Thyrotropin, prolactin and growth hormone response to synthetic thyrotropin-releasing hormone in newborn infants.

The effects of 50 microgram synthetic thyrotropin-releasing hormone (TRH) intravenously on thyrotropin (TSH), prolactin (PRL) and growth hormone (GH) levels were studied in 8 normal male newborns during the first hours of life. Mean plasma GH concentrations were similar to baseline values during the period of study; on the contrary, plasma PRL and TSH values increased in all infants after TRH administration. These data demonstrate a normal pituitary reserve of PRL and TSH in the early period of human life.     

Development of contrast sensitivity in infants with prenatal and neonatal thyroid hormone insufficiencies

Thyroid hormone is essential for normal brain development including structures critical for visual processing. While chick and rodent models have demonstrated abnormal visual development following prenatal thyroid hormone loss, comparable data do not exist in the human. To determine whether human infants with intrauterine and early postnatal thyroid hormone insufficiencies have compromised visual abilities, we investigated contrast sensitivity and visual acuity development in 13 infant offspring of women with hypothyroidism during pregnancy (HYPO), 16 preterm infants born between 32 and 35 weeks gestation, 12 infants with congenital hypothyroidism (CH), and 20 typically developing infants. All were assessed with the sweep visual evoked potential technique at 3, 4.5, and 6 months (corrected) age. Results showed significantly reduced contrast sensitivity but normal visual acuity in HYPO and CH groups relative to controls (p < 0.003 and p < 0.05 respectively). Stratification of the HYPO group into subgroups based on maternal TSH levels during the first half of pregnancy revealed lower contrast sensitivities for infants whose mothers' TSH values were above than below the median (p < 0.05). In the CH group, those with an absent thyroid gland and/or a newborn TSH value above 200 mIU/L had lower contrast sensitivities than did those with other etiologies or TSH levels below 100 mIU/L (p < 0.05). There were no significant effects involving the preterm group. These results indicate that thyroid hormone is important for human visual development.     

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.     

Serum thyroid hormones and pituitary response to thyrotropin-releasing hormone in epileptic children receiving anti-epileptic medication

Thyroid hormones and pituitary function were assessed in 49 children with epilepsy who were receiving either a single medication of carbamazepine, phenobarbital and valproate or a combination of carbamazepine with phenobarbital or valproate. All therapeutic regimens except valproate monotherapy were associated with low levels of circulating thyroxine, free tri-iodothyronine and free thyroxine. Carbamazepine with valproate was associated with the lowest serum concentration of thyroid hormones. It seems probable that accelerated hormone metabolism is responsible for these hormonal changes. However, all drug regimens also had effects on the function of the hypothalamic pituitary axis. Because of these findings, thyroid hormones should be checked frequently during anti-epileptic drug treatment, although clinical hypothyroidism was not seen in our patients.     

Reduction of mortality rate in premature infants by substitution of thyroid hormones

Our previous examinations had shown that 9 of 13 premature infants with severe respiratory distress had hypothyroid T4-values. On the basis of these results a prospective study was initiated. Every second neonate born after less than 37 weeks gestation or weighing less than 2200 g and admitted to our intensive care unit since Janary 1979 received a prophylactic dose of 25 g l-Thyroxine and 5 g Tri-iodothyronine daily. Five of the patients inadvertently did not receive the drug and were included in the non-treated group which thus numbered 55. Both groups were nearly identical with regard to gestational age, birth weight and Apgar score.In the treated group of 45 infants three (=6.6%) died. In the untreated group of 55 infants 16 (=29%) died. The probability that the different mortality in the two groups was due to chance alone is less than 0.5% (²-test: P<0.005). In 14 of the 55 non-treated patients transient hypothyroidism developed. Five patients with transient hypothyroidism and 2 patients with low T4-values without a TSH-increase were treated with thyroid hormone after ascertainment of their serum thyroxine levels and six survived.The analysis of the prophylactically treated cases showed that the dosage of 25 g l-Thyroxine and 5 g Tri-iodothyronine in critically ill infants (i.e., those who were mechanically ventilated or had sepsis) was rarely sufficient to produce normal serum thyroxine levels. In these children thyroxine usually rose to normal levels only when they had passed the acute stage of the disease. It therefore seems advisable to double the dose of thyroid hormone during the acute stage of the disease.     

