Umbilical artery eucapnic pH to assess fetal well-being.

BACKGROUND: Umbilical artery gas results help obstetricians assess fetal well-being during labor and guide screening decisions on eligibility for therapeutic hypothermia (ie, whole-body or head cooling). The accuracy of results, especially for the base deficit on arterial cord gas analysis, in predicting brain injury is questioned. A novel biomarker specifically calculated for fetal acid-base physiology and response to asphyxia-neonatal eucapnic pH as a marker of neonatal metabolic acidosis-has the potential to be an accurate predictor of hypoxic-ischemic encephalopathy. OBJECTIVE: We aimed to compare false-negative rates of hypoxic-ischemic encephalopathy for umbilical artery pH, base deficit, and neonatal eucapnic pH in assessing fetal acid-base balance as a marker of fetal well-being and predicting acute brain injury. STUDY DESIGN: This is a retrospective single-center cohort study of newborns ≥ 35 weeks of gestation diagnosed with hypoxic-ischemic encephalopathy. We compared false-negative rates for any grade of hypoxic-ischemic encephalopathy using unilateral paired chi-square statistical analysis based on cutoff values for umbilical artery pH ≤7.00, base deficit ≥16 mmol/L, base deficit ≥12 mmol/L and neonatal eucapnic pH ≤7.14. We performed an analysis of variance between umbilical artery pH, base deficit, and neonatal eucapnic pH for each hypoxic-ischemic encephalopathy grade. RESULTS: We included 113 newborns. False-negative rate for hypoxic-ischemic encephalopathy was significantly higher for base deficit <16 mmol/L (n=78/113; 69.0%) than <12 mmol/L (n=46/113; 40.7%), pH >7.00 (n=41/113; 36.3%), or neonatal eucpanic pH >7.14 (n=35/113; 31.0%) (P<.0001). All true-positive cases were identified using only umbilical artery pH and neonatal eucapnic pH. Base deficit ≥16 or ≥12 mmol/L did not add any value in identifying newborns with hypoxic-ischemic encephalopathy when using umbilical artery pH and neonatal eucapnic pH. No association emerged between any marker and hypoxic-ischemic encephalopathy severity grading. CONCLUSION: Our findings support the accuracy of neonatal eucapnic pH to assess fetal well-being during labor and to improve predictive performance for acute brain injury. Neonatal eucpanic pH, in addition to umbilical artery pH, may be a viable alternative in identifying newborns at risk for hypoxic-ischemic encephalopathy.

Is it time to end the use of base deficit for fetal well-being assessment?

Authors have expressed reservations regarding the use of base deficit measured in umbilical artery blood samples to assess fetal well-being during the course of labor and to predict neonatal neurologic morbidity. Despite its integration into clinical practice for more than 50 years, obstetricians and maternal-fetal medicine specialists may not realize that this marker has significant limitations in accurately identifying neonatal metabolic acidosis as a proxy for fetal well-being. In brief, there are 2 large families of base deficit, namely whole blood and extracellular fluid. Both rely on equations that use normal adult acid-base characteristics (pH 7.40 and partial CO2 pressure of 40 mm Hg) that overlook the specificity of the normal in utero acid-base status of pH 7.27 and partial CO2 pressure of 54 mm Hg. In addition, it ignores the unique characteristic of the in utero fetal response to acute hypoxia. The dependence on placental circulation for CO2 elimination may lead to extremely high values (up to 130 to 150 mm Hg) during hypoxic events, a phenomenon that is absent in adults with acute metabolic acidosis who can hyperventilate. The dispute over if to include a correction for high partial CO2 pressure in the bicarbonate estimation, as presented in the Great Trans-Atlantic Debates, remains unresolved. The key constants computed for adult acid-base physiology in the current base deficit algorithms, without accounting for the impact of high partial CO2 pressure or other fetal characteristics of buffering capacity (eg, differences in body water content composition, plasma protein, and hemoglobin attributes), may lead to an overestimation of metabolic acidosis, especially in newborns who are experiencing hypercarbia during the early stages of the hypoxic response. These unrecognized limitations impact the base deficit results and may mislead clinicians on fetal well-being assessments when discussing the management of fetal heart rate monitoring and neonatal outcomes. Based on our arguments, we believe that it is prudent to consider an alternative to base deficit for drawing conclusions regarding fetal well-being during the course of birth management. We propose a marker specifically related to the newborn acid-base physiology--the neonatal eucapnic pH correction. This marker can be added to arterial cord blood gas analysis, and we have described how to interpret it as a marker of neonatal metabolic acidosis.

