Cord Blood Gas


Introduction

James et al. reported in 1958 that gas analysis of blood samples obtained from a clamped umbilical cord could reflect fetal hypoxia.[1] Since then, cord blood gas analysis has become widely performed to objectively determine the fetal metabolic condition at the time of delivery when umbilical circulation stops.[2] Multiple studies showed that this analysis, when combined with other neonatal factors, can help identify infants at risk for neonatal encephalopathy, which is vital for the early initiation of neuroprotective therapeutic strategies.[3]

Specimen Collection

The umbilical vein is easier to sample due to its large diameter. However, umbilical artery blood gas analysis gives more accurate information about the fetal metabolic condition and correlates better with neonatal outcomes.[4]

Oxygenated blood is carried from the placenta to the fetus through the umbilical vein, whereas blood rich in carbon dioxide eliminated by the fetus returns to the placental circulation through the umbilical arteries. Consequently, venous cord blood gas analysis mainly reflects placental metabolism, whereas arterial sampling more accurately reflects fetal metabolism.

Veins are more compressible than arteries. Thus, in umbilical cord compression, venous flow from the placenta to the fetus decreases more than arterial flow. To meet their metabolic demands, fetal tissues will respond by increasing their extraction of oxygen. Consequently, there is more carbon dioxide eliminated through the umbilical arteries, which renders the arterial cord blood more acidotic, while the umbilical venous acid-base status remains equilibrated by the normally functioning placenta. The severity of cord compression has a significant effect on the arteriovenous pH difference. Thus, it is always essential to obtain both venous and arterial blood samples for analysis.[5]

Procedures

Ideally, double clamping of a 10 cm to 20 cm umbilical segment should occur as early as possible after delivery. Blood drawn into a pre-heparinized syringe from this isolated segment should be immediately placed in ice and transported to the laboratory for analysis.

Studies have shown, pH, pO2, and pCO2 measured from clamped portions of the umbilical cord remain reliable for up to 60 minutes after birth.[6] However, segments that remain in continuity with the placenta are affected by the ongoing placental metabolism that causes the obscuring of the measurements as early as 20 minutes after delivery.[7]

Lactate levels obtained from samples after 20 minutes of birth are also unreliable, regardless of collecting the sample from a clamped or unclamped cord.[7]

Therefore, it is imperative to note the timing of blood sampling and the source of the sample: a clamped or unclamped segment.[3]

Indications

The American College of Obstetricians and Gynecologists and the American Academy of Pediatrics now recommend umbilical cord blood gas analysis to be performed in all high-risk deliveries in which there is a suspicion of a fetal metabolic abnormality. Examples include category III fetal heart rate tracings and low Apgar scores at birth.[8]

In some centers, this practice is routinely performed after all deliveries, regardless of the presence or absence of risk factors.[3]

Potential Diagnosis

Cord blood gas analysis is an objective measure of the fetal metabolic condition at the time of delivery. By determining fetal acid-base status, it helps identify infants at risk for neonatal encephalopathy.

Pathological acidosis reflects significant fetal distress due to hypoxic stress. As an isolated finding, it poorly predicts the risk of hypoxic-ischemic injury.[9][10][11] However, when combined with other abnormal clinical findings such as non-reassuring fetal heart tracings, low Apgar scores, or the requirement for resuscitation, it strongly serves as an indicator for early-onset seizures and other adverse neonatal neurological sequelae.[12]

Normal and Critical Findings

Since fetal CO2 gets carried by the umbilical arteries, the expectation is that arterial cord blood gas will be slightly more acidotic than venous cord blood gas. Studies showed that in term infants with uncomplicated delivery, the mean cord arterial pH is 7.24 to 7.27, and the mean cord venous pH 7.32 to 7.34.[13][14][15][16] Preterm newborns were found to have a higher pH, and observations noted a gradual reduction with increasing gestational age.[17][18] A cord pH less than 7, when combined with other abnormal clinical findings, strongly correlates with adverse neonatal outcomes.[12]

