Neonatal polycythemia: I. Criteria for diagnosis and treatment.

In order to better define criteria for diagnosis and treatment of neonatal polycythemia, 74 neonates with peripheral venous hematocrit levels greater than or equal to 65% were studied. The hematocrit levels of capillary (Cap Hct), peripheral venous (PV Hct), and umbilical venous (UV Hct) blood was measured. Viscosity of umbilical venous blood (UV eta) was determined. Mean +/- SE Cap Hct (75 +/- 0.5%) was significantly higher than PV Hct (71 +/- 1.0%, P less than .001) and PV Hct was higher than mean UV Hct (63 +/- 0.6%, P less than .001). Cap Hct correlated with neither PV Hct nor UV Hct, but PV Hct and UV Hct correlated moderately (r = .54, P less than .001). Of the neonates with UV Hct greater than or equal to 63%, 80% and UV eta in excess of 3 SD above the normal mean (in excess of 14.6 cps at shear rate 11.5 sec(-1)), whereas 94% of the neonates with UV Hct less than 63% had UV eta within normal range. Neonates with hyperviscosity were seen with two or more clinical symptoms more often than their peers with normal viscosity (P less than .04). Partial exchange transfusion in 21 neonates reduced mean UV Hct from 61 +/- 1.1% to 50 +/- 1.0% (P less than .001) and mean UV eta from 13.0 +/- 0.64 cps to 8.6 +/- 0.54 cps (P less than .001). These data suggest that Cap Hct and PV Hct may be used to screen neonates for polycythemia, but that the final diagnosis and therapeutic decisions should be based on UV Hct or even preferably on UV eta. They further suggest that UV Hct greater than or equal to 63% is strongly indicative of hyperviscosity and should be treated by partial exchange transfusion.

Neonatal polycythemia: II. Plasma, blood and red cell volume estimates in relation to hematocrit levels and quality of intrauterine growth.

Volumes of plasma (PV), blood (BV), and red cells (RCV) were estimated within 32 hours of birth in 39 neonates with normal growth, 14 neonates with intrauterine growth retardation, and 20 neonates with macrosomia. Total PV, BV, and RCV increased linearly with birth weight and were unaffected by deviation in the quality of fetal growth. In proportion to body weight, PV/kg, BV/kg, and RCV/kg correlated neither with birth weight nor with the quality of intrauterine growth. Neonates with umbilical vein hematocrit (UV Hct) levels 51% to 60%, 61% to 65%, and 66% to 77% had progressively lower, but not statistically different, mean PV/kg (38.1 +/- 4.49, 37.6 +/- 5.41, and 34.8 +/- 5.16 ml/kg, respectively). On the other hand, they had progressively higher mean BV/kg (90 +/- 10.1 vs 101 +/- 13.7 ml/kg, P less than .002, and vs 110 +/- 19.0 ml/kg, P less than .001). They also had progressively higher mean RCV/kg (52 +/- 7.4, 64 +/- 8.7, and 75 +/- 16.4 ml/kg, P less than .001). Although PV/kg did not correlate with UV Hct, both BV/kg and RCV/kg increased linearly with increasing UV Hct (r = .58 and r = .79, respectively). Volume estimates were repeated after partial exchange transfusion in 29 neonates. Mean UV Hct decreased from 63 +/- 5.9% preexchange to 51 +/- 5.2% postexchange (P less than .001), mean PV increased from 37.7 +/- 5.56 to 47.6 +/- 7.99 ml/kg (P less than .001) and mean RCV decreased from 67 +/- 16.5 to 51 +/- 12.3 ml/kg (P less than .001). Despite precautions to keep the partial exchange isovolemic, mean BV decreased from 105 +/- 18.7 to 98 +/- 18.0 ml/kg (P = .001) and the mean PV increase (10 ml/kg) was less than the mean RCV decrease (16 ml/kg). These data suggest that neonates with polycythemic have normal PV but their RCV and BV are elevated in direct proportion to UV Hct. "Isovolemic" partial exchange transfusion decreases UV Hct, RCV, and BV and increases PV.

Dexamethasone effects on the hospital course of infants with bronchopulmonary dysplasia who are dependent on artificial ventilation.

A randomized double-blind placebo-controlled trial was conducted to evaluate the effects of enterally administered dexamethasone on the hospital course of infants with bronchopulmonary dysplasia. A total of 23 infants with a birth weight less than 1500 g who were dependent on artificial ventilation 3 to 4 weeks of age received dexamethasone (n = 12) or saline placebo (n = 11). Dexamethasone (0.5 mg/kg per day) was given in tapering doses for 7 days followed by hydrocortisone (8 mg/kg per day) which was progressively reduced for a total of 17 days of therapy. Infants who received dexamethasone required less oxygen on days 8 and 17 (P less than .05) and were more likely to extubate 8 days after therapy than infants in the control group (respectively 8/12 vs 3/11 infants, P less than .05; P = .12 after Yates correction). The use of dexamethasone significantly shortened median duration of mechanical ventilation (4 vs 22 days, P less than .05) but had no effect on length of oxygen therapy, hospitalization, home oxygen therapy, occurrence and severity of retinopathy of prematurity, rate of growth, and mortality. No significant complications resulted from dexamethasone therapy. Measurements of plasma dexamethasone levels confirmed the absorption of drug from the gastrointestinal tract (23.7 ng/mL in dexamethasone vs 4.6 ng/mL in the control group, P less than .05). Dexamethasone administration resulted in short-term improvements in pulmonary function but did not ameliorate the hospital course of infants with bronchopulmonary dysplasia.

Maternal diabetes and neonatal macrosomia. I. Postpartum maternal hemoglobin A1c levels and neonatal hypoglycemia.

Hemoglobin A1c (HgbA1c) levels were determined within 24 hours after delivery in 88 nondiabetic and 73 diabetic women belonging to White's classes A to D. Diet-controlled gestational diabetic women had mean (+/- SE) Hgb A1c levels similar to those of nondiabetics (5.8 +/- 0.18% vs 5.7 +/- 0.08%). Mean Hgb A1c levels were higher in insulin-requiring gestational (6.4 +/- 0.20%, P less than .05) and permanent (6.5 +/- 0.27%, P less than .05) diabetics than in nondiabetics. The proportions of subjects with levels above the normal range were also larger in the insulin-requiring groups. Mean Hgb A1c levels and the proportions of abnormally high levels were similar for mothers of macrosomic and of normally grown neonates in the nondiabetic as well as in the various diabetes groups. There was no correlation between maternal Hgb A1c level and neonatal birth weight, either real or relative. There were also no statistically significant differences in mean Hgb A1c levels between mothers of neonates with or without hypoglycemia within four hours of birth. Hgb A1c measurement did not permit differentiation between those mothers of macrosomic neonates who were diabetic and those who were not. In conclusion, although Hgb A1c level has been shown to reflect diabetic control, our data suggest that it may not be reliable as an indicator of fine tuning during the third trimester of pregnancy or as a predictor of the effects of diabetes on the fetus.

Fat emulsion tolerance in very low birth weight neonates: effect on diffusion of oxygen in the lungs and on blood pH.

Forty-one very low birth weight neonates (820 to 1,510 g and 27 to 34 weeks of gestation) requiring total parenteral nutrition were randomly assigned to one of three regimens of administration of fat emulsion for a period of eight days. Groups I and II received the emulsion at a constant rate for, respectively, 24 and 16 hours, beginning with a daily dosage of 1 g/kg and increasing daily by 1 g/kg to a maximum of 4 g/kg. Group III received the emulsion at a constant rate or 4 g/kg for 24 hours. Blood pH and alveolar-arteriolar gradient of oxygen diffusion in the lungs were measured at regular intervals. The various regimens and rates of fat infusion appeared to have no deleterious effect on blood pH and alveolar-arteriolar oxygen diffusion gradient. Infusion rates as used in the study for appropriate for gestational age very low birth weight neonates appear to be safe, although caution is always warranted when dealing with tiny neonates whose pulmonary reserve is minimal. In view of data from other studies, it is suggested to infuse fat at a constant rate for 24 hours to avoid overloading the clearance mechanisms of fat particles from plasma.

Neonatal paroxysmal supraventricular tachycardia with hydrops.

A critically ill infant with paroxysmal supraventricular tachycardia and hydrops fetalis responded well to aggressive management. Care must be taken to avoid digitalis toxicity. Procaine amide or quinidine are effective alternate therapies.

Coxsackievirus group B antibodies in the ventricular fluid of infants with severe anatomic defects in the central nervous system.

Ventricular fluids from four of 28 newborn infants who were initially seen with severe congenital anatomic defects in the central nervous system contained neutralizing antibody to at least one serotype of coxsackieviruses group B. Two of the four infants with anti-coxsackieviruses group B antibody in the ventricular fluid did not have a detectable level of the same antibody(ies) in their serum. The ventricular fluid of one of the infants had immunoglobulin M neutralizing antibody directed against coxsackievirus B6. Of 11 mother-infant pairs that had neutralizing antibody to coxsackieviruses group B in both sera, nearly half had antibodies directed against more than one serotype. These data suggest the possibility of an association between congenital infections with coxsackieviruses group B and rare severe CNS defects.

Feeding the low-birthweight infant: orally or parenterally?: II. Corrected bromide space in parenterally supplemented infants.

Previously published data suggested that the faster rate of weight gain observed in parenterally supplemented neonates compared to their orally fed peers might be attributable to water retention rather than to more rapid tissue accretion. The present study was designed to test that hypothesis by observing changes in extracellular water, estimated as corrected bromide space (CBS). Ten neonates with a mean birthweight of 1,250 gm (range, 800 to 1,980 gm) and a mean gestational age of 31 weeks (range, 24 to 38 weeks) were randomly assigned to a 67 cal/dl formula feeding or an oral 100 cal/dl formula feeding supplemented parenterally with dextrose and amino acids. CBS was estimated within 19 hours of birth and between the 7th and 28th postnatal days. Mean total daily water and protein intakes during the intervening period were similar for orally fed and supplemented neonates, but the latter took significantly less orally and received more parenterally. CBS increased in all but one of the supplemented neonates whereas two of four orally fed babies had decreasing values and one had stable values. Shorter times before regaining birthweight, faster rates of weight gain, and lower arterial pH were associated with larger CBS as well as with parenteral supplementation. These data suggest that parenteral supplementation may result in water retention and/or shifts from the intracellular to the extracellular space. Previously reported earlier and greater mean daily weight gains in supplemented babies may be related to water accumulation rather than tissue accretion, but definitive conclusions must await further studies, including concomitant estimates of total and extracellular body water.

Maternal administration of vitamin K does not improve the coagulation profile of preterm infants.

The effect of maternal administration of vitamin K1 on cord blood prothrombin time, activated partial thromboplastin time, activity of factors II, VII, and X, and antigen levels of factors II and X in infants less than 35 weeks' gestation was evaluated. Pregnant women in preterm labor were randomly assigned to receive 10 mg of vitamin K1 intramuscularly or no injection. If delivery did not occur in 4 days, the dose of vitamin K1 was repeated. Women who continued their pregnancy 4 days beyond the second dose received 20 mg of vitamin K1 orally daily until the end of the 34th week of gestation. The birth weights of infants ranged from 370 to 2550 g and gestational age ranged from 22 to 34 weeks. The prothrombin time, activated partial thromboplastin time, factors II, VII, and X activity, and factors II and X antigen levels were not statistically different in either group of infants. Intraventricular hemorrhage occurred in 25 of 51 control infants and 25 of 47 vitamin K-treated infants. More control infants had grade III intraventricular hemorrhage on day 1 (P = .032), but on day 3 and 14 of life, the severity of intraventricular hemorrhage was comparable in both groups. Infants in whom an intraventricular hemorrhage developed were significantly smaller, younger, and more critically ill than infants without intraventricular hemorrhage. Administration of vitamin K1 to pregnant women at less than 35 weeks' gestation does not improve the hemostatic defects nor does it reduce the incidence or severity of intraventricular hemorrhage in their infants.

Placental transfer of vitamin K1 in preterm pregnancy.

Seventy-eight women at earlier than 35 weeks' gestation with premature rupture of membranes and/or preterm labor were randomly assigned to receive either 10 mg vitamin K1 intramuscularly (IM) or no treatment. If delivery did not occur within 4 days, the dose of vitamin K1 was repeated. Women whose pregnancies continued beyond 8 days received 20 mg of vitamin K1 orally every day until the end of the 34th week or until delivery, whichever occurred earlier. The median maternal plasma vitamin K1 level was significantly higher in treated than in untreated subjects (11.592 versus 0.102 ng/mL; P less than .001). The median cord plasma levels were 0.024 ng/mL in the treated group and 0.010 ng/mL in the controls, a significant difference (P = .046). Median plasma vitamin K1 levels were comparable in mothers receiving the drug by the IM route only and by both the IM and oral routes (10.533 versus 11.928 ng/mL; P = .460). The infants of the latter group, however, had significantly higher median cord plasma levels (0.42 versus 0.017 ng/mL; P less than .001). There was no correlation between cord plasma vitamin K1 levels and gestational age or duration of maternal supplementation with vitamin K1. We conclude that, in preterm pregnancies, vitamin K1 crosses the placenta slowly and to a limited degree.

Estimation of extracellular fluid volume by bromide dilution in infants less than 1000 grams birth weight.

We measured extracellular fluid volume by bromide dilution within 12 h of birth in 32 infants less than 1000 g birth weight. Mean (+/- S.D.) birth weight and gestational age were 763 +/- 123 g and 26 +/- 1 week, respectively. Mean extracellular fluid volume was 360 +/- 86 ml (477 +/- 107 ml/kg). These results are similar to extracellular fluid volume estimates from previous carcass analysis data. Wide variability is observed with both methods suggesting that biologic variability may be important.

Maternal diabetes and neonatal macrosomia. II. Neonatal anthropometric measurements.

Anthropometric measurements were obtained within 12 h of birth in 52 infants of non-diabetic mothers and 61 infants of diabetic mothers. Most of the diabetic patients were under good control, only ten of 61 having postpartum hemoglobin A1c levels in excess of normal. Neonates were grouped as normally-grown or macrosomic. Birthweight, crown-heel length, head circumference and skinfold thickness were measured. In each diabetes class, macrosomic neonates had larger mean length, head circumference and skinfold thickness than their normally-grown peers. At equal birthweight, neonates of gestational diabetic mothers and of non-diabetic mothers were similar in length, head circumference and skinfold thickness. Neonates of permanently insulin-requiring diabetics were similar to their non-diabetic peers in length and head circumference but had thicker skinfold thicknesses. Anthropometric measurements do not permit differentiation of the origin of neonatal macrosomia.

Maternal diabetes and neonatal macrosomia. III. Neonatal body water estimates.

Body water estimates were obtained within 12 h of birth in 52 infants of non-diabetic mothers and 61 infants of diabetic mothers. Neonates were grouped as normally-grown or macrosomic. Total body water and extracellular water were estimated from antipyrine space and corrected bromide space, respectively. Intracellular water was assumed to be the difference between total and extracellular water. Infants of diabetic mothers, whether normally-grown or macrosomic, had markedly less mean total body water than normally-grown neonates of non-diabetic mothers. No effect of neonatal macrosomia or maternal diabetes on extracellular and intracellular water estimates could be detected with the techniques used. It is suggested that changes in total body water occur as a result of excessive fat accretion during fetal life.

Biomedical technology: to use or not to use?

The past 30 years have seen tremendous advances in biomedical technology that have changed dramatically the practice of medicine in general, of neonatology in particular. All changes have not been for the best, however. The price tag has been especially steep, but there have been adverse effects on the quality of medicine as well. The reasons we rely on high technology, its risks and pitfalls, and our future handling of decisions regarding using or not using biotechnology deserve careful consideration, including financial factors that physicians have been loath traditionally to address. If the medical profession is to avoid becoming enslaved to technology, our future decisions must be better informed, more rational, and based on more scientific facts than they have been in the past. Above all, physicians must avoid becoming mere technicians at the expense of the traditional humanistic approach to patient care.

Body fluid compartments in neonates weighing 1000 grams or less.

Data on body water content and distribution in normally grown neonates weighing 500 to 1000 grams are presented, compared to data from full-term neonates, and discussed in the context of the continuum in growth from fertilized ovum to neonate at term.

Chemical dilution and clearance studies to estimate amniotic fluid volume and amniotic fluid ingestion in normal baboon pregnancies.

Amniotic fluid volume (AFV) and amniotic fluid ingestion rate (or fetal swallowing rate, FSR) were estimated by inulin and para-aminohippurate (PAH) dilution in 14 normal baboon pregnancies. Mean (± SE) AFV was significantly lower at 137-140 days of pregnancy (preterm) than at 173-178 days (term) (inulin: 326 ± 22.9 ml vs 483 ± 55.9 ml, P = 0.014; PHA:269 ± 39.4 ml vs 471 ± 39.4 ml, P = 0.002). In proportion to fetal weight, however, mean AFV was similar throughout the third trimester of pregnancy (inulin: 582 ± 40.9 ml/kg; PAH: 541 ± 39.8 ml/kg). Mean FSR was lower in preterm than in term animals when estimated by inulin dilution (587 ± 55.5 ml/day vs 784 ± 55.0 ml/day, P = 0.030) but not when estimated by PAH dilution (753 ± 65.7 ml/day vs 625 ± 50.6 ml/day). In proportion to their weights, however, preterm fetuses swallowed amniotic fluid more rapidly than term fetuses (inulin: 1,216 ± 117.6 ml/kg/day vs 840 ± 67.5 ml/kg/day, P = 0.025; PAH: 1,561 ± 142.9 ml/kg/day vs 682 ± 62.7 ml/kg/day, P < 0.001). Furthermore, our data suggest that the commonly accepted technique for estimating AFV may be based on inaccurate premises, that insulin may be a better marker than PAH to estimate AFV and FSR, and that needle aspiration of amniotic fluid does not appear to be an adequate technique to validate chemical dilution methods. Our data, however, provide estimates which indicate that the baboon is an appropriate animal model in which to seek refinements and validation of our techniques.

Advances in perinatal care: 1970--1980.

Although recognition of the neonate as an entity deserving special consideration was slow at first, the rise of perinatology to the rank of subspecialty has occurred swiftly over the last 25 years. Considerable improvements in both the quantity and quality of perinatal survival have resulted. The more significant recent advances in selected areas (hemolytic diseases, hyperbilirubinemia, maternal diabetes, hyaline membrane disease, nutrition of the tiny premature neonate, infections, monitoring and mother-child interaction) are discussed, and speculations are made about the next five years.

Amniotic fluid composition in normal baboon pregnancies.

In order to compare the chemical composition of baboon and human amniotic fluid, 70 amniotic fluid samples were obtained from 58 normal baboon pregnancies at times ranging from 88 to 178 days (term, 180 days). Protein content averaged (+/- S.E.) 0.67 +/- 0.26 gm/dl, osmolality averaged 263 +/- 1.1 mOsm/kg, and pH averaged 7.74 +/- 0.034 units. These variables were not affected by length of gestation. Creatinine content increased parabolically with duration of gestation (r = 0.74; p less than 0.001). Forty percent of the samples had delta OD450 values of 0; the others had delta OD450 values ranging from 0.002 to 0.145. No decline in delta OD450 with gestational maturity was evident. These data suggest that the chemical environment of the baboon fetus is similar but not identical to that of the human fetus.

Autospec: computerized processing of the data output from a spectrophotometer in a biochemical laboratory.

Autospec was designed to acquire data output from a Beckman DU series 60 spectrophotometer and to process these data with an IBM or IBM-compatible computer. It functions in conjunction with the Beckman DU Data Capture and Lotus 1-2-3 softwares. Autospec automatically stores data produced by the spectrophotometer, determines standard curves and calculates unknown concentrations of the substance being assayed. The principal features of Autospec are simplicity of use, adaptability and flexibility, minimal intervention from the operator, standardized print-outs of all data in tabular and graphic forms, accuracy of computations, speed of operation, and ease of storage and back-up of data files.

Neonatal nutrition: an overview.

Some everyday practices in infant feeding, such as waiting eight hours after birth, have no logical or scientific foundation and their value should be reassessed. The first feeding should always be with sterile water because it is less irritating to bronchoalveolar epithelia than are dextrose solutions. Large, low-birth-weight infants present few feeding problems but require closer supervision than normal mature neonates. Optimal feeding techniques have not yet been devised for tiny preterm or ill neonates. Application of special techniques to provide these infants with even minimal caloric requirements for several days or weeks after birth should only be attempted in centers capable of providing special, around-the-clock care and meticulous monitoring of metabolic parameters.