What we really want to know is how well babies are when we deliver them. More than that, we want to know how they will be–will their neurodevelopment be as expected? Will they be healthy? And as obstetricians, we want to know what we can do to positively impact those favorable health outcomes. Thus is the quest for surrogates–objective measures at the time of birth to tell us that the infants we deliver are well. Or alternatively, to identify the rare occasion when an infant is at significantly increased risk. Much of what we do is deliver term infants, even in the face of risk factors for early deliveries. While most term-born infants are healthy, they still represent the largest group of infants who will go on to manifest morbidities such as neurodevelopmental delay. One of the most extreme of these morbidities is cerebral palsy, for which hypoxic ischemic encephalopathy is a marker in the neonatal period. To come to a diagnosis of hypoxic ischemic encephalopathy, one must have the necessary but not sufficient criteria ≥34 weeks including umbilical arterial pH <7.00 or base excess ≥12 mmol/L with early onset of moderate to severe encephalopathy and no other identifiable causes. Short of this severe uncommon phenotype, many term infants will have a single component. Umbilical cord arterial acid-base assessment is one objective measure that is clinically available and can give insight to the metabolic status of the infant. For decades, low pH has been measured at birth in an effort to assess risk. Many have wondered whether there are superior surrogate markers to pH, such as elevated base excess or lactate, as well as whether any of them are actually reasonable surrogates at all.

In 1997, Dr Low et al published a case-control study in the American Journal of Obstetrics and Gynecology aimed to estimate the threshold of elevated umbilical cord arterial base excess that may be associated with neonatal complications. This followed prior work by the same group that demonstrated increased morbidity among infants born at 32-36 weeks with increasing metabolic acidosis as measured by increased base excess. Dr Low and colleagues reported an increased risk of moderate to severe neonatal complications at term, such as encephalopathy and respiratory disease, with base excess ≥12 mmol/L. The authors advocated for routine evaluation of the umbilical cord gas parameters given that, while rare in anatomically normal term infants, it may enable identifying the infants with metabolic acidosis of sufficient severity to increase risk on injury. Since that time, the base excess threshold of 12 mmol/L has been considered a marker for risk and has been used in studies testing interventions for neuroprotection.

In this month’s issue of the American Journal of Obstetrics and Gynecology , Dr Knutzen and colleagues present a cohort study to compare arterial umbilical cord elevated base deficit to decreased pH in their ability to identify term infants without anomalies at risk for morbidity and mortality. The authors hypothesized that in the setting of acidemia, the addition of base excess would not add to the ability of low pH to identify at-risk term infants. Outcomes examined included moderate to severe encephalopathy or death, as well as neonatal intensive care unit admission and Apgar score at 5 minutes of life <7. The authors also examined 2 composite outcomes: one to reflect neurologic morbidity and a second to reflect systemic morbidity. They found that in the setting of acidemia, the metabolic component did not add additional value in identifying term infants with morbidity.

Knutzen and colleagues raise several important points in their discussion. It is not surprising that base excess did not add additional information in the patients with a low pH since the 2 measures are not independent. In fact, base excess is a calculated value from pH and carbon dioxide. Umbilical arterial pH falls when hypoxia leads to anaerobic metabolism and the production of hydrogen ions overwhelm the fetal buffer capacity. Recently, lactate has been suggested as an alternative surrogate for neonatal risk since it is a direct product of anaerobic metabolism and can be measured directly from the umbilical cord arterial sample. Several studies have suggested that lactate in the umbilical artery is at least as good as pH in identifying those infants with increased risk of morbidity.

In a retrospective cohort study published late last year, Dr Tuuli and colleagues examined the superiority of lactate to either pH or base excess for identifying term infants at increased risk of morbidity at an institution with a policy of universal arterial cord gas sampling. Similar to the study in the present edition by Knutzen et al, Tuuli and colleagues tested and compared the value of these surrogate markers and risk of clinically meaningful neonatal morbidity. They found that elevated umbilical arterial lactate (>3.9 mmol/L) was more sensitive and specific for neonatal morbidity than low pH or elevated base excess.

As Dr Knutzen and authors discuss, their findings do not negate the importance of increase base excess as it may add information regarding possible mechanism and timing of injury. But the clinical utility of base excess added to an already low pH is questionable, particularly as it relates to identifying term infants at risk of important morbidity. The author’s efforts to correlate and compare these surrogate markers to meaningful neonatal morbidity should be applauded, as it is only through studies of this design that we can begin to identify appropriate surrogates in term infants for morbidity and test interventions. Correlating the value of surrogate measures to predict other intermediate measures, such as Apgar scores and neonatal intensive care unit admissions that are themselves surrogates, is of little clinical utility. We need to work toward a marker, or more likely a group of them, to enable the identification of term infants at risk of morbidity. Umbilical arterial measures will surely be some important component, but most term infants with low pH, elevated base excess, or even elevated lactate develop normally. Despite this, there remain term-born infants without robust markers for the morbidities that they ultimately develop but are not evident at birth. Given recent advanced in the pediatric realm with regard to neuroprotection for the preterm and encephalopathic infants, it is quite possible that term infants with mild injury not clinically apparent may benefit from intervention. To know that, we need to work toward identifying objective, robust surrogates for those kids to test interventions for improved outcomes.