Does maternal oxygen administration during non-reassuring fetal status affect the umbilical artery gas measures and neonatal outcomes?

PURPOSE: To clarify whether maternal oxygen administration during vaginal delivery improves umbilical artery (UA) gas measurements and neonatal outcomes. METHODS: Singleton pregnancies requiring operative vaginal delivery or emergency cesarean section (CS) due to non-reassuring fetal status (NRFS) during vaginal delivery at our hospital from 2018 to 2021 were retrospectively investigated. Intrapartum fetal wellbeing was evaluated based on the 5-tier fetal heart rate (FHR) pattern which is a delivery management method widely used in Japan. Operative vaginal deliveries or emergency CS was performed under integrated judgment in NRFS. Patients were divided into the oxygen group to whom oxygen (10 L/min) was supplied by a facemask and the room air group. The UA gas measurements and neonatal outcomes were compared. The oxygen administration was classified by conditions before and after the coronavirus disease 2019 pandemic. As a secondary evaluation, stratification of FHR pattern levels and factors associated with UA pH < 7.15 were examined. RESULTS: A total of 250 patients required obstetric surgical delivery due to NRFS, including 140 (56%) and 110 (44%) in the oxygen and room air groups, respectively. No differences in maternal background factors were found between both groups, except for maternal age. UA gas measurements and neonatal outcomes also showed no significant differences. No significant factors were extracted in the multivariate analysis for UA pH < 7.15. CONCLUSIONS: Trans-maternal oxygen administration for intrapartum NRFS did not affect neonatal cord blood gasses or neonatal outcomes. Thus, routine oxygen administration for intrapartum NRFS may not always be necessary.

Umbilical cord gas analysis: clinical implications of a comprehensive, contemporary determination of normal ranges.

BACKGROUND: Umbilical cord gases are often used to assess the impact of labor and delivery on the fetus. However, no large series exists that reflects contemporary obstetrical practice or that analyzed blood gas ranges by route of delivery. Baseline, prelabor acid-base status in the human fetus is also poorly defined, rendering the assessment of blood gas changes during labor difficult. OBJECTIVE: This study aimed to define normal umbilical cord gas and lactate values, stratified by mode of delivery, in a large contemporary series in which universal umbilical cord gas evaluation was dictated by protocol. STUDY DESIGN: This was a retrospective cohort study. We analyzed the umbilical cord gas and lactate data of an unselected population of infants born between March 2012 and April 2022 at a large teaching hospital. These values were then analyzed by mode of delivery and, for cesarean deliveries, by indication for cesarean delivery and type of anesthesia. Umbilical cord gas values from infants delivered by elective cesarean delivey under general anesthesia without labor were considered representative of baseline, prelabor values. RESULTS: Data were available for 45,475 infants. The median arterial pH values and interquartile ranges for vaginal births, elective cesarean deliveries without labor, and cesarean deliveries performed for fetal heart rate concerns were 7.27 (0.09), 7.27 (0.06), and 7.25 (0.09), respectively. Arterial lactate values for these same 3 groups were 4.1 (2.5), 2.5 (1.2), and 4.0 (2.8) mmoles/L, respectively. Because of the very large sample size, most comparisons yielded differences that were statistically significant, but clinically irrelevant. Of all the infants, 14% had an arterial pH <7.20; a pH value of 7.1 represents 2 standard deviations from the mean. CONCLUSION: This large, population-based study of umbilical cord gas and lactate levels in an unselected population, stratified by delivery mode, represents a previously unavailable benchmark for the evaluation of umbilical cord gases. Arterial umbilical cord pH values for infants delivered by elective caesarean delivery without labor (median pH 7.28) reflect a lower prelabor fetal pH baseline than previously assumed. This finding, coupled with our determination that a 2 standard deviation below normal pH limit of 7.1, instead of the historic arbitrary pH of 7.2 threshold, helps to explain the poor positive predictive value of electronic fetal heart rate monitoring, a test designed to detect arterial pH levels that have fallen from an assumed baseline near pH 7.4 to an assumed potentially injurious pH level of <7.2. Uncomplicated labor, even when prolonged, does not generally lead to a clinically significant cumulative hypoxic stress to the human fetus. These findings, along with our determination that there is no difference in the acid-base status among infants delivered by cesarean delivery for fetal heart rate concerns, help to explain the failure of current approaches in labor and delivery management to reduce the rates of neonatal hypoxic-ischemic encephalopathy and cerebral palsy, conditions that almost always reflect developmental events rather than the effects of labor on the fetus.

