Umbilical cord blood lactate: A valuable tool in the assessment of fetal metabolic acidosis

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1 European Journal of Obstetrics & Gynecology and Reproductive Biology 139 (2008) Umbilical cord blood lactate: A valuable tool in the assessment of fetal metabolic acidosis Anne Cathrine Gjerris a, *, Jette Stær-Jensen a, Jan Stener Jørgensen b, Thomas Bergholt a, Carsten Nickelsen a a Department of Obstetrics and Gynaecology, Hvidovre University Hospital, 2100 Copenhagen, Denmark b Department of Obstetrics and Gynaecology, Odense University Hospital, Odense, Denmark Received 2 November 2005; received in revised form 19 September 2007; accepted 12 October 2007 Abstract Objective: The aim of the present study was (1) to evaluate the relationship between umbilical cord arterial blood lactate and ph, standard base excess (SBE), and actual base excess (ABE) at delivery and (2) to suggest a cut-off level of umbilical cord arterial blood lactate in predicting fetal asphyxia using ROC-curves, where an ABE value less than 12 was used as gold standard for significant intrapartum asphyxia. Study design: This is a descriptive study of umbilical cord arterial blood samples from 2554 singleton deliveries. The deliveries took place at the Department of Obstetrics and Gynaecology, Hvidovre University Hospital, Copenhagen, Denmark where umbilical cord blood sampling and blood gas analysis is part of the routine assessment of all newborns. Results: We found significant correlations between lactate and ph (r = 0.73), lactate and SBE (r = 0.76), and lactate and ABE (r = 0.83). ROC-curves suggested a lactate cut-off level of 8 mmol/l for indicating intrapartum asphyxia. Conclusion: Lactate in arterial umbilical cord blood might be a more direct and accordingly more correct indicator of fetal asphyxia at delivery than ph and SBE (or ABE). Its potential as a predictor of neonatal outcome needs to be evaluated in future studies. # 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Umbilical cord blood; Lactate; Metabolic acidosis; Newborn assessment 1. Introduction Evaluation of the state of the newborn has usually been based on Apgar scores and blood gas parameters of umbilical cord blood. Fetal acidosis and hypoxia at delivery has been assessed by the use of indirect measures such as ph and SBE. However, these values together with carditocography (CTG) have proved to be insufficient in predicting adverse neonatal outcome [1]. During anaerobic metabolism, lactate production is predominant and causes increasing metabolic acidosis. Therefore, lactate concentration in umbilical cord blood at * Corresponding author. Tel.: / ; fax: address: ac@gjerris.dk (A.C. Gjerris). delivery might be a more precise tool in the assessment of fetal metabolic acidosis during labour. As lactate influences SBE and ph, a strong correlation between these parameters would be expected. Previous studies by Nordstrom [2] have shown that the main contributor to the fetal lactate increase during labour is the fetus itself not significantly influenced by maternal or by the uteroplacental lactate production. Some authors [3] found no significant correlation between umbilical cord blood lactate and SBE or ph, whereas others [1,4,5] found a positive, though not strong, correlation. The aim of this study was to evaluate the correlation between arterial umbilical cord blood lactate and standard and actual base excess as well as ph. A strong correlation would indicate that arterial umbilical cord blood lactate is a direct measure of metabolic acidosis /$ see front matter # 2007 Elsevier Ireland Ltd. All rights reserved. doi: /j.ejogrb

