Pituitary-thyroid responsiveness to thyrotropin-releasing hormone in preterm and small-for-gestational age newborns.

A dose of 40 microgram TRH was injected intravenously in 12 preterm (PT) and 15 small-for-gestational age (SGA) babies (with advanced gestational ages) between 5 and 167 hours after birth. Serum-thyrotropin (TSH) was measured prior to and 30 and 180 min after TRH; serum-thyroxine (T4) and serum-triiodothyronine (T3) were measured prior to and 180 min after TRH. The percentage increase in serum-TSH in PT and SGA babies was comparable to that of fullterm newborns. The serum-TSH 30 min after TRH in SGA newborns was significantly correlated to basal TSH values, such a correlation could not be shown in the preterms. One SGA and four PT babies had a repeat TRH-test performed later in infancy: In all but one PT with a gestational age of 27 weeks the TSH rise was lower than in the neonatal period. The thyroid hormone responses after TRH were similar in the two groups of babies. The percentage increase above basal levels were: Median serum-T3 increase about 46% and median serum-T4 increase about 14%. It is concluded that in low-birth-weight newborn babies the pituitary TSH response to exogenous TRH was like that detected in fullterm newborns and more pronounced that later in infancy. The effect of endogenous TSH as measured by thyroid hormone increases was of the same magnitude as observed in fullterms and in adults.     

Plasma protein Z levels in healthy and high-risk newborn infants

AIM: To evaluate plasma protein Z (PZ) levels in healthy and high-risk newborn infants. METHODS: A longitudinal observational study was conducted. Inclusion criteria were: healthy term and preterm newborns normal for gestational age and newborns belonging to one of the following groups: newborns small for gestational age (SGA), newborns affected by respiratory distress syndrome (RDS), newborns from mothers with pre-eclampsia. Newborns with sepsis, congenital malformation or haemorrhagic disorders were excluded. Plasma PZ levels, protein C (PC) concentration, PC activity and protein-induced vitamin K absence levels were measured. RESULTS: 53 newborns were enrolled into the study. PZ and PC antigen levels varied significantly among analysed subgroups on day 1 (p < 0.01): lower levels of these inhibitors were found in RDS newborns (group C), newborns from mothers affected by pre-eclampsia (group D) and SGA newborns (group E) than in healthy term and preterm newborns (groups A and B). CONCLUSION: PZ deficiency occurs in newborns affected by severe RDS, in newborns from pre-eclamptic mothers and in SGA newborns, probably owing to activated coagulation in the first two conditions and to reduced PZ synthesis in the last condition.     

PITUITARY-THYROID RESPONSIVENESS TO THYROTROPIN-RELEASING HORMONE IN PRETERM AND SMALL-FOR-GESTATIONAL AGE NEWBORNS

Abstract. A dose of 40 μg TRH was injected intravenously in 12 preterm (PT) and 15 small-for-gestational age (SGA) babies (with advanced gestational ages) between 5 and 167 hours after birth. Serum-thyrotropin (TSH) was measured prior to and 30 and 180 min after TRH; serum-thyroxine (T₄) and serum-triiodothyronine (T₃) were measured prior to and 180 min after TRH. The percentage increase in serum-TSH in PT and SGA babies was comparable to that of fullterm newborns. The serum-TSH 30 min after TRH in SGA newborns was significantly correlated to basal TSH values, such a correlation could not be shown in the preterms. One SGA and four PT babies had a repeat TRH-test performed later in infancy: In all but one PT with a gestational age of 27 weeks the TSH rise was lower than in the neonatal period. The thyroid hormone responses after TRH were similar in the two groups of babies. The percentage increase above basal levels were: Median serum-T₃ increase about 46% and median serum-T₄ increase about 14%. It is concluded that in low-birth-weight newborn babies the pituitary TSH response to exogenous TRH was like that detected in fullterm newborns and more pronounced than later in infancy. The effect of endogenous TSH as measured by thyroid hormone increases was of the same magnitude as observed in fullterms and in adults.     

Normal thyroid function in young adults who were born very preterm

There is some evidence for elevated thyrotropin (TSH) levels in children born preterm, but follow-up studies into adulthood are lacking. We tested whether thyroid function in young adults born at a gestational age < 32 weeks, with either an appropriate (appropriate for gestational age, AGA) or low birth weight for gestational age (small for gestational age, SGA), differed from that in age-matched controls. We made our measurements when the study participants reached 21 years of age. Serum concentrations of TSH and free T4 (fT4) and body composition were measured in subjects born preterm and AGA (n = 29) or SGA (n = 28), and in non-preterm controls (n = 30). The TSH and fT4 concentrations of participants were within normal limits. Free T4 levels in subjects born preterm were slightly higher than those in controls: 17.0 +/- 2.4 (AGA) and 17.2 +/- 1.7 (SGA) vs. 16.1 +/- 1.9 pmo/L (p = 0.04). TSH concentrations did not differ between groups. From these preliminary data, we conclude that young adults born preterm have a normal thyroid function.     

