Effect of maternal administration of thyrotropin releasing hormone on the preterm fetal pituitary-thyroid axis

We evaluated the response of preterm fetuses to maternal intravenous injection of 400 micrograms of thyrotropin releasing hormone (TRH) between 30 minutes and 5 hours before delivery (n = 12). An additional seven mothers received saline solution and served as control subjects. There were no statistically significant differences in gestational age, birth weight, or Apgar scores between groups. At delivery, concentrations of maternal thyrotropin were elevated in the TRH group compared with the control group (12.0 +/- 1.6 vs 5.6 +/- 0.5 mU/L; p less than 0.005); however, maternal triiodothyronine (T3) values remained unchanged. Significant elevations of fetal thyrotropin and T3 were observed after maternal administration of TRH compared with control subjects (45.8 +/- 7.7 vs 8.4 +/- 0.9 mU/L (p less than 0.002) and 1.3 +/- 0.07 vs 0.7 +/- 0.04 nmol/L or 87 +/- 5 vs 49 +/- 3 ng/dl (p less than 0.001), respectively). Fetal thyroxine (T4) and prolactin values were also elevated after exposure to TRH (135 +/- 5 vs 86 +/- 10 nmol/L or 10.5 +/- 0.4 vs 6.7 +/- 0.8 micrograms/dl (p less than 0.001) and 212 +/- 31 vs 105 +/- 28 micrograms/L (p less than 0.05), respectively). Two hours after birth, a significant increase in T3 but not T4 levels was observed in both groups of infants. These data indicate that fetal exposure to a single dose of TRH via maternal administration of this hormone results in marked stimulation of the preterm fetal pituitary-thyroid axis, as in the fetus at term, and that this treatment does not inhibit the early postnatal surge of T3.     

The effects of intranasally sprayed synthetic TRH on TSH and on PRL secretion in children

The effects of intranasally applied TRH on serum TSH and PRL were investigated in ten healthy, prepubertal children. Serum levels of T4, T3, TSH, and PRL were all in the normal range. Synthetic TRH, 500 micrograms, in water was insufflated in one nostril. Intranasal TRH induced a prompt rise of TSH and PRL in all children with peak values at 30 min. TSH: 10.29 +/- 1.24 microU/ml; PRL: 25.12 +/- 3.53 ng/ml (mean +/- SEM). TSH values were still significant raised 120 min after the insufflation (P less than 0.025) whereas the PRL values did not differ significantly. A dose-dependent TSH release following intranasal sprayed TRH was shown. delta TSH and TSH values at 120 min were significantly higher in children receiving greater than 10 micrograms/kg TRH than in children receiving less than 10 micrograms/kg (P less than 0.025; P less than 0.05). Dose dependent differences in PRL release following intranasal TRH were not shown. Any side effects of intranasally applied TRH were not observed. Intranasal insufflation of synthetic TRH seems to be a valuable and harmless tool for the evaluation of pituitary TSH and PRL secretory reserve.     

Plasma thyroid hormones and prolactin in premature infants and their mothers after prenatal treatment with thyrotropin-releasing hormone.

We assayed TSH, triiodothyronine, free thyroxine, and prolactin (PRL) in plasma of women and infants participating in a trial of prenatal thyrotropin-releasing hormone (TRH) treatment for prevention of newborn lung disease. Women in labor at 26-34 wk of gestation received 400 micrograms of TRH i.v. every 8 h (one to four doses) plus 12 mg betamethasone (one or two doses); controls received saline plus betamethasone. Mean cord concentrations in control infants were TSH 9.7 mU/L, triiodothyronine 0.6 nmol/L (40.2 ng/dL), free thyroxine 14.4 pmol/L (1.13 ng/dL), and PRL 67.6 micrograms/L. TRH increased maternal plasma TSH by 100% at 2-4 h after treatment and decreased levels by 28-34% at 5-36 h. In cord blood of treated infants delivered at 2-6 h, TSH, triiodothyronine, and PRL were all increased about 2-fold versus control, and free thyroxine was increased 19%; the response was similar after one, two, three, or four doses of TRH. In treated infants delivered at 13-36 h, cord TSH and triiodothyronine levels were decreased 62 and 54%, respectively, and all thyroid hormones were lower after birth at 2 h of age versus control. We conclude that prenatal TRH administration increases thyroid hormones and PRL in preterm fetuses to levels similar to those normally occurring at term. Pituitary-thyroid function is transiently suppressed after treatment to a greater extent in fetus than mother, and infants born during the early phase of suppression do not have the normal postnatal surge in thyroid hormones.     

