Umbilical cord blood gas and lactate levels as a marker of birth asphyxia in neonates with particular reference to resource limited countries

Birth asphyxia remains an important cause of neonatal mortality and morbidity in the developing world. Babies who suffer birth asphyxia may develop cerebral palsy, learning difficulties and epilepsy. Early diagnosis and prompt placement of rehabilitative measures would help to reduce the burden of complications arising as a result of birth asphyxia. Time and again effort has been made to develop markers that would help in predicting outcome of neonates who have had an asphyxial insult. One such parameter that is now routinely being used in the developed world is the measurement of umbilical cord blood lactate level measured from blood gases. This review highlights the importance of early diagnosis of birth asphyxia and the role of umbilical cord blood lactate level in identifying babies who have had birth asphyxia in resource limited countries with a particular reference to Pakistan

Oxidative stress in perinatal asphyxia in relation to outcome.

Objective. To study the serum levels of oxidative stress markers - malondialdehyde (MDA) and protein carbonyl in babies with perinatal asphyxia and to correlate their levels with the outcome in terms of mortality and neurodevelopmental sequelae. Methods. A group of 40 term AGA (appropriate for gestational age) infants with perinatal asphyxia were selected as cases and same number of healthy babies as controls. Serum levels of oxidative stress markers - malondialdehyde and protein carbonyl were determined in cord blood and at 48 hours of life. Their levels were correlated with the outcome of perinatal asphyxia in terms of mortality and the long term neurological outcome. Results. MDA and protein carbonyl, in cord blood were significantly higher among cases (5.88±1.40 μmol/L and 1.50±0.48 nmol/mg of protein respectively) than controls (3.11±0.82 μmol/L and 0.83±0.19 nmol/mg of protein respectively). Among the cases, MDA and protein carbonyl values at 48 hours of life (7.52 ± 1.06 μmol/L and 2.91 ± 0.62 nmol/mg of protein respectively) were significantly higher than those at birth. MDA at birth and 48 hours was significantly higher among babies who had seizures than those who remained seizure free. These values were also significantly higher in babies who expired as compared to those who survived. Protein carbonyl values though higher in those who had seizures and in those who expired, were not statistically significant from controls. MDA and protein carbonyl at birth and 48 hours were higher in babies with developmental delay but the association was not statistically significant. Conclusions. In hypoxic ischemic encephalopathy (HIE), oxidative stress markers MDA and protein carbonyl are high at birth and rise further at 48 hours and the values correlate with the morbidity and mortality. Therefore, determining the serum levels of oxidative stress markers MDA and protein carbonyl will be of benefit in predicting the outcome in perinatal asphyxia.

Electrolyte status in birth asphyxia.

Objective. To study electrolyte status in asphyxiated newborns of different severity in early neonatal period and compare with controls. Methods. Sodium, potassium and total calcium levels were estimated in the serum samples of asphyxiated newborns of different severity and control group immediately after birth. Results. Mean serum sodium level was significantly lower (122.1 ± 6.0 mEq/L vs 138.8 ± 2.7 mEq/L; P < 0.001), mean serum potassium was higher (5.05 ± 0.63 mEq/L vs 4.19 ± 0.40 mEq/L; P < 0.001) and mean serum calcium level was found lower (6.85 ± 0.95 mg/dl vs 9.50 ± 0.51 mg/dl; P < 0.001) in cases than controls. Among cases, a strong positive linear correlation was found between the serum sodium, serum calcium levels and their Apgar scores, between sodium levels and total calcium levels and significant negative linear correlation between Apgar scores and serum potassium level. Conclusion. Among cases, hyponatremia and hypocalcemia developed early and simultaneously and the decrease in their serum levels was directly proportional to each other and to the degree of asphyxia. Though, mean potassium level was within the normal limit, the value was higher among cases than controls and directly proportional to asphyxia.

Evaluation of lactate dehydrogenase, creatine kinase and hepatic enzymes for the retrospective diagnosis of perinatal asphyxia among sick neonates.

It is difficult to make a retrospective diagnosis of perinatal asphyxia in symptomatic neonates delivered non-institutionally. We studied serum creatine kinase muscle-brain fraction (CK-MB), lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (SGOT) and glutamic pyruvate transaminase (SGPT) for differentiating asphyxiated (n=25) from non-asphyxiated (n=20) neonates who present with non-specific signs of sickness. CK-MB was assayed at 8 and 24 h; and LDH, SGOT and SGPT at 72 h of life. On comparing cases and controls, median 8-hr CK-MB [80 U/L vs. 26 U/L respectively, P< 0.001], median 24-hr CK-MB [33.5 U/L vs. 21.5 U/L respectively, P=0.009] and median LDH [965 U/L vs. 168 U/L respectively, P< 0.001] were higher in asphyxiated neonates. Raised LDH had 100% sensitivity, while CK-MB had 100% specificity for asphyxia. LDH had the highest area under ROC curve (0.998). We conclude that LDH at 72 hr of life is most accurate at differentiating asphyxiated from non-asphyxiated symptomatic neonates.

S100B protein related neonatal hypoxia

A participação de marcadores bioquímicos na avaliação de quadros de asfixia neonatal é cada vez mais relevante. A proteína S100B é de particular importância neste campo. O objetivo deste estudo foi procurar destacar a importância da proteína S100B na avaliação de recém-nascidos a termo com quadro de encefalopatia hipóxico-isquêmica, assim como correlacionar com outras substâncias que também participam do processo isquêmico. Foram analisados 21 casos de recém nascidos a termo que desenvolveram encefalopatia hipóxico-isquêmica no período de setembro de 2003 a outubro de 2004. Realizadas coletas no 1º e 4º dia de vida e dosadas, por método imunocitoquímico, a proteína S100B e o lactato. Observou-se correlação positiva entre as duas substâncias, assim como quando comparadas entre si nas suas respectivas dosagens, obteve-se significância estatística.

Magnesium therapy in birth asphyxia.

OBJECTIVE: Glutamate plays a critical role in the hypoxic ischaemic neuronal death. Two mechanisms of glutamate- induced neuronal death have been identified. One is rapid cell death that occurs in minutes and the second is delayed cell death that occurs over hours and is initiated principally by the activation of the N-methyl D-Aspactate (NMDA) receptor. Magnesium (Mg) is an NMDA receptor blocker. Systemic administration of Mg after a simulated hypoxic ischaemic insult has been shown to limit neuronal injury in several animal models. However, before embarking on to the use of Mg for neuronal protection in the human neonate it is important to study the safety and side effects of Mg administration. METHODS: Forty terms, appropriate for gestational age babies with severe birth asphyxia (1 min Apgar score < 3 and 5 min Apgar score < 6), were randomly assigned to either the study group or the control group. Infants in both groups were treated as per unit protocol except that babies in the study group received intravenous injection of magnesium sulphate 250 mg/kg within half an hour of birth and subsequently 125 mg/kg at 24 and 48 hours of life. RESULTS: The mean cord blood serum Mg levels were 0.78 (+/- 0.047) mmol/L in the control group and 0.779(+/-0.045) mmol/L in the study group. The serum Mg levels at 3, 6, 12, 24, 48 and 72 hours of life were 1.87(+/-0.6), 1.65(+/-0.059), 1.468 (+/-0.91), 1.881 (+/- 0.053), 1.916 (+/- 0.053) and 1.493 (+/- 0.084) mmol/L respectively in the study group. All these values were significantly higher than those obtained in the control group (p< 0.001). No significant alterations in heart rate, respiratory rate, oxygen saturation and mean arterial pressure were seen, following magnesium infusion with either 250 mg/kg or 125 mg/kg dose. The serum Mg levels in the study group ranged between 1.493 (+/- 0.084) and 1.916(+/-0.053) mmol/L, which are considered to be in the neuroprotective range. CONCLUSION: Injection MgSO4 administered in a dose of 250 mg/kg and 125 mg/kg as an intravenous infusion is safe and the Mg levels obtained are in the range considered to be neuroprotective.

Scalp stimulation benefit in predicting of fetal asphyxia

The term of fetal asphyxia is accepted when the arterial blood gases are below the 5th percentile value of a normal population: pH < 7.12 PO2 < 6.5 PCO2 > 71.2 base deficit < -10 So it is important to differentiate between fetal asphyxia and other terms like: Fetal acidosis : A pathologic condition characterized by an increased concentration of hydrogen ions in the tissues and in the blood. Fetal hypoxia : A pathologic condition characterized by a decreased concentration of oxygen in the tissue and in the blood. Fetal distress: unspecific state of fetal jeopardy that may or may not be caused by asphyxia. Clinical indicators of fetal asphyxia: 1] Meconium in the amniotic fluid. 2] Low Apgar score. 3] Bad neurologic outcome of the newborn. Biophysical indicators of fetal asphyxia: 1] Fetal heart rate monitoring. 2] FHR response to scalp stimulation. 3] FHR response to VAST. Biochemical indicators of fetal asphyxia: 1] Fetal-scalp blood gases. 2] Continuous pH measurement. 3] Infra-red light oxymetry. 4] Near infrared spectroscopy. The management of early stages of fetal asphyxia depends on intrauterine resuscitative measures, which consist of: 1] Lateral position. 2] Hydration. 3] Administration of oxygen. 4] Discontinuation of oxytocin. 5] Inhibition of uterine activity. In our research we studied 50 women at labor who have non reassuring FHR patterns and the most important results were as follows: 1-The presence of meconium in the amniotic fluid is unreliable indicator and it can not be depended on it in predicting of fetal asphyxia, only in the case of severe meconium passage with a sensitivity of 63%. 2-Late decelerations are diagnosed in 58% of cases, and variable decelerations in 38%, but the most important association is the late decelerations with elevated basal FHR with true positive of 72.7%, and true negative of 89.7%. 3-When there is no response to scalp stimulation, the fetus is acidotic or preacidotic in 88% of cases. 4-Poor response is associated in 50% of cases with acidotic or preacidotic fetus. 5-Good response is not associated with any acidotic fetus, and preacidotic fetus is seen in only 7.4% of cases, and the lowest value of pH with good response is 7.232. 6-Scalp stimulation test will suffice the evaluation in 54% of cases. 7-Patients, who are managed by waiting and observation only, have no improvement in FHR pattern, and fetal acidosis is seen in 28.6% of cases. 8-The outcome of patients, who are managed by intrauterine resuscitative measures, is better, but FSST is still the end point in the management of patient with partial improvement. -9-50% of cesarean sections, which are done primarily for nonreassuring FHR pattern, are unwarranted by fetal distress, and only 28.6% of these cesarean sections are for really acidotic fetuses. 10-The dependence on FSST as an indicator to remove to cesarean section in patients, who are managed primarily conservatively, will reduce the rate of this removing from 50% to about 20%, and the usage of fetal scalp sampling will reduce this rate to about 10% only. 11-The specificity of FSST to low P02 is 83%, whereas the sensitivity of this test will reach 73.7%. 12-We can not find any association between the severity of response to FSST and P02 value. 13-All cases of fetal hypercarbia are associated with positive FSST [the sensitivity is 73.7% but the specificity is 100%]. 14-Respiratory acidosis is associated with lower Apgar score at the first and 5th minute in comparing with metabolic acidosis. 15-The very low first minute Apgar score is associated with abnormal fetal pH values in 80% of cases, and with positive FSST in 90% of cases. 16-29.16% of newborns with Apgar score [> 7/10] at the first minute, have abnormal pH values, and 37.5% of those newborns have positive FSST. 17-All newborns with very low Apgar score at 5th minute have abnormal pH values, and positive FSST

Value of nucleated red blood cells in predicting severity and outcome of perinatal asphyxia.

The objective of the study was to assess nucleated red blood cell counts in cord blood in a group of asphyxiated infants, and to determine its predictive value for short-term outcome. A prospective case control study was undertaken on cord blood samples collected from fifty six term neonates with perinatal asphyxia and an equal number of normal appropriately matched controls for cord blood pH and nucleated RBC counts. Babies were followed up in nursery till discharge. Statistical analysis employed were ANOVA test, logistic and linear regression analysis. There was a significant increase in the number of nucleated red blood cells in cases as compared to controls. Low Apgar, cord blood pH and neonatal outcome correlated well with nucleated RBC counts. Nucleated red blood cell count at birth is a useful predictor of severity and short-term outcome of perinatal asphyxia.

Gasimetria do cordão umbilical: quando e por quê? / Umbilical cord gas: when and why?

O diagnóstico preciso de hipóxia perinatal é motivo de controvérsias na literatura. O índice de Apgar tem sido amplamente utilizado, entretanto gera conflitos quanto ao seu valor preditivo em relação ao estado neurológico fetal. Vários estudos vêm sendo desenvolvidos e preconizam a análise da gasimetria do cordão umbilical como um dado preciso e objetivo...

Effect of birth asphyxia on serum calcium levels in neonates.

Serum calcium and phosphorus levels were measured at birth, 6 hours, 24 hours, and on 5th day of life in 35 neonates with birth asphyxia (one-minute Apgar score of 6 or less), and in 37 neonates without asphyxia (one-minute Apgar score of 7 or more). Infants were divided into three groups: FT-AGA (n = 30, asphyxia = 15), FT-IUGR (n = 20, asphyxia = 10) and PT-AGA (n = 22, asphyxia = 10). Asphyxiated infants--FT-AGA as well as FT-IUGR--had significantly lower serum calcium levels than control infants during each of the time period studied. In PT-AGA infants with asphyxia, the serum calcium was significantly low only on 5th day of life. Lack of calcium intake, and hyperphosphatemia were identified as possible risk factors for low serum calcium in asphyxiated infants. No change in serum calcium levels was found in bicarbonate-treated asphyxiated infants in comparison to those who did not receive sodium bicarbonate. In view of the high incidence of low serum calcium in asphyxiated infants, serial monitoring of serum calcium levels is recommended in these infants.

Plaquetopenia en asfixia perinatal y síndrome de aspiración de meconio / Throbocytopenia in newborn babies with perinatal asphyxia and meconium aspiration syndrome

Introducción. Debido a que la plaquetopenia se presenta en 50-75 por ciento de los recién nacidos con septicemia, con frecuencia se considera a este dato como signo fundamental y casi exclusivo de infección neonatal. Sin embargo, en fecha reciente se ha demostrado su multicausalidad. El objetivo de este reporte es el presentar los niveles de plaquetas en neonatos con asfixia perinatal y síndrome de aspiración de meconio. Material y métodos. Se estudiaron tres grupos de recién nacidos a término. El grupo A con 27 niños que tuvieron asfixia perinatal; el grupo B con 26 neonatos que además tuvieron síndrome aspiración de meconio, y el C o grupo control con 53 recién nacidos sanos. Se consideró asfixia perinatal cuando el pH de la sangre obtenida de arteria umbilical fue menor a 7.10; se documentó síndrome de aspiración de meconio en base clínico-radiológica; se consideró trombocitopenia a la cuenta de plaquetas menor a 150,000/mm3. A todos los niños se les cuantificó plaquetas en las primeras 24, a las 48 y 72 h del nacimiento. Los resultados se evaluaron con las pruebas de ANOVA, t de Student, chi cuadrado o de probabilidad exacta de Fisher. Resultados. Los tres grupos tuvieron características generales similares. El Apgar al minuto fue de 4.0ñ1.4, 3.4ñ1.8 y 8.1ñ0.5 respectivamente, con diferencia significativa de los primeros con el tercer grupo. La incidencia de plaquetopenia fue del 44.4, 57.7 y 5.7 por ciento en el primer día; se presentó en 25.9, 32 y 0 por ciento en el segundo día y del 11.5, 19 y 0 por ciento en el tercer día, con diferencia significativa en las tres determinaciones, de los dos primeros grupos con el tercero. Conclusiones. Con los hallazgos se confirma la hipotesis de que la asfixia perinatal se asocia con plaquetopenia, y que el síndrome de aspiración de meconio no incrementa la frecuencia o intensidad del descenso de las plaquetas

Reliability of capillary blood gas estimation in neonates.

In order to compare the reliability of capillary blood gases to the arterial blood gases, we studied fifty one neonates with moderate birth asphyxia. A significant difference (p less than 0.05) was found between the capillary and the arterial blood gas values with respect to blood pH, PCO2 PO2 and oxygen saturation. However, the levels of blood bicarbonate as assessed by the 2 samples were comparable. Capillary blood gas values are unsatisfactory indicators of the arterial blood gas values and may result in inappropriate management.