The American College of Obstetricians and Gynecologists' (the College) Task Force on Neonatal Encephalopathy and Neurologic Outcomes clearly delineated multiple objective criteria to consider when defining an acute intrapartum hypoxic event sufficient to cause cerebral palsy in the newborn. According to the College's Task Force, cord blood analysis demonstrating metabolic acidemia is one of the diagnostic elements that is potentially indicative of intrapartum hypoxia.1 A causative link should be suspected when metabolic acidemia occurs in conjunction with early neonatal encephalopathy, ischemia-induced neuroimaging patterns, and a type of cerebral palsy that could be caused by hypoxia (either spastic quadriplegic or dyskinetic type). The Task Force stressed that such criteria should be carefully reviewed before “birth asphyxia” or “hypoxic–ischemic encephalopathy” is diagnosed.
The incidence of acidemia in term or near-term neonates and the consequences of such acidemia are largely based on small observational studies.2–9 Our purposes were to estimate the incidence of metabolic acidemia in singleton neonates born between 35 and 42 weeks of gestation, assess the association of metabolic acidemia with obstetric complications as well as its association with neonatal morbidity and mortality. The occurrence of neonatal seizures in the first 24 hours was used as the primary outcome measure as a marker for likely encephalopathy. Metabolic acidemia was defined as an umbilical artery pH less than 7.0 and base deficit of 12 mmol/L or greater as recommended by the College's Task Force.1
MATERIALS AND METHODS
Selected obstetric outcomes for all women who give birth at Parkland Hospital, Dallas, Texas, as well as neonatal outcomes are entered into a computerized database. Nurses attending each delivery complete an obstetric data sheet, which is entered into a specialized database and checked for consistency and completeness before electronic storage. Data on neonatal outcomes are abstracted from discharge records. Parkland Hospital is a tax-supported institution serving the medically indigent of Dallas County and has a level III neonatal intensive care unit adjacent to the labor and delivery units. The obstetrics service is staffed by house officers and faculty members of the Department of Obstetrics and Gynecology at the University of Texas Southwestern Medical School, and the neonatology service is staffed by house officers and faculty members of the Department of Pediatrics.
Umbilical artery blood is obtained for acid-base analysis from all live births, and the results are entered into the obstetrics database. From January 1, 1988, to December 31, 2013, there were 343,054 singleton cephalic live births at 35 weeks of gestation or greater with no malformations and 323,027 (95%) had complete cord blood gas analyses. The missing 5% of cord gases were the result of either insufficient sample collection or premature clotting of the umbilical artery vessels before cord blood collection. Complete gas analyses included pH, base deficit, pCO2, and HCO3. Stillbirths, multiple gestations, deliveries before 35 weeks of gestation, and neonates with congenital anomalies, incomplete cord blood gases, or nonvertex presentation were excluded from analysis (Fig. 1). Umbilical blood samples were drawn from a doubly clamped segment of cord into a 3-mL plastic syringe flushed with a 1,000-micron/mL solution of heparin. These samples were placed into ice for transport to the hospital laboratory for analysis. Blood gas analysis was immediately performed using Corning Biomedical 278 and 288; Nova Biomedical, Stat Profile 5 and 9; and Radiometer ABL 620 and 700 blood gas analyzers.
For the purposes of this analysis, metabolic umbilical artery acidemia was defined as pH less than 7.0 and base excess of 12 mmol/L or greater.1 Selected outcomes in these neonates were compared with the remainder of the cohort with pH values 7.0 or higher. This analysis was accomplished using deidentified data and was approved by the institutional review board at the University of Texas Southwestern Medical School. The risk of metabolic acidemia was calculated for selected obstetric interventions and complications. Changes in the incidence of metabolic acidemia were also examined according to gestational age in weekly increments and year of delivery.
Statistical analysis was performed using Pearson χ2 test or Fisher's exact test as appropriate for categorical data, Student's t test for continuous data, and Mantel-Haenszel test for trend. Univariable risk of individual intrapartum events for metabolic acidemia is expressed as relative risk (RR) with 95% confidence interval (CI). Multiple logistic regression analyses were performed to estimate the association between obstetric complications and metabolic acidemia. P values of <.05 were considered significant. When cell sizes are zero, the odds ratio and 95% CI are unstable estimates. In this case, the logit estimate is used to approximate the estimate.
Between January 1988 and December 2013, a total of 1,265 (3.9/1,000 live births) singleton neonates were identified with metabolic acidemia. Shown in Table 1 are the maternal characteristics of live births with metabolic acidemia compared with those with a cord pH 7.0 or greater. Metabolic acidemia, defined by a pH less than 7.0 and a base excess 12 mmol/L or greater, was significantly increased in neonates born to women younger than 15 years or older than 35 years and to those who were nulliparous. Said another way, metabolic acidemia was statistically lower in women between the ages of 15 and 35 years.