Maternal respirations on room air yielded mean cord venous pO2 of 43.5 mmHg and mean cord arterial pO2 of 31.5 mmHg.[19] With the mother on supplemental O2, the mean cord arterial pO2 was never found to be higher than 37.5 mmHg.[20] Therefore a pO2 value greater than 37.5 mmHg is more likely to have occurred due to the presence of air bubbles in the collected sample.[21]

Apart from measuring pH, pCO2, and pO2, blood gas analyzers also calculate base excess. In a term newborn with uncomplicated delivery, cord arterial base excess varies from -5.6 to -2.7 meq/L and cord venous base excess from -4.5 to -2.4 meq/L.[13][14][15][16] When combined with other abnormal clinical findings, a base deficit of more than 12 meq/L strongly correlates with adverse neonatal outcomes.[16]

Lactic acid is the final product of anaerobic metabolism that does not cross the placenta. It can give accurate information about the fetal metabolic condition, and its measurement is as helpful as cord arterial pH in predicting poor neonatal outcomes.[22][23]  

Interfering Factors

Delayed sampling (beyond 60 minutes from a doubly clamped umbilical segment and beyond 20 minutes from an unclamped segment) renders the measurement of pH, pCO2, and pO2 unreliable.[6][7] Similarly, delayed interpretation after sampling makes these measurements unreliable as well.

Delayed cord clamping may alter blood gas analysis. Sampling should be done soon after birth from the unclamped cord to obtain the most accurate information. Delay in clamping the cord after delivery also decreases the reliability of measurements.[24]

Other factors that may influence cord blood values include the mode of delivery and fetal presentation. Uterine contractions cause metabolic stress and a lower cord pH, whereas infants born by elective C-section without labor have a higher cord pH.[14] Similarly, fetuses with breech presentation are born with a lower cord pH when compared to those with cephalic presentation.[25]

Complications

Cord blood gas analysis per se does not have any complications. However, a potential medico-legal concern may arise in centers practicing universal sampling when an abnormally low pH is found and documented in the medical record of vigorous newborns.[26] Although studies found that isolated acidosis in the absence of any other abnormal clinical finding at birth is a poor predictor of neonatal outcomes, practitioners may prefer in this case to repeat a blood gas analysis one to two hours after birth to document a “normal” pH.

Patient Safety and Education

Cord blood gas analysis at birth is safe for the infant and its mother, with no complications reported. All mothers should receive education regarding the clinical significance of an abnormal result.

Clinical Significance

Fetal acidemia is most commonly a mixed respiratory and metabolic acidosis. An initial respiratory acidosis arises when uteroplacental or fetal circulation is impaired. With the ongoing impairment of oxygen delivery to the placenta and fetal tissues, the metabolism shifts towards anaerobic glycolysis, with subsequent additional metabolic acidosis. It is at this stage that acidosis becomes clinically significant.[27][28]

Some experts define pathological acidosis as the level at which the risk of adverse sequelae arises. Interestingly, a pH as low as 7.00 is usually tolerated by the fetus without any adverse outcome.[29][30] Most infants with a cord pH less than 7.00 do not develop neurologic problems after birth, nor even when followed for 6.5 years.[11][31][32][33] However, an isolated respiratory acidosis is very rarely associated with poor outcomes.[34] Thus, infants born with a pH less than 7.00 and without other abnormal clinical findings typically do not require any further investigation or NICU admission.[32]

When a pH less than 7.00 and/or a base deficit of more than 12 meq/L are associated with other abnormal findings such as abnormal fetal heart tracings, 5-minutes Apgar scores equal to or less than 5, a requirement for intubation, they become strong predictors of poor neurological sequelae.[12] Eighty percent of these newborns with clinical indicators of acidemia with a low pH develop seizures in the first few days after birth.[35][36] Previous studies have shown that cord pH less than 7.00 is proportional to the risk and the severity of neurologic abnormalities. Furthermore, 80% of infants born with a cord pH less than 6.70 develop symptoms and signs of neonatal encephalopathy.[28][37][38][39]

In conclusion, cord blood gas analysis is a recommended procedure in all high-risk deliveries. A pH less than 7.00 in non-vigorous newborns strongly correlates with the development of neonatal encephalopathy. Identifying infants at risk is important for the early initiation of neuroprotective therapies.


