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Relative Value of Markers of Birth Asphyxia in Infants Developing Hyposic-Ischemic Encephalopathy (HIE)

Background: Previous etiologic studies have defined intrauterine growth retardation (IUGR) based on a single cut-off (usually

With parental informed consent 38 of 49 infants of 22-24 weeks have been treated intensively at our institution during 1990-94. Of the 49, 17 (35%) survived. Mean weights were 650g (survivors) and 539g (deaths). Survival rates were higher at 24 than 22 weeks (53% vs 23%), with higher Apgar scores (53% vs 16%), and when a full course of steroids was given (63% vs 21%). Survival was not influenced by route of delivery, nor by infant sex.

Extract: Acid-base balance in blood and hydrogen ion, phosphorus concentrations, and acid-base excretion in urine were measured in 10 infants with respiratory distress syndrome (RDS), in 8 control full term infants, and in 7 control premature infants on days 1, 2, and 3 of life. Infants with RDS were acidemic in comparison with full term and premature control infants. Hydrogen ion concentrations in urine were similar for premature control subjects and acidemic infants with RDS but lower in comparison with those of full term control infants. The inability of infants with RDS, in the face of acidemia, to create an appreciable urine to plasma hydrogen ion concentration gradient provided evidence for a renal tubular deficiency in hydrogen ion secretion. Phosphate levels in urine and, as a result, titratable acid were usually low in the three groups of infants. Relative phosphaturia did occur in some infants with RDS, but, because of the deficiency in hydrogen ion secretion, urinary phosphate was often not utilized as titratable acid. At high urinary concentrations of hydrogen ion (above 400 μmEq/liter), control premature infants and acidemic infants with RDS excreted urine having lower ammonium concentration than that found in control full term infants. The inability of infants with RDS with acidemia to excrete ammonium when hydrogen ion concentrations in urine were high was evidence of a renal tubular deficiency in ammonia production. Infants with RDS differed from control premature infants by having high hydrogen ion and bicarbonate concentrations in blood in relation to higher blood PCO2 values. In addition, at low hydrogen ion concentrations in urine, infants with RDS excreted urine that contained higher concentrations of bicarbonate than that found in control premature infants. Because infants with RDS did not excrete ammonium, they could not compensate for the increased acid load and bicarbonate excretion associated with respiratory acidemia. In addition, they could not compensate for the low titratable acid, which resulted from decreased excretion of phosphate, characteristic of the newborn period. Infants with RDS did not respond to acidemia by increasing net acid excretion in urine beyond that excreted by control infants. Indeed, some infants with RDS inappropriately excreted base, thereby aggravating their already existing acidemia. Speculation: Low gestational and postnatal age is the likely etiologic factor responsible for the decreased capacity for urinary acid excretion seen in infants with RDS. The apparent improvement in renal tubula hydrogen ion secretion with increasing gestational age may be associated with maturation of an enzyme system such as carbonic anhydrase. Likewise, the apparent improvement in renal tubular ammonia production with increasing gestational age may occur in relation to maturation of an enzyme system such as glutaminase.

This therapeutic trial of rapid alkali therapy immediately after birth was initiated because of 1. the observation that prognosis in respiratory distress syndrome (RDS) is worse the longer that acidosis persists, as well as 2. the recently proposed hypothesis that the pathogenesis of RDS may be pulmonary hypoperfusion caused by hypoxemia and acidosis. From 1960–1964, and again in 1966, consecutively delivered infants with RDS were treated with slow drip infusions of sodium bicarbonate (5–15 mEq/100 ml 10 % G/W, at 65 ml/kg/day until capillary pH rose to 7.35 (Pediat. Clin. N. Amer. 8: 525 [1961]). In 1965 a trial of rapid correction of acidosis was made in which pH was corrected up to 7.35 within 3 h of birth, using a solution of 20 mEq Na bicarb/100 ml 10% G/W. The rates of flow ranged from 10–50 ml/kg/3 h. Other than rapidity of alkali administration, therapy was similar to that used before and after. Mortality in RDS infants weighing 1001–2500 g was 61 out of 257 (23.7 %) with slow correction, and 16 out of 41 infants (39.0 %) with rapid correction (P < 0.05). (SPR)

The role of placental transfusion in the development of RDS is still in dispute. Red cell volume is closely related to placental transfusion in prematures with 32 ± 3 ml/kg beign found after immediate and 48 ± 6 ml/kg after 5 min delayed cord clamping. In order to determine whether the degree of placental transfusion was related to the incidence or severity of RDS, red cell volume was measured at age 4 hours in 262 premature infants by I125 albumin and venous hematocrit × 0.87 to obtain total body hematocrit. Red cell volumes averaged 39.7 ml/kg in unaffected premature infants and 37.1 ml/kg in those with RDS (PO.O2). RDS survivors had a higher red cell volume (37.7 ml/kg) than fatal cases (33.8 ml/kg). The 87 infants with the samlest red cell volumes (mean 30.1 ml/kg) had a 10.3% risk of death from RDS: the 88 with intermediate red cell volume (38.0 ml/kg) had a 5.7% risk, and the 87 with the largest red cell volumes (47.9 ml/kg) had only a 2.3% risk of death from RDS, even though the birthweights and gestational ages of the three groups were identical. From this data, a placental transfusion seems to greatly reduce the risk of death from respiratory distress syndrome.

Oxygen therapy for RDS may improve the course of the syndrome by increasing pulmonary perfusion, improving myocardial, renal and cerebral function, and by preventing lactic acidosis. Conversely, it may aggravate the disease by pulmonary toxicity. In an attempt to assess the balance between benefits and risk, oxygen therapy for RDS was given during the first 72 h of life according to liberal indications in 75 infants (for PaO2 below 80 or PcapO2 below 55 mm Hg), and according to more restricted indications in 75 others (for PaO2 below 40 or PcapO2 below 35 mm Hg). The 2 groups were well matched and had a similar severity of RDS at 1 h of age. Concentrations of oxygen exceeding 60% ambient were required in 50% of liberal and 10% of restricted oxygen cases. Mortality was similar among the 45 infants weighing 500–1,250 g (68% liberal vs. 69% restricted). Infants weighing more than 1,250 g had a higher mortality when treated with liberal than with restricted oxygen (2% of 51 vs. 9% of 54). The liberal group developed more severe respiratory distress, more rales, faster respirations and more severe x-ray changes. Their pCO2 and lactic acid rose to higher levels and they required 30% more bicarbonate to maintain a blood pH of 7.35. Liberal oxygen as defined therefore, conferred no apparent benefit and caused significant pulmonary oxygen toxicity.