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Byline: Adnan Halim, Abdul Wahid Hussain, Isbah Gul, Madiha Halim, Farhan Halim and Salman Ali

Keywords: Diagnostic accuracy, Neonatal birth asphyxia, Plasma lactate.


A study conducted in India has shown that the prevalence of birth asphyxia is 18.1%1. Most common cause of neonatal morbidity and mortality is birth asphyxia2. Definition of birth asphyxia is "the failure to initiate and sustain breathing at birth" by World Health Organization13. There is an estimate by World Health Organization (WHO) that about 8 to 9 million neonates suffer from the birth asphyxia annually. There is a death of around 1.2 million neonates after the birth asphyxia. There is almost same number of neonates who survive the episode of birth asphyxia, have a poor neuro-developmental outcome2,3. Birth asphyxia is a cause of about 29% of the neonatal deaths as per World Health Organization (WHO) statistics. This results to a considerable load of long term neurological disability and impairment4.

Lack of oxygen supply to the body organs is called Perinatal asphyxia which can occur immediately before, during or after delivery5. Antepartum factors result in about 20 percent of cases5,6 thirty five percent due to Intrapartum events5-7 and postnatal insults in approximately 10 percent cases whereas in 35 percent cases the cause is intrauterine growth retardation7.

A lot of problems are associated with perinatal asphyxia. These include central nervous system dysfunction, congestive heart failure, cardiogenic shock, persistent pulmonary hypertension, respiratory distress syndrome and gastro intestinal perforations8 other conditions such as prematurity and congenital anomalies can also obstruct the initiation of adequate breathing at birth and consequently oxygen supply to the body resulting in perinatal asphyxia at later stages5,6,9.

Outcome of perinatal asphyxia can be altered by timely diagnosis and resuscitation. It is vital to look for helpful predictors early in the course of the disease, preferably within the first 6 hours after birth like APGAR score, pH of the blood and plasma lactate levels10.

Predictive value of pH, and lactate for the occurrence of hypoxia was compared by Shah et al8 and the study found that the plasma lactate has sensitivity of 94% and specificity of 67%. Whereas the gold standard for diagnosis of hypoxic ischemic encephalopathy is low arterial pH along with clinical evidence of low APGAR score. This has sensitivity 96% and specificity 98%8.

This study was designed to find out the diagnostic accuracy of plasma lactate in patients of asphyxia by taking pH as gold standard. A considerable number of deaths occur along with severe disabling neurological complications because of birth asphyxia. Therefore, reliable and sensitive investigations are required to be identified to minimize the mortality and morbidity associated with birth asphyxia.


This cross-sectional validation study was conducted at the Paediatrics Department, Pak Emirates Military Hospital, Rawalpindi, a tertiary care hospital. Duration of study was six months from 05 May to 05 November 2013. Sample size was calculated using World Health Organization (WHO) Calculator by taking sensitivity of 94% and 67%, prevalence of 18.1% and precision of 6% and 10% with 9% confidence interval. Total sample size was 240 neonates. Samples were selected through non-probability purposive sampling. Neonates with APGAR score less than 3 at 1 and 5 minutes, gestational age greater than 34 weeks and birth weight greater than 2000 grams were included in the study. Whereas the neonates with life threatening congenital malformations, chromo-somal abnormalities like trisomy 13, 18 and 21, congenital hydrocephalus, trauma like cephalo-hematoma, sub aponeurotic hemorrhage and caput succedaneum, Pulmonary disease like respiratory distress syndrome were excluded from the study.

Study was commenced after taking informed consent from parents of neonates. Information regarding gestational age, prenatal history and birth history was obtained from the parents. Plasma lactate and pH of the neonates were sent to Armed Forces Institute of Pathology (AFIP), Rawalpindi in heparinized sample bottles along with ice packs. The samples were stored at 0AoC to -2AoC. Tests were analyzed within six hours of delivery via IGI - 13100 Philips gas analyzer and were reported by a classified pathologist.


True positive (a)###False positive (b)

False Negative (c)###True Negative (d)

###+###Plasma Lactate###-

Data was entered in predesigned structured proforma. Data was analyzed by statistical software version SPSS version 18. Quantitative data like gestational age and baby's weight was analyzed by calculating mean and standard deviation. Qualitative data like sex, and true positive cases was analyzed by calculating frequency and percentages. 2x2 tables was prepared to find out the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of plasma lactate by taking pH as gold standard. Birth asphyxia was confirmed by blood pH to be less than 7. A plasma lactate concentration higher than 3.6 mmol/L within first 6 hours of delivery was considered as increased lactate levels whereas level below 3.6 mmol/l were considered normal. The percentage of patients with increased lactate levels and acidic Ph were taken as true positive cases. The percentage of patients with normal plasma lactate levels and normal pH were taken as true negative.

The percentage of patient diagnosed as having birth asphyxia by increased level of plasma lactate and normal pH were taken as false positive cases. Whereas the false negative cases were the percentage of patients having birth asphyxia diagnosed on normal levels of plasma lactate and acidic pH. Data was expressed by using tables.

Table-I: Gestational age, gender distribution and mean weight of neonates (n=240).

Age(in weeks)###No. of patients###Percentage

(37.75 +- 2.91)



Gender Distribution




Mean Weight(grams)###2350.238###161.73

Table-II: Diagnostic accuracy of plasma lactate in neonatal birth asphyxia by taking pH as gold standard (n=240).

###Gold standard

Plasma lactate###Birth asphyxia(pH###Birth asphyxia(pH###Total


Increased###True positive(a)###False positive(b)###a+b


Normal###False negative(c)###True negative(d)###c+d





A total of 240 cases fulfilling the inclusion and exclusion criteria were enrolled in the study to determine the diagnostic accuracy of plasma lactate in neonatal birth asphyxia by taking pH as gold standard.

Mean Gestational age of the subjects was 37.75 +- 2.91 weeks, 52.5% (n=126) of neonates were between 34-37 weeks while 47.5% (n=114) neonates were between 38-40 weeks of gestation (table-I). Mean weight of the neonates was 2350.238 +- 161.73 grams. Gender distribution among neonates shows that 58.75% (n=141) males and 41.25% (n=99) females (table-I).

Diagnostic accuracy of plasma lactate in neonatal birth asphyxia by taking pH as gold standard was calculated, where True positive were noted as 194 (80.83%), false positive 7 (2.92%), true negative 31 (12.92%) and false negative were 8 (3.33%), whereas sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate were calculated as 81.58%, 96.52%, 81.58% and 93.75% respectively (table-II).


Birth asphyxia is a global problem for the neonatologists. It leads to serious sequelae with regards to neonatal mortality and morbidity12. Social, educational and economical standards of a community are reflected by its perinatal and neonatal mortality and birth asphyxia is a leading cause of this. 98% of approximately one million neonatal deaths occurring due to birth asphyxia are reported from the low and low middle income countries (LMIC)15. There are varying effects of birth asphyxia on the neonatal brain. This depends upon the gestational age of the baby and the severity and time of onset of the asphyxiating event(s). The asphyxiating event can occur at any point in the infant's antepartum, intrapartum and postpartum life. Various neuro-developmental outcomes develop in neonates surviving the birth asphyxia like learning problems, intellectual disability and cerebral palsy16-18.

Forty one million disability adjusted life years are caused by birth asphyxia making this as one of the top causes of neonatal morbidity and mortality in the low middle income countries. Neonatal asphyxia requires immediate resuscitation at birth. About 6-10 percent of all neonates require some sort of intervention to initiate and establish normal breathing. Neonatal mortality and morbidity can be decreased effective by timely apprehending and managing the neonatal birth asphyxia and initiating the resuscitation timely and effectively. As the survivors who survive the birth asphyxia live with some sort of disability. These children add a considerable burden on the health care system in a resource deficient countries. They also have low quality of life of the survivor neonates. Although, hypoxicischemic encephalopathy (HIE) is the hallmark of severe asphyxia, such cases can often exhibit multisystem failure involving the heart, kidneys and gastrointestinal systems.

This in itself may pose difficult problems whereby optimal treatment of one system, e.g., volume expansion, may adversely affect another, e.g. acute renal failure.

This study was planned to find out the diagnostic accuracy of plasma lactate in patients of asphyxia by taking pH as gold standard. Birth asphyxia leads to a significant number of deaths and severe neurological complications. Therefore, reliable and sensitive investigations are required to be identified to minimize the mortality and morbidity associated with birth asphyxia.

Our findings are close to the findings of Shah et al9 who compared the predictive value of pH, and lactate for the occurrence of hypoxia and found the sensitivity of 94% and specificity of 67% of plasma lactate.

It was predicted in a study that in neonates with severe hypoxemia requiring extracorporeal membrane oxygenation, plasma lactate values above 15 mmol/l lead to death by Cheung et al11. It was also recently recognized that plasma lactate values above 15 mmol/l predict unfavor-able developmental outcome in survivors with severe hypoxemia11. This has shown the impor-tance of plasma lactate in predicting birth asphyxia and its prognosis; however, the levels of plasma lactate were not used to predict the neonatal mortality.

There is very limited data available analyzing diagnostic accuracy of plasma lactate in neonatal birth asphyxia. There is requirement of further studies to authenticate the findings of current study, so that the morbidity may be identified to minimize the mortality and morbidity associated with birth asphyxia.


The study concluded about a higher diagnostic accuracy of plasma lactate by taking pH as gold standard for the diagnosis of neonatal birth asphyxia. But to establish these findings on a solid ground a larger multi-centric study is needed.


We acknowledge the support of pathologists of AFIP for their support in test contributing.


This study has no conflict of interest to be declared by any author.


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Publication:Pakistan Armed Forces Medical Journal
Date:Feb 28, 2019

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