri biyopsinin histopatolojik ince- lemesinde normal görünümlü epidermis altında orta dermiste yarık benzeri boşluklar, dilate kan damarları, iğ

臺北醫學大學 生物統計研究中心 2 在能力評量上,有兩種型式可供選擇: “自我挑戰” 及 “接受測驗”。 “自 我挑戰”