Nicholas M. Nelson

Endogenous production of carbon monoxide in normal and erythroblastotic newborn infants

The endogenous production of carbon monoxide ( V(CO)) in newborn infants was measured by serial determinations of blood carboxyhemoglobin during rebreathing in a closed system. Mean V(CO) in nine full-term infants was 13.7 +/-3.6 mul CO/kg per hr (SD), and in four erythroblastotic infants V(CO) ranged from 37 to 154 mul CO/kg per hr preceding exchange transfusion. Mean red cell life-span (MLS) and total bilirubin production were calculated from V(CO). MLS in normal newborns was 88 +/-15 days (SD), and bilirubin production was 8.5 +/-2.3 mg/kg per 24 hr. This is more than twice the amount of bilirubin normally produced in the adult per kilogram of body weight. Normal infants achieved a net excretion of bilirubin of at least 5.6 +/-2.3 mg/kg per 24 hr (SD) as calculated from the bilirubin production and the measured rise in serum bilirubin concentration.The measurement of V(CO) should prove valuable in the study of red blood cell survival and bilirubin metabolism in the newborn infant.

Changes in Umbilical-Cord Blood Oxygen Affinity after Intrauterine Transfusions for Erythroblastosis

Abstract The oxygen affinity of umbilical-cord blood was measured in 15 infants who received intrauterine transfusions (IUT) of adult blood for severe erythroblastosis fetalis (EF), seven infants with EF and various degrees of anemia who did not receive IUT, and nine infants unaffected by EF. Adult erythrocytes retained their characteristic oxygen-binding properties after a prolonged residence: 56 ± 21 days (mean ±S.D.) in the fetus. Infants who received 2 to 4 IUT had a mean P50 (half-saturation oxygen tension at pH 7.40) of 27.1 mm of mercury. Erythroblastotic infants without IUT and normal infants had a P50 of 20.8 mm of mercury. A significant correlation was observed between the oxygen affinity of blood and the percentage of fetal hemoglobin. A negative regression of P50 on total hemoglobin concentration was seen in infants with IUT but not in the others. Infants who received IUT had increased concentrations of red-cell 2,3-diphosphoglycerate (2,3-DPG). Normal fetal growth and lack of acidosis at birt...

A SIMPLE DEVICE FOR REDUCING INSENSIBLE WATER LOSS (IWL) IN LOW BIRTH WEIGHT INFANTS

IWL was measured in 5 non-distressed premature infants, 1-4 days old, by a multiple weighing technique using an electronic balance inside an incubator. The babies were studied naked before and after being covered with a transparent “thermal blanket” made from plastic packing material. Operative incubator temperature was within the thermoneutral zone and relative humidity between 25 and 40%. Consecutive three hour Δ weight measurements were made 30-60 minutes after gavage milk feeds. IWL was determined as Δ weight. Pulmonary water loss, assumed to be constant, was excluded from the calculation. Consecutive paired iWL studies:Use of the thermal blanket produced a 70% mean reduction in IWL and a net caloric saving of 27 kcal/kg/day (t=3.4; p<.01). There was minimal interference with nursing care. The results indicate that (1) the simple insulating blanket used is a highly effective means of reducing IWL, (2) the caloric saving achieved by reducing IWL and evaporative heat loss may be an important determinant of intact survival in the high-risk infant.

The effect of exchange transfusion on endogenous carbon monoxide production in erythroblastotic infants

In order to elucidate the mechanism of the “late” postexchange transfusion bilirubin rebound, we measured endogenous carbon monoxide production in infants with erythroblastosis fetalis before and after exchange transfusions. The rate of carbon monoxide production was markedly increased before the first exchange transfusion and remained elevated until two, or in one case until three, exchange transfusions had been completed. Normal rates of carbon monoxide production were found when falling levels of serum bilirubin concentration indicated that further exchange transfusions were not necessary. These findings suggest that a continued increase in heme turnover is largely responsible for the “late” bilirubin rebound which occurs after exchange transfusions.

Ventilatory Disturbance and Arterial-Alveolar N 2 Differences During Recovery from Hyaline Membrane Disease

In infants recovering from hyaline membrane disease (HMD) persistent hypoxemia has been identified which seems not to result from venoarterial shunting [ADAMSON et al., Pediatrics 44: 168, 1969] but which could be due either to pulmonary diffusing defect or to ventilation/perfusion imbalance. Since the arterial-alveolar N2 difference (aADN2) and venous-alveolar N2 difference (vADN2) are unaffected by diffusion defect or by venoarterial shunting but are increase by impairment of ventilation with respect to perfusion, we have measured vADM2 in a group of 10 normal low birth weight infants and in 4 infants convalescing from HMD. (Simultaneous comparison of vADN2 and aADN2 in seven infants revealed no significant difference.) In antoher 4 infants convalenscing from HMD the alveolar-arterial O2 difference (AaDO2) and arterial-alveolar CO2 difference (aADCO2) were also examined.Unlike the hypoxemia seen in infants with early and developing HMD (which is due to an inequality of perfusion and a persistence of venoarterial shunting), the present findings suggest that it is inequality of ventilation which is mainly responsible for persistent hypoxemia during convalescence from HMD.

FUROSEMIDE (FS) IN HYALINE MEMBRANE DISEASE (HMD)

We conducted a random blind study to assess the effect of IV FS 2 mg/kg or 5% DW in 0.25 NaCl (control) on interstitial fluid mobilization and cardiorespiratory function in 7 infants with HMD. Criteria for entry into the trial were: peripheral edema and FiO2>.4 to maintain PaO2>50 torr. Echocardiogram and multiple gas analyses were performed in the 2 hours preceding and following the treatment. Results (mean ± SD):In spite of the diuresis, measurements of dynamic skinfold thickness did not confirm mobilization of subcutaneous interstitial water. We conclude that FS has a potent diuretic effect in infants with HMD but it does not improve cardiorespiratory function acutely. This may be due to failure to mobilize pulmonary interstitial fluid in the time period tested.

CEREBRAL METABOLIC EFFECTS OF NEONATAL HYPOGLYCEMIA AND ANOXIA

To ascertain cerebral metabolic responses to hypoglycemia with superimposed hypoxia, newborn rats were given regular insulin (30 u/kg s.c.). Animals were observed for up to 2 hrs with no ill effects, inspite of blood glucose concentrations of 0.75 mM/1. When exposed to 100% N2 at 37°C, these animals survive only 1/10 as long as littermate controls with normal blood glucose levels (4.7 mM/1). Treatment of hypoglycemic rats with glucose (25 mM/kg s.c.) 30 min prior to N2 exposure prevented the anoxic vulnerability. Glycolytic intermediates & high-energy phosphate reserves (mM/kg w.w.) in brains of control (C) hypoglycemic (H) & hypoglycemic-glucose treated (H-G) animals breathing air were:The cerebral metabolic rate (CMR) was not altered by hypoglycemia & averaged 2.32 mM∼P/kg/min. Following 2.5 min of N2 exposure, the cerebral energy stores ATP & P-Cr in hypoglycemic rats were lower by 24 & 51%, respectively, compared to normoglycenic animals subjected to the same degree of anoxia. Thus, reduced anoxic resistance of hypoglycemic neonates is not primarily a function of lower brain glycogen level* or altered CMR. Endogenous cerebral glucose stores combined with continued circulating glucose (cerebrovascular perfusion) appears critical for maintaining perinatal hypoxic survival.

CALCIUM HOMEOSTASIS IN EXCHANGE TRANSFUSION

The effect of exchange transfusion (ET) on plasma ionized calcium (Ca++) was studied in 27 exchange transfusions on 19 infants using CPD blood. The addition of 0.1 g Ca gluconate per 100 ml exchanged did not prevent a fall in Ca++ in term or preterm infants (Group I). ET was then performed with 0.5 g CaCl2 (Group II) or 0.1 g CaCl2 (Group III) added to 450 ml heparinized CFD blood. In Group iI Ca++ and total Ca increased markedly during the ET, the total Ca reaching 15.5 rag/100 ml in one case. However, Ca levels were normal within 30 minutes of the end of the ET. In Group III, although Ca++ levels in the donor blood were very low (0.6±0.21 mg/100 ml) the fall in Ca++ was abolished during ET in term infants. Nevertheless, the decline in Ca++ could not be prevented in the preterm infants although total Ca increased. Mechanisms of Ca homeostasis during ET are complex and it may not be possible to achieve normal Ca++ levels without excessive elevation of total Ca. However, addition of Ca to the donor blood will prevent the fluctuation in Ca++ seen with intermittent Ca administration. In addition, it appears that in vitro titration of donor blood with CaCl2 to normocalcemic levels should not be used as a means of determining the appropriate dose of Ca in ET.

Nitrogen excretion by newborn infants during oxygen breathing

Summary 1. An average N 2 -excretion curve has been determined for infants breathing oxygen. 2. Infants excrete relatively more nitrogen during oxygen breathing than do adults. 3. The infant excretion curve for nitrogen should probably be used for correction of nitrogen-washout studies in the newborn.

THE EFFECT OF CLOTHING ON THE GROWTH OF VERY LOW BIRTHWEIGHT |[lpar]|VLBW|[rpar]| INFANTS

VLBW infants are frequently nursed naked in incubators. A plastic shield or clothing will reduce insensible water loss (IWL) radiant heat loss and caloric expenditure. We studied 6 VLBW infants (680-1300g, gestation 28-31 wks) with and without clothes to assess the effect on growth. To enter the study, infants had to have regained their birth weight and be thriving. They were nursed in servocontrolled incubators, relative humidity 25-401 and abdominal skin temperature was maintained at 36.5°C. Infants were studied for one week naked (diapers only) and one week clothed (shirts, socks, caps), the order being randomized using a balanced latin square design and each serving as his own control. Caloric intake per kg body weight was constant for each study period. Mean weight gain over one week when clothed was 157±28g (SD) versus 97±44g (SD) when naked (p<0.05). No significant differences were found in length, head circumference or skinfold thickness measured at 15 and 60 seconds using Harpenden calipers. (The Δ skinfold thickness at 15-60 seconds reflects subcutaneous interstitial water and that at 60 seconds subcutaneous fat.)These data suggest that clothing VLBW infants reduces caloric expenditure and has a significant effect on their weight gain. This gain probably represents an increase in tissue mass and not water retention.