2 A.C. Gjerris et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 139 (2008) during labour, and presumably a better predictor of fetal asphyxia. Additionally, on background of our data, we define a cutoff level of lactate indicating intrapartum asphyxia. 2. Materials and methods During the period 1 January December 2001, 4214 women delivered singleton babies at the Department of Obstetrics and Gynecology at Hvidovre University Hospital, Copenhagen, Denmark. All deliveries are systematically evaluated by umbilical blood sampling, and 2554 umbilical arterial cord blood samples including ph, SBE, ABE and lactate were eligible for the present study representing 60.6% of all deliveries during the study period. Of these 2554 deliveries 7.6% (179) were delivered by elective and 11.8% (303) by emergency caesarean section. The overall caesarean section rate in the study period was 17.0% among the 4214 deliveries. Data were found in the local electronic obstetrical database. Umbilical cord blood sampling was performed according to the standard procedures [6] Arterial umbilical cord blood was drawn from a doubleclamped segment of the umbilical cord into plastic syringes prepared with a heparin solution. The acid base analysis was performed in an automatic blood gas analyser (ABL 700 Radiometer Copenhagen). From sampling to analysis the median time was 6.00 min (5th percentile = 1.0 min, 95th percentile = min) and mean was min (1S.D.). Sampling was carried out by midwives trained in this procedure. In order to determine a lactate value of umbilical cord artery blood indicating fetal metabolic acidosis receiver operating characteristic (ROC) curves were established. Each lactate level (1 16 mmol/l) has a corresponding pair of true-positive (sensitivity) and false-positive (1-specificity) rates representing one point on the ROCcurve [7]. SBE < 10, respectively ABE < 12 were used as true indicators of significant asphyxia Statistics Data are presented as median and mean 1S.D. We evaluated the relationship between levels of lactate and standard base excess (SBE), actual base excess (ABE) and ph, respectively by calculating Pearsons correlation coefficient (r). A value of P < 0.05 was regarded as significant. Statistical evaluation was performed using Microsoft Excel 2002 for Windows. 3. Results In the study period umbilical cord artery blood samples with full blood gas analysis were identified from 2554 newborns with no regard to mode of delivery. We found a close correlation between lactate in arterial cord blood and SBE (r = 0.76, P < 0.001), and the correlation was even stronger between lactate and ABE (r = 0.83, P < 0.001). As expected lactate also correlated significantly to ph (r = 0.73, P < 0.001) (Figs. 1 3). The median of lactate was 4.30 mmol/l, of ph 7.28, of SBE: 3.94 and of ABE: 4.53, respectively. Fig. 1. Scattered diagram showing the relationship between umbilical arterial cord blood lactate concentrations and standard base excess, y = x, r = 0.76, and P < Fig. 2. Scattered diagram showing the relationship between umbilical arterial cord blood lactate concentrations and actual base excess, y = x, r = 0.83, and P <

3 18 A.C. Gjerris et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 139 (2008) Fig. 3. Scattered diagram showing the relationship between umbilical arterial cord blood lactate concentrations and ph, y = x, r = 0.73, and P < Fig. 5. Receiver operating characteristic (ROC) curve. ROC-curve for umbilical arterial cord blood lactate concentration (mmol/l) to diagnose umbilical artery SBE < 10 mmol/l. The mean value of lactate concentration in arterial cord blood was mmol/l (1S.D.) with the range of mmol/l. Mean of ph (1S.D.), mean of SBE mmol/l (1S.D.) and mean of ABE mmol/l (1S.D.). The medians and means were almost identical. As demonstrated in Fig. 4 the umbilical cord blood lactate values are not normally distributed. The receiver operator curves are shown in Figs. 5 and 6. The point nearest to the left hand corner maximizes the sum of sensitivity and specificity and represents the best value (cut-off). When comparing with SBE < 10 mmol/l the lactate value is 7 and comparing with ABE < 12 mmol/l the value is Discussion Asphyxia is an imprecise term, but is usually defined as fetal hypoxia causing fetal acidosis and depression. To most obstetricians the condition means a state of the fetus with depressed vital functions and an increased risk of Fig. 4. Frequency histogram showing the distribution of lactate concentration (mmol/l). Total number of measurements = Fig. 6. Receiver operating characteristic (ROC) curve. ROC-curve for umbilical arterial cord blood lactate concentration (mmol/l) to diagnose umbilical artery ABE < 12 mmol/l.

