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Acidemia in neonates with a 5-minute Apgar score of 7 or greater – What are the outcomes?

American Journal of Obstetrics and Gynecology, In Press, Uncorrected Proof, Available online 31 May 2016, Available online 31 May 2016

Background

The Apgar score is universally used for fetal assessment at the time of birth, whereas, the collection of fetal cord blood gases is performed commonly in high-risk situations or in the setting of Apgar scores of <7, which is a less standardized approach. It has been well-established that neonatal acidemia at the time of delivery can result in significant neonatal morbidity and death. Because of this association, knowledge of the fetal acid-base status and detection of acidemia at the time of delivery can serve as a sensitive and useful component in the assessment of a neonate’s risk. Umbilical cord blood gas analysis is an accurate and validated tool for the assessment of neonatal acidemia at the time of delivery. Because the collection of fetal cord blood gases is not a standardized practice, it is possible that, with such a varied approach, some cases of neonatal acidemia are not detected, particularly in the setting of reassuring Apgar scores.

Objective

In a setting of universally obtained cord blood gases, we sought to identify the rates of acidemia and associated factors in neonates with 5-minute Apgar scores of ≥7.

Study Design

This retrospective cohort study identified all term, singleton, nonanomolous neonates with 5-minute Apgar scores of ≥7. The incidence of umbilical artery pH ≤7.0 or ≤7.1 and base excess ≤–12 mmol/L or ≤–10 mmol/L were examined overall and in association with obstetric complications and adverse neonatal outcomes. Chi-squared tests were used to compare proportions, and multivariable logistic regression was used to control for potential confounders.

Results

In this cohort, the incidence of an umbilical artery pH of ≤7.0 was 0.5%, of a pH ≤7.1 was 3.4%, of a base excess ≤–12 mmol/L was 1.4%, and of ≤–10 mmol/L was 4.0%. Rates of neonatal acidemia were greater in the setting of meconium (4.3% vs 3.2%; P<.001), placental abruption (13.2% vs 3.4%; P<.001), and cesarean deliveries (5.8% vs 2.8%; P<.001), despite normal 5-minute Apgar scores. Additionally, umbilical artery pH ≤7.0 was associated with an increased risk of respiratory distress syndrome (adjusted odds ratio, 6.5; 95% confidence interval, 2.9–14.3) and neonatal intensive care unit admission (adjusted odds ratio, 10.8; 95% confidence interval, 6.8–17.4). Base excess of ≤–12 mmol/L was also associated with an increased risk of neonatal sepsis (adjusted odds ratio, 4.7; 95% confidence interval, 1.9–12.1). Finally, when examined together, neonates with both a pH of ≤7.0 and base excess of ≤–12 mmol/L continued to demonstrate an increased risk of neonatal intensive care unit admission and respiratory distress syndrome, with adjusted odds ratios of 9.6 and 6.0, respectively. This risk persisted in neonates with a pH of ≤7.1 and base excess of ≤–10 mmol/L as well, with adjusted odds ratios of 4.5 and 1.1, respectively.

Conclusion

Because neonates with reassuring Apgar scores have a residual risk of neonatal acidemia that is associated with higher rates of adverse outcomes, the potential utility of obtaining universal cord blood gases should be further investigated.

Key words: acidemia, Apgar, neonatal outcome, umbilical cord blood gas.

Fetal and subsequent neonatal acidemia is associated with multiorgan dysfunction, hypoxic ischemic encephalopathy, seizures, cerebral palsy, long-term neurologic deficits, and neonatal death.1, 2, 3, 4, 5, and 6 Because of this association, knowledge of the fetal acid-base status and detection of acidemia at the time of delivery can serve as a sensitive and useful component in the assessment of a neonate’s risk of morbidity and death. Umbilical cord blood gas analysis is an accurate and validated tool for the assessment of neonatal acidemia at time of delivery.