A comparison of criteria for defining metabolic acidemia in live-born neonates and its effect on predicting serious adverse neonatal outcomes.

BACKGROUND: Metabolic acidemia is a known risk factor for serious adverse neonatal outcomes in both preterm and term infants. OBJECTIVE: This study aimed to evaluate the clinical significance of delivery umbilical cord gas measurements with regard to serious adverse neonatal outcomes, and to determine if distinct thresholds for defining metabolic acidemia differ in their ability to predict such adverse neonatal complications. STUDY DESIGN: This is a retrospective cohort study of singleton live-born deliveries between January 2011 and December 2019. Stratification according to gestational age at birth (≥35 and <35 weeks of gestation) was performed, and comparisons of maternal characteristics, obstetrical complications, intrapartum events, and adverse neonatal outcomes were made between neonates with metabolic acidemia and those without. Metabolic acidemia (based on delivery umbilical cord gas analyses) was defined using both American College of Obstetricians and Gynecologists and Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria. The primary outcome of interest was hypoxic-ischemic encephalopathy requiring whole-body hypothermia. RESULTS: A total of 91,694 neonates born at ≥35 weeks of gestation met the inclusion criteria. By American College of Obstetricians and Gynecologists criteria, 2659 (2.9%) infants had metabolic acidemia. Neonates with metabolic acidemia were at markedly increased risk for neonatal intensive care unit admission, seizures, need for respiratory support, sepsis, and neonatal death. Metabolic acidemia by American College of Obstetricians and Gynecologists criteria was associated with an almost 100-fold increased risk of hypoxic-ischemic encephalopathy requiring whole-body hypothermia (relative risk, 92.69; 95% confidence interval, 64.42-133.35) in neonates born at ≥35 weeks of gestation. Diabetes mellitus, hypertensive disorders of pregnancy, postterm deliveries, prolonged second stages, chorioamnionitis, operative vaginal deliveries, placental abruption and cesarean deliveries were associated with metabolic acidemia in neonates born ≥ 35 weeks of gestation. The highest relative risk was in those diagnosed with placental abruption (relative risk, 9.07; 95% confidence interval, 7.25-11.36). The neonatal cohort born <35 weeks of gestation had similar findings. When comparing those infants born ≥ 35 weeks of gestation with metabolic acidemia by American College of Obstetricians and Gynecologists criteria vs Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria, the Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria identified more neonates at risk for serious adverse neonatal outcomes. In particular, 4.9% more neonates were diagnosed with metabolic acidemia, and 16 more term neonates were identified as requiring whole-body hypothermia. Mean 1-minute and 5-minute Apgar scores were similar and reassuring among neonates born at ≥35 weeks of gestation with and without metabolic acidemia as defined by both American College of Obstetricians and Gynecologists and Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria (8 vs 8 and 9 vs 9, respectively; P<.001). Sensitivity and specificity were 86.7% and 92.2%, respectively, with the Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria, and 74.2% and 97.2% with the American College of Obstetricians and Gynecologists criteria. CONCLUSION: Infants with metabolic acidemia identified on cord gas collection at delivery are at considerably greater risk of serious adverse neonatal outcomes, including an almost 100-fold increased risk of hypoxic-ischemic encephalopathy requiring whole-body hypothermia. Use of the more sensitive Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria for defining metabolic acidemia identifies more neonates born at ≥35 weeks of gestation at risk for adverse neonatal outcomes, including hypoxic-ischemic encephalopathy requiring whole-body hypothermia.