4 A.C. Gjerris et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 139 (2008) long-term morbidity. Intrapartum asphyxia is estimated to be accountable for 7 15% of neonatal mortality and severe morbidity [8 10]. Over the last decades different criteria have been used in an attempt to identify the neonates who have been exposed to intrapartum asphyxia. The Apgar score was devised in 1952 by Virginia Apgar as a simple and repeatable method to quickly and summarily assess the health of newborn children. However, it gives no information of acidosis/hypoxia and has a very low predictive value in identifying long-term morbidity [11,12]. ph levels in umbilical cord blood are found to have a correlation to neurological development in some studies [13,14] but not in others [15,16]. There is no international consensus about a lower ph threshold with definitions of acidosis during labour ranging from a ph of 7.00 to 7.20 [17]. ph by itself only indicates the degree of acidosis but not the aetiology. Respiratory acidosis is far more harmless to the fetus and neonate than metabolic acidosis [17]. Respiratory acidosis is a result of accumulating carbon dioxide usually caused by compression of the umbilical cord, decreased fetal cardiac output or insufficient placental perfusion. Metabolic acidosis develops in the late stage of fetal hypoxia when oxygen supply to the fetus becomes insufficient and the metabolism of carbohydrates is converted into anaerobic metabolism with the production of lactic acid. When the concentration of lactate rises, the SBE and ABE levels decrease. SBE has so far been regarded the most precise parameter in indicating fetal and neonatal asphyxia with the best correlation to long-term morbidity [18]. The levels of SBE and ABE are the results of the lactate concentration. Therefore, theoretically at least, lactate would seem the most direct parameter expressing the severity of metabolic acidosis. Electrodes in the acid base laboratory measure ph and pco 2 while the metabolic component is a value calculated by an inbuilt logarithm of the machine. The metabolic component can be described as SBE, ABE or BD. ABE and BD are equal values with an opposite sign. ABE is a compute for the buffer capacity in the actual blood sample. SBE is a compute for the buffer capacity of the whole body s extra cellular fluid compartment. Lactate as well as ABE are measured in the actual blood sample, and lactate has a slow diffusion rate over the capillary membrane. Therefore, we find it most logical to combine ABE and lactate. Lactate has the obvious advantage of being directly measurable, whereas base excess is calculated. Hence, any error in the variables entering into the formula will create artificial errors, as for example when contact with air will provide artificially high BE levels because of the decrease in pco 2. The International Cerebral Palsy Task Force uses a threshold of SBE 10 to define metabolic acidosis [18]. At SBE values < 10, ABE is approximately 1 2 mmol/l lower which gives a threshold for ABE 12 mmol/l concordant with Lows definition [19]. These are the values used as the gold standard for moderate asphyxia. Previous studies of lactate levels in umbilical cord blood samples are few and the variations in mean values are remarkable ranging from 2.55 to 4.22 mmol/l [3,20 24]. In this study we found a mean of mmol/l which is slightly higher than in other studies. A reason for this could be due to the fact that we did not differentiate between modes of delivery. Westgren found that mean values of lactate concentrations differed according to different delivery populations: mmol/l (1S.D.) by vacuum extraction, mmol/l (1S.D.) by emergency caesarean, and mmol/l (1S.D.) by spontaneous vaginal delivery [1]. The lactate cut-off value at 8 mmol/l found in this study is also relatively high compared to other studies where cut-off levels from 3.2 to 7.0 mmol/l have been suggested [1,20,23,24]. One reason could be the use of different methods of measurement: a test strip method versus full blood gas analysis. According to Nordstrom [25,26] it is not possible to compare lactate measurements measured with different lactate meters because of the difference in calibration and use of different blood compartments (this could also explain the great variations in mean values). Another explanation could be that we have set our cut-off value in accordance with SBE and ABE as the gold standard for metabolic asphyxia, whereas others have calculated it statistically, based on the assumption of lactate being normally distributed, which is not found in our study. In accordance with our findings, da Silva et al. [27] found that lactacidaemia lower than 5 mmol/l were not followed by neurological complications while plasma lactate concentration greater than 9 mmol/l was associated with moderate or severe encephalopathy. The strong correlation found between lactate and ph (r = 0.73) or ABE (r = 0.83) is highly significant. This strong correlation suggests that the lactate value could be used as a supplement to or instead of ph. A study by Kruger [28] showed scalp-lactate to be a better predictor for hypoxic ischemic encephalopathy than ph and therefore a better predictor for neonatal outcome. On the other hand it has been shown by Westgren [1] that ph and lactate were equally accurate predictors of neonatal outcome, and, according to Ruth and Raivio [16], neither lactate nor ph were good predictors of neurological development at 1 year of age. A recent paper has found a higher sensitivity and specificity of lactate measurements early in life (within 3 h) for adverse outcome for preterm babies with a cut-off at 5.7 mmol/l compared to other blood gas parameters and 1 and 5 min Apgar [22]. Further studies of umbilical cord blood lactate in relation to instrumental deliveries, obstetrical complications, perinatal outcome and long-term outcome are, however, needed before the lactate value can be recommended as the primary or only acid base parameter measured at delivery.

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