The components of umbilical cord blood gas, which most commonly are used as a means of capturing neonates who are at risk for adverse outcomes, are pH and base excess. Studies have demonstrated an increased risk of neonatal morbidity when umbilical artery cord pH is ≤7.0.1 and 7 Recent studies have also demonstrated that even moderate degrees of fetal acidemia (pH threshold of ≤7.10) may place neonates at risks for adverse outcomes.2 and 8 Base excess is an additional threshold value that is used to indicate the severity and duration of neonatal acidemia. At the time of delivery, base excess levels of ≤–12 mmol/L (10%) and ≤–16 mmol/L (40%) are associated with moderate-to-severe newborn infant complications.3 and 4

Although pH and base excess are useful tools in the prediction of adverse outcomes, universal umbilical cord blood gas analysis at the time of delivery is not a routine practice. The American College of Obstetricians and Gynecologists recommends the use of selective umbilical cord blood sampling.6 and 7 Common thresholds for obtaining neonatal cord blood gases are a 5-minute Apgar score of <7 and in patients who are at high risk for neonatal asphyxia (ie, cord prolapse, placental abruption). Because the collection of fetal cord blood gases is not a standardized practice, there is great variation in collection practice among institutions and among providers within the same institution. It is possible that, with such a varied approach, some cases of neonatal acidemia are not detected, particularly in the setting of reassuring Apgar scores. Additionally, it is unclear whether cases of neonatal acidemia with a normal Apgar score by 5 minutes are clinically important.

The objective of our study was to assess the rate of neonatal acidemia that occurs in neonates with a 5-minute Apgar score of ≥7. Additionally, we sought to determine factors that are associated with an increased risk of neonatal acidemia in this setting and their associated outcomes.

Materials and Methods

This is a retrospective cohort study of all nonanomalous, term, singleton neonates who were born at Moffitt-Long Hospital from 1990 until 2009 with a 5-minute Apgar score of ≥7 (N=26,669) in a setting where routine collection of cord blood gases was attempted in every delivery. Deliveries were excluded if the 5-minute Apgar score was <7 (n=873) or if a cord blood gas was not obtained, was inadequate, or was only a venous sample (n=3385). Approval from the institutional review board at Oregon Health & Science University was obtained. All diagnoses were made by the providing clinicians. Detailed information on all deliveries during the study time frame were abstracted from the medical records by trained abstractors and recorded in an electronic database. The abstracted data were reviewed monthly by a Neonatologist and Maternal Fetal Medicine specialist to ensure accuracy.

Within the cohort of deliveries with a 5-minute Apgar score of ≥7, the incidence of deliveries with an umbilical artery pH ≤7.0, pH ≤7.1, base excess ≤–12 mmol/L, and base excess ≤–10 mmol/L were then identified. To identify risk factors for abnormal cord blood gases in this setting, these groups were then examined in a variety of maternal subgroups that included mode of delivery and those women with placental abruption, presence of meconium, shoulder dystocia, and preexisting maternal conditions such as gestational diabetes mellitus, chronic hypertension, and preeclampsia.

Next, several neonatal outcomes were compared between acidemic and nonacidemic neonates who had 5-minute Apgar scores of ≥7. Neonatal outcomes that were examined included neonatal intensive care unit (NICU) admission, meconium aspiration syndrome (MAS), respiratory distress syndrome (RDS), and neonatal sepsis.

Chi-squared tests were used to compare proportions and potential confounders that were controlled for the use of multivariable logistic regression. The potential confounding variables that were examined were race/ethnicity, maternal age, parity, insurance status, gestational diabetes mellitus, chronic hypertension, and preeclampsia. A probability value of <.05 was considered statistically significant. Multivariable analyses are presented as odds ratios with 95% confidence intervals (CIs).

Results

Of the 26,669 deliveries that met the inclusion criteria, the overall incidence of an umbilical artery pH ≤7.0 was 0.5% (n=133), of umbilical artery cord pH ≤7.1 was 3.4% (n=906), of base excess ≤–12 mmol/L was 1.4% (n=373), and of base excess ≤–10 mmol/L was 4.0% (n=1067). Maternal characteristics between those with and without a neonate with an umbilical artery pH of ≤7.1 were similar with respect to insurance status and rates of gestational diabetes mellitus and chronic hypertension but differed in regards to maternal age, parity, and rates of preeclampsia (Table 1). Women who delivered neonates with a pH of ≤7.1 were more likely to be nulliparous and >35 years old and to have preeclampsia.

Table 1 Maternal demographics

Demographic pH, %
>7.1 ≤7.1
Paritya
 Nulliparous 96.9 3.1
 Multiparous 96.2 3.8
Age, yb
 <35 96.8 3.2
 >35 95.7 4.3
Raceb
 White 96.0 4.0
 Black 96.4 3.6
 Hispanic 96.3 3.7
 Asian 97.6 2.4
 Other 98 2
Insurance type
 Public 96.6 3.4
 Private 96.9 3.1
Gestational diabetes mellitus
 Yes 96.6 3.4
 No 96.0 4.0
Chronic hypertension
 Yes 96.6 3.4
 No 96.2 3.8
Preeclampsiab
 Yes 96.6 3.4
 No 94.6 3.4

aP<.05

bP<.001.

Sabol & Caughey. Neonatal acidemia with 5-minute Apgar ≥7. Am J Obstet Gynecol 2016.

The incidence of abnormal cord blood gases was compared with obstetric complications that included placental abruption, presence of meconium, shoulder dystocia, mode of delivery, maternal gestational diabetes mellitus, chronic hypertension, and preeclampsia. Rates of neonatal acidemia (pH ≤7.1), despite a normal 5-minute Apgar score, were greater in the setting of meconium (4.3% vs 3.2%; P<.001), placental abruption (13.2% vs 3.4%; P<.001), cesarean deliveries (5.8% vs 2.8%; P<.001), and pregnancies that were complicated by preeclampsia (6.3% vs 3.9%; P<.001; Table 2).

Table 2 Incidence of neonatal acidemia with 5-minute Apgar scores of ≥7

Characteristic pH ≤7.0, % Base excess ≤–12 mmol/L, % pH ≤7.1, % Base excess ≤–10 mmol/L, %
Meconium
 Yes 0.7a 2.0b 4.3b 5.2b
 No 0.4 1.2 3.2 3.7
Abruption
 Yes 3.6b 3.7 13.2b 8.6a
 No 0.5 1.4 3.4 4.0
Mode of delivery
 Cesarean 1.0b 1.7a 5.8b 4.6a
 Vaginal 0.3 1.3 2.8 3.9
Shoulder dystocia
 Yes 0.5 1.5 3.6 4.2
 No 0.3 0.6 3.4 2.8
Operative delivery
 Yes 0.5 1. a 4.3b 5.4
 No 0.4 1.3 3.3 3.8
Gestational diabetes mellitus
 Yes 1.1 1.3 4.8 3.4
 No 0.8 1.7 4.0 4.5
Chronic hypertension
 Yes 0.5 1.4 4.5 4.9
 No 0.8 1.7 4.0 4.5
Preeclampsia
 Yes 1.6a 2.8a 6.3b 7.8b
 No 0.7 1.7 3.9 4.42

aP<.05

bP<.001.

Sabol & Caughey. Neonatal acidemia with 5-minute Apgar ≥7. Am J Obstet Gynecol 2016.

With regard to neonatal outcomes, a cord blood gas with pH of ≤7.0 and ≤7.1 was associated with increased rates of RDS, MAS, and NICU admissions. Similarly, a cord blood gas base excess of ≤–10 mmol/L or ≤–12 mmol/L was also associated with these outcomes in addition to increased rates of neonatal sepsis (Table 3).

Table 3 Neonatal outcomes with a 5-minute Apgar score >7

Cord blood gas component Meconium aspiration syndrome, % Respiratory distress syndrome, % Sepsis, % Neonatal intensive care unit admission, %
pH
 ≤7.1 1.7a 4.7b 0.4 11.4b
 >7.1 0.7a 1.0b 0.2 4.3b
 ≤7.0 1.9a 7.6b 0 28.9b
 >7.0 0.7a 1.1b 0.2 4.4b
Base excess, mmol/L
 >–10 0.6b 1.1a 0.2b 4.4b
 ≤–10 1.7b 2.0a 1.0b 8.0b
 >–12 0.7b 1.1a 0.2b 4.5b
 ≤–12 2.6b 2.9a 1.4b 9.7b2

aP<.05

bP<.001.

Sabol & Caughey. Neonatal acidemia with 5-minute Apgar ≥7. Am J Obstet Gynecol 2016.

Multivariable regression analyses were performed to control for potential confounding variables that included parity, maternal age, maternal race/ethnicity, insurance type, chronic hypertension, gestational diabetes mellitus, and preeclampsia. After we controlled for these variables, we determined that neonates with a pH of ≤7.0, despite an Apgar of >7 at 5-minutes, had a statistically significant increased risk of RDS and NICU admission with an adjusted odds ratio (aOR) of 6.5 (95% CI, 2.9–14.3) and 10.8 (95% CI, 6.8–17.4) respectively (Table 4). Similarly, in neonates with a pH ≤7.1 and normal Apgar scores, there were also statistically significant increases in rates of MAS, RDS, and NICU admissions (Table 4).

Table 4 Multivariable regressiona results for neonatal outcomes in neonates with a 5-minute Apgar score of >7 and pH ≤7.0 and pH ≤7.1 compared pH >7.0 and pH >7.1

Outcomes Adjusted odds ratio 95% Confidence interval P value
pH ≤7.0
 Meconium aspiration syndrome 1.47 0.20–10.72 .699
 Respiratory distress syndrome 6.47 2.93–14.28 <.001
 Neonatal intensive care unit admission 10.84 6.76–17.38 <.001
pH ≤7.1
 Meconium aspiration syndrome 2.43 1.30–4.53 .005
 Respiratory distress syndrome 4.60 3.10–6.84 <.001
 Sepsis 1.67 0.60–4.65 .328
 Neonatal intensive care unit admission 3.68 2.81–4.82 <.001b

aRegression adjusted for parity, maternal age, maternal race/ethnicity, insurance type, chronic hypertension, gestational diabetes mellitus, and preeclampsia

bP<.05.

cP<.001.

Sabol & Caughey. Neonatal acidemia with 5-minute Apgar ≥7. Am J Obstet Gynecol 2016.

Similar to the low pH thresholds, base excess thresholds were examined as well. A base excess of ≤–12 mmol/L was associated with a statistically significant increase in MAS (aOR, 4.2; 95% CI, 2.1–8.4), neonatal sepsis (aOR, 4.7; 95% CI, 1.9–12.1), RDS (aOR, 2.2; 95% CI, 1.1–4.4), and NICU admission (aOR, 2.9; 95% CI, 2.0–4.4). Similar trends were also seen with a base excess of ≤–10 mmol/L (Table 5).

Table 5 Multivariable regressiona results for neonatal outcomes in neonates with a 5-minute Apgar score of >7 and base excess of ≤–12 mmol/L and ≤–10 mmol/L compared with those with a base excess of >–12 mmol/L and >–10 mmol/L

Outcomes Adjusted odds ratio 95% Confidence interval P value
Base excess ≤–12 mmol/L
 Meconium aspiration syndrome 4.21 2.12–8.38 <.001
 Respiratory distress syndrome 2.21 1.08–4.53 .03
 Sepsis 4.72 1.85–12.05 .001
 Neonatal intensive care unit admission 2.92 1.96–4.35 <.001
Base excess ≤–10 mmol/L
 Meconium aspiration syndrome 2.67 1.57–4.53 <.001
 Respiratory distress syndrome 1.40 0.811–2.43 .225
 Sepsis 3.13 1.56–6.25 .001
 Neonatal intensive care unit admission 2.33 1.77–3.07 <.001b

aRegression adjusted for parity, maternal age, maternal race/ethnicity, insurance type, chronic hypertension, gestational diabetes mellitus, and preeclampsia

bP<.05.

Sabol & Caughey. Neonatal acidemia with 5-minute Apgar ≥7. Am J Obstet Gynecol 2016.

P<.001.

Finally, to better capture and evaluate the effects of a mixed or metabolic acidosis in neonates with an Apgar score of ≥7 at 5-minutes, a combined variable that encompassed both pH and base excess was created. When we examined them together, we found that neonates with both a pH ≤7.0 and base excess ≤–12 mmol/L continued to demonstrate an increased risk of NICU admission and RDS, with aORs of 9.6 and 6.0, respectively. This risk persisted in neonates with a pH ≤7.1 and base excess ≤–10 mmol/L as well, with aORs of 4.5 and 1.1 (Table 6).

Table 6 Combined impact of low pH and elevated base excess on neonatal outcomes in neonates with a 5-minute Apgar score >7

Outcomes No acidemia Acidemia
pH >7.0 & base excess >–12 mmol/L pH >7.1 & base excess >–10 mmol/L pH ≤7.0 & base excess ≤–12 mmol/L pH ≤7.1 & base excess ≤–10 mmol/L
Meconium aspiration syndrome, % 99.3 99.3 0.7 0.7
 Adjusted odds ratio (95% confidence interval) 2.5 (0.3–18.6) 2.1 (0.9–5.2)
Respiratory distress syndrome, % 98.9 98.9 1.1a 1.1a
 Adjusted odds ratio (95% confidence interval) 6.0 (2.1–16.9)a 3.4 (1.9–6.2)a
Sepsis, % 99.8 99.8 0.2 0.2b
 Adjusted odds ratio (95% confidence interval) ?? 2.3 (0.7–7.4)
Neonatal intensive care unit admission, % 95.5 95.6 4.5a 4.4a
 Adjusted odds ratio (95% confidence interval) 9.6 (5.2–17.8)a 4.6 (3.3–6.5)a

aP<.001

bP<.05.

Regression adjusted for parity, maternal age, maternal race/ethnicity, insurance type, chronic hypertension, gestational diabetes mellitus, and preeclampsia.

Sabol & Caughey. Neonatal acidemia with 5-minute Apgar ≥7. Am J Obstet Gynecol 2016.

Comment

The Apgar score was proposed in 1952 as a means of rapidly evaluating the clinical status of a newborn infant and currently remains an accepted method for newborn infant assessment immediately after delivery.9 In many institutions, it is not common practice to obtain a cord blood gas, as a means of additional assessment, in deliveries with an Apgar score of ≥7, despite literature to suggest poor correlation between Apgar scores at 1 and 5 minutes and resultant neonatal acid-base status.10 and 11 Neonatal acidemia occurs in 1–2% of deliveries; it generally has been believed that acidemia in clinically vigorous neonates is insignificant.7 Albeit rare, our study demonstrates that, in the setting of normal Apgar scores, there is still a residual risk of neonatal acidemia. Similar to other studies, our study found that neonatal acidemia is associated with adverse neonatal outcomes. However, our study uniquely demonstrates that neonates with acidemia at the time of delivery, despite a normal Apgar score, have worse outcomes compared with their nonacidemic counterparts.

The American College of Obstetrics & Gynecology endorses the Apgar score as a tool to identify the need for immediate neonatal resuscitation but cautions that it is not predictive of “individual neonatal mortality or neurologic outcomes and thus should not be used for that purpose.”9 It is not meant to be used in lieu of a cord blood gas for the assessment of neonatal acid-base status, but rather in conjunction with umbilical cord blood gas for an overall impression of neonatal status. Furthermore, there are limited studies on the acid-base status of neonates with normal Apgar scores, which is likely because of variations in umbilical cord blood sampling practices.

By taking advantage of a clinical setting that attempted to obtain universal cord blood gases, our study begins to fill this gap in knowledge by assessing a large cohort of neonates with normal Apgar scores and comparing the incidence of acidemia with subsequent neonatal outcomes. Our study demonstrated that, even in neonates born with a reassuring clinical status, acidemia can still occur and that neonates with acidemia are at a significantly higher risk of having RDS, MAS, and admission to the NICU. These risks were further increased with the severity of acidemia.

We acknowledge that the incidence of neonatal acidemia in the setting of normal Apgar scores and reassuring clinical status is an overall rare occurrence; our study accounts for just 0.5–3.4% of deliveries. We also acknowledge that most neonates who are born with acidemia will not require additional intervention or develop subsequent morbidity. With that being said, Malin et al,1 in a recent systemic review and meta-analysis of umbilical cord pH and perinatal and long-term outcomes, concluded that “increased initial surveillance of neonates born with a low arterial cord pH, regardless of their clinical condition, is warranted as the odds of complications have been shown to be higher in this group.” Based on the findings of our study, we agree with this conclusion and find merit in universal umbilical cord blood sampling as a method of identifying neonates who are at risk.

Although the current study demonstrated specific neonatal complications that are associated with abnormal umbilical artery cord blood gases, additional benefits to universal cord blood gas collection may exist from a quality standpoint. First, when cord blood gases are obtained only in the setting of a low Apgar score, they are often being done in an emergent setting. Obtaining cord blood gases in this setting is extremely important; therefore, having a routine approach to collection is likely to improve the probability of a successful and interpretable cord blood gas sample. Second, the information from the cord blood gas, normal or abnormal, can be useful in interpreting the fetal heart rate monitoring strip for quality improvement purposes. Given our relatively poor ability to interpret and use fetal heart rate monitoring, especially its correlation with identifying neonatal acidemia, opportunities to improve its predictive ability should be embraced.12, 13, 14, and 15

When discussing the benefits of universal cord blood gas collection, we would be remiss to not address the medico-legal implications and associated costs. The actual cost of cord blood gas collection is relatively inexpensive, approximately $3.50–$5.00 per sample; however, there is wide variation in the cost charged by the hospital.7 In our current medico-legal environment, there is understandable concern surrounding universal cord blood gas analysis and implications of unexpected neonatal acidemia. One must remember, however, that the vast majority of neonates who are born with acidemia will not go on to experience any long-term neurologic deficits and that the majority of neonates who have cerebral palsy are not acidemic at birth.7 and 16

This study is not without limitations. Because of the retrospective nature of this study, we were unable to control for all possible confounding variables and were limited to information previously obtained. Thus, there may be persistent confounding in our multivariable results. We were also unable to assess long-term neonatal outcomes that included developmental delay, neurologic morbidity, and cerebral palsy. Additionally, although cord blood gases were attempted to be collected universally, they were missing in 13% of deliveries that met the inclusion criteria. It is possible that such cord blood gases would be more likely to be absent in certain high-risk settings such as placental abruption with decreased cord blood available for collection. If these missing cord blood gases were more common among high-risk patients, this would have biased our results slightly towards underestimates of the frequency of acidemia in these neonates with normal Apgar scores. Alternatively, if they were more likely to be missing because the urgency to obtain them was lower, then our results would mildly overestimate the rate of abnormal cord blood gases.

Furthermore, given the limitations of a retrospective study, we were unable to evaluate how the knowledge of acidemia in a clinically vigorous neonate may have changed or influenced clinical management and practice patterns within the institution. We were unable to assess whether knowledge of acidemia at the time of delivery biased the treatment that the neonate received. We were also unable to assess whether the knowledge of fetal acidemia at the time of delivery had any impact on management or short- or long-term outcomes. Further investigation into how the knowledge of umbilical cord pH at the time of delivery influences management and outcomes is needed.

Despite these limitations, the results of this study demonstrate the frequency and potential risks of neonatal acidemia, even in the setting of a normal 5-minute Apgar score. It is our belief, based on the data presented, that broad or universal umbilical cord blood gas collection at the time of delivery would be a clinically beneficial practice to better stratify neonatal risk levels and, at minimum, demands further investigation.

References

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  • 2 P. Yeh, K. Emary, L. Impey. The relationship between umbilical cord arterial pH and serious adverse neonatal outcome: analysis of 51,519 consecutive validated samples. BJOG. 2012;119:824-831 Crossref
  • 3 J.A. Low, B.G. Lindsay, E.J. Derrik. Threshold of metabolic acidosis associated with newborn complications. Am J Obstet Gynecol. 1997;177:1391-1394 Crossref
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  • 14 S.L. Clark, M.L. Gimovsky, F.C. Miller. The scalp stimulation test: a clinical alternative to fetal scalp blood sampling. Am J Obstet Gynecol. 1984;148:274-277 Crossref
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Footnotes

Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR

Corresponding author: Bethany Sabol, MD.

The authors report no conflict of interest.

Cite this article as: Sabol BA, Caughey AB. Acidemia in neonates with a 5-minute Apgar score of 7 or greater – What are the outcomes?. Am J Obstet Gynecol 2016;•••:••••.