Perinatal serum bone Gla-protein and vitamin D metabolites in preterm and fullterm neonates

Whether the hypocalcemia often found in premature neonates results from an adaptation to extrauterine life or an expression of imbalanced mineral homeostasis has yet to be established. We compared serum levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D [1,25-(OH)2D], and bone Gla-protein (BGP), a specific marker of bone formation during the first month of life in fullterm and preterm neonates. Measurements were performed in cord blood and on days 1, 5, and 30 of life. In maternal blood, mean serum 1,25-(OH)2D concentrations were higher in the mothers of premature than in those of fullterm neonates, and serum BGP concentrations were lower than those in nonpregnant women. In cord blood mean serum BGP levels were 2-3 times higher than in adults. Serum BGP increased significantly on days 5 and 30 in fullterm infants. In preterm infants, and increase was found only on day 30. Mean serum 25-hydroxyvitamin D and 1,25-(OH)2D concentrations were lower in neonates than in mothers, but not different in fullterm and preterm neonates. In fullterm infants serum 1,25-(OH)2D increased rapidly from birth to day 5 and decreased on day 30. The pattern was similar in preterm infants, but 1,25-(OH)2D was higher than in fullterm infants on day 30. No sustained correlation between serum BGP and 1,25-(OH)2D levels was found. These data support the contention that changes in 1,25-(OH)2D reflect the perinatal equilibration of calcium homeostasis. Serum BGP may be a potential marker of bone growth in premature neonates.     

Thyroid function modulates thymic endocrine activity

The thymus produces humoral factors that induce proliferation and differentiation of T-cells, which are responsible for cell-mediated immunity. Recent data in animals suggest that such thymic hormone activity is modulated by the neuroendocrine network and, in particular, by thyroid hormones, but no information is presently available in humans. To study this question, we measured the circulating thymic factor called thymulin (Zn-FTS) in hyperthyroid and hypothyroid patients. Thymulin levels were higher in hyperthyroid patients than in normal subjects, whereas hypothyroid patients had lower thymulin levels than normal subjects. A significant correlation was found between circulating thymulin and serum T4 and T3 levels. Thymulin changes could be reversed by appropriate treatment in both groups of patients. Recent data indicate that zinc is required to confer biological activity on thymic hormone molecules. This raised the question of whether the influence of thyroid status on thymulin activity could be mediated by changes in serum zinc concentrations. No support for such an explanation was obtained by thymulin measurements by a modified bioassay using an optimal zinc concentration in the assay system. In conclusion, thyroid status modulates thymic endocrine function in humans. Whether and to what extent such modulation is relevant to the function of the immune system remain to be established.     

The quantity of thyroid hormone in human milk is too low to influence plasma thyroid hormone levels in the very preterm infant

BACKGROUND: Thyroid hormone is crucial for brain development during foetal and neonatal life. In very preterm infants, transient low levels of plasma T4 and T3 are commonly found, a phenomenon referred to as transient hypothyroxinaemia of prematurity. We investigated whether breast milk is a substantial resource of thyroid hormone for very preterm neonates and can alleviate transient hypothyroxinaemia. Both the influence of breast feeding on plasma thyroid hormone levels and the thyroid hormone concentration in preterm human milk were studied. METHODS: Two groups were formed from the placebo group of a randomized thyroxine supplementation trial in infants born at < 30 weeks' gestational age on the basis of the mean breast milk intake during the third, fourth and fifth weeks of life. One group received more than 50% breast milk (mean breast milk intake 84%, n = 32) and the other group less than 25% breast milk (mean breast milk intake 3.3%, n = 25). Plasma thyroid hormone concentrations were compared between the two groups. Breast milk was collected from mothers of infants participating in the same trial and the thyroxine concentration in breast milk was measured with RIA after extraction. RESULTS: No significant differences were found between both groups in plasma concentrations of T4, free T4, T3, TSH, rT3 and thyroxine-binding globulin (TBG), which were measured once a week. Thyroxine concentration in breast milk ranged between 0.17 microg/l and 1.83 microg/l (mean 0.83, SD 0.3 microg/l) resulting in a maximum T4 supply of 0.3 microg/kg via ingested breast milk. In formula milk, the T4 concentration was equally low. Protease treatment did not influence the measured T4 concentrations. CONCLUSIONS: No differences in plasma thyroid hormone between breast milk-fed and formula-fed infants were found. The amount of T4 present in human milk and formula milk is too low to alter the hypothyroxinaemic state of preterm infants.     

Functional hypersomatotropism in small for gestational age (SGA) newborn infants

Basal plasma GH levels and the GH responses to an injection of 1 microgram/kg 1-44(NH2) GHRH were determined on day 3 postnatally in 5 small gestational age (SGA) twin newborns and their appropriate gestational age (AGA) co-twins, and in 10 SGA singleton newborns and 6 AGA singleton newborns. The mean basal plasma GH level was higher in the SGA than in the AGA infants but the difference was significant only for singleton newborns (p less than 0.01). The mean peak plasma GH level was markedly increased in SGA compared to AGA infants (p less than 0.05 for twins, p less than 0.01 for singletons). Twelve SGA infants re-tested at 1 month had lower basal and peak plasma GH levels (p less than 0.001 and p less than 0.01). In 21 SGA and 17 AGA infants, serum IGF-I, measured by RIA between 12 and 96 hours after birth, was significantly higher in SGA than in AGA (p less than 0.001). These results suggest that, whatever the mechanism, functional hypersomatotropism is present at day 3 in SGA infants. This hypersomatotropism may participate in the early catch-up growth process.     

Thyroid function in the preterm infant.

Thyroid gland function develops and matures during fetal life, with production of serum thyroxine (T4) concentrations beginning around 12 weeks gestation and increasing to term. Infants born prior to term have lower cord serum T4 concentrations that correlate with gestational age or birth weight. This is partially the result of lower thyroxine-binding globulin (TBG) concentrations. The cord serum free thyroxine (FT4) concentrations also correlate with gestational age, but they are not proportionately as low as the cord T4 concentration. Preterm infants have a postnatal thyrotropin (TSH) surge and rise in serum T4 and triiodothyronine (T3), which is qualitatively similar to, but quantitatively smaller than, term infants. In contrast to term infants, preterm infants often experience a fall in serum T4 and T3 in the first week of life to below birth levels. This drop appears to be the result of many factors, including nutritional problems and decreased hepatic TBG production, immaturity of hypothalamic-pituitary control of the thyroid gland, immaturity of the thyroid gland itself, and increased tissue utilization of T4. These changes are impacted by complications of prematurity, such as respiratory distress syndrome (RDS), which result in nonthyroidal illness-like changes. Again, serum FT4 seems less affected, and when measured by equilibrium dialysis may be in the normal range for age. Several studies have correlated different measures of morbidity and mortality in the preterm infant with lower serum T4 concentrations. However, as with adults, it may be that low serum T4 concentrations are a marker of the sickest preemies. Also, as with adults, this has led to speculation that T4 treatment might be beneficial in improving these complications of prematurity, in particular the neurological outcome. While some studies appear to show improvement in some facet of medical complications with T4 treatment, most show no effect. Regarding neurological outcome, the 2 best controlled trials do not show improvement in neuropsychiatric testing outcome assessed up to 2 years of age. One study, however, showed an IQ that was 18 points higher in the T4-treated subgroup less than 27 weeks gestational age. It may be that the most preterm infants, eg, those less than 27 weeks of age, are at a disadvantage compared with their intrauterine counterparts, in that they lack the maternal thyroid hormone contribution and are forced to adapt to extrauterine life before their hypothalamic-pituitary-thyroid axis is mature enough to deal with tissue thyroxine demands. Further controlled studies are needed to determine if this subgroup of infants indeed may benefit from transient thyroid hormone supplementation.     

Neuroendocrine-thymus interactions. I. In vitro modulation of thymic factor secretion by thyroid hormones

Several in vivo experimental and clinical studies suggest that the production of thymic hormones, such as thymulin (Zn-FTS), is modulated by thyroid hormones. It was not determined in these studies, however whether such modulation is exerted directly on the thymic epithelial cells which synthesize and secrete thymic hormones. In order to discriminate between direct and indirect modulation, the effect of thyroid hormones on the in vitro production of thymulin by whole thymic organ culture, as detected by the rosette inhibition assay, has been investigated. Donors of thymuses were young 6N-propyl-2 thiouracil (PTU)-treated hypothyroid Balb/c mice and normal littermates. Thymuses from hypothyroid mice were shown to produce concentrations in vitro nearly undetectable of thymic hormone, when compared to thymuses from normal mice. The in vitro addition of triiodothyronine (T3) caused a complete recovery of the thymic hormone production by thymuses from hypothyroid mice and an increased synthesis even by normal thymuses over control values. The complete blockade of in vitro thymic hormone production with cycloheximide, which inhibits mRNA and protein synthesis but not thyroid hormone permissive actions, suggests that the T3 induced increment of thymic hormone level in the supernatant is due to de novo synthesis. Furthermore, the number of thymulin-producing cells, as detected by immunofluorescence using a specific antithymulin monoclonal antibody, which is quite low in thymuses from hypothyroid mice, is completely regained after in vitro incubation with T3. These findings support the idea that the modulation of thyroid hormones on thymic endocrine activity is directly exerted at thymic level.     

Thyroid function in seventy-five healthy preterm infants thirty to thirty-five weeks of gestational age: a prospective and longitudinal study during the first year of life.

Thyroid function was evaluated in 75 healthy preterm infants, 30-35 weeks of gestational age. Serum thyrotropin (TSH), thyroxine (T(4)), triiodothyronine (T(3)), free T(4) (immunochemoluminescence) and reverse triiodothyronine (rT(3)) (radioimmunoassay) were measured in the mother and in the cord at delivery and in the preterm infants at 1 hour, 24 hours, 1 week, 3 weeks, 2 months, 4 months, 6 months, and 12 months of postnatal age. These values were compared to those of healthy full-term infants of the same postnatal age (22 at 24 hours from our hospital and from previously reported data at others times). Mean 24-hour TSH values were significantly lower (p < 0.001) in preterm than in full-term infant populations (12.38 +/- 6.13 microIU/mL versus 22.02 +/- 13.28 microIU/mL); however, all TSH values of preterm infants were in the range of the full-term values. Mean 24-hour free T(4) values were similar in preterm and full-term infants (1.88 +/- 0.46 ng/dL versus 2.01 +/- 0.54 ng/dL) and all preterm infants had free T(4) values within the range of those of full-term infants at 24 hours. Mean T(4) and T(3) values were significantly lower in preterm than in full-term neonates at 1 hour and 24 hours of age. Mean 24-hour rT(3) values were significantly higher in preterm than in full-term newborns. From 1 week onwards, all thyroid function values were in the same range in both populations. In conclusion, individual thyroid function was similar in healthy preterms and full-terms from the first 24 hours of life. Normative data in preterm infants during the first year of life applying the latest luminescence techniques currently used worldwide are reported.     

Early indicators of chronic lung disease in preterm infants with respiratory distress syndrome and their inhibition by melatonin

Improved survival from advances in neonatal care has resulted in an increased number of infants at risk for chronic lung disease (CLD). Recently, it was reported that inflammatory mediators such as interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha and IL-8 are present in higher concentrations in lung lavage from babies who develop CLD. Previously, we found that melatonin reduced the rises in proinflammatory cytokines (IL-6, IL-8 and TNF-alpha) and nitrite/nitrate levels in the serum of preterm newborns with respiratory distress syndrome (RDS). The values correlated with gestational age and iatrogenic trauma in the form of oxygen exposure and mechanical ventilation. Increased concentrations of proinflammatory cytokines may, therefore, be the most valuable early indicator of developing CLD and these measurements may assist in selecting infants for interventions such as melatonin treatment or more selective blockage of components of inflammation. In the current study, we extend the original observations and report results in which 120 newborns diagnosed with RDS were either treated with melatonin (60 children) or given placebo (60 children). The cytokine measures were consistent with the previously reported findings and showed that melatonin reduced these values and also lowered nitrite/nitrate levels in serum of newborns with respiratory distress. Furthermore, when nonmelatonin-treated newborns who developed CLD (eight infants) were examined separately, they had levels of IL-6, IL-8, TNF-alpha and nitrite/nitrate values much higher than those in children who did not develop CLD. Two of the nonmelatonin-treated newborns died while no children who received melatonin died. Melatonin was well tolerated by the newborns.     

Changes in plasma thyroid hormone levels after a single dose of triiodothyronine in premature infants of less than 30 weeks gestational age

OBJECTIVE: Evaluation of thyroid hormone response to a single administration of triiodothyronine (T3) early postnatally to premature infants of <30 weeks gestational age. DESIGN: A prospective clinical trial with historical control. METHODS: Ten infants born <28 weeks gestational age and ten infants born between 28 and 30 weeks gestational age were given 0.5 microg/kg T3 intravenously at 12 h after birth. The infants <28 weeks gestational age were also treated with thyroxine (T4; 8 microg/kg, once daily) during the first 6 weeks of life. Premature infants from a previous trial served as a matched historical control group. Analysis of variance for repeated measurements was performed. RESULTS: For the infants <28-30 weeks gestational age mean plasma T3 concentrations were significantly higher in the T3-treated group (P=0.027) for at least 2 weeks, whereas mean plasma levels of T4, free T4 and TSH were comparable. For the infants <28 weeks gestational age plasma T3 levels were also significantly different after correction for gestational age (P=0.0002), with either comparable or higher values in the T3-treated infants up to 56 days after injection of T3. Mean plasma free T4 levels were lower during the first 3 days and higher or comparable thereafter (P=0.0014), and TSH suppression was more evident in the T3-treated infants (P=0.003). CONCLUSION: A single administration of T3 to premature infants <30 weeks gestational age early postnatally results in a sustained increase of plasma T3 levels during the first weeks of life. In infants of 28-30 weeks gestational age this occurs without change in plasma free T4 levels, whereas in infants <28 weeks gestational age a transient decrease of plasma free T4 was present. The increase in plasma T3 is possibly caused by a T3-induced increase of type I deiodinase activity.     

Cord blood leptin concentrations in relation to intrauterine growth

OBJECTIVE: Leptin, a hormone that signals the amount of energy stores to the brain, has recently been shown to play a role in the regulation of several hypothalamic pituitary axes, including the growth hormone axis. To investigate a potential association between cord blood leptin concentrations and intrauterine growth we measured leptin concentrations in the cord blood of small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA) healthy newborns. PATIENTS AND MEASUREMENTS: Cord blood leptin concentrations were evaluated in 25 SGA, 100 AGA, and 45 LGA, neonates. RESULTS: Leptin was detectable in all newborns in concentrations comparable with those found in adults. Moreover, SGA newborns had lower leptin concentrations (3.70 +/- 1.81 micrograms/l) than AGA (5.65 +/- 4.98 micrograms/l) and LGA newborns (11.99 +/- 7.06 micrograms/ l)(P < 0.01). Cord blood leptin concentrations were significantly associated with ponderal index, cord blood insulin concentrations, placental weight and maternal serum leptin concentrations. Importantly, the association between cord blood leptin concentrations and intrauterine growth status persisted after adjusting for adiposity, placental weight, maternal serum leptin concentrations and cord blood insulin concentrations. CONCLUSIONS: Cord blood leptin concentrations are independently associated with intrauterine growth. Future studies are needed to elucidate the underlying mechanism and clarify the role of leptin in regulating growth and controlling appetite in newborns.     

Serum adrenal steroid concentrations in premature infants

To evaluate serum adrenal steroid concentrations in preterm infants, 17-hydroxyprogesterone (17-OHP), 17-hydroxypregnenolone, 11-deoxycortisol, cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate, androstenedione, 18-hydroxycorticosterone, and aldosterone values were determined in 9 sick and 13 healthy premature infants. Serum steroid concentrations were compared to previously reported data from healthy full-term infants. 17-OHP, 11-deoxycortisol, and aldosterone values were higher in sick preterm infants than in healthy preterm infants. Compared to healthy full-term infants, the premature infants-had significantly higher 17-hydroxypregnenolone, 17-OHP, and DHEA sulfate concentrations. Cortisol values were not different between the sick and healthy preterm infants and were similar to full-term values. Aldosterone values were also similar between the premature and the full-term infants. The findings of elevated steroid precursors in preterm infants and low cortisol levels in stressed sick preterm infants may indicate a relative immaturity of adrenal enzyme activity and inadequate adrenal reserve for stress.     

Vascular endothelial growth factor in preterm infants with respiratory distress syndrome

Respiratory distress syndrome (RDS) secondary to surfactant deficiency is a common cause of morbidity and mortality in premature infants. Increasing evidence suggests that vascular endothelial growth factor (VEGF) may contribute to surfactant secretion and pulmonary maturation. However, differences in cord blood VEGF concentrations in infants with and without respiratory distress syndrome have not been reported. We hypothesized that premature infants with higher VEGF levels in cord blood had a lower risk of developing RDS. Cord blood samples were obtained from preterm infants born at 32 weeks of gestation or earlier. Infants were excluded if there was evidence of prenatal maternal infection or any infection within the first 3 days of life. Cord blood VEGF levels were measured using an enzyme-linked immunosorbent assay (ELISA). We found that neonates with clinically diagnosed RDS had a lower gestational age (GA), lower birth weight (BW), higher incidence of mechanical ventilation requirements, longer duration of mechanical ventilation, and lower Apgar scores at 1 and 5 min. Infants with RDS had significantly lower cord blood VEGF levels. GA, BW, premature rupture of membranes (PROM), and antenatal steroid treatment were not associated with changes in cord blood VEGF levels. The specificity of cord blood VEGF above 34 pg/ml for predicting the absence of RDS was 86%, the sensitivity was 53%, the positive predictive value was 84%, and the negative predictive value was 56%. Our data demonstrated that cord blood VEGF elevation was significantly correlated with an absence of RDS.     

Transient cholestasis in newborn infants with perinatal asphyxia.

In asphyxiated newborn infants, cholestasis often leads to extensive investigations and a cause can rarely be found. OBJECTIVE: To assess the frequency of transient neonatal cholestasis in an unselected group of asphyxiated newborn infants in a mother-child centre. METHOD: Charts of 181 asphyxiated newborn infants born with appropriate birth weight for gestational age (AGA) or small weight for gestational age (SGA) at Sainte-Justine Hospital, Montreal, Quebec between 1989 and 1993 were reviewed. RESULTS: Transient neonatal cholestasis was found in 8.5% of asphyxiated AGA and 33% of SGA newborn infants, compared with 3.94% cholestasis of any etiology in nonasphyxiated SGA infants. Asphyxiated neonates born before the age of 35 weeks had an increased risk for transient neonatal cholestasis (odds ratio 2.84, CI 1.0-8.1) CONCLUSION: Transient neonatal cholestasis is associated with several contributing factors related to the severity of the neonatal distress. Asphyxia is frequently accompanied by cholestasis in this group of newborns and without symptoms other than uncomplicated cholestasis. Investigations should be focussed on conditions requiring immediate therapy.     

Opsonic defense to Staphylococcus epidermidis in the premature neonate

The determinants of opsonic defense to Staphylococcus epidermidis were studied in 47 premature newborns. Opsonic activity for S. epidermidis in serum from premature newborns proved to be proportional to gestational age (r = .664, P less than .001). The level of IgG antibodies to staphylococcal peptidoglycan in neonatal sera was similarly proportional to gestational age (r = .604, P less than .001). However, all opsonic activity of premature neonatal serum proved to be heat labile, i.e., dependent on activation of complement. Thus, no heat-stable, IgG-dependent opsonic activity to S. epidermidis was detected in any of the preterm sera, despite the presence of IgG antibodies to peptidoglycan. Further studies with purified IgG isolated from paired sera from term neonates and their mothers revealed that at similar concentrations the opsonic activity to S. epidermidis of neonatal, transplacentally derived IgG was only 26% of the activity of maternal IgG, a finding that may explain the absence of heat-stable opsonic activity in preterm newborns.     

Quantitation of urinary somatomedin-C and growth hormone in preterm and fullterm infants and normal children

Urinary GH and somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) excretion were measured in 12-h urine collections obtained from 43 infants (27 stable preterm infants and 16 healthy fullterm infants) and 31 normal children, aged 3-17 yr. Urinary Sm-C/IGF-I was excreted as the free hormone, since no binding of radiolabeled Sm-C/IGF-I to any urine protein with a mol wt similar to those described for plasma Sm-C/IGF-I-binding proteins was found. The preterm infants excreted significantly more urinary GH [13.5 +/- 2.1 (+/- SE) ng/kg.12 h] than either the fullterm infants (5.3 +/- 1.6 ng/kg.12h) or the children (0.27 +/- 0.02 ng/kg.12 h; P less than 0.01). The mean urinary Sm-C/IGF-I excretion in the preterm infants (98.9 +/- 7.5 mU/kg.12 h) was comparable to that in fullterm infants (87.6 +/- 9.7 mU/kg.12 h); both groups excreted significantly more urinary Sm-C/IGF-I than children (28.4 +/- 2.1 mU/kg.12 h; P less than 0.01). The group differences were similar when the results were expressed in terms of creatinine excretion. Urinary GH excretion correlated positively with urinary Sm-C/IGF-I excretion (r = 0.68). The higher output of these peptides in rapidly growing infants and their positive correlation in urine provide additional support for the Sm hypothesis.     

Relationship between serum erythropoietin levels and rT3, T4 concentrations in elderly patients with non-thyroidal illnesses

Thyroid function, plasma erythropoietin and tumor necrosis factor (TNF-alpha) concentrations were measured in 28 elderly patients with chronic non-thyroidal illnesses (NTI) and in 8 healthy subjects as a control group. In the NTI group, the existence of an impairment of thyroid function has been demonstrated in about 85% of the subjects, with a lower T(3) concentration; a low T(3) syndrome with low T(3) levels and high reverse-T(3) (rT(3)) plasma concentrations could be found in 25% of the subjects. A direct correlation between erythropoietin and rT(3) and an inverse correlation between erythropoietin and T(4) were found on NTI patients with endocrine abnormalities.     

Variation of serum ferritin in low birth weight infants with maternal ferritin, birth weight and gestational age.

Serum ferritin measured at birth in 69 low birth weight infants proved to vary with gestational age as well as with weight. The increase with gestational age was even more striking when the infants small for gestational age were excluded. The relation between maternal and infant serum ferritin concentration was investigated for 2 groups of infants and their mothers (*preterm and term infants, respectively). Neither in preterm nor in term infants was the serum ferritin found to vary with that in the respective mothers.     

Development of the human coagulation system in the healthy premature infant

This study was designed to determine the postnatal development of the human coagulation system in the healthy premature infant. Consecutive mothers of healthy premature infants born at either St Joseph's Hospital or McMaster University Medical Centre in Hamilton were asked for consent. One hundred thirty-seven premature infants (30 to 36 weeks of gestational age) entered the study. The premature infants did not have any major health problems and did not require ventilation or supplemental oxygen. Demographic information and a 20-mL blood sample were obtained in the postnatal period on days 1, 5, 30, 90, and 180. Between 40 and 96 premature infants were studied on each day for each of the following tests: prothrombin time, activated partial thromboplastin time, thrombin clotting time, plasminogen; 13 factor assays [fibrinogen, II, V, VII, VIII, IX, X, XI, XII, XIII, high-mol-wt kininogen (HMWK), prekallikrein (PK), von Willebrand factor (vWF)] and eight inhibitors [antithrombin III (AT-III), heparin cofactor II, alpha 2-antiplasmin, alpha 2-macroglobulin, alpha 1-antitrypsin, C1 esterase inhibitor, protein C (PC), and protein S (PS)]. A combination of biologic and immunologic assays were used. Between 30 to 36 weeks there was a minimal effect of gestational age for levels of AT-III, PC, and factors II and X only; therefore, the entire data set was used to generate reference ranges for these components of the coagulation system for premature infants. Next, the results for the premature infants were compared with those of a previously published study in 118 fullterm infants and with those for adults. An effect of gestational age was shown for plasminogen, fibrinogen, factors II, V, VIII, IX, XI, XII, HMWK, and all eight inhibitors. In general, the postnatal maturation towards adult levels was accelerated in premature infants as compared with the fullterm infants. By 6 months of age, most components of the coagulation system in premature infants had achieved near adult values.     

Reference ranges and factors affecting the human corticotropin-releasing hormone test in preterm,very low birth weight infants

This prospective study aims to investigate the factors that influence the human CRH (hCRH) test and to provide reference ranges for plasma corticotropin (ACTH) and serum cortisol concentrations of the stimulation test in preterm, very low birth weight (VLBW) infants. Two hundred twenty-six hCRH tests were performed on 137 VLBW infants at d 7 and 14 of life. Plasma ACTH did not differ significantly between infants whose mothers did not receive antenatal corticosteroids (group 1) and those whose mothers received one or two doses (group 2) or more than two doses (group 3) of the drug. However, plasma ACTH levels at d 7 were found to be significantly higher in infants with severe lung disease who required intermittent positive-pressure ventilation (IPPV) or high-frequency oscillation ventilation (HFOV), compared with those who had milder pulmonary disease and did not require mechanical ventilation or needed only continuous positive airway pressure (CPAP) support (P < 0.011). A significantly higher rate of increase in plasma ACTH concentration at d 7 was also observed in infants whose mothers suffered from antepartum hemorrhage (P < 0.016). In contrast, infants in group 2 had significantly lower serum cortisol, compared with group 1 infants (P < 0.05), whereas group 3 infants did not have serum cortisol levels significantly different from those of patients in group 1 or 2. Significant positive correlation between serum cortisol at d 7 and the time interval between the last dose of antenatal dexamethasone and delivery was also observed in group 3 infants (r > 0.33, P < 0.045). In addition, infants who required IPPV or HFOV had significantly lower serum cortisol at d 7 (P < 0.0001), but this pattern of cortisol response was reversed on d 14, with infants requiring IPPV or HFOV having significantly higher serum cortisol (P < 0.036). The reference ranges for plasma ACTH and serum cortisol concentrations of the hCRH test at d 7 and 14 were also provided for group 1 and group 2 infants. This study demonstrates that even one or two doses of antenatal corticosteroids cause adrenal suppression in VLBW infants. Maternal antepartum hemorrhage also influences the pituitary response of preterm newborns in the first week of life. The change in the pattern of cortisol response in sick ventilated (IPPV or HFOV) infants during the first 2 wk of life suggests that a proportion of preterm infants may have inadequate adrenal response to stress in early postnatal life, but it is likely that rapid adaptation of the hypothalamic-pituitary-adrenal axis results in enhanced and more appropriate cortisol response by d 14. The percentile distribution of plasma ACTH and serum cortisol responses provides useful statistical reference data for interpretation of the hCRH test in VLBW infants and may also assist in facilitating the use of corticosteroids replacement therapy in cases with clinical manifestations suggestive of adrenal insufficiency.     

Cord blood lipoprotein-cholesterol: relationship birth weight and gestational age of newborns

Umbilical plasma levels of lipoproteins-cholesterol were measured in 60 premature (less than 37 weeks), 60 small for gestational age (SGA, greater than 37 weeks), and 60 full term newborns (greater than 37 weeks) to ascertain the relationship between gestational age, infant's weight and concentration of plasma lipoprotein cholesterol. Umbilical levels of total cholesterol (TC), unesterified cholesterol (UC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in premature newborns were significantly higher (P less than .001) than in term infants. The levels of TC, UC, HDL-C and very low density lipoprotein cholesterol (VLDL-C) were substantially higher (P less than .05) in umbilical cord plasma of SGA newborns than in cord plasma of full term newborns. Lecithin:cholesterol acyltransferase activity in cord plasma was indirectly assessed by measuring the ratio of esterified cholesterol to unesterified cholesterol (CE/UC). This ratio was significantly lower (P less than .01) in preterm and SGA than in full term newborns. In addition, plasma TC, UC, LDL-C and HDL-C levels were inversely correlated with gestational age of newborns. By contrast, CE/UC ratio had an inverse correlation with gestational age and HDL-C of the newborns. These findings suggest that the levels of TC in newborns are regulated by the uptake of LDL-C by the fetal adrenal and, additionally, by the lecithin:cholesterol acyltransferase (LCAT) activity of newborn plasma. Only by careful follow-up of hyperlipidemic neonates can the true incidence of familial hyperlipoproteinemia and the value of early diagnosis be assessed.