Details

Author

Hala Saneh

Updated:

4/3/2023 5:34:49 PM

References


[1]

JAMES LS, WEISBROT IM, PRINCE CE, HOLADAY DA, APGAR V. The acid-base status of human infants in relation to birth asphyxia and the onset of respiration. The Journal of pediatrics. 1958 Apr:52(4):379-94     [PubMed PMID: 13539725]


[2]

ACOG Committee on Obstetric Practice. ACOG Committee Opinion No. 348, November 2006: Umbilical cord blood gas and acid-base analysis. Obstetrics and gynecology. 2006 Nov:108(5):1319-22     [PubMed PMID: 17077266]

Level 3 (low-level) evidence

[3]

Armstrong L, Stenson BJ. Use of umbilical cord blood gas analysis in the assessment of the newborn. Archives of disease in childhood. Fetal and neonatal edition. 2007 Nov:92(6):F430-4     [PubMed PMID: 17951550]


[4]

Malin GL, Morris RK, Khan KS. Strength of association between umbilical cord pH and perinatal and long term outcomes: systematic review and meta-analysis. BMJ (Clinical research ed.). 2010 May 13:340():c1471. doi: 10.1136/bmj.c1471. Epub 2010 May 13     [PubMed PMID: 20466789]

Level 1 (high-level) evidence

[5]

Martin GC, Green RS, Holzman IR. Acidosis in newborns with nuchal cords and normal Apgar scores. Journal of perinatology : official journal of the California Perinatal Association. 2005 Mar:25(3):162-5     [PubMed PMID: 15605072]


[6]

Duerbeck NB, Chaffin DG, Seeds JW. A practical approach to umbilical artery pH and blood gas determinations. Obstetrics and gynecology. 1992 Jun:79(6):959-62     [PubMed PMID: 1579322]


[7]

Armstrong L, Stenson B. Effect of delayed sampling on umbilical cord arterial and venous lactate and blood gases in clamped and unclamped vessels. Archives of disease in childhood. Fetal and neonatal edition. 2006 Sep:91(5):F342-5     [PubMed PMID: 16638782]


[8]

. Executive summary: Neonatal encephalopathy and neurologic outcome, second edition. Report of the American College of Obstetricians and Gynecologists' Task Force on Neonatal Encephalopathy. Obstetrics and gynecology. 2014 Apr:123(4):896-901. doi: 10.1097/01.AOG.0000445580.65983.d2. Epub     [PubMed PMID: 24785633]


[9]

Fee SC, Malee K, Deddish R, Minogue JP, Socol ML. Severe acidosis and subsequent neurologic status. American journal of obstetrics and gynecology. 1990 Mar:162(3):802-6     [PubMed PMID: 2107746]


[10]

Lavrijsen SW, Uiterwaal CS, Stigter RH, de Vries LS, Visser GH, Groenendaal F. Severe umbilical cord acidemia and neurological outcome in preterm and full-term neonates. Biology of the neonate. 2005:88(1):27-34     [PubMed PMID: 15731553]


[11]

Hafström M, Ehnberg S, Blad S, Norén H, Renman C, Rosén KG, Kjellmer I. Developmental outcome at 6.5 years after acidosis in term newborns: a population-based study. Pediatrics. 2012 Jun:129(6):e1501-7. doi: 10.1542/peds.2011-2831. Epub 2012 May 7     [PubMed PMID: 22566423]


[12]

Perlman JM, Risser R. Can asphyxiated infants at risk for neonatal seizures be rapidly identified by current high-risk markers? Pediatrics. 1996 Apr:97(4):456-62     [PubMed PMID: 8632928]


[13]