Association of umbilical cord blood gas values with mortality and severe neurologic injury in preterm neonates <29 weeks' gestation: a national cohort study.

BACKGROUND: Umbilical cord arterial and venous blood gas values reflect the acid-base balance status of a newborn at birth. Derangement in these values has been linked to poor neonatal outcomes in term and late preterm neonates; however, the utility of these values in preterm neonates of <29 weeks' gestation is unclear. OBJECTIVE: This study aimed to determine the associations of umbilical cord arterial and venous blood gas values with neonatal mortality and severe neurologic injury in extremely preterm neonates and to identify the cutoff values associated with 2.5-fold increases or decreases in the posttest probabilities of outcomes. STUDY DESIGN: This was a retrospective cohort study of neonates who were born at 23+0 to 28+6 weeks' gestation between January 1, 2018 and December 31, 2019, and who were admitted to neonatal units in Canada. EXPOSURE: Various cut-offs of umbilical cord blood gas values and lactate values were studied. MAIN OUTCOMES AND MEASURES: The main outcomes were mortality before discharge from the neonatal unit and severe neurologic injury defined as grade 3 or 4 periventricular or intraventricular hemorrhage or periventricular leukomalacia. The outcome rates were calculated for various cutoff values of umbilical cord blood gas parameters and were adjusted for birthweight, gestational age, sex, and multiple births. Likelihood ratios were calculated to derive posttest probabilities. RESULTS: A total of 1040 and 1217 neonates had analyzable umbilical cord arterial and venous blood gas values, respectively. In the cohort, the mean (standard deviation) gestational age was 26.5 (1.5) weeks, the mean birthweight was 936 (215) g, the prevalence of mortality was 10% (105/1040), and the prevalence of severe neurologic injury was 9% (92/1016). An umbilical cord arterial pH of ≤7.1 and base excess of ≤-12 mmol/L were associated with >2.5-fold higher posttest probability of mortality, and an umbilical cord arterial or venous lactate value of <3 was associated with a 2.5-fold lower posttest probability of mortality. An umbilical cord arterial lactate value of <3 was associated with a lower posttest probability of severe neurological injury. CONCLUSION: In preterm neonates of <29 weeks' gestation, low umbilical cord arterial pH and high umbilical cord arterial base excess values were associated with a clinically important increase in the posttest probability of mortality, whereas low umbilical cord arterial or venous lactate values were associated with a decrease in the posttest probability of mortality.

Shoulder dystocia, umbilical cord blood gases and neonatal encephalopathy.

The interpretation of umbilical cord gases may not be straightforward following shoulder dystocia. We reviewed Perinatal and Maternal Mortality Review Committee data from New Zealand infants with moderate and severe neonatal encephalopathy (NE) for 2010-2017 inclusive. If one or more of: pH of ≤7.1; base excess of ≤-12 mmol/L; or lactate of ≥6 mmol/L were present it was considered an abnormal result. One-third (12/36) of infants born following shoulder dystocia had documented umbilical cord gases within the normal range. It is important for clinicians to be aware of this possibility when assessing newborn infants with NE.

Umbilical artery base deficit/excess: sailing blindly in a thick fog.

Assessing the wellbeing of newborns at birth with base deficit (BD)/base excess(BE) is well anchored in clinicians' practice. However, clinicians may not fully understand the concepts behind BD and the concerns regarding the validity of BD results provided by the hospital laboratory. These concerns are linked to the inconsistencies between the equations to calculate BD, and that these equations do not consider the aspects of acid-base physiology at birth. Additionally, the evidence-based supporting BD threshold in the literature to help physicians in making decisions is rather insufficient. These considerations support the need to review practice guidelines that use BD to guide decisions and bring to an end to clinicians to sail blindly in a thick fog.

Comparisons between umbilical cord biomarkers for newborn hypoxic-ischemic encephalopathy.