Plasma prolactin and clinical outcome in preterm infants.

Plasma prolactin was measured weekly in 280 preterm infants. The complex gestational age dependent pattern of postnatal prolactin release has been defined and reference standards provided. Plasma prolactin was higher in girls, with increasing divergence between the sexes from the third week onwards, and higher after two weeks, in infants of mothers with pregnancy related hypertension. Diet, assigned randomly, exerted a major effect on plasma prolactin, with significantly higher values in infants fed donor breast milk or standard formula than in those fed a protein, energy, and mineral enriched preterm formula. After adjusting for confounding factors, infants with the lowest plasma prolactin concentrations (less than 1000 mU/l, 32.9 micrograms/l) occurring usually at a nadir between days 5 and 12, showed a 120% increase in the duration of ventilatory assistance required, a 20% increase in the number of days to attain full enteral feeds, and a 30% decrease in length gain. We suggest preterm birth disrupts the normal perinatal pattern of prolactin release and that those infants who develop relatively low plasma concentration have an adverse outcome. Our data add to the broader debate on whether preterm infants require multiple endocrine replacement treatment.     

Postnatal intestinal disturbances in small-for-gestational-age premature infants after prenatal haemodynamic disturbances

Uteroplacental insufficiency leads to fetal growth retardation, which is a major cause of perinatal and postnatal morbidity. In the present study we investigated the relationship between prenatal haemodynamic disturbances and postnatal intestinal perfusion and gastrointestinal function in small-for-gestational-age neonates. Prospectively, 114 preterm neonates with a birthweight below 1500 g were assigned to one of two groups according to their prenatal Doppler sonographic measurements: neonates with or without prenatal haemodynamic disturbances. We defined a pathological fetal perfusion by a pulsatility index of uterine arteries, umbilical artery and fetal thoracic aorta above the 90th percentile and by a pulsatility index of middle cerebral artery below the 10th percentile of a normal group. We compared the postnatal respiratory and intestinal adaptation in both groups as well as the blood flow velocity waveforms of the superior mesenteric artery in all neonates. Postnatally, all 36 neonates with prenatal haemodynamic disturbances were classified to be small for gestational age. Thirty-one of these neonates developed abdominal problems with delayed meconium passage, abdominal distension, bilious vomiting and a delay in tolerating in enteral feeding within the first days of life. Six of them needed surgical intervention, but none of these infants revealed typical signs of necrotizing enterocolitis. In contrast, all neonates after normal prenatal perfusion were classified to be appropriate for gestational age. Only 19 of 78 neonates of this group showed signs of intestinal disturbances postnatally. By Doppler sonographic investigations we found significant lower systolic, mean and end-diastolic flow velocities and higher pulsatility indices of the superior mesenteric artery in neonates with prenatal haemodynamic disturbances. This may occur as a result of postnatal persistent redistribution of regional blood flow and results in gastrointestinal problems and may adversely affect gut motility.     

Type of feeding does not influence thyroid hormone levels in premature infants

Thirty premature neonates (mean gestational age 31.8 +/- 3.90 weeks; mean birth weight 1569 +/- 236 g) were divided into three groups receiving breast milk, Robolact and Pre-Aptamil formula feeding. The infants with and without neonatal idiopathic respiratory distress syndrome (IRDS) were separately evaluated. No effect of the type of feeding and of a previously experienced IRDS on the blood T3-, T4-, and THS-levels could be demonstrated at the age of 6 weeks.     

Thyroid-stimulating hormone, prolactin, and growth hormone response to thyrotropin-releasing hormone in treated children with congenital hypothyroidism