Thorp JA, Sampson JE, Parisi VM, Creasy RK. Routine umbilical cord blood gas determinations? American journal of obstetrics and gynecology. 1989 Sep:161(3):600-5     [PubMed PMID: 2782341]


[14]

Riley RJ, Johnson JW. Collecting and analyzing cord blood gases. Clinical obstetrics and gynecology. 1993 Mar:36(1):13-23     [PubMed PMID: 7679616]


[15]

Helwig JT, Parer JT, Kilpatrick SJ, Laros RK Jr. Umbilical cord blood acid-base state: what is normal? American journal of obstetrics and gynecology. 1996 Jun:174(6):1807-12; discussion 1812-4     [PubMed PMID: 8678144]


[16]

Victory R, Penava D, Da Silva O, Natale R, Richardson B. Umbilical cord pH and base excess values in relation to adverse outcome events for infants delivering at term. American journal of obstetrics and gynecology. 2004 Dec:191(6):2021-8     [PubMed PMID: 15592286]


[17]

Nicolaides KH, Economides DL, Soothill PW. Blood gases, pH, and lactate in appropriate- and small-for-gestational-age fetuses. American journal of obstetrics and gynecology. 1989 Oct:161(4):996-1001     [PubMed PMID: 2801852]


[18]

Weiner CP, Sipes SL, Wenstrom K. The effect of fetal age upon normal fetal laboratory values and venous pressure. Obstetrics and gynecology. 1992 May:79(5 ( Pt 1)):713-8     [PubMed PMID: 1565354]


[19]

Thorp JA, Trobough T, Evans R, Hedrick J, Yeast JD. The effect of maternal oxygen administration during the second stage of labor on umbilical cord blood gas values: a randomized controlled prospective trial. American journal of obstetrics and gynecology. 1995 Feb:172(2 Pt 1):465-74     [PubMed PMID: 7856671]

Level 1 (high-level) evidence

[20]

Khaw KS, Wang CC, Ngan Kee WD, Pang CP, Rogers MS. Effects of high inspired oxygen fraction during elective caesarean section under spinal anaesthesia on maternal and fetal oxygenation and lipid peroxidation. British journal of anaesthesia. 2002 Jan:88(1):18-23     [PubMed PMID: 11883375]


[21]

Piggott SE, Bogod DG, Rosen M, Rees GA, Harmer M. Isoflurane with either 100% oxygen or 50% nitrous oxide in oxygen for caesarean section. British journal of anaesthesia. 1990 Sep:65(3):325-9     [PubMed PMID: 2121203]


[22]

Piquard F, Schaefer A, Dellenbach P, Haberey P. Is fetal acidosis in the human fetus maternogenic during labor? A reanalysis. The American journal of physiology. 1991 Nov:261(5 Pt 2):R1294-9     [PubMed PMID: 1951778]


[23]

Revathy Natesan S. Routine measurements of cord arterial blood lactate levels in infants delivering at term and prediction of neonatal outcome. The Medical journal of Malaysia. 2016 Jun:71(3):131-3     [PubMed PMID: 27495887]


[24]

Xodo S, Xodo L, Berghella V. Delayed cord clamping and cord gas analysis at birth. Acta obstetricia et gynecologica Scandinavica. 2018 Jan:97(1):7-12. doi: 10.1111/aogs.13233. Epub 2017 Nov 1     [PubMed PMID: 28921502]


[25]

Daniel Y, Fait G, Lessing JB, Jaffa A, Gull I, Shenav M, Peyser MR, Kupferminc MJ. Umbilical cord blood acid-base values in uncomplicated term vaginal breech deliveries. Acta obstetricia et gynecologica Scandinavica. 1998 Feb:77(2):182-5     [PubMed PMID: 9512324]


[26]

Thorp JA,Dildy GA,Yeomans ER,Meyer BA,Parisi VM, Umbilical cord blood gas analysis at delivery. American journal of obstetrics and gynecology. 1996 Sep;     [PubMed PMID: 8828408]