BACKGROUND: Cord blood umbilical artery (Ua) pH, base deficit (BD), and pH eucapnic Blickstein/Green-50 may mislead clinicians to identify newborns at risk for hypoxic-ischemic encephalopathy. Neonatal eucapnic pH (pH euc-n Racinet-54) may be a comprehensive alternative. The goal of the study is to compare the predictive performance of these four biomarkers for the combined primary outcome of hypoxic-ischemic encephalopathy/death. METHODS: This retrospective cohort study includes newborns ≥35 weeks gestational age. Receiver operating characteristics curves analysis was performed for Ua cord pH, BD, pH euc-n Racinet-54, and pH eucapnic Blickstein/Green-50 for the global cohort and for two subgroups of newborns with Ua cord pH ≤ 7.15. Cutoff values were derived for all four markers. RESULTS: From the original cohort of 61,037 newborns born between 1 January 2007 and 31 December 2016, we excluded cases with major congenital malformations and missing/incomplete data. The global cohort includes 51,286 newborns and 60 newborns afflicted with hypoxic-ischemic encephalopathy (HIE)/death. The area under the curves (AUC) derived from the global cohort were comparable between Ua cord pH (0.95; 95%CI = 0.94-0.95), BD (0.93; 95%CI = 0.93-0.93), pH euc-n Racinet-54 (0.93; 95% CI = 0.93-0.93), and lower for pH Blickstein/Green-50 (0.78; 95% CI = 0.77-0.78) (p < .05). Within newborn with severe acidemia (pH ≤ 7.00) and moderate acidemia (7.00 ≤ pH ≤ 7.15), pH euc-n Racinet-54 had the largest AUC and best positive likelihood ratios especially for sensitivity ≥ 0.80 to minimize false negative cases. CONCLUSION: In this large retrospective study, predictive performance for Ua cord pH, BD, and pH euc-n Racinet-54 are comparable when applied to the global group. For newborns with Ua cord pH ≤ 7.00 and Ua cord 7.00 ≤ pH ≤ 7.15, pH euc-n Racinet-54 appears better to identify those with HIE/death, especially when the target is sensitivity > 80%. Prospective studies will confirm if pH euc-n Racinet-54 is a better alternative to Ua cord pH and BD to evaluate newborn acid-base physiology.

The role of umbilical cord gas studies in the prediction of adverse neonatal outcomes in scheduled nonlaboring term singleton cesarean deliveries.

BACKGROUND: Most major societies do not state a specific recommendation against or in favor of routine umbilical cord gas studies sampling. OBJECTIVE: We aimed to study the correlation between abnormal umbilical cord gas studies (using 5 different definitions) and adverse neonatal outcomes in scheduled nonlaboring term singleton cesarean deliveries. STUDY DESIGN: The medical charts, surgical records, and neonatal charts of all singleton cesarean deliveries at 370/7-416/7 weeks of gestation between January 2009 and May 2018 from a single tertiary center were reviewed. The cohort of singleton cesarean deliveries was divided into those with "normal" vs "abnormal" umbilical cord gas studies with the 5 different definitions: (1) definition A: pH ≤7.15; (2) definition B: pH ≤7.15 and base excess ≤-12 mmol/L; (3) definition C: pH ≤7.1l (4) definition D: pH ≤7.1 and base excess ≤-12 mmol/L, and (5) definition E: pH <7.0 and base excess ≤-12 mmol/L. Adverse neonatal outcomes included Apgar scores at 5 minutes ≤7, neonatal sepsis, blood transfusion, phototherapy, respiratory morbidity (presence of respiratory distress syndrome, transient tachypnea of the newborn infant, mechanical ventilation, need for respiratory support, or meconium aspiration), cerebral morbidity (presence of intraventricular hemorrhage, seizures, or hypoxic-ischemic encephalopathy), necrotizing enterocolitis, or death. Composite adverse outcome was ≥1 of the aforementioned complications. RESULTS: Overall, 3001 singleton cesarean deliveries were included. The rate of abnormal umbilical cord gas studies with the use of definitions A-E was 2.6%, 0.3%, 1.2%, 0.3%, and 0.1%, respectively. The overall rate of adverse neonatal outcome for the entire cohort was 14.43% (433/3001). There was no correlation between abnormal umbilical cord gas studies and composite adverse neonatal outcome with the use of any of the definitions A-E (P=.2, P=.3, P=.2, P=.3, P=.1, respectively). The sensitivity and specificity of abnormal umbilical cord gas studies as a predictor of composite adverse neonatal outcome were calculated for each of the abnormal umbilical cord gas studies definitions; although the sensitivity was extremely low (0-2.07%), the specificity was high (97.2-99.9%) CONCLUSION: Abnormal umbilical cord gas studies are an uncommon finding in cases of singleton term singleton cesarean deliveries and do not correlate with adverse neonatal outcomes. Therefore, the clinical usefulness and cost-effectiveness of obtaining these studies routinely should be questioned.