The purpose of the present study was to assess thyroid-stimulating hormone (TSH), prolactin, and growth hormone responses to TRH stimulation in 12 congenitally hypothyroid children adequately treated with L-thyroxine from the first weeks of life. Although clinically euthyroid, six of these children were found to have abnormally high basal serum TSH concentrations despite clinical euthyroidism. Serum triiodothyroxine and L-thyroxine concentrations were normal and did not differ whether the children had elevated or normal basal serum TSH. All six of the children with high basal TSH had an exaggerated TSH response to TRH and 4 of them also had an augmented prolactin response to TRH. The children with normal basal TSH concentrations had normal TSH and prolactin responses to TRH. An abnormal ("paradoxical") elevation of growth hormone concentration in response to TRH was found in four of seven children in a separate group of patients who had prolonged, untreated primary hypothyroidism, but such responses were not found in any of the adequately treated children. These findings suggest the following conclusions: 1) the phenomenon of high serum concentrations of TSH in conjunction with normal L-thyroxine and triiodothyronine levels (and clinical euthyroidism), is prevalent in congenital hypothyroid patients. 2) These patients have an exaggerated response of their pituitary thyrotroph and lactotroph cells to TRH, presumably caused by selective and relative resistance of these cells to the inhibitory effects of thyroid hormones. 3) Congenital hypothyroidism is not associated with abnormal somatotroph cell responses to TRH.     

Growth hormone levels during the first week of life in full-term normal infants, infants of diabetic mothers and in premature infants

Growth hormone levels during insulin- and glucose load have been studied, in normal infants, infants of diabetic mothers and in premature infants during the first week of life.
Base levels of HGH were elevated in all patients when compared to older infants. The highest levels were present on the first day of life. Lower levels were found in infants of diabetic mothers than in the other patients studied.
Insulin-induced hypoglycaemia increased HGH levels in all patients. The increase was more pronounced at the age of one day as compared, to 5—6 days if the absolute levels were compared. The increase was more moderate in infants of diabetic mothers. If the response to hypoglycaemia is expressed as the per cent maximal increment from basic levels no difference in response can be shown between the first day of life and the age of 5—6 days or between normal infants and infants of diabetic mothers. For premature infants the response in per cent increment was more pronounced at the end of the first week and of much higher degree than for other infants studied.
Hyperglycaemia induced an increase in HGH levels comparable to that found during hypoglycaemia. The differences between the groups studied are the same as for hypoglycaemia.     

Leptin and metabolic hormones in infants of diabetic mothers

AIMS: To investigate the effect of maternal diabetes on leptin in term newborns and to determine whether leptin correlates with insulin and its associated biochemical parameters in support of the hypothesis that a functional "adipoinsular axis" might exist at this stage of development. METHODS: A total of 116 term newborns were prospectively enrolled and categorised into three groups: 44 were infants of non-diabetic mothers (control group C); 41 were infants born to mothers with gestational diabetes on dietary treatment (group D); and 31 were infants born to mothers with gestational or pregestational diabetes on insulin treatment (group I). RESULTS: No significant difference in serum leptin was observed between the three groups; the results of the study population were therefore pooled and analysed. Serum leptin correlated significantly with serum insulin, insulin:glucose ratio, birth weight, body length, body mass index, placenta weight, and maternal HbA(1c). Female infants had significantly higher serum leptin than male infants. All parameters except placenta weight and body length remained significantly associated with serum leptin when multivariate stepwise regression analysis was applied. Subgroup analysis revealed a significant correlation between serum leptin and cortisol in group D. CONCLUSIONS: There was no significant difference in serum leptin between infants born to diabetic and non-diabetic mothers, though infants born to mothers requiring insulin treatment had the highest median serum leptin concentrations. The significant association between serum leptin and insulin or insulin:glucose ratio supports the hypothesis that a functional adipoinsular axis might exist in term newborns. Furthermore, the significant correlation between maternal HbA(1c) and circulating leptin of the studied infants suggests that the clinical control of maternal diabetes could affect the regulation of serum leptin in these infants.     

Chlamydial infection of mothers and their infants.

In 340 women, cultured prospectively during their pregnancies, the rate of infection with Chlamydia trachomatis was 8.8%. The women with positive cultures tended to be younger and more often single and black than their counterparts with negative cultures. There were no statistically significant clinical differences between the two groups. Eighteen children born to Chlamydia culture-positive women and 16 born to negative women were followed for nine months to examine the potential effects of maternal infection on infant growth, development, and illness. Eleven of 18 study patients had culture or tear antibody evidence of Chlamydia infection, as opposed to one of the control subjects (P = 0.00093). Eight of these 11 had clinical conjunctivitis, and two of the eight developed pneumonia. Growth retardation and developmental abnormalities were not detected in either group. It is concluded that maternal carriage of C. trachomatis is associated with a high incidence of clinical illness in the offspring.