Fetal arginine vasopressin under basal and hypoosmolal conditions

Blood samples (4 ml) for plasma arginine vasopressin (AVP) measurements were obtained at 3- to 4-hour intervals under basal conditions for 1-2 days from 5 date-bred ewes with chronic maternal and fetal vascular catheters. In addition, 6 chronically catheterized ewes were infused with 2 liters of 0.45% NaCl over 30 min. Fetal and maternal blood samples were obtained before and after the infusion period for measurement of plasma osmolality and AVP concentrations. In the first study, maternal and fetal plasma AVP levels correlated significantly (p less than 0.01, by linear regression analysis) under basal conditions. In the second study, baseline mean (+/- SEM) plasma osmolality was similar for pregnant ewes and fetuses (303 +/- 3.1 and 302 +/- 2.4 mosm/kg, respectively). There was a significant (each, p less than 0.01 by paired t test) decrease from baseline in maternal and fetal osmolality during the 30 min after completion of the hypotonic saline (to 292 +/- 4.7 and 296 +/- 2.4 mosm/kg, respectively). Fetal plasma AVP levels decreased 17 +/- 6% by 30 min following the completion of water loading (1.7 +/- 0.07 to 1.4 +/- 0.16 microU/ml; p less than 0.05). Maternal plasma AVP levels decreased 16 +/- 4% by 30 min after completion of infusion (1.6 +/- 0.14 to 1.38 +/- 0.6 microU/ml; p less than 0.05). These results indicate that maternal and fetal plasma AVP levels correlate under basal conditions and that maternal water loading, which significantly decreases fetal plasma osmolality, significantly suppresses fetal plasma AVP concentrations.     

Growth hormone secretion in response to the administration of thyrotropin releasing hormone (TRH) in children with insulin-dependent diabetes mellitus]

In this study the Authors examined the response in growth hormone (GH) to thyrotrophin releasing hormone (TRH) administration in a group composed of 29 children (17 males, 12 females) suffering from insulin-dependent diabetes mellitus (IDDM) (group 1). All subjects were prepubertal, had a chronological age of 8.82 +/- 1.76 years (m +/- SD), a bone age of 8.60 +/- 1.65 years; the time elapsed since the diagnosis was 2.45 +/- 1.51 years, glycosylated hemoglobin (HbA1c) was 7.33 +/- 1.80%. Some of the same subjects (all those with a response in GH to TRH higher than 4 ng/ml; no. 11; group 2) were examined again 12-18 months later; as controls, 13 short children were also examined (group 3). All the subjects of the three groups showed a TSH peak ranging from 10-25 microU/ml, whereas GH peak resulted higher than 4 ng/ml ("paradoxical" response) in 6 subject of the group 1 and in an only subjects of the group 2. All the responders of the 3 groups showed a value in HbA1c higher than 8%. A significant difference was not present between males and females in GH and TSH values. Cortisol levels and glycaemia remained almost constant during the performance of the tests. By considering all the groups, TSH and GH values during TRH-test were not correlated with glycaemia, chronological age, bone age, the time elapsed since the diagnosis, height, height velocity, HbA1c values. In conclusion, our data demonstrated that "paradoxical" response in GH to TRH administration was present only in some subjects and particularly in those with a poor metabolic control of the disease.     