Delayed cord clamping and cord gas analysis at birth.

Delayed cord clamping for at least 60 s in both term and preterm babies is a major recent change in clinical care. Delayed cord clamping has several effects on other possible interventions. One of these is the effect of delayed cord clamping on umbilical artery gas analysis. When indicated, umbilical artery gas analysis can safely be done either with early cord clamping or, probably most of the times it is necessary, during delayed cord clamping with the cord still unclamped. Paired blood samples (one from the umbilical artery and one from the umbilical vein) can be taken from the pulsating and unclamped cord, immediately after birth, during delayed cord clamping, without any effect on either the accuracy of umbilical artery gas analysis or the transfusion of blood through delayed cord clamping. Umbilical artery gas analysis should instead not be done after delayed cord clamping, since delayed cord clamping alters several acid-based parameters and lactate values.

Can venous cord gas values predict fetal acidemia?

BACKGROUND: Umbilical cord arterial blood gas values are used to diagnose fetal acidemia; however, arterial cord blood specimens are frequently not available. OBJECTIVE: We sought to assess whether umbilical cord venous blood gas values can be used to reliably predict fetal acidemia. STUDY DESIGN: This is an observational study of women with a singleton gestation at a single tertiary care hospital who delivered from September 2010 through August 2015 and had both umbilical cord arterial and venous blood gas samples measured. Fetal acidemia was defined in 2 ways: (1) umbilical cord arterial pH <7.0, and (2) umbilical cord arterial base deficit ≥12 mEq/L. Receiver operating characteristic curves for fetal acidemia were generated using umbilical cord venous blood gas values and the areas under the curve were calculated. Umbilical cord venous blood gas cutoffs associated with <1%, <5%, <10%, and <50% probability of acidemia were calculated. RESULTS: Of the 36,325 women who met inclusion criteria, 563 (1.5%) had an umbilical cord arterial pH <7.0 and 1535 (4.2%) had an umbilical cord arterial base deficit ≥12 mEq/L. Umbilical cord venous pH was highly predictive of umbilical cord arterial pH <7.0 (area under the curve, 0.955; 95% confidence interval, 0.946-0.965). Similarly, umbilical cord venous base deficit was highly predictive of umbilical cord arterial base deficit ≥12 mEq/L (area under the curve, 0.967; 95% confidence interval, 0.963-0.971). While the combination of venous pH and base deficit was statistically significantly more predictive of umbilical cord arterial pH <7.0 (area under the curve, 0.961; 95% confidence interval, 0.952-0.969; P < .001), this difference has negligible clinical meaning. Similarly, the combination of venous pH and base deficit (area under the curve, 0.967; 95% confidence interval, 0.962-0.971) was no more predictive than venous base deficit alone in the prediction of umbilical cord arterial base deficit ≥12 mEq (P = .622). The likelihood of an arterial cord venous pH <7.0 was <1%, <5%, <10%, and <50% with cord venous pH of 7.22, 7.16, 7.14, and 7.07, respectively. The likelihood of an arterial cord base deficit ≥12 mEq/L was <1%, <5%, <10%, and <50% with cord venous base deficit of 7.0, 8.5, 9.2, and 11.3, respectively. CONCLUSION: Umbilical cord venous pH and base deficit are each highly predictive of fetal acidemia, and can be used to evaluate the likelihood of fetal acidemia in the absence of umbilical cord arterial blood gas values.