Shown in Table 2 are outcomes for the 1,265 neonates delivered with metabolic acidemia compared with neonates without this finding. Our primary outcome, seizures within 24 hours of birth, was significantly increased in the presence of metabolic acidemia with an RR of 60 (95% CI 47–77). Rates of metabolic acidemia and seizures did not differ by weekly gestational age increments (data not shown). Overall, seizures were diagnosed in 367 of 323,027 (1.1/1,000, 95% CI 1.0–1.3) neonates with 19.1% (95% CI 15.2–23.5) occurring in fetuses with metabolic acidemia for a prevalence of 5.5% (70/1,265, 95% CI 4.3–6.9). Examination of other neonates born with metabolic acidemia showed a significantly increased proportion of 5-minute Apgar scores of 4 or less (8.9% compared with 0.1%, P<.001). Actually, all recorded measures of neonatal morbidity were significantly increased in the presence of metabolic acidemia except for necrotizing enterocolitis requiring surgery. These differences remained significant after adjustment for age, race, nulliparity, and year of delivery.
The RRs for metabolic acidemia were studied in relation to a variety of obstetric complications and interventions (Fig. 2). As for neonatal morbidity, virtually every recorded obstetric complication, except placenta previa, postterm pregnancy, and shoulder dystocia, was associated with metabolic acidemia with RRs ranging from approximately 2 for the majority of measures to as high as 35 for placental abruption. These results were adjusted for interactive effects using logistic regression: diabetes, chorioamnionitis, prolonged second stage of labor, forceps, cesarean delivery for dystocia or fetal distress, umbilical cord prolapse, and placental abruption remained significant associations for metabolic acidemia.
Shown in Table 3 is an analysis of obstetric complications in the 1,265 neonates with metabolic acidemia according to the presence or absence of seizures in the newborn period. Only cesarean delivery for nonreassuring fetal tracing and placental abruption were significantly associated with newborn seizures in neonates with metabolic acidemia. These associations were unchanged after adjustment for age, race, nulliparity, and year of delivery. Specifically, cesarean delivery for fetal distress (nonreassuring fetal heart rate) was increased in neonates with both metabolic acidemia and neonatal seizures (51% compared with 24%, P<.001). Thirty-six neonates with metabolic acidemia who were delivered by cesarean for fetal distress had seizures and 18 of these underwent cesarean delivery within 1 hour of admission. The average time from admission to delivery in these 18 women was 14.4 minutes. Of the remaining 18, concurrent risk factors to include listeriosis (n=1), chorioamnionitis (n=2), postterm pregnancy (n=2), preeclampsia (n=2), gestational hypertension (n=1), and overt diabetes (n=2) were identified. Thus, only eight of the neonates with metabolic acidemia and seizures who were delivered by cesarean for fetal distress had no other pregnancy complication or evidence of nonreassuring fetal status on presentation to the labor and delivery unit.
In this analysis of more than 323,000 singleton, cephalic liveborn neonates delivered at 35 weeks of gestation or greater, metabolic acidemia as defined by the College's Task Force on Neonatal Encephalopathy1 was present in 1,265 newborns or 3.9/1,000 live births. Virtually every recorded measure of neonatal morbidity as well as death was significantly increased when metabolic acidemia was present. Neonatal seizures were significantly associated with metabolic acidemia (RR 60, 95% CI 47–77) and occurred in 70 (5.5%) of these acidemic neonates. Conversely, more than 94% of newborns with metabolic acidemia did not develop seizures within 24 hours of birth. Using seizures as an index of neonatal encephalopathy in neonates with metabolic acidemia, such seizures were only associated with cesarean delivery for abnormal fetal heart rate pattern and placental abruption.
There were a total of 36 neonates with metabolic acidemia and seizures who were delivered by cesarean for nonreassuring fetal status. Half of these neonates with seizures and acidemia (n=18) were deemed not preventable because a nonreassuring fetal heart rate was already present on admission to the labor and delivery unit. Similar results were reported by Phelan and Ahn10 who showed that fetal neurologic injury associated with fetal heart patterns were typically present on admission rather than developing during labor in the hospital. Consequently, when considered together with cases of placental abruption (n=12), 30 of 48 total cases of metabolic acidemia and seizures (63%) were not preventable.
We urge caution in drawing conclusions about the preventability of metabolic acidemia–related neonatal seizures. Most would accept that placental abruption, a sudden catastrophic event, is generally not preventable. However, the same cannot necessarily be said about a nonreassuring fetal tracing prompting urgent cesarean delivery. Because approximately half of our neonates apparently developed metabolic acidemia–related neonatal seizures after admission, they could be considered potentially preventable. These 18 neonates out of 323,027 live births, however, were extremely rare (6/100,000 births, 95% CI 3–9). Similarly, studies of neonates with cerebral palsy in the United States11 and in Australia12 have shown that a very small number of brain-damaged neonates had intrapartum risk factors such as cesarean delivery for nonreassuring fetal status.
In summary, we found that metabolic acidemia occurs in 3.9 per 1,000 live births (1,265/323,027, 95% CI 3.7–4.1) at or beyond 35 weeks of gestation and that neonatal seizures related to metabolic acidemia are rare, occurring in 2 per 10,000 live births (70/323,027, 95% CI 1.7–2.7). The only pregnancy complications found to be associated with metabolic acidemia–related neonatal seizures were cesarean delivery for nonreassuring fetal tracing and placental abruption, and almost two thirds of these were not preventable. We find that the rate of potentially preventable metabolic acidemia–related neonatal seizures in live births at or beyond 35 weeks of gestation is extremely rare, occurring in 6 of 100,000 births. Furthermore, approximately 80% of seizures in neonates at this gestational age occur in nonacidemic neonates.
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