The effect of hypoxia on neurohypophyseal hormone release in fetal and maternal sheep

The effect of hypoxemia on arginine vasopressin (AVP) and oxytocin (OT) release was investigated in the chronically catheterized fetus and ewe. During 30 min of 10% maternal oxygen delivery, mean (+/- SEM) arterial PO2 decreased from 105 +/- 10.6 to 48 +/- 3.5 mm Hg in the ewe and from 21 +/- 1.3 to 12 +/- 0.8 mm Hg in the fetus (each P less than 0.001). Arterial PCO2 decreased from 35 +/- 4.4 to 29 +/- 1.0 mm Hg in the ewe, whereas fetal PCO2 decreased from 43 +/- 2.3 to 35 +/- 3.5 mm Hg (P less than 0.05). Blood pH increased from 7.44 +/- 0.03 to 7.56 +/- 0.04 in the ewe (P less than 0.01) and from 7.36 +/- 0.004 to 7.40 +/- 0.006 in the fetuses (P less than 0.01). Baseline mean AVP levels were identical in ewes and fetuses (0.7 +/- 0.1 microU/ml). After 30 min of hypoxia, plasma AVP levels remained unchanged in the ewes (0.9 +/- 0.1), but increased dramatically in the fetuses (47 +/- 21 microU/ml) (P less than 0.001). There was a highly significant correlation between the duration of hypoxia and log fetal AVP concentrations (r = 0.85). The log fetal plasma AVP also was inversely correlated to the log fetal PO2 values (r = 0.83). Mean baseline fetal and maternal plasma OT levels were 2.6 +/- 0.5 microU/ml and 2.2 +/- 0.5 microU/ml, respectively. After 30 min of hypoxia fetal and maternal OT values were 2.9 +/- 0.8 microU/ml (not significant).     

Thyrotropin and prolactin response to thyrotropin-releasing hormone in healthy and asphyxiated full-term neonates

To evaluate the effect of perinatal asphyxia on the pituitary response to thyrotropin-releasing hormone (TRH) in full-term newborn infants, serum thyrotropin (TSH) and prolactin (PRL) levels were measured before and 30 and 180 min after i.v. administration of 40 micrograms TRH. Birth weight, gestational and postnatal age were similar in the healthy (group NA) and in the asphyxiated (group A) babies. Hormone levels were determined by radioimmunoassay using commercial kits. It was demonstrated that the basal TSH level was slightly higher and the basal PRL level significantly (p less than 0.05) higher in group A than in group NA. In response to TRH administration in group A a marked increase in PRL occurred from 6781 +/- 887 to 11 072 +/- 1318 and 9636 +/- 1024 mU/l at 0, 30 and 180 min, respectively. A similar response was seen in group NA; the values, however, remained significantly lower during the TRH-test. The respective PRL values at 0, 30 and 180 min were 4672 +/- 411, 7945 +/- 343 (p less than 0.05) and 5963 +/- 372 mU/l (p less than 0.05). TRH administration also resulted in a significant elevation of the serum TSH level from 6.20 +/- 1.30 to 49.02 +/- 7.25 (p less than 0.01) and 18.72 +/- 6.35 mU/l (p less than 0.05) in group A, and from 3.90 +/- 0.57 to 24.01 +/- 3.81 (p less than 0.01) mU/l in group NA, but in group NA the 180 min TSH value of 6.07 +/- 1.25 mU/l did not differ statistically from the basal level (p greater than 0.1). It is concluded that the pituitary PRL and TSH reserves are maintained in full-term newborn infants recovering from perinatal asphyxia whose biochemical findings are indicative of subclinical hypothyroidism.     