SERUM CONCENTRATIONS OF THYROXINE-BINDING GLOBULIN, PREALBUMIN AND ALBUMIN IN HEALTHY FULLTERM, SMALL-FOR-GESTATIONAL AGE AND PRETERM NEWBORN INFANTS

Abstract. Jacobsen, B. B., Peitersen, B., Andersen, H. J. and Hummer, L. (The University Clinic of Paediatrics, Children's Hospital Fuglebakken and the Departments of Nuclear Medicine, Rigshospitalet, Copenhagen, Denmark). Serum concentrations of thyroxine-binding globulin, prealbumin and albumin in healthy fullterm, small-for-gestational age and preterm newborn infants. Acta Paediatr Scand, 68: 49, 1979.—Simultaneous serum concentrations of thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin (Alb) were measured in 130 fullterm, 32 small-for-gestational age and 25 preterm infants during their first six days of life. In all infants serum concentrations of TBG were higher and serum TBPA and Alb were lower than in male adults. Even higher serum TBG levels wer found in the mothers. There was no correlation between serum concentrations in paired maternal and cord sera. In infants with birth weights appropriate for gestation serum TBG, TBPA, and Alb concentrations increased progressively with gestational age. In small-for-gestational age infants born at term serum concentrations of TBG and Alb were lower than those in full-term, but higher than those in premature newborns. Serum TBPA in small-for-gestational age babies was evne lower than seen in prematures. A positive correlation was found between thyroid hormones and TBG concentrations, not between serum TBPA and thyroid hormones. The ratios between serum concentration of thyroid hormones and proteins might indicate that more thyroid hormonebinding sites are occupied in fullterm than in low birth-weight newborns. However, the main reason for the different serum levels of thyroid hormones in fullterm, small-for-gestational age and preterm babies is probably the various serum TBG concentrations demonstrated in these infants.     

早产儿暂时性甲状腺功能低下替代治疗临床研究进展

早产儿暂时性甲状腺功能低下(THOP)发生率高,是否给予甲状腺素替代治疗存在分歧.有关THOP的临床研究提示,THOP甲状腺素替代治疗不能降低病死率、呼吸疾病发生率,可降低动脉导管未闭的发生率.胎龄小于28周THOP早产儿给予甲状腺素替代治疗可能改善神经发育预后,胎龄大于28周不能改善神经发育.未来研究应按胎龄确定早产儿甲状腺素正常值;设计良好的根据胎龄分层的临床随机研究,以明确甲状腺素替代治疗对远期神经发育的影响.     

小于胎龄儿新生儿期ghrelin水平与生长轴关系的研究

目的通过比较小于胎龄儿（SGA）与适于胎龄儿（AGA）新生儿早期血ghrelin水平和代谢促生长轴各因素的差别和相关性，探索ghrelin在SGA发病机制中的作用。方法通过配对对17例SGA和17例AGA的血清ghrelin、IGF-1、生长激素、胰岛素、血糖浓度进行比较并分析其差异的意义。结果与AGA组相比，SGA组血ghrelin水平显著升高（P〈0．05），血IGF-1、胰岛素水平显著下降（P〈0．05），血生长激素和血糖水平差异无统计学意义。结论与AGA相比，SGA新生儿有高ghrelin血症。SGA新生儿的高血ghrenlin水平伴随其低下的出生体重、身长、血IGF-1、胰岛素水平，在一定程度上反映了其宫内营养不良状况。ghrelin作为胰岛素的反调节激素，SGA的ghrelin高分泌可能是宫内能量负平衡所致低胰岛素、低IGF-1状态反馈和／或重整性调控的结果。     

早产儿暂时性甲状腺功能低下替代治疗临床研究进展

早产儿暂时性甲状腺功能低下(THOP)发生率高,是否给予甲状腺素替代治疗存在分歧.有关THOP的临床研究提示,THOP甲状腺素替代治疗不能降低病死率、呼吸疾病发生率,可降低动脉导管未闭的发生率.胎龄小于28周THOP早产儿给予甲状腺素替代治疗可能改善神经发育预后,胎龄大于28周不能改善神经发育.未来研究应按胎龄确定早产儿甲状腺素正常值;设计良好的根据胎龄分层的临床随机研究,以明确甲状腺素替代治疗对远期神经发育的影响.     

Resistin in preterm and term newborns: relation to anthropometry, leptin, and insulin

This study aimed to investigate 1) the plasma resistin concentration at birth, 2) the relationship of resistin with leptin and insulin, and 3) the association of resistin with anthropometric indexes in newborn infants. Blood samples for hormonal assay were obtained from preterm and term newborns within the first 2 h of life and before milk feeding or energy intake. Although these infants required blood sampling for clinical reasons, all were proved to be noninfected. Plasma resistin was significantly higher in term than in preterm infants. It was also significantly correlated with serum leptin, and both hormones were significantly associated with gestational age and anthropometric indexes. Infants who were born vaginally were found to have significantly higher plasma resistin levels compared with those who were born by cesarean section. In the multivariate forward stepwise regression models, resistin was found to be significantly associated with the mode of delivery and gestational age or birth weight. The association among resistin, leptin, and anthropometric indexes suggested that both hormones might be gestation related. A high circulating resistin level at term gestation could be advantageous to the infant by promoting hepatic glucose production and preventing hypoglycemia after birth. Infants who were born vaginally had significantly higher plasma resistin levels, suggesting that this hormone might also be associated with stress or inflammation induced by the birth process.     

Dopamine infusion and anterior pituitary gland function in very low birth weight infants

BACKGROUND: Previous studies demonstrated that dopamine infusion reduces plasma concentration of thyroxine (T4), thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) in adults, children, and infants. OBJECTIVES: The purpose of this prospective observational study was to evaluate the relationship between dopamine infusion and the dynamics of T4, TSH, PRL, and GH in preterm newborns weighing less than 1,500 g (very low birth weight infants, VLBW) admitted in a neonatal intensive care unit of a university hospital over a one year period. METHODS: A total of 97 preterm newborns were enