Fetal and Neonatal Cortical Adrenal Function in Birth Asphyxia

ABSTRACT. Eighteen newborn infants, gestational age between 36 and 42 weeks with birth asphyxia were compared with 23 normal newborn infants to determine serum cortisol and dehydroepiandrosterone sulfate levels in cord blood and in venous blood samples collected 12–18 hours after birth. Both groups were similar in gestational age, birthweight, proportion of small for gestational age and large for gestational age infants, proportion of infants delivered by cesarean section with and without labor, and proportion of mothers with pre-eclampsia. There was no antenatal exposure to corticosteroid. The asphyxiated newborn infants had a significantly higher mean cord serum level of cortisol, and a significantly lower mean cord serum level of dehydroepiandrosterone sulfate than the control group. Mean serum cortisol and dehydroepiandrosterone sulfate levels collected 12–18 hours after birth were similar between both groups. It is suggested that elevated cord serum level of cortisol is related to birth asphyxia stress stimulating the adrenal definitive zone, and the low cord serum level of dehydroepiandrosterone sulfate is secondary to a transient hypoxemic-ischemic insult to the adrenal fetal zone.     

Early hypoadrenalism in premature infants at risk for bronchopulmonary dysplasia or death

AIM: To study the relationship between serum cortisol and dehydroepiandrosterone sulphate (DHEAS) concentrations and death or bronchopulmonary dysplasia at 36 weeks of postmenstrual age in preterm infants. METHODS: Prospective measurement of cord, day of birth (D0) and day 4 (D4) serum cortisol and DHEAS concentrations and performance of low-dose (LD) ACTH tests in 89 preterm infants with gestational age <34 weeks at birth and in need of mechanical ventilation. RESULTS: Serum DHEAS levels correlated negatively with gestational age. At all sampling times, basal serum cortisol levels correlated positively with gestation-adjusted DHEAS levels (r = 0.39-0.46, p = 0.0032-<0.0001). The mean cord, D0 basal and stimulated cortisol, and cord and D0 DHEAS adjusted for gestational age were lower in the poor than good outcome infants (p < 0.02 for all). In the multiple logistic regression analyses, gestational age was the most significant factor affecting outcome, but low cord and D0 basal and stimulated cortisol and gestation-adjusted DHEAS levels also predicted poor outcome (OR 5.7-22; p = 0.049-0.014). CONCLUSIONS: Low cord and first day serum cortisol and DHEAS levels associated with poor outcome in preterm infants, which suggests general relative adrenocortical insufficiency in some premature newborns.     

The influence of labor and delivery on preterm fetal adrenal function

The influence of labor and route of delivery upon umbilical cord serum levels of cortisol and dehydroepiandrosterone sulfate in one hundred sixty-nine preterm infants not exposed prenatally to corticosteroids was studied. Vaginally born infants (group A, n = 89) presented a higher mean cord cortisol and dehydroepiandrosterone sulfate concentrations than those delivered by cesarean section (group B, n = 80). Although there were no differences in cortisol and dehydroepiandrosterone sulfate levels between infants delivered by cesarean section after spontaneous onset of labor (group B-I, n = 42) and those without labor (group B-II, n = 38), the mean cortisol and dehydroepiandrosterone sulfate concentrations were higher in group A than in group B-I. There was a correlation between umbilical cord cortisol and dehydroepiandrosterone sulfate levels. It is concluded that there is no association between the presence of labor and high cord serum levels of cortisol and dehydroepiandrosterone sulfate and there is an association between vaginal delivery and high cord cortisol and dehydroepiandrosterone sulfate levels in preterm infants. It is suggested that the stress of vaginal delivery stimulates the secretion of fetal cortisol and dehydroepiandrosterone sulfate in preterm infants.     

Quantitation of T cells in venous blood of healthy neonates

Quantitation of T Cells in blood is the part of the diagnostic workup for cellular immunity. Specimens of venous blood were collected within 24 hours of birth from 51 healthy, appropriate for gestational age infants. T lymphocytes were identified on the basis of their ability to form rosettes with sheep erythrocytes. The lymphocytes were harvested from peripheral venous blood, which is considered to be more representative of the immune status in the newborn than the cord blood. In the newborn infants the proportion in T cells was found to be considerably diminished in comparison to previously reported values for adults. Preterm infants, especially those with gestational age of 34 wk or less had significantly lower percentage of T cells in their blood as compared with term infants. The proportion of T cells was statistically reduced in infants weighing 2000g or less in contrast to those weighing 2500 g or more.     

Steroid and growth hormone levels in premature infants after prenatal betamethasone therapy to prevent respiratory distress syndrome

Prenatal maternal therapy with glucocorticoid reduces the incidence of respiratory distress syndrome (RDS) in premature infants. To investigate the effects of this treatment on the fetal endocrine system, we determined serum concentrations of betamethasone, cortisol, dehydroepiandrosterone sulfate, growth hormone, and prolactin in cord blood of 215 treated infants and 117 untreated infants of 26--36 wk of gestation. Cortisol levels are suppressed within 6 hr of betamethasone treatment, decrease to 45% of the concentration in untreated infants (8.4 micrograms/dl), and return to normal by 7 days. Dehydroepiandrosterone sulfate is reduced maximally by 65% and returns to normal concentrations (123.5 micrograms/dl in 7 1/2 days. The suppression of both steroids was similar after treatment with 12 mg betamethasone (acetate and phosphate) daily 2 times or with 6 mg betamethasone (alcohol) twice daily 4 times. Peak betamethasone levels were higher after the 12 mg dose, but the two-treatment regimens produced a similar total exposure of the fetus to elevated serum glucocorticoid activity for 2 1/2 days and decreased plasma activity for the subsequent 4 1/2 days. Treated infants with low cortisol concentrations at birth increased their cortisol levels severalfold after birth in response to either intrapartum asphyxia or RDS. Betamethasone therapy did not affect cord serum prolactin levels, but the concentration of growth hormone was reduced at all ages. The suppression was greatest (53% decrease) among infants of 28 less than 32 wk, and, among older infants, there was a subsequent increase above control levels between 2 and 4 days after treatment. This study indicates that prenatal betamethasone treatment causes a transient suppression of fetal growth hormone and presumably those pituitary hormones which regulate steroid production by both the definitive and fetal zones of the fetal adrenal. However, the suppression of fetal cortisol does not interfere with the pituitary-adrenocortical response to stress after birth.     

Transient elevation of aldosterone levels in perinatal asphyxia

Abstract We measured plasma aldosterone levels in cord blood and peripheral blood collected 18–24 h after birth in 19 asphyxiated and 19 normal term newborn infants. The asphyxiated newborn infants had significantly higher aldosterone levels in cord blood than the normal newborn infants. At 18–24 h after birth there was no difference between the groups with respect to aldosterone levels. There was a positive significant correlation between aldosterone levels and PCO₂ in cord blood by multiple linear regression analysis. There is a transient elevation of aldosterone levels in perinatal asphyxia.     

Colloid osmotic pressure of umbilical cord plasma in healthy and sick newborn infants

Colloid osmotic pressure of umbilical cord plasma was measured in 242 healthy infants, in 34 infants with respiratory distress syndrome (RDS), in 18 infants with asphyxia, in 13 infants who were small for gestational age, in 15 infants born to mothers with diabetes mellitus, and in 18 infants born to mothers with pregnancy-induced hypertension. In healthy infants, colloid osmotic pressure correlated highly significantly with umbilical cord blood total protein level, gestational age, and birth weight. In infants with RDS, no correlation between colloid osmotic pressure and gestational age or birth weight was found. Infants with RDS and gestational age between 36 and 38 weeks had significantly lower colloid osmotic pressure than healthy infants, whereas colloid osmotic pressure of infants with RDS and gestational age between 32 and 35 weeks did not differ from that of healthy infants of corresponding gestational age. Healthy term infants delivered by cesarean section had significantly lower colloid osmotic pressure than infants delivered vaginally. Infants with asphyxia had significantly higher colloid osmotic pressure than healthy infants. Colloid osmotic pressure is related to the lung maturity of the near-term and term neonate. Infants with a colloid osmotic pressure greater than 16 mm Hg are unlikely to develop RDS.     

Prolactin in umbilical cord blood and the respiratory distress syndrome.

Prolactin was measured in umbilical cord serum obtained from 77 newborn infants of gestational age 28 to 40 weeks. A positive correlation with gestational age was demonstrated. Between 30 and 36 weeks of gestation the elevation of the regression line of the concentration of cord PRL versus gestation age was significantly lower (P less than 0.05) for those infants who developed respiratory distress syndrome compared to the regression line for infants who did not develop RDS. Between 32 and 33.5 weeks, the mean +/- SEM cord PRL concentration in infants who developed RDS (101.7 +/- 9.5 ng/ml) was significantly less (P less than 0.025) than the PRL concentration in those who did not develop RDS (161.8 +/- 18.9 ng/ml). Cord PRL did not correlate with cord cortisol or dehydroepiandrosterone sulfate concentrations. Cord growth hormone concentrations did not show any relationship to the occurrence of RDS. Serum PRL was not suppressed in a further 114 infants whose mothers were treated prenatally with betamethasone. These findings raise the possibility of a role of PRL in fetal lung maturation.     

CORD PLASMA HYPOXANTHINE AS A MEASURE OF FOETAL ASPHYXIA

ABSTRACT. The clinical value of cord plasma hypoxanthine (HX) determination as a measure of foetal asphyxia was investigated. HX levels found in mixed cord plasma from 50 infants with clinical signs of perinatal asphyxia were compared to the levels found in 29 infants delivered after risk pregnancies and in 62 control neonates. All infants were assessed by three clinical scores: Apgar score, a clinical asphyxia score and perinatal reduced optimality score. In half of the infants cord blood pH, lactate and base excess were also determined. The mean cord plasma HX level in asphyctic infants was significantly higher than the mean HX level found in the two non-asphyxiated groups. The concentration of HX correlated significantly to the clinical asphyxia score, reduced optimality score and to cumulative Apgar score, but no correlation was found to 1 and 5 min Apgar score. Cord plasma HX also correlated significantly to pH and lactate in cord blood. However, the correlation of HX to these two laboratory measures of asphyxia was no longer significant, when infants with birth weights/gestational ages below 1.0 SD were considered. This was found to be due to the lack of lactate elevation in these infants during asphyxia. Two newborn infants with substantially elevated HX levels, with only minor signs of clinical asphyxia turned out on follow-up with spastic diplegia. It is suggested that the assay of cord plasma HX may add additional information to previously used hypoxia parameters and may be a more reliable index of perinatal asphyxia in the growth-retarded infant, than lactate and pH at birth.     

The influence of the mode of delivery on the umbilical cord serum aldosterone levels in preterm newborn infants

The influence of the mode of delivery on the umbilical cord serum aldosterone levels in preterm newborn infants was studied. Sixty-four newborn infants gestational age less than 37 weeks were sequentially included in the study. Umbilical cord blood was collected just after birth and the aldosterone level was measured by radioimmunoassay. The median aldosterone level of the whole studied sample was 74.5 ng/dl (range: 22.00-280.00 ng/dl). The aldosterone level of the 31 newborn infants delivered vaginally was similar of the 33 newborn infants delivered by cesarean-section. When the cesarean group was subdivided in presence or not of labor prior to delivery, the aldosterone levels of those delivered after labor was significantly higher than those without labor. It is suggested that some event associated to the mode of delivery or the presence of labor prior to delivery may influence aldosterone levels in preterm newborn infants.     

Umbilical cord dehydroepiandrosterone sulfate and cortisol levels in preterm infants born to pre-eclamptic mothers

The influence of early-onset pre-eclampsia upon the umbilical cord serum levels of cortisol and dehydroepiandrosterone sulfate was studied in fifty-one preterm infants not exposed prenatally to corticosteroids. Preterm infants born to pre-eclamptic mothers (group A) presented lower dehydroepiandrosterone sulfate levels than preterm infants born to non-preeclamptic mothers (group B). The umbilical cord serum levels of cortisol were similar between both groups. It is suggested that the decrease in the cord serum levels of dehydroepiandrosterone sulfate in preterm infants of pre-eclamptic mothers plays an important role in the pathogenesis of the subnormal maternal urinary estriol excretion, and that the accelerated pulmonary and cerebral maturation of preterm infants born to pre-eclamptic mothers is not explained by an increased fetal serum cortisol concentration.     

围产期窒息后血浆cTnI、CK-MBmass的影响因素及临床应用价值

为探讨围产期窒息后血浆心肌肌钙蛋白I（cTnI）、肌酸激酶心型同工酶质量（CK-MBmass）的影响因素及临床应用价值。对71例围产期窒息新生儿及27例对照组新生儿生后6小时－48时血浆cTnI、CK-MBmass水平进行测定，运用逐步回归等方法进行分析。结果显示：（1）血浆cTnI水平的变化与胎龄、5分钟Apgar评分有关。（2）围产期窒息组足月儿（59例）cTnI明显高于对照组足月儿（19）；重度窒息组（17例）与轻度窒息组（16例）比较，cTnI差异无显著性，而CK-MBmass差异有非常显著性；围产期窒息组的重度心脏损害患儿（8例）cTnI、CK-MBmass水平明显高于无重心脏损害患儿（63例）。表明围产期窒息持续时间越长cTnI的水平越高。相对于CK-MBmass而言，cTnI对心肌损伤的敏感性可能稍差，而且由于cTnI的水平随着胎龄的增加而增加，因此这一指标在判断早产儿心肌损伤时有一定的局限性。     

血清S100B蛋白在新生儿窒息后脑损伤中的临床意义

目的：S100B蛋白是一种脑特异性蛋白,可反映脑损伤的程度。该研究旨在探讨窒息新生儿脐血及生后血清S100B蛋白的变化及对新生儿窒息诊断和窒息后脑损伤判断的价值。方法：对窒息新生儿的脐血及生后1,3,7d血清S100B蛋白变化进行分析。结果：①窒息新生儿脐血S100B蛋白水平高于正常对照组,差异有显著性(P<0.05),轻度窒息与重度窒息患儿脐血S100B蛋白含量差异无显著性;②出生后1～7d内轻度窒息患儿血清S100B蛋白无明显变化,重度窒息脑损伤患儿血清S100B蛋白呈逐渐增高趋势,生后第7天时重度窒息脑损伤患儿血清S100B蛋白明显高于轻度窒息患儿(P<0.01);③死亡的窒息患儿生后第7天的血清S100B蛋白含量高于存活儿,但差异无显著性(P>0.05);④发生颅内出血和/或脑水肿的患儿生后第3天血清S100B蛋白含量增高,差异有显著性(P<0.05)。结论：血清S100B蛋白检测有助于新生儿窒息的诊断及窒息后脑损伤的判断。     

Association between serum leptin and anthropometric parameters at birth and at 15th day of life in infants born asymmetrically small for gestational age

The aim of this study was to investigate changes in skinfold measurements taken at three sites, mid-arm circumference and umbilical circumference during the first 15 days of life; and to evaluate relationships between anthropometric measurements and umbilical cord blood serum leptin levels in infants born small for gestational age (SGA) and appropriate for gestational age (AGA) infants. Of 50 newborn infants, 25 were SGA and 25 were AGA. Neonates' weight, mid-arm circumference (MAC), umbilical circumference (UC), and triceps, subscapular and periumbilical skinfold thicknesses were measured (Holtain callipers) immediately after delivery. Anthropometric parameters were measured again at 15th days of age. At birth, mean birth weight, mean skinfold thickness, MAC and UC measurements in the AGA group were significantly higher than those of the SGA group. These differences were also found on the 15th day. Birth weight correlated with all skinfold thicknesses, MAC and UC at birth. Weight at 15th day of life correlated with skinfold thicknesses, MAC and UC at 15th day of life. Cord blood leptin level was significantly lower in the SGA than in the AGA infants. This difference continued on the 15th day. When cord blood leptin level was compared with that of the 15th day, we found that leptin levels in the cord blood were significantly higher. There were significantly positive correlations between leptin levels and birth weight and skinfold thicknesses when the infants were all grouped together. When the newborns were grouped according to birth weight, there were positive correlations between cord blood serum leptin levels and these parameters in the AGA group, but no correlation in the SGA group. At the 15th day of life serum leptin levels correlated with weight, subscapular and triceps skinfold thickness in the AGA group, but only with triceps skinfold thickness in the SGA group.     

Tactile-kinesthetic stimulation effects on sympathetic and adrenocortical function in preterm infants

The purpose of our study was to investigate the neuroendocrine response in preterm infants to a pattern of tactile-kinesthetic stimulation that facilitates their growth and development. Preterm infants (mean gestational age 30 weeks, mean birth weight 1176 gm) received normal nursery care or tactile-kinesthetic stimulation for three 15-minute periods at the start of three consecutive hours each day for 10 days. On day 1 and day 10 of the study, a 24-hour urine sample was collected for norepinephrine, epinephrine, dopamine, cortisol, and creatinine assay and a blood sample was taken by heel stick for cortisol and growth hormone assay. Urine norepinephrine and epinephrine values increased significantly only in the stimulated babies. Urine dopamine and cortisol values increased in both groups, and serum growth hormone decreased in both groups. Individual differences in urine norepinephrine, epinephrine, dopamine, and cortisol values were highly stable across the 10 days despite a 10-fold range of values among the infants. The results of this study suggest that tactile-kinesthetic stimulation of preterm infants has fairly specific effects on maturation and/or activity of the sympathetic nervous system. In addition, this study has defined catecholamine and cortisol secretion across gestational age in normal preterm infants. Finally, these data suggest that highly stable individual levels of catecholamine and cortisol secretion are established by birth in humans.     

Serum tri-iodothyronine, thyroxine, and thyrotrophin concentrations in newborns during the first 2 days of life.

The serum concentrations of tri-iodothyronine (T3), thyroxine (T4), and thyrotrophin (TSH) were measured in 10 term newborn infants between birth and the age of 2 days by radioimmunoassay. The mean concentration of T3 in maternal serum was 1.62 mug/l, and it increased from the low cord blood level of 0-63 mug/l to the peak value of 1-76 mug/l within the first 2 hours of life. Mean serum T4 concentrations increased from the cord blood level of 145 mug/l to the peak value of 205 mug/l within the first 24 hours of life. The postnatal increase of the mean serum TSH concentrations from the cord blood level of 5-7 mU/l to the peak value of 20-6 mU/l within 2 hours was similar to the increase of T3. These data confirm earlier reports which show that T3 secretion is low at birth and TSH secretion is stimulated strongly but transiently after birth, and that the low T3 secretion is rapidly normalized in 2 hours along with the TSH release. Because of these strong and rapid changes, we recommend screening of the function of the pituitary-thyroid axis in neonates after the age of 24 hours.     

Increased adrenocortical and adrenomedullary hormonal activity in 12-year-old children born small for gestational age

OBJECTIVES: To determine whether adrenal hormonal activity is altered in children born small for gestational age (SGA), and whether concentrations of adrenal hormones relate to those of serum lipids or to anthropometric measures. STUDY DESIGN: We studied 55 SGA children and 55 appropriate for gestational age (AGA) children at the age of 12 years in a case-control setting. The concentrations of fasting serum cortisol, dehydroepiandrosterone sulfate (DHEAS), plasma epinephrine (E), and norepinephrine (NE) were analyzed. RESULTS: The SGA children had significantly higher mean concentrations of serum DHEAS (3.53 vs 2.89 micromol/L, P =.009) and plasma E (0.33 vs 0.25 nmol/L, P =.005) than their age- and sex-matched control subjects. The mean serum cortisol and plasma NE concentrations did not differ significantly between the groups. However, the SGA children in the highest quartile for serum cortisol had significantly higher concentrations of plasma E (0.50 vs 0.28 nmol/L, P <.001), serum LDL (3.21 vs 2.73 mmol/L, P =.025) and total cholesterol (5.06 vs 4.42 mmol/L, P =.021) than the SGA children in the lower cortisol quartiles. The factors associating with high levels of plasma E in the SGA children were high level of serum cortisol [odds ratio (OR) = 3.8, 95% confidence interval (95% CI) = 1.5-10], LDL cholesterol (OR = 3.9, 95% CI = 1.3-12), male sex (OR = 8.3, 95% CI = 1.0-68) and low birth weight (OR = 1.4, 95% CI = 1.0-1.8) in multiple logistic regression analysis. CONCLUSIONS: Twelve-year-old children born SGA had increased DHEAS and epinephrine levels in circulation. High serum cortisol concentrations are associated with high epinephrine, LDL, and total cholesterol levels.     

Effect of perinatal factors on cord blood thyroid stimulating hormone levels

OBJECTIVE: To study the influence of perinatal factors on cord blood (CB) TSH levels. INFANTS AND METHODS: In a prospective cross-sectional study, CB TSH levels were measured in 1,590 live-born infants using IRMA. The effect of various perinatal factors on the CB TSH levels was analyzed statistically. RESULTS: The mean TSH level in the study group was 10.6 +/- 6.7 microU/ml (range 0.01-66.4 microU/ml). A significant fall in CB TSH levels was noted with increasing gestational age. A similar decline was noted in TSH levels with increase in birth weight. No significant difference in TSH levels was noted between males and females, or AGA and SGA (n = 296) infants. Infants with birth asphyxia (Apgar score < 4 at 5 min) had significantly higher CB TSH levels (mean 31 microU/ml, n = 18) as compared to those without (mean 10.4 microU/ml) (p < 0.01). The highest TSH levels were noted in neonates delivered by forceps extraction (mean 29.4 microU/ml, n = 17) and lowest levels in infants born by elective Caesarian section (mean 8.7 microU/ml, n = 149). CONCLUSION: CB TSH levels fall with increase in gestational age while birth asphyxia and difficult deliveries tend to elevate them.     

颅内出血早产儿生后四天内脑血流变化及围生因素分析

目的　探讨颅内出血早产儿生后 4d内脑血流动力学的变化及颅内出血与围生因素的关系。方法　应用经颅多谱勒超声 (TCD)检测 2 9例颅内出血早产儿脑血流速度、阻力指数的变化及脑血流速度与平均动脉血压的关系 ,分析临床围生相关因素 ,并与同期无颅内出血的 2 8例早产儿进行比较。结果　颅内出血组早产儿于生后 2 4、4 8、72h脑血流速度增快 ,出生 2 4h平均脑血流速度与平均动脉血压相关 ,且与出生窒息、胎龄、出生体重、高PaCO2 有关。结论　颅内出血早产儿于生后 2 4h内存在脑血流自主调节功能破坏 ,生后 3d脑血流存在过度灌注 ;且出生窒息 ;胎龄 <32周、出生体重 <15 0 0 g及PaCO2 >6 6 7kPa为颅内出血的高危因素。     

Neonatal hyperviscosity: I. Incidence.

Capillary hematocrits were performed on 790 infants during the first four hours after birth. These infants were delivered between August 8 and December 7, 1974, at the University of Colorado Medical Center, which is at an altitude of 1,061 m above sea level. When the capillary hematocrit was 7% or greater, venous hematocrit and blood viscosity were determined. Capillary hematocrits obtained from warmed heels in the first hour after birth were spuriously high and not consistently related to venous hematocrit. Venous polycythemia, defined as a hematocrit of 65% or greater, occurred in 4% of the newborn population. Hyperviscosity (greater than 2 SD above the mean for newborns) occurred in 5% of the newborn infants. At a venous hematocrit of 65% or greater, hyperviscosity was predictable, but some infants with venous hematocrits between 60% and 64% also had hyperviscosity of the blood. The incidence of polycythemia and hyperviscosity was further related to birth weight and gestational age. The infants who were small for gestational age were at highest risk of polycythemia and hyperviscosity, followed by infants who were large for gestational age. However, the greatest number of infants with hyperviscosity were term appropriate for gestational age. Preterm infants with gestational ages of less than 34 weeks were not affected.