Circulating thyrotropin in the ovine fetus: evidence for pulsatile release and the effect of hypothermia in utero

The secretion of thyrotropin (TSH) has been investigated in the chronically catheterized ovine fetus (term 145-150 days). Forty-two random plasma samples from 25 fetuses (86-149 days of gestation) were measured for TSH concentrations by radioimmunoassay. Plasma TSH concentrations were highest in the youngest fetuses [86-110 days, 3.9 +/- (SD) 5.5 microU/ml, n = 13]. Thereafter TSH concentrations declined to 0.4 +/- 0.6 microU/ml (n = 13, p less than 0.05) at 130-150 days of gestation. However, serial sampling at 15-20 min intervals for 180 min from 14 individual fetuses (91-139 days) showed that TSH was secreted in a markedly exaggerated pulsatile manner compared to that observed after birth. The mean amplitude of TSH pulses fell (p less than 0.005) from 5.9 +/- 8.1 microU/ml in the fetuses to 2.1 +/- 1.1 microU/ml in five neonatal lambs (6-22 days) and to 1.5 +/- 0.4 microU/ml in three adult nonpregnant ewes. The mean pulse frequency for the 14 fetuses was 0.7 +/- 0.3 pulses/h and was reduced (p less than 0.001) to 0.3 +/- 0.1 pulses/h in lambs and to 0.3 +/- 0.1 pulses/h in the ewes. In the neonate, hypothermia is a potent stimulus to TSH release. To examine the ontogeny of this response, the temperature of the fetus in utero (106-127 days of gestation) was lowered by circulating water (14-18 degrees C) at either a fast or slow rate through a coil placed either externally around the fetus or internally in the fetal esophagus and stomach.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment for acute lymphoblastic leukemia in children is associated with papillary carcinoma of thyroid, but not with thyroid disfunction

AIM: The treatment of acute lymphoblastic leukemia (ALL) in children may cause sequelae, some appearing only at long-term follow-up. We investigated the thyroid gland morphology and the function of the pituitary-thyroid axis in a group of patients treated for ALL in childhood. METHODS: A cohort study was conducted at a tertiary medical center. Thirty-three children (22 males and 11 females; age: 11.9+/-3 years; range: 6 to 18 years) were studied. The mean age at the time of chemotherapy and prophylactic cranial irradiation (12-24 Gy) was 5.5+/-2.6 years (range: 1 to 14 years). The average length of the follow-up was 6.1+/-3 years (range: 2 to 12 years). Thyroid morphology (n=33) was evaluated by palpation and ultrasonography. Thyroid function (n=30) was evaluated measuring total T3 and T4, and by the thyrotrophin-releasing hormone (TRH) test. Prolactin secretion was assessed before and after injection of TRH to evaluate the diagnostic test accuracy. RESULTS: One out of the 33 children (3%) was found to have a papillary carcinoma of thyroid four years after ALL treatment. Thyroid function was normal in all the patients, however one case (3%) showed high TSH (9.2 microU/mL) and prolactin (37.5 ng/mL) basal levels, but normal responses to TRH (TSH = 17.8 microU/mL; prolactin = 82.3 ng/mL). These hormonal alteration were not confirmed at follow-up: TSH = 1.6 microU/mL and prolactin = 13.7 ng/mL. CONCLUSIONS: In this cohort of patients, the treatment of ALL was associated with one case of thyroid carcinoma, but it did not produce adverse effect on the thyroid function, at least after a follow-up lasted on average 6 years.     

Significance of transient postnatal hypothyroxinemia in premature infants with and without respiratory distress syndrome

The significance of relatively low thyroxine (T4) levels in preterm infants with and without respiratory distress syndrome (RDS) was assessed by evaluating the free T4 level, the thyrotropin (TSH) response to thyrotropin releasing hormone (TRH), and intellectual development in infants less than or equal to 35 weeks with cord blood T4 concentrations less than 6.5 microgram/100 ml. Fifty-four (19 well, 28 with RDS, and seven without RDS and sick) of 215 premature infants (25%) and 27 of 8,831 term infants (0.3%) had cord T4 levels less than 6.5 microgram/100 ml. Serum T4 levels were measured in 39 surviving preterm infants (20 RDS and 19 well) during the first 5 days of life and at 2, 4, 24, and 52 weeks postnatally. Serum total T4 level during the first week was 4.5 +/- 0.3 microgram/100 ml (mean +/- SEM). Free T4 levels ranged from 1.1 to 2.2 ng/100 ml (normal adult range 0.8 to 2.3 ng/100 ml). Administration of TRH resulted in a clear increase in both TSH and T4 levels in all infants. T4 levels increased significantly (r = .70, P less than .01) with increasing postnatal age, reaching stable levels by 6 to 7 weeks. Developmental quotients obtained in the infants with low T4 levels were no different from those found in a matched control population at 12 months of age. The low T4, free T4, and TSH concentrations and normal TSH responses to TRH found in these infants are characteristic of hypothalamic (tertiary) hypothyroidism, but differ from classic tertiary hypothyroidism in that the disorder was transient. The normal intellectual development at 12 months of age and the spontaneous increase in T4 levels that occurs over the first six weeks of life suggest that the low T4 levels in these infants reflect a benign relative delay in maturation of hypothalamic-pituitary-thyroid control.     

Effect of dexamethasone on rat plasma platelet activating factor acetylhydrolase during the perinatal period

It has been previously reported that the administration of dexamethasone (DEX) to adult rats increases the activity of plasma platelet-activating factor acetylhydrolase (PAF-AH) and prevents the development of intestinal necrosis caused by platelet activating factor (PAF) injection. In this report, we examined the effect of DEX administration on plasma PAF-AH activity during the perinatal period. Timed-pregnant rats received DEX (0.2–1.0 mg/kg/d) or normal saline (controls) on days 16–18 (early group) or days 18–20 (late group) of gestation. Maternal plasma PAF-AH activity was lower in late gestation than in postpartum period (P < 0.001). Fetal and neonatal plasma PAF-AH activity was higher than maternal values (P < 0.05). No changes of PAF-AH activity were seen in maternal, fetal or neonatal plasma after prenatal DEX administration at the aforementioned doses. A higher dose of DEX (1.3 mg/kg/d × 4d) or cortisone (200 mg/kg/d) produced an elevation of maternal plasma PAF-AH activity (DEX 79.2 ± 3.0, cortisone 70.5 ± 1.9 vs. controls 49.4 ± 2.3 nmol/min/ml, P < 0.01), but resulted in a high fetal mortality. Treatment of newborn rats with DEX (0.5 mg/kg/d) on days 1–3 after birth, increased plasma PAF-AH activity on day 4 (DEX 292 ± 5 versus controls 140 ± 9 nmol/min/ml, P < 0.001) and day 6 (DEX 302 ± 12 versus controls 136 ± 6 nmol/min/ml, P < 0.001). Postnatal administration of DEX increases the plasma PAF-AH activity in the rat. Only high doses of prenatal corticosteroids that cause fetal death can elevate maternal plasma PAF-AH activity.     

Effect of low-dose dopamine infusion on prolactin and thyrotropin secretion in preterm infants with hyaline membrane disease

The effect of low-dose (2-4 micrograms/kg/min) and long-term (greater than or equal to 46 h) dopamine infusion on serum prolactin and thyrotropin concentrations was investigated in 8 preterm infants with hyaline membrane disease. Dopamine was administered for systemic hypotension and/or for impending renal failure. Serum prolactin decreased from 1,314.5 +/- 422.7 microU/ml to 489.9 +/- 464.1 microU/ml (p less than 0.005), while serum thyrotropin fell from 3.77 +/- 2.27 microU/ml to 1.01 +/- 0.25 microU/ml (p less than 0.025) during dopamine infusion. Our data indicate that exogenous dopamine exerts an inhibitory effect on the secretion of prolactin and thyrotropin even in the sick preterm neonate. The role of prolactin in fetal lung maturation and in regulation of the neonatal tissue water stores is discussed. The results of the present study are also useful in explaining the renal effects of long-term low-dose dopamine infusion in the sick preterm infant.     

Ovine placental and fetal arginine metabolism at normal and increased maternal plasma arginine concentrations

Arginine (A) may play a significant role in fetal growth, by stimulating insulin secretion and as a precursor for both polyamine synthesis and nitric oxide production. To determine whether increased maternal plasma A concentrations can enhance delivery of A to the fetus, uterine, umbilical, and net uteroplacental (UP) A uptake rates were measured in 12 pregnant ewes at 129.6 +/- 0.4 d gestation (mean +/- SEM) during normal and after 3 h of increased maternal plasma A concentrations. With a 2.7-fold increase in maternal plasma A concentrations (p < 0.001), there were significant increases in uterine A uptake (13.8 +/- 1.0 to 41.3 +/- 7.7 micromol/min, p < 0.005), umbilical A uptake (3.3 +/- 0.5 to 5.2 +/- 0.8 micromol.min(-1).kg(-1) fetus, p < 0.005), UP A uptake (17.8 +/- 6.2 to 89.2 +/- 20.3 micromol.min(-1).kg(-1) placenta, p < 0.01), fetal arterial A concentration (98.7 +/- 6.3 to 137.1 +/- 9.9 microM, p < 0.001), maternal A disposal rate (143.7 +/- 9.4 to 217.0 +/- 6.7 micromol/min, p < 0.001), fetal A disposal rate (7.9 +/- 0.8 to 9.9 +/- 1.1 micromol.min(-1).kg(-1), p < 0.05), fetal A oxidation rate (1.31 +/- 0.24 to 1.84 +/- 0.36 micromol.min(-1).kg(-1), p < 0.05), and plasma insulin concentration in both fetus (16 +/- 2 to 20 +/- 2 microU/mL, p < 0.001) and mother (24 +/- 3 to 32 +/- 4 microU/mL, p < 0.001). Thus, increased maternal plasma A concentration increases maternal, UP, and fetal A net uptake, and increases insulin secretion in mother and fetus. The 4.2-fold larger increase in UP than net fetal A uptake could represent preferential UP A metabolism relative to fetal A metabolism, relatively limited placental-fetal A transport capacity compared with uterine A uptake capacity, or both; responsible mechanisms remain unknown.     

Thyroid function in healthy premature infants.

Thyroid function was studied in healthy premature and term infants between 12 hours and 3 months of age. T4 and FT4I followed parallel courses in both groups; during the first 45 days, however, the values were significantly lower in premature infants under 34 weeks' EGA than in term infants (P less than 0.001). The post-delivery peak in TSH concentration (mean +/- SD) was 71.8 +/- 19.2 microunits/ml in the premature infants. In five premature infants, injection of TRH elicited a TSH increment of 29.4 +/- 20.7 microunits/ml at 30 minutes. T3 concentration was not significantly different in premature and term infants.     

Decreased prolactin secretion in childhood obesity

Twelve obese patients and 7 control subjects, age and sex matched, whose weights were greater than 200% of ideal weight and 100% of ideal body weight, respectively, underwent intravenous insulin and thyroid releasing hormone (TRH) tests. Serial prolactin growth hormone, insulin, blood sugar, cortisol, glucagon, thyrotropin stimulating hormone, thyroxine, and triiodothyronine were obtained by RIA. Obese patients showed no significant differences from controls in basal and nadir glucose, basal and peak glucagon, cortisol, and thyroid responses to both tests. Basal insulin levels were higher (36 +/- 9.4 vs 10 +/- 2.3 microU/ml, P less than 0.05) and peak growth hormone responses after insulin were lower in the obese group (6.1 +/- 1.1 vs 12.7 +/- 3.7 ng/ml, P less than 0.05) than in controls. Whereas all control subjects had prolactin responses to both tests, five of 12 obese patients had no responses to insulin. Obese patients had lower prolactin responses at 30 minutes after insulin (5.4 +/- 0.7 vs 12.9 +/- 3.7 ng/ml, P less than 0.05) and lower prolactin responses at 60 minutes after TRH (9.9 +/- 1.7 vs 20.4 +/- 5.9 ng/ml, P less than 0.05). Maximum prolactin responses after TRH were lower in obese patients (9.9 +/- 2.0 vs 28.8 +/- 10.9 ng/ml, P less than 0.05). Maximum prolactin responses after insulin were lower in obese patients (6.2 +/- 4.1 vs 28.9 +/- 18.3 ng/ml). Thus prolactin secretion in childhood obesity is decreased after both stimuli, but more so after IV insulin that TRH, and suggests that, as in adult hypothalamic obesity, neuroendocrine regulation of prolactin release in obese children is impaired.     

Placental transfer of lidocaine and elimination from newborns following obstetrical epidural and pudendal anesthesia

Following local anesthetic use, maternal and umbilical serum levels of lidocaine were determined at delivery by means of a gas-chromatography-mass-spectrometry technique in 13 cases. In six cases, where delivery was performed by cesarean section, lidocaine was used for epidural analgesia. The dose given averaged 4.0 +/- 1.7 mg/kg, and the time between analgesia and delivery was 22.0 +/- 4.5 minutes. The mean umbilical serum level of lidocaine was 1.19 +/- 0.79 micrograms/ml and that of the maternal serum was 2.18 +/- 1.25 micrograms/ml. The fetal to maternal ratio was 0.52 +/- 0.18. Lidocaine levels of neonatal plasma were followed at 3, 6, 12, and 24 hours after delivery, and the mean half-life was found to be 6.7 +/- 1.3 hours. In the other seven cases, lidocaine was given in normal vaginal delivery for pudendal nerve block, and the dose was as small as 0.79 +/- 0.06 mg/kg. The mean umbilical and maternal serum concentrations of lidocaine were 0.064 +/- 0.039 micrograms/ml and 0.143 +/- 0.071 micrograms/ml, respectively, and the ratio was 0.45 +/- 0.16. Lidocaine given to the mothers crossed to the fetuses readily and resulted in neonatal plasma levels that were half those of the mothers'. The elimination of lidocaine from the newborn after birth was prolonged so that it might prevent the adaptation of the infant to postnatal circumstances. Viewed from the standpoint of infant care, anesthetics at delivery should be given to the mother only when the benefit obtained by their use outweighs any possible disadvantages.     

Hormone ontogeny in the ovine fetus. IV. Serum somatomedin activity in the fetal and neonatal lamb and pregnant ewe: correlation with maternal and fetal growth hormone, prolactin, and chorionic somatomammotropin.

Somatomedin (SM) activity was measured by a placental membrane receptor assay using 125I-labeled somatomedin A, as radioligand in serum samples obtained from 33 ovine fetuses, 14 neonatal lambs, 8 pregnant, and 3 postpartum ewes. The mean serum concentration of SM activity in eight adult rams was 2.06 +/- 0.12 U/ml. In fetal sheep, SM activity was detected at 66 days gestation (term 147 days), in the youngest fetus studied. Before 100 days of gestation, SM was lower (P less than 0.001) in fetal sheep (1.08 +/- 0.18 U/ml) than in adult rams. In fetuses between 101 and 125 days, SM rose (P less than 0.001) to 2.64 +/- 0.32 U/ml. In late gestation fetal serum SM fell but during the neonatal period it rose to 3.38 +/- 0.3 U/ml, higher (P less than 0.01) than that in adult rams. Serum SM activity in the pregnant ewe prior to 100 days was 1.01 +/- 0.11 U/ml, increased (P less than 0.05) to 1.75 +/- 0.21 U/ml between 125 days and term, and rose further to 2.56 +/- 0.32 U/ml in the postpartum period. Maternal concentrations of serum SM in late gestation were significantly less than in the fetus. Gel chromatography of fetal, maternal, and neonatal sera indicated that over 90% of SM activity circulated in high-molecular weight form. The rise in SM activity in fetal serum between 100 and 125 days parallels the rise in fetal growth hormone and prolactin concentrations; however, in maternal serum the increase in SM activity is associated with rising maternal chorionic somatomammotropin concentrations.     

Combined effects of corticosteroid, thyroid hormones, and beta-agonist on surfactant, pulmonary mechanics, and beta-receptor binding in fetal lamb lung

We studied the interactions of corticosteroids, thyroid hormones, and beta-agonist on surfactant phospholipids, pulmonary mechanics, and beta-receptor binding in fetal lambs. We infused cortisol (450 micrograms/h for 48 h), thyrotropin-releasing hormone (TRH) (25 micrograms/h for 48 h), and ritodrine (1.3 micrograms/kg/min for 24 h) independently, and in double (cortisol plus beta-agonist, cortisol plus TRH), and in triple (cortisol plus TRH plus beta-agonist) combinations into chronically catheterized fetal lambs between 0.88 and 0.90 gestation. Infusion of the triple combination of cortisol plus TRH plus beta-agonist resulted in a 20.9-fold increase in the saturated phosphatidylcholine content of fetal lung lavage, in a 5.8-fold increase in the saturated phosphatidylcholine content of whole fetal lung, and in a 13.3-fold increase in the saturated phosphatidylcholine content of fetal tracheal fluid. In addition, lung stability to inflation increased 3-fold, and lung stability to deflation increased 8-fold. The increases in the saturated phosphatidylcholine content of fetal lung lavage and tracheal fluid were greater than the effects of each hormone acting independently, or in the double combinations. The beta-receptor maximal binding capacity was increased 30% by the combined infusion of cortisol and TRH. In addition, the maximal binding capacity after cortisol plus TRH plus beta-agonist infusion was 54% greater than the maximal binding capacity after beta-agonist infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Short-term hyperthyroidism followed by transient pituitary hypothyroidism in a very low birth weight infant born to a mother with uncontrolled Graves' disease

Transient hypothyroxinemia in infants born to mothers with poorly controlled Graves' disease was first reported in 1988. We report that short-term hyperthyroidism followed by hypothyroidism with low basal thyroid-stimulating hormone (TSH) levels developed in a very low birth weight infant born at 27 weeks of gestation to a noncompliant mother with thyrotoxicosis attributable to Graves' disease. We performed serial thyrotropin-releasing hormone (TRH) tests in this infant and demonstrated that TSH unresponsiveness to TRH disappeared at 6.5 months of age. The maternal thyroid function was free triiodothyronine (FT(3)), 21.1 pg/mL; free thyroxine (FT(4)), 8.1 ng/dL; TSH, <0.03 microU/mL; thyroid-stimulating hormone receptor antibody, 52% (normal: <15%); thyroid-stimulating antibody, 294% (normal: <180%); and thyroid-stimulation blocking antibody, 9% (normal: <25%) on the day of delivery. A nonstress test revealed fetal tachycardia >200 beats per minute, and a male infant weighing 1152 g was born by emergency cesarean section. Thyroid-stimulating hormone receptor antibody was 16% and thyroid-stimulating antibody was 370% in the cord blood. We administered 10 mg/kg per day of oral propylthiouracil from day 1. Tachycardia along with elevated FT(4) and FT(3) levels in the infant decreased from 200/minute to 170/minute, 4.7 ng/dL to 2.9 ng/dL, 7.0 pg/mL to 4.8 pg/mL, respectively, in the first 33 hours. At 5 days, FT(4) and FT(3) were 1.1 ng/dL and 2.9 pg/mL, respectively, and we stopped propylthiouracil administration. Although FT(4) decreased to 0.4 ng/dL, TSH was quite low and did not respond to intravenous TRH by 14 days of age. We began daily levothyroxine 5-micro/kg supplementation. The responsiveness of TSH to TRH did not become significant until 4 months old and normalized at 6.5 months old. At this time, levothyroxine was stopped. We conclude that placental transfer of thyroid hormones may cause hyperthyroidism in the fetal and early neonatal periods and lead to transient pituitary hypothyroidism in an infant born to a mother with uncontrolled Graves' disease.