Reference ranges for thyroid function tests in premature infants beyond the first week of life.

OBJECTIVES: To establish reference ranges for the more sensitive assays of thyrotropin and the best available assays of free thyroxine in premature infants after the first week of life. STUDY DESIGN: Free thyroxine measurements by direct equilibrium dialysis and thyrotropin measurements by third generation immunometric assay were measured in 120 healthy premature infants 25 to 36 weeks' gestation at birth and every 3 weeks until hospital discharge. Infants were stratified by postconceptional age. Differences in free thyroxine and thyrotropin levels among groups were determined by ANOVA. Correlations between hormone measurements and gestational and postnatal ages were sought by linear regression analysis. Reference ranges were determined as arithmetic (free thyroxine) and geometric (thyrotropin) mean+/-2 SD ranges. RESULTS: From 120 infants, 164 samples were obtained and grouped by postconceptional age at sampling. Free thyroxine was not different among postconceptional age groups and did not correlate with gestational or postnatal age. The free thyroxine reference range based on these data was 10 to 33 pmol/l (0.8 to 2.6 ng/dl). Thyrotropin did not correlate with gestational age. There was a clinically trivial but statistically significant (r(2)=0.03, p<0.05) correlation of thyrotropin with postnatal age. The thyrotropin reference based on these data was 0.8 to 12 mU/l. CONCLUSIONS: Free thyroxine was closely regulated in these premature infants and levels were similar to those in older children and adults, once the natal surge in thyrotropin has subsided. After the first week of life a single range for each hormone appeared appropriate for all premature infants until 40 weeks postconceptional age.

Serum free thyroxine concentration is not reduced in premature infants with respiratory distress syndrome.

OBJECTIVE: We used improved methods of assay to determine whether pituitary-thyroid function is altered in premature infants with respiratory distress syndrome (RDS) during the first week of postnatal life. METHODS: Serum free thyroxine (T4) was measured by direct equilibrium dialysis, total thyroxine (TT4) by radioimmunoassay, and thyrotropin by a sensitive immunometric assay in 90 premature infants (45 healthy control subjects and 45 with RDS) during their first week of life after 25 to 30 weeks of gestation. Infants in the RDS group received exogenous surfactant therapy. RESULTS: Free T4 and thyrotropin concentrations of infants were not significantly different between RDS and control groups. As expected, infants with RDS had significantly lower serum total T4 concentrations compared with control infants (p < 0.001). This difference was present even after stratification for gestational age (25- to 27-week group, p = 0.012; 28- to 30-week group, p = 0.002). Lower total T4 concentrations were attributable to lower T4 binding to serum proteins among infants with RDS compared with control subjects, especially in the 25- to 27-week gestation group (p = 0.0075). CONCLUSION: These data indicate that pituitary-thyroid function is not altered in premature infants with RDS. The low total T4 state in these premature infants is attributable solely to reduced serum T4 binding, as is often seen in acute nonthyroidal illnesses.

Pretransplant risk factors and causes of death or graft loss after heart transplantation during early infancy. Pediatric Heart Transplant Team, Loma Linda.

BACKGROUND: This study was performed to report causes of death or graft loss and to identify possible pretransplant risk factors for death or graft loss in infants after heart transplantation. METHODS AND RESULTS: Pretransplant risk factors were compared for 153 infants registered for heart transplantation within 90 days of life and transplanted from November 1985 to June 1994. Factors assessed were diagnosis, age at transplantation, race, weight, blood type, sex, donor/recipient blood type match, sex match, weight ratio, fetal registration, locale of pretransplant waiting period, mechanical ventilation, ischemic time, and the need for atrial septostomy or septectomy pretransplantation. No factor was associated with death or graft loss at 1 month or 1 year. Causes of death or graft loss were determined using clinical course and pathology data when available. Death or grafts lost at 1 month, 1 year, and > 1 year were 14, 13, and 15, respectively. Causes of death or graft loss expressed as a percent (at 1 month, 1 year, and > 1 year, respectively) were acute rejection (14, 23, 27), chronic rejection and posttransplant coronary disease (0, 8, 47), infectious causes (21, 15, 13), early graft failure (21, 0, 0), technical issues (21, 23, 0), chronic graft dysfunction (0, 15, 0), and miscellaneous (21, 15, 13). The graft loss rate at 1 year was significantly correlated (linear regression, r2 = .66; P < .05) with the year of transplantation. Actuarial survival in this population was 91% at 1 month, 81% at 1 year, and 73% at 3 years. CONCLUSIONS: Heart transplantation in the young infant can be performed with acceptable short-term and midterm results. Causes of death or graft loss and survival are similar to adult data. No pretransplant risk factors were identified. The experience level of the transplant team members affects survival. The diagnosis and management of rejection remain a major challenge.

Reference ranges for newer thyroid function tests in premature infants.

OBJECTIVE: To establish reference ranges for recently developed assays of thyroid function in premature infants. METHODS: We measured serum free thyroxine (T4) by direct equilibrium dialysis and serum thyrotropin by a sensitive immunometric method in 104 preterm infants (25 to 36 weeks of gestational age) during the first week of life. RESULTS: The free T4 level correlated positively with gestational age (p < 0.0001; r2 = 0.09) and differed significantly between adjacent gestational age groups (p < 0.05). Free T4 concentrations (mean +/- SD) for the 25- to 27-, 28-to 30-, 31- to 33-, and 34- to 36-week groups were 18.0 +/- 5.2, 25.7 +/- 9.0, 30.9 +/- 9.0, 36.0 +/- 10.3 pmol/L (1.4 +/- 0.4, 2.0 +/- 0.7, 2.8 +/- 0.8 ng/dl), respectively. Two reference ranges for free T4 were determined, one for 25 to 30 weeks (6.4 to 42.5 pmol/L (0.5 to 3.3 ng/dl) and one for 31 to 36 weeks (16.7 to 60.5 pmol/L (1.3 to 4.7 ng/dl)). The logarithm of the value for thyrotropin correlated positively with gestational age (p < 0.001; r2 = 0.08); one reference range of 0.5 to 29 mU/L was determined for thyrotropin. CONCLUSION: This study extends information on thyroid function of preterm infants and establishes reference ranges for this population.

Strategies for prolonged survival before heart transplantation in the neonatal intensive care unit.

From 1989 through 1992 we followed more than 200 fetuses and newborn infants referred for heart transplantation, of whom more than 140 were ultimately registered to receive a transplant. During this time, the interval before these infants underwent transplantation ranged from 1 day to 6 months. This experience left us with more questions than answers about the appropriate preoperative management of these patients. This article will focus on some of these areas of controversy. Our initial concern about the long-term management of these newborn infants was that ductal closure would be a major threat to their survival. However, our experience has proved otherwise. Although maintenance of ductal patency is a necessity for most neonatal transplantation candidates (83% have hypoplastic left-heart syndrome [HLHS] or one of its variants), the ductus has remained responsive to prostaglandin E1 (PGE1) infusion in most infants. For the rare infant whose ductus begins to close despite adequate PGE1 infusion, other innovative procedures (such as mechanical stenting of the ductus) have been devised and are currently under evaluation. Although ductal closure has not been a frequent occurrence in newborn infants awaiting heart transplantation, the variable shunting of blood through the ductus can cause significant and rapid changes in hemodynamics. This has prompted efforts to improve the balance between pulmonary and systemic vascular resistances by use of pharmacologic agents or by altering the mixture of inhaled gases. Attempts to decrease the PGE1 infusion and minimize exposure to other pulmonary vasodilators have been routine.(ABSTRACT TRUNCATED AT 250 WORDS)

Anencephaly: clinical determination of brain death and neuropathologic studies.

Twelve liveborn anencephalic infants were serially examined to determine if they would meet our clinical criteria for whole brain death within a 7-day period: Protocol 1 infants (6) received intensive care including intubation from birth; and Protocol 2 infants (6) received intensive care during the period in which death was imminent. Brain death was determined by absence of brainstem function, including loss of all cranial nerve responses and sustained apnea (PCO2 greater than 60 torr) for 48 hours with confirmation of findings by an outside consulting child neurologist. The initial examinations of these 12 infants revealed spontaneous movements and startle myoclonus (12), suck, root, and gag responses (7), increased tone (8), deep tendon reflexes (9), absent pupillary responses (9), absent oculocephalic and corneal responses (6), absent auditory/Moro responses (7), and nonvisualization of the optic nerve (8). Mild depression of neurologic function occurred during the first several days of life; subsequently, the infants' responses were easier to elicit and more sustained. Only 2 infants met the clinical criteria for brain death. Neuropathologic findings indicated that observed complex motor responses were not based upon cortical activity because no infant had a normally-formed cerebrum. Brainstem neuronal activity may have accounted for these motor responses in some patients but even at this level neurons were scanty or absent. Our findings suggest that, although rare, clinical brain death can be determined in liveborn anencephalic infants; ophthalmologic and otologic developmental abnormalities may confound examination of cranial nerve function; and absence of cortical neurons supports the widely held opinion that these infants do not experience sensation.

Experience with anencephalic infants as prospective organ donors.

Recent advances have made organ transplantation in newborns feasible, but the paucity of organs small enough for this age group remains a major limitation. Because anencephalic infants can survive for no more than a few weeks, they have been considered as possible organ donors for other infants. Under current law, however, they cannot be used as donors until their brain-stem activity ceases and the criteria for total brain death are thereby met. If anencephalic infants receive customary care, their solid organs usually undergo irreversible hypoxic injury during the process of dying and become unsuitable for donation by the time of death. We modified the medical care of 12 live-born anencephalic infants for one week to determine whether organ viability could be maintained and whether the criteria of total brain death could be met. Six received intensive care from birth, and six only when signs of imminent death developed. Only two infants met the criteria for total brain death within one week, and no solid organs were procured. Most organs were suitable for transplantation at birth. When intensive care was provided from birth, organ function was maintained; however, brain-stem activity ceased in only one infant within the first week. When intensive care was delayed until death was imminent, most organs were damaged to an extent that made them no longer suitable for transplantation. Our findings suggest that it is usually not feasible, with the restrictions of current law, to procure solid organs for transplantation from anencephalic infants.

Does gastric acid protect the preterm infant from bacteria in unheated human milk?

Although preterm mother's milk has greater nutritional and anti-infective properties than donor milk, it may be highly contaminated with bacteria. We therefore asked three questions: what is the fate of these bacteria in the preterm infant's stomach, is gastric pH important, and what factors affect gastric pH? pH, colony count and bacterial identification were performed on the milk and on serial gastric aspirates in 20 preterm infants on 25 occasions. Seventeen milk samples grew bacteria, five potentially pathogenic and 12 non-pathogenic. Twelve of 25 prefeeding gastric samples were sterile, but following the feeding all the samples grew non-pathogenic bacteria and 70% grew potential pathogens. With time pH decreased and by 2-h samples with pH less than 3.5 had no bacterial growth; Candida albicans still flourished in a low pH (mean 2.8). We concluded that a low gastric pH may be more important than the bacterial count of the milk. In a second study, 91 serial gastric pH measurements were made on 12 preterm infants. pH tended to decrease with increasing age and was significantly lower in infants fed exclusively human milk (2.7 vs. 3.6; human milk versus formula P less than 0.02) We speculate that human milk may influence gastric acid production and thus protect the preterm infant from bacteria in the milk.

Pulse oximetry--an alternative to transcutaneous PO2 in sick newborns.

In summary, the pulse oximeter provides a reliable, continuous assessment of oxygenation in newborn infants. Its rapid response time and ease of use make it a practical device for use on all sick newborns. To avoid hyperoxia it should be used in conjunction with arterial blood gas measurements and we recommend a high SaO2 alarm of 92% in infants with predominantly fetal hemoglobin. Finally, it is an improved way of monitoring oxygenation in very immature infants and in infants with bronchopulmonary dysplasia.

Noninvasive monitoring of blood gases in the newborn.

The authors review the function, reliability, risks, and clinical applications of skin surface blood gas monitoring that have become evident during the first decade of its clinical use. Also discussed is the problem of data expression and the recent developments in this area.

Head position affects intracranial pressure in newborn infants.

We studied the effects of six different head positions on intracranial pressure and cerebral blood flow velocity in six infants with a recent history of asphyxia and eight without. ICP was measured noninvasively using a transfontanel pressure transducer, and CBF was assessed using the continuous-wave Doppler method. We found that ICP was lowest with the head elevated and in the midline (P less than 0.01), and that ICP was higher in all infants in the dependent position (P less than 0.001). This increase was significantly greater in those who had had an episode of asphyxia during the 48 to 72 hours prior to the study (P less than 0.02). Therefore, we recommend a head elevation of 30 degrees in the midline in any infant with increased ICP or at high risk for cerebral injury, and caution against the use of the dependent position in these infants.