[27]

van den Berg PP, Nelen WL, Jongsma HW, Nijland R, Kollée LA, Nijhuis JG, Eskes TK. Neonatal complications in newborns with an umbilical artery pH { 7.00. American journal of obstetrics and gynecology. 1996 Nov:175(5):1152-7     [PubMed PMID: 8942481]


[28]

Goodwin TM, Belai I, Hernandez P, Durand M, Paul RH. Asphyxial complications in the term newborn with severe umbilical acidemia. American journal of obstetrics and gynecology. 1992 Dec:167(6):1506-12     [PubMed PMID: 1471655]


[29]

Low JA, Lindsay BG, Derrick EJ. Threshold of metabolic acidosis associated with newborn complications. American journal of obstetrics and gynecology. 1997 Dec:177(6):1391-4     [PubMed PMID: 9423740]


[30]

Yeh P, Emary K, Impey L. The relationship between umbilical cord arterial pH and serious adverse neonatal outcome: analysis of 51,519 consecutive validated samples. BJOG : an international journal of obstetrics and gynaecology. 2012 Jun:119(7):824-31. doi: 10.1111/j.1471-0528.2012.03335.x. Epub     [PubMed PMID: 22571747]


[31]

Winkler CL, Hauth JC, Tucker JM, Owen J, Brumfield CG. Neonatal complications at term as related to the degree of umbilical artery acidemia. American journal of obstetrics and gynecology. 1991 Feb:164(2):637-41     [PubMed PMID: 1992716]


[32]

King TA, Jackson GL, Josey AS, Vedro DA, Hawkins H, Burton KM, Burks MN, Yellin WM, Laptook AR. The effect of profound umbilical artery acidemia in term neonates admitted to a newborn nursery. The Journal of pediatrics. 1998 Apr:132(4):624-9     [PubMed PMID: 9580760]


[33]

Nagel HT, Vandenbussche FP, Oepkes D, Jennekens-Schinkel A, Laan LA, Gravenhorst JB. Follow-up of children born with an umbilical arterial blood pH { 7. American journal of obstetrics and gynecology. 1995 Dec:173(6):1758-64     [PubMed PMID: 8610758]


[34]

Low JA, Panagiotopoulos C, Derrick EJ. Newborn complications after intrapartum asphyxia with metabolic acidosis in the term fetus. American journal of obstetrics and gynecology. 1994 Apr:170(4):1081-7     [PubMed PMID: 8166190]


[35]

Portman RJ, Carter BS, Gaylord MS, Murphy MG, Thieme RE, Merenstein GB. Predicting neonatal morbidity after perinatal asphyxia: a scoring system. American journal of obstetrics and gynecology. 1990 Jan:162(1):174-82     [PubMed PMID: 2301489]


[36]

Carter BS, McNabb F, Merenstein GB. Prospective validation of a scoring system for predicting neonatal morbidity after acute perinatal asphyxia. The Journal of pediatrics. 1998 Apr:132(4):619-23     [PubMed PMID: 9580759]

Level 1 (high-level) evidence

[37]

Low JA, Galbraith RS, Muir DW, Killen HL, Pater EA, Karchmar EJ. Factors associated with motor and cognitive deficits in children after intrapartum fetal hypoxia. American journal of obstetrics and gynecology. 1984 Mar 1:148(5):533-9     [PubMed PMID: 6199975]


[38]

Low JA, Galbraith RS, Muir DW, Killen HL, Pater EA, Karchmar EJ. Motor and cognitive deficits after intrapartum asphyxia in the mature fetus. American journal of obstetrics and gynecology. 1988 Feb:158(2):356-61     [PubMed PMID: 2449078]


[39]

Sehdev HM, Stamilio DM, Macones GA, Graham E, Morgan MA. Predictive factors for neonatal morbidity in neonates with an umbilical arterial cord pH less than 7.00. American journal of obstetrics and gynecology. 1997 Nov:177(5):1030-4     [PubMed PMID: 9396887]