Accepted Manuscript

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

Bethany A. Sabol, MD, Aaron B. Caughey, MD PhD

PII: S0002-9378(16)30251-4
DOI: 10.1016/j.ajog.2016.05.035
Reference: YMOB 11124

To appear in: American Journal of Obstetrics and Gynecology

Received Date: 5 April 2016

Revised Date: 22 May 2016
Accepted Date: 24 May 2016

Please 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?, American Journal of Obstetrics and Gynecology (2016), doi:
10.1016/j.ajog.2016.05.035.

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
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1 Acidemia in neonates with a 5-minute Apgar score of 7 or greater What are the outcomes?

2 Bethany A. SABOL, MD1, Aaron B. CAUGHEY, MD PhD1

4 (1) Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland,

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5 OR

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7 The authors report no conflict of interest

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9 This research was presented as a poster at the 35th Society of Maternal-Fetal Medicine Annual

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Meeting in San Diego, California, February 2-8th, 2015
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11 Funding: None

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13 Corresponding Author:
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14 Bethany Sabol, MD
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15 Department of Obstetrics and Gynecology, Mail code L-466

16 3181 SW Sam Jackson Park Road

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17 Portland, OR 97239-3098

18 Work Phone: (503) 494-2685

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19 Home phone: (920) 277-1582

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20 Email: sabol@ohsu.edu

21 Abstract Word Count: 465

22 Manuscript Word Count: 2,325

23 Table 4 for publication in the print issue

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24 CONDENSATION: Neonatal acidemia can occur in the setting of a 5-minute Apgar of 7 or

25 greater and is associated with adverse neonatal outcomes.

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27 SHORT TITLE: Neonatal acidemia with 5-minute Apgar 7

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47 ABSTRACT

48 Background: The Apgar score is universally used for fetal assessment at the time of birth,

49 whereas, collection of fetal cord blood gases is performed commonly in high risk situations or in

50 the setting of Apgar scores <7, which is a less standardized approach. It has been well

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51 established that neonatal acidemia at the time of delivery can result in significant neonatal

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52 morbidity and mortality. Due to this association, knowledge of the fetal acid-base status and

53 detection of acidemia at the time of delivery can serve as a sensitive and useful component in

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54 assessing a neonates risk. Umbilical cord blood gas analysis is an accurate and validated tool for

55 assessment of neonatal acidemia at time of delivery. As collection of fetal cord blood gases is

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not a standardized practice, it is possible that with such a varied approach, some cases of
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57 neonatal acidemia are not detected, particularly in the setting of reassuring Apgar scores.

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

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60 Study Design: This retrospective cohort study identified all term, singleton, nonanomolous
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61 neonates with 5-minute Apgar scores 7. The incidence of umbilical artery pH 7.0 or 7.1 and

62 base excess -12 mmol/L or -10 mmol/L were examined overall and in association with
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63 obstetric complications and adverse neonatal outcomes. Chi-squared tests were utilized to

64 compare proportions and multivariable logistic regression was used to control for potential
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65 confounders.
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66 Results: In this cohort, the incidence of an umbilical artery pH 7.0 was 0.5%, pH 7.1 was

67 3.4%, base excess -12 mmol/L was 1.4% and -10 mmol/L was 4.0%. Rates of neonatal

68 acidemia were greater in the setting of meconium (4.3% versus 3.2%; p<0.001), placental

69 abruption (13.2% versus 3.4%; p<0.001), and cesarean deliveries (5.8% versus 2.8%; p<0.001)
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70 despite normal 5-minute Apgar scores. Additionally, umbilical artery pH 7.0 was associated

71 with increased risk of respiratory distress syndrome (Adjusted Odds Ratio 6.5; 95% Confidence

72 Interval 2.9-14.3) and neonatal intensive care unit admission (Adjusted Odds Ratio 10.8; 95%

73 Confidence Interval 6.8-17.4). Base excess -12 mmol/L was also associated with an increased

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74 risk of neonatal sepsis (Adjusted Odds Ratio 4.7; 95% Confidence Interval 1.9-12.1). Finally,

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75 when examined together, neonates with both a pH 7.0 and base excess -12 mmol/L continued

76 to demonstrate increased risk of neonatal intensive care unit admission and respiratory distress

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77 syndrome, with adjusted odds ratios of 9.6 and 6.0 respectively. This risk persisted in neonates

78 with a pH 7.1 and base excess -10 mmol/L as well, with adjusted odds ratios of 4.5 and 1.1

79 (Table 6).
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80 Conclusion: As neonates with reassuring Apgar scores have a residual risk of neonatal acidemia

81 associated with higher rates of adverse outcomes, the potential utility of obtaining universal cord
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82 blood gases should be further investigated.

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84 Key Words: Acidemia, Apgar, neonatal outcomes, umbilical cord gas

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93 INTRODUCTION

94 Fetal and subsequent neonatal acidemia is associated with multi-organ dysfunction,

95 hypoxic ischemic encephalopathy, seizures, cerebral palsy, long-term neurologic deficits, and

96 neonatal death.1-6 Due to this association, knowledge of the fetal acid-base status and detection of

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97 acidemia at the time of delivery can serve as a sensitive and useful component in assessing a

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98 neonates risk of morbidity and mortality. Umbilical cord blood gas analysis is an accurate and

99 validated tool for assessment of neonatal acidemia at time of delivery.

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100 The components of umbilical cord blood gas most commonly utilized as a means of

101 capturing neonates at risk for adverse outcomes are pH and base excess. Studies have

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demonstrated an increased risk of neonatal morbidity when umbilical artery cord pH is 7.0.1,7
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103 Recent studies have also demonstrated that even moderate degrees of fetal acidemia (pH

104 threshold of 7.10) may place neonates at risks for adverse outcomes.2,8 Base excess is an
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105 additional threshold value used to indicate the severity and duration of neonatal acidemia. At the
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106 time of delivery, base excess levels of -12mmol/L (10%) and -16mmol/L (40%) are
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107 associated with moderate to severe newborn complications. 3,4

108 Although pH and base excess are useful tools in predicting adverse outcomes, universal
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109 umbilical cord blood gas analysis at the time of delivery is not a routine practice. The American

110 College of Obstetricians and Gynecologists recommends the use of selective umbilical cord
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111 blood sampling.6, 7 Common thresholds for obtaining neonatal cord blood gases are a 5-minute
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112 Apgar score of < 7 and in patients at high risk for neonatal asphyxia (i.e. cord prolapse, placental

113 abruption). As collection of fetal cord blood gases is not a standardized practice, there is great

114 variation in collection practice between institutions, and amongst providers within the same

115 institution. It is possible that with such a varied approach, some cases of neonatal acidemia are
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116 not detected, particularly in the setting of reassuring Apgar scores. Additionally, it is unclear

117 whether cases of neonatal acidemia with a normal Apgar score by 5 minutes are clinically

118 important.

119 The objective of our study was to assess the rate of neonatal acidemia occurring in

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120 neonates with a 5-minute Apgar score 7. Additionally, we sought to determine factors

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121 associated with an increased risk of neonatal acidemia in this setting and their associated

122 outcomes.

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123 MATERIALS and METHODS

124 This is a retrospective cohort study of all nonanomalous, term, singleton neonates born at

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Moffitt-Long Hospital from 1990 until 2009 with a 5-minute Apgar score 7 (N=26,669) in a
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126 setting where routine collection of cord blood gases were attempted in every delivery. Deliveries

127 were excluded if the 5-minute Apgar score was < 7 (N=873) or if a cord blood gas was not
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128 obtained, was inadequate, or was only a venous sample (N=3,385). Approval from the
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129 institutional review board at Oregon Health & Science University was obtained. All diagnoses
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130 were made by the providing clinicians. Detailed information on all deliveries during the study

131 time frame were abstracted from the medical records by trained abstractors and recorded in an
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132 electronic database. The abstracted data was reviewed monthly by a Neonatologist and Maternal

133 Fetal Medicine specialist to ensure accuracy.

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134 Within the cohort of deliveries with a 5-minute Apgar score 7, the incidence of
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135 deliveries with an umbilical artery pH 7.0, pH 7.1, base excess -12 mmol/L, and base excess

136 -10 mmol/L were then identified. In order to identify risk factors for abnormal cord blood

137 gases in this setting, these groups were then examined in a variety of maternal subgroups

138 including those women with placental abruption, presence of meconium, shoulder dystocia,
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139 mode of delivery, and preexisting maternal conditions such as gestational diabetes, chronic

140 hypertension, and preeclampsia.

141 Next, several neonatal outcomes were compared between acidemic and non-acidemic

142 neonates who had 5-minute Apgar scores of greater than or equal to 7. Neonatal outcomes

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143 examined included Neonatal Intensive Care Unit (NICU) admission, meconium aspiration

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144 syndrome (MAS), respiratory distress syndrome (RDS), and neonatal sepsis.

145 Chi-squared tests were utilized to compare proportions and potential confounders were

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146 controlled for using multivariable logistic regression. The potential confounding variables

147 examined were race/ethnicity, maternal age, parity, insurance status, gestational diabetes, chronic

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hypertension, and preeclampsia. A p-value of < 0.05 was considered statistically significant.
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149 Multivariable analyses are presented as odds ratios (OR) with 95% confidence intervals.

150 RESULTS
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151 Of the 26,669 deliveries meeting inclusion criteria, the overall incidence of an umbilical
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152 artery pH 7.0 was 0.5% (N=133), umbilical artery cord pH 7.1 was 3.4% (N=906), base
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153 excess -12 mmol/L was 1.4% (N=373), and base excess - 10 mmol/L was 4.0% (N=1,067).

154 Maternal characteristics between those with and without a neonate with an umbilical artery pH
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155 7.1 were similar with respect to insurance status and rates of gestational diabetes and chronic

156 hypertension, but differed in regards to maternal age, parity, and rates of preeclampsia (Table 1).
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157 Women who delivered neonates with a pH 7.1 were more likely to be nulliparous, over 35, and
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158 have preeclampsia.

159 The incidence of abnormal cord blood gases was compared with obstetrical

160 complications including placental abruption, presence of meconium, shoulder dystocia, mode of

161 delivery, maternal gestational diabetes, chronic hypertension and preeclampsia. Rates of neonatal
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162 acidemia (pH 7.1) despite a normal 5-minute Apgar score, were greater in the setting of

163 meconium (4.3% versus 3.2%; p<0.001), placental abruption (13.2% versus 3.4%; p<0.001),

164 cesarean deliveries (5.8% versus 2.8%; p<0.001), and pregnancies complicated by preeclampsia

165 (6.3% versus 3.9%; p<0.001) (Table 2).

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166 With regard to neonatal outcomes, a cord blood gas with pH 7.0 and pH 7.1 was

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167 associated with increased rates of RDS, MAS, and NICU admissions. Similarly, a cord blood gas

168 base excess of -10 mmol/L or -12 mmol/L was also associated with these outcomes in

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169 addition to increased rates of neonatal sepsis (Table 3).

170 Multivariable regression analyses were performed to control for potential confounding

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variables including parity, maternal age, maternal race/ethnicity, insurance type, chronic
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172 hypertension, gestational diabetes, and preeclampsia. After controlling for these variables, we

173 determined that neonates with a pH 7.0 despite an Apgar of 7 or more at 5-minutes had a
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174 statistically significant increased risk of RDS and NICU admission with an adjusted odds ratio of
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175 6.5 (95% CI 2.9-14.3) and 10.8 (95% CI 6.8-17.4) respectively (Table 4). Similarly, in neonates
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176 with a pH 7.1 and normal Apgar scores there were also statistically significant increases in rates

177 of MAS, RDS and NICU admissions (Table 4).

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178 Similar to the low pH thresholds, base excess thresholds were examined as well. A base

179 excess -12 mmol/L was associated with a statistically significant increase in MAS (aOR 4.2;
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180 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),
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181 and NICU admission (aOR 2.9; 95% CI 2.0-4.4). Similar trends were also seen with a base

182 excess of -10 mmol/L (Table 5).

183 Finally, in order to better capture and evaluate the effects of a mixed or metabolic

184 acidosis in neonates with an Apgar score of 7 or more at 5-minutes, a combined variable
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185 encompassing both pH and base excess was created. When examined together, we found that

186 neonates with both a pH 7.0 and base excess -12 mmol/L continued to demonstrate increased

187 risk of NICU admission and RDS, with adjusted odds ratios of 9.6 and 6.0 respectively. This risk

188 persisted in neonates with a pH 7.1 and base excess -10 mmol/L as well, with adjusted odds

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189 ratios of 4.5 and 1.1 (Table 6).

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190 COMMENT

191 The Apgar score was proposed in 1952 as a means of rapidly evaluating the clinical

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192 status of a newborn and currently remains an accepted method for newborn assessment

193 immediately after delivery.9 In many institutions, it is not common practice to obtain a cord

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blood gas, as a means of additional assessment, in deliveries with an Apgar score of 7 despite
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195 literature to suggest poor correlation between Apgar scores at 1 and 5 minutes and resultant

196 neonatal acid-base status.10,11 Neonatal acidemia occurs in 1-2% of deliveries and it has generally
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197 believed that acidemia in clinically vigorous neonates is insignificant.7 Albeit rare, our study
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198 demonstrates that in the setting of normal Apgar scores, there is still a residual risk of neonatal
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199 acidemia. Similar to other studies, our study found that neonatal acidemia is associated with

200 adverse neonatal outcomes. However, our study uniquely demonstrates that neonates with
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201 acidemia at the time of delivery, despite a normal Apgar score, have worse outcomes compared

202 to their non-acidemic counterparts.

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203 The American College of Obstetrics & Gynecology endorses the Apgar score as a tool to
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204 identify the need for immediate neonatal resuscitation, but cautions that it is not predictive of

205 individual neonatal mortality or neurologic outcomes and thus should not be used for that

206 purpose.9 It is not meant to be used in lieu of a cord blood gas for assessment of neonatal acid-

207 base status, but rather in conjunction with umbilical cord blood gas for an overall impression of
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208 neonatal status. Furthermore, there are limited studies on the acid-base status of neonates with

209 normal Apgar scores, which is likely because of variations in umbilical cord blood sampling

210 practices.

211 By taking advantage of a clinical setting that attempted to obtain universal cord blood

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212 gases, our study begins to fill this gap in knowledge by assessing a large cohort of neonates with

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213 normal Apgar scores and comparing the incidence of acidemia with subsequent neonatal

214 outcomes. Our study demonstrated that even in neonates born with a reassuring clinical status,

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215 acidemia can still occur and neonates with acidemia are at a significantly higher risk of having

216 RDS, MAS, and admission to the NICU. These risks were further increased with the severity of

217 acidemia.
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218 We acknowledge that the incidence of neonatal acidemia in the setting of normal Apgar

219 scores and reassuring clinical status is an overall rare occurrence, in our study accounting for just
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220 0.5-3.4% of deliveries. We also acknowledge that the majority of neonates born with acidemia
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221 will not require additional intervention or develop subsequent morbidity. With that being said,
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222 Malin et al in a recent systemic review and meta-analysis of umbilical cord pH and perinatal and

223 long term outcomes concluded that increased initial surveillance of neonates born with a low
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224 arterial cord pH, regardless of their clinical condition, is warranted as the odds of complications

225 have been shown to be higher in this group.1 Based on the findings of our study we agree with
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226 this conclusion and find merit in universal umbilical cord blood sampling as a method of
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227 identifying neonates at risk.

228 While the current study demonstrated specific neonatal complications associated with

229 abnormal umbilical artery cord blood gases, additional benefits to universal cord blood gas

230 collection may exist from a quality standpoint. First, when cord blood gases are only obtained in
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231 the setting of a low Apgar score, they are often being done in an emergent setting. Obtaining

232 cord blood gases in this setting is extremely important; therefore, having a routine approach to

233 collection is likely to improve the probability of a successful and interpretable cord blood gas

234 sample. Second, the information from the cord blood gas, normal or abnormal, can be useful in

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235 interpreting the fetal heart rate monitoring strip for quality improvement purposes. Given our

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236 relatively poor ability to interpret and utilize fetal heart rate monitoring, especially its correlation

237 with identifying neonatal acidemia, opportunities to improve its predictive ability should be

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238 embraced.12-15

239 When discussing the benefits of universal cord blood gas collection, we would be remiss

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to not address the medico-legal implications and associated costs. The actual cost of cord blood
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241 gas collection is relatively inexpensive, about $3.50-$5.00 per sample, however there is wide

242 variation in the cost charged by the hospital.7 In our current medico-legal environment there is
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243 understandable concern surrounding universal cord blood gas analysis and implications of
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244 unexpected neonatal acidemia. One must remember, however, that the vast majority of neonates
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245 born with acidemia will not go on to suffer any long term neurologic deficits and that majority of

246 neonates who develop cerebral palsy are not acidemic at birth.7,16
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247 This study is not without limitations. Due to the retrospective nature of this study we

248 were unable to control for all possible confounding variables and were limited to information
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249 previously obtained. Thus, there may be persistent confounding in our multivariable results. We
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250 were also unable to assess long-term neonatal outcomes including developmental delay,

251 neurologic morbidity, and cerebral palsy. Additionally, while cord blood gases were attempted to

252 be collected universally, they were missing in 13% of deliveries meeting inclusion criteria. It is

253 possible that such cord blood gases would be more likely to be absent in certain high-risk
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254 settings such as placental abruption with decreased cord blood available for collection. If these

255 missing cord blood gases were more common among high-risk patients, this would have biased

256 our results slightly towards underestimates of the frequency of acidemia in these neonates with

257 normal Apgar scores. Alternatively, if they were more likely to be missing because the urgency

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258 to obtain them was lower, then our results would mildly overestimate the rate of abnormal cord

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259 blood gases.

260 Furthermore, given the limitations of a retrospective study, we were unable to evaluate

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261 how the knowledge of acidemia in a clinically vigorous neonate may have changed or influenced

262 clinical management and practice patterns within the institution. We were unable to assess if

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knowledge of acidemia at the time of delivery biased the treatment the neonate received. We
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264 were also unable to assess if the knowledge of fetal acidemia at the time of delivery had any

265 impact on management, short, or long term outcomes. Further investigation into how the
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266 knowledge of umbilical cord pH at the time of delivery influences management and outcomes is
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267 needed.
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268 Despite these limitations, the results of this study demonstrate the frequency and potential

269 risks of neonatal acidemia even in the setting of a normal 5-minute Apgar score. It is our belief,
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270 based on the data presented, that broad or universal umbilical cord blood gas collection at the

271 time of delivery would be a clinically beneficial practice to better stratify neonatal risk levels and
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272 at minimum demands further investigation.

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277 ACKNOWLEDGEMENTS

278 Bethany A. Sabol, MD, Aaron B. CAUGHEY, MD PhD1

279 Department of Obstetrics and Gynecology

280 Oregon Health and Science University, Portland, OR

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281 No funding or disclosures

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283 Aaron B. Caughey, MD PhD

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284 Department of Obstetrics and Gynecology

285 Oregon Health and Science University, Portland, OR

286 No funding or disclosures

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300 REFERENCES

301 1. Malin GL, Morris RK, Khan KS. Strength of association between umbilical cord pH and

302 perinatal and long-term outcomes: systematic review and meta-analysis. BMJ

303 2010;13(340):c1471.

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304 2. Yeh P, Emary K, Impey L. The relationship between umbilical cord arterial pH and

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305 serious adverse neonatal outcome: analysis of 51,519 consecutive validated samples.

306 BJOG 2012;119(7):82431.

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307 3. Low JA, Lindsay BG, Derrik EJ. Threshold of metabolic acidosis associated with

308 newborn complications. Am J Obstet Gynecol 1997; 177:1391-4.

309
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4. Low JA. Intrapartum fetal asphyxia: definition, diagnosis and classification. Am J Obstet
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310 Gynecol 1997; 176:957-9.
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311 5. Low JA, Panagiotopoulos C, Derrik EJ. Newborn complications after intrapartum asphyxia

312 with metabolic acidosis in the term fetus. Am J Obstet Gynecol 1994; 170:1081-7.
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313 6. American College of Obstetricians and Gynecologists Committee on Obstetric Practice.

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314 Umbilical cord blood gas and acid-base analysis. ACOG Committee opinion no. 348. Obstet
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315 Gynecol 2006; 108:1319-22.

316 7. Thorp JA, Dildy GA, Yeomans ER, et al. Umbilical cord blood gas analysis at delivery. Am J
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317 Obstet Gynecol 1996;175(3 pt 1): 517-22.

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318 8. Victory R, Penava D, da Silva O, Natale R, Richardson B. Umbilical cord pH and base excess

319 values in relation to adverse outcome events for infants delivering at term. Am J Obstet Gynecol

320 2004; 191:20218.

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321 9. American College of Obstetricians and Gynecologists. The Apgar score. Committee

322 Opinion No. 644. American College of Obstetricians and Gynecologists. Obstet Gynecol

323 2015; 126:e52-5.

324 10. Sykes GS, Johnson P, Ashworth F, Molloy PM, Gu W, Stirrat GM. Do Apgar scores indicate

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325 asphyxia? Lancet 1982;1: 494-5.

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326 11. Silverman F, Suidan J, Wasserman J, Antoine C, Young BK. The Apgar score: is it enough?

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327 Obstet Gynecol 1985;66: 331-6.

328 12. Williams KP, Galerneau F. Intrapartum fetal heart rate patterns in the prediction of neonatal

329
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acidemia. Am J Obstet Gynecol 2003;188:8203.
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330 13. Banta HD, Thacker SB. Costs and benefits to electronic fetal monitoring: a review of the
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331 literature. Rockville (MD): National Center for Health Services Research. Report No. DHEW-

332 PHS- 79-3245.

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333 14. Clark SL, Gimovsky ML, Miller FC. The scalp stimulation test: a clinical alternative to fetal

334 scalp blood sampling. Am J Obstet Gynecol 1984; 148:274-7.

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335 15. Tejani N, Mann L, Bhakthavathsalan A, Weiss RR. Correlation of fetal heart rate-uterine
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336 contraction patterns and fetal scalp blood pH. Obstet Gynecol 1975; 46:392-6.
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337 16. American College of Obstetricians and Gynecologists Task Force on Neonatal

338 Encephalopathy. Executive summary: Neonatal encephalopathy and neurologic outcome, second

339 edition. Obset Gynecol. 2014; 123(4):896-901.

340
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341 TABLES

342 Table 1. Maternal Demographics

Characteristic pH > 7.1 pH 7.1

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Parity*

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Nulliparous 96.9% 3.1%

Multiparous 96.2% 3.8%

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Maternal Age

<35 years old 96.8% 3.2%

>35 years old 95.7%

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Maternal Race
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White 96.0% 4.0%

Black 96.4% 3.6%

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Hispanic 96.3% 3.7%

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Asian 97.6% 2.4%

Other 98% 2%
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Insurance Type
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Public Insurance 96.6% 3.4%

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Private Insurance 96.9% 3.1%

Maternal Gestational Diabetes

Gestational Diabetes 96.6% 3.4%

No Gestational Diabetes 96.0% 4.0%

Maternal Chronic Hypertension

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Chronic Hypertension 96.6% 3.4%

No Chronic Hypertension 96.2% 3.8%

Maternal Preeclampsia

Preeclampsia 96.6% 3.4%

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No Preeclampsia 94.6% 3.4%*

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p < 0.05; p < 0.001

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359 Table 2. Incidence of neonatal acidemia with 5-minute Apgar scores of 7 or greater

Characteristic pH 7.0 BE -12 mmol/L pH 7.1 BE -10 mmol/L

Meconium

Yes 0.7%* 2.0% 4.3% 5.2%

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No 0.4% 1.2% 3.2% 3.7%

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Abruption

Yes 3.6% 3.7% 13.2% 8.6%*

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No 0.5% 1.4% 3.4% 4.0%

Mode of Delivery

Cesarean 1.0% 1.7%*

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Vaginal 0.3% 1.3% 2.8% 3.9%
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Shoulder Dystocia

Yes 0.5% 1.5% 3.6% 4.2%

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No 0.3% 0.6% 3.4% 2.8%

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Operative Delivery

Yes 0.5% 1.8%* 4.3% 5.4%

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No 0.4% 1.3% 3.3% 3.8%

Gestational Diabetes
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Yes 1.1% 1.3% 4.8% 3.4%

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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%

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Preeclampsia

Yes 1.6%* 2.8%* 6.3% 7.8%

No 0.7% 1.7% 3.9% 4.4%*

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p < 0.05; p < 0.001

BE = Base Excess

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377 Table 3. Neonatal Outcomes with a 5-minute Apgar greater than 7

Cord Blood Gas MAS RDS Sepsis NICU

Component Admission
pH 7.1 1.7%* 4.7% 0.4% 11.4%

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pH > 7.1 0.7%* 1.0% 0.2% 4.3%

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pH 7.0 1.9%* 7.6% 0.0% 28.9%

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0.7%* 1.1% 4.4%

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pH > 7.0 AN 0.2%

Base Excess 0.6% 1.1%* 0.2% 4.4%

M

> -10 mmol/L

Base Excess 1.7% 2.0%* 1.0% 8.0%

D

-10 mmol/L
TE

Base Excess 0.7% 1.1%* 0.2% 4.5%

> -12 mmol/L

EP

Base Excess 2.6% 2.9%* 1.4% 9.7%*

C

-12 mmol/L
AC

*
p < 0.05; p < 0.001

MAS = Meconium Aspiration Syndrome; RDS = Respiratory Distress Syndrome; NICU =

Neonatal Intensive Care Unit

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Sabol 21

378 Table 4. Multivariable regression results for neonatal outcomes in neonates with a 5 minute

379 Apgar > 7 and pH 7.0 and pH 7.1 compared pH > 7.0 and pH > 7.1

Outcomes pH 7.0 aOR 95 % CI p-value

MAS 1.47 0.20-10.72 0.699

PT
RDS 6.47 2.93-14.28 < 0.001

RI
NICU Admission 10.84 6.76-17.38 < 0.001

Outcomes pH 7.1

SC
MAS 2.43 1.30-4.53 0.005

RDS 4.60 3.10-6.84 < 0.001

Sepsis 1.67
U 0.60-4.65 0.328
AN
NICU Admission 3.68 2.81-4.82 < 0.001*
M

*
p < 0.05; p < 0.001. Regression adjusted for parity, maternal age, maternal race/ethnicity,
D

insurance type, chronic hypertension, gestational diabetes, and preeclampsia.

TE

aOR = adjusted odds ratio; CI = confidence interval; MAS = Meconium Aspiration Syndrome;

RDS = Respiratory Distress Syndrome; NICU = Neonatal Intensive Care Unit

EP

380

381
C

382
AC

383

384

385
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Sabol 22

386 Table 5. Multivariable regression results for neonatal outcomes in neonates with a 5 minute

387 Apgar greater than 7 and base excess -12 mmol/L and -10 mmol/L compared to those with a

388 base excess > -12 mmol/L and > -10 mmol/L

Outcomes aOR CI p-value

PT
BE -12 mmol/L
MAS 4.21 2.12-8.38 < 0.001

RI
RDS 2.21 1.08-4.53 0.03

Sepsis 4.72 1.85-12.05 0.001

SC
NICU Admission 2.92 1.96-4.35 < 0.001

U
Outcomes
BE -10 mmol/L
AN
MAS 2.67 1.57-4.53 < 0.001

RDS 1.40 0.811-2.43 0.225

M

Sepsis 3.13 1.56-6.25 0.001

NICU Admission 2.33 1.77-3.07 < 0.001*

D
TE

*
p < 0.05; p < 0.001. Regression adjusted for parity, maternal age, maternal race/ethnicity,

insurance type, chronic hypertension, gestational diabetes, and preeclampsia.

EP

BE = base excess; aOR = adjusted odds ratio; CI = confidence interval; MAS = Meconium

Aspiration Syndrome; RDS = Respiratory Distress Syndrome; NICU = Neonatal Intensive Care
C

Unit
AC
 ACCEPTED MANUSCRIPT
Sabol 23

Table 6. Combined impact of low pH and elevated base excess on neonatal outcomes in neonates

with a 5-minute Apgar greater than 7

No Acidemia Acidemia

PT
Outcomes pH >7.0 & pH >7.1 & pH 7.0 & pH 7.1 &

BE > -12 mmol/L BE > -10 mmol/L BE -12 mmol/L BE -10 mmol/L

RI
MAS 99.3% 99.3% 0.7% 0.7%

aOR (95% CI) --- --- 2.5 (0.3-18.6) 2.1 (0.9-5.2)

SC
RDS 98.9% 98.9% 1.1% 1.1%

6.0 (2.1-16.9) 3.4 (1.9-6.2)

U
aOR (95% CI) --- ---

0.2%*
AN
Sepsis 99.8% 99.8% 0.2%

aOR (95% CI) --- --- 2.3 (0.7-7.4)

M

NICU 95.5% 95.6% 4.5% 4.4%

Admission
--- --- 9.6 (5.2-17.8) 4.6 (3.3-6.5)
D

aOR (95% CI)

TE

*
p < 0.05; p < 0.001. Regression adjusted for parity, maternal age, maternal race/ethnicity,
EP

insurance type, chronic hypertension, gestational diabetes, and preeclampsia.

BE = base excess; aOR = adjusted odds ratio; CI = confidence interval; MAS = Meconium
C

Aspiration Syndrome; RDS = Respiratory Distress Syndrome; NICU = Neonatal Intensive Care
AC

Unit