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Year : 2014  |  Volume : 9  |  Issue : 1  |  Page : 7-10

Umbilical artery pH at birth and neurobehavioral outcome in early preterm infants: A cohort study

Department of Pediatrics, Lady Hardinge Medical College and Associated Hospitals, Neonatal Nursery, New Delhi, India

Date of Web Publication25-Apr-2014

Correspondence Address:
Bhanu Kiran Bhakhri
Department of Pediatrics, All India Institute of Medical Sciences, Virbhadra Road, Rishikesh - 249 201, Uttarakhand
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1817-1745.131470

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Objective: The objective of the following study is to determine the effect of umbilical artery pH at birth on early neurobehavioral outcome of preterm infants as assessed by Neurobehavioral Assessment of Preterm Infants (NAPI) tool. Materials and Methods: Prospective cohort study conducted at the neonatal unit in a tertiary care center in North India. Preterm neonates < 34 weeks of gestation were enrolled at birth and divided into cases (umbilical artery pH < 7.2) and controls (umbilical artery pH > 7.2). At 34 weeks postconceptional age, the motor development and vigor (MDV) and alertness and orientation (AO) domains of neurobehavior were assessed by NAPI and compared among groups. Results: Hundred preterm neonates were enrolled in the study out of which 76 (30 cases and 46 controls) were finally analyzed. The groups were comparable in terms of gestational age, mode of delivery, birth weight and requirement of resuscitative measures at birth. There was no significant difference in incidence of meningitis, intraventricular hemorrhage, jaundice and hypoxic ischemic encephalopathy among the groups; however hypoglycemia was observed more commonly among cases. The MDV score (mean ± standard deviation [SD] [95% confidence interval]) was found to be significantly lower among cases compared to controls (37.0713 ± 13.616 [32.099-42.0431] vs. 47.506 ± 14.0692 [43.367-51.655]) (P = 0.002). Similarly, lower AO scores were observed among the cases. Conclusion: A low umbilical artery pH at birth is a predictor of poor early neurobehavioral outcome in preterm neonates.

Keywords: Asphyxia, developmental delay, encephalopathy

How to cite this article:
Seth B, Datta V, Bhakhri BK. Umbilical artery pH at birth and neurobehavioral outcome in early preterm infants: A cohort study. J Pediatr Neurosci 2014;9:7-10

How to cite this URL:
Seth B, Datta V, Bhakhri BK. Umbilical artery pH at birth and neurobehavioral outcome in early preterm infants: A cohort study. J Pediatr Neurosci [serial online] 2014 [cited 2022 Jun 27];9:7-10. Available from: https://www.pediatricneurosciences.com/text.asp?2014/9/1/7/131470

   Introduction Top

During the event of birth, the severity and duration of asphyxia experienced by a preterm newborn is proportional to the magnitude of resultant brain injury and the long term neuromorbidity. [1] Umbilical cord blood acid-base status analysis is an objective way of assessing the metabolic status of an asphyxiated newborn at birth. [2] The Neurobehavioral Assessment of the Preterm Infant (NAPI) measures the developmental maturity of preterm infants. It is a reliable tool to identify lags in development, as early as 32 weeks postconceptional age (PCA), providing an opportunity for early interventions. [3]

The study intends to evaluate the relation between umbilical artery pH at birth in early preterm infants (gestational age < 34 weeks) and their neurobehavioral characteristics at 34 weeks PCA assessed by NAPI.

   Materials and Methods Top

This was a prospective cohort study performed at neonatal care unit of a tertiary care referral center in North India between May and October 2011 as a short term project under Indian Council of Medical Research. Consecutively delivered early preterm newborns with or without birth asphyxia, less than 34 completed weeks of gestational age by date of last menstrual period or first trimester ultrasonogram, admitted in neonatal care unit were enrolled in the study after informed consent from parents/guardian. Newborns with significant morbidities likely to affect the clinical course (major malformations, suspected genetic/metabolic defects, risk factors for sepsis, gestational age < 28 weeks, intrapartum trauma or exposure to opioids or magnesium sulfate) were excluded. The number of eligible subjects presenting during the specified period were enrolled for the study.

Soon after birth, 0.5 ml blood was drawn from the umbilical artery from the maternal end of cord and analyzed for pH analysis within 15 min of sampling. Subjects were divided on the basis of pH less than 7.2 (cases) or more than 7.2 (controls) 7.2. Subjects were kept admitted at least until 34 weeks PCA, as per standard care for early preterm newborns. The recorded information comprised of the antenatal (maternal morbidities, medication exposure, socio-economic status by modified Kuppuswamy's scale [4] etc.) intrapartum (birth weight, Apgar score, resuscitation details etc.,) and neonatal (morbidities, required interventions and outcome) details. For final analysis, the score for motor development and vigor (MDV) and alertness and orientation (AO) domains of neurobehavior were assessed by NAPI at 34 completed weeks of PCA. The observer conducting NAPI was kept blinded for details of subjects to minimize the potential bias.

The recorded information was entered into Excel, Microsoft, Washington 2007. The quantitative variables were depicted as mean ± SD (95% confidence interval [CI]). Unpaired Student's t and Mann-Whitney tests were used to compare continuous data and Chi-square test was used for categorical data between the groups. Null hypothesis was rejected if P < 0.05 using SPSS 16, SPSS Inc, Chicago.5. Various predictive factors for low MDV and AO score < 2 SD of the reference mean [3] were assessed using regression analysis. The study was approved by Institute Ethics Committee.

   Results Top

During the study period, 100 eligible newborns (41 cases, 59 controls) were enrolled. Subsequent to follow-up until 34 weeks PCA, the neurobehavior could be assessed only in 76 newborns (30 cases, 46 controls) secondary to requested discharges, mortality or critical illness precluding the assessment [Figure 1]. The relevant baseline antenatal and intrapartum variables were comparable among the groups [Table 1]. The mean value of umbilical artery pH among cases and controls was 7.07 ± 0.12 and 7.30 ± 0.05 respectively (P < 0.05).
Figure 1: Flow diagram depicting number of subjects in each stage of the study

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Table 1: Baseline antenatal and intrapartum variable among the groups

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The variables depicting the clinical course of newborns until final assessment at 34 weeks PCA are listed in [Table 2]. Hypoglycemia was seen significantly more frequently among cases, other recorded morbidities and requirement of interventions were similar among cases and controls.
Table 2: Clinical characteristics of cases and controls during follow-up until fi nal assessment at 34 weeks post-conceptional age

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Statistically significant difference was observed between mean MDV scores (37.0713 ± 13.616 {95% CI: 32.099-42.0431} among cases and 47.506 ± 14.0692 {43.367-51.655} among controls, P = 0.002) and AO scores (40.669 ± 17.236 {35.248-46.963} among cases against 51.060 ± 18.383 {45.640-56.482} among controls, P = 0.016) in neurobehavioral assessment by NAPI. Of the 76 newborns assessed by NAPI, low MDV score was observed in 27 and 4 had low AO score. Pathological jaundice and requirement of inotropic support, along with cord pH < 7.2, were predictive of low MDV score. Requirement of inotropic support was also predictive of low AO score.

   Discussion Top

The study indicates the potential role of low umbilical arterial pH as a predictor for neurobehavioral characteristics at 34 weeks PCA in early preterm newborns. The other predictors of neurobehavior namely pathological jaundice and requirement of inotropic support are suggested. However, the results need to be interpreted with the background of some study limitations. Due to the restricted period of enrollment, adequately powered sample could not be achieved. Of the 100 initially enrolled newborns, primary outcome could be assessed only in 76. An adequately powered study using more objective clinical and investigational marker of metabolic status at birth is likely to provide further insight into the suggested relationship.

Umbilical cord blood analysis is the most objective way to assess fetal metabolic condition at birth and promising associations have been suggested between umbilical artery pH and clinically important neonatal outcomes. [2],[5] Though there is a debate regarding exact pH cut off for defining significant acidemia, we used the cut off pH < 7.2 as it is suggested as a reasonable marker of pathological fetal acidemia. [6]

The NAPI was used to monitor the developmental progress of preterm newborns. The reliability and the developmental and clinical validity of this test have been investigated and normative data has been established. [3],[7] There is a correlation between neurobehavioral assessment by NAPI at neonatal period and Bayley Scales of Infant Development scores at 18 months. [8]

The study groups were comparable in terms of potentially confounding antenatal and intrapartum factors such as maternal hemoglobin level, mode of delivery, birth weight, gestational age and requirement of resuscitation. During the follow-up until 34 weeks PCA, no significant difference was noted among exposure to various morbidities and interventions, except for hypoglycemia, among the groups. Higher incidence of hypoglycemia among the cases is likely to be a reflection of hemodynamic and metabolic derangements in cases with umbilical artery pH < 7.2.

The controls in our study showed a significantly mature neurobehavior at 34 weeks PCA, in terms of MDV and AO scores, compared to cases. The causative association has previously been reported between cord pH at birth and the impairment of neurodevelopment during childhood. [9],[10] Our observation indicates the possibility of early diagnosis of these infants, hence the early institution of therapeutic and rehabilitative interventions. However, our results are contrary to the results of Svirko et al. demonstrating no cognitive impairment in infants with cord pH > 7.0 and Hüseman et al., stating poor predictive value of markers of perinatal acidosis for neurodevelopmental impairment in very low birth weight infants. [9],[11]

Our study suggests the factors affecting early neurobehavior. Pathological jaundice and requirement of inotropic support, along with cord pH < 7.2, were found to be associated with poor neurobehavioral maturity. Requirement of intubation, 5 min Apgar score < 5 along with cord pH < 7 has been proposed as predictors of seizures by Perlman and Risser, we could not find any reported predictive factors for early neurobehavior. [12]

In view of utilization of minimally invasive interventions to detect the neurological abnormalities at an early stage, our observations are likely to be useful for the resource poor settings in the countries facing a significant burden of perinatal asphyxia and consequent morbidities.

   Acknowledgments Top

Indian Council for Medical Research (ICMR).

   References Top

1.Low JA, Panagiotopoulos C, Derrick EJ. Newborn complications after intrapartum asphyxia with metabolic acidosis in the preterm fetus. Am J Obstet Gynecol 1995;172:805-10.  Back to cited text no. 1
2.Armstrong L, Stenson BJ. Use of umbilical cord blood gas analysis in the assessment of the newborn. Arch Dis Child Fetal Neonatal Ed 2007;92:F430-4.  Back to cited text no. 2
3.Korner AF, Constantinou J, Dimiceli S, Brown BW Jr, Thom VA. Establishing the reliability and developmental validity of a neurobehavioral assessment for preterm infants: A methodological process. Child Dev 1991;62:1200-8.  Back to cited text no. 3
4.Kumar N, Shekhar C, Kumar P, Kundu AS. Kuppuswamy′s socioeconomic status scale-updating for 2007. Indian J Pediatr 2007;74:1131-2.  Back to cited text no. 4
5.Malin GL, Morris RK, Khan KS. Strength of association between umbilical cord pH and perinatal and long term outcomes: Systematic review and meta-analysis. BMJ 2010;340:c1471.  Back to cited text no. 5
6.Kato EH, Yamada H, Matsumoto Y, Hattori S, Makinoda S, Fujimoto S. Relation between perinatal factors and outcome of very low birth weight infants. J Perinat Med 1996;24:677-86.  Back to cited text no. 6
7.Snider L, Tremblay S, Limperopoulos C, Majnemer A, Filion F, Johnston C. Construct validity of the neurobehavioral assessment of preterm infants. Phys Occup Ther Pediatr 2005;25:81-95.  Back to cited text no. 7
8.Stephens BE, Liu J, Lester B, Lagasse L, Shankaran S, Bada H, et al. Neurobehavioral assessment predicts motor outcome in preterm infants. J Pediatr 2010;156:366-71.  Back to cited text no. 8
9.Svirko E, Mellanby J, Impey L. The association between cord pH at birth and intellectual function in childhood. Early Hum Dev 2008;84:37-41.  Back to cited text no. 9
10.Dennis J, Johnson A, Mutch L, Yudkin P, Johnson P. Acid-base status at birth and neurodevelopmental outcome at four and one-half years. Am J Obstet Gynecol 1989;161:213-20.  Back to cited text no. 10
11.Hüseman D, Metze B, Walch E, Bührer C. Laboratory markers of perinatal acidosis are poor predictors of neurodevelopmental impairment in very low birth weight infants. Early Hum Dev 2011;87:677-81.  Back to cited text no. 11
12.Perlman JM, Risser R. Can asphyxiated infants at risk for neonatal seizures be rapidly identified by current high-risk markers? Pediatrics 1996;97:456-62.  Back to cited text no. 12


  [Figure 1]

  [Table 1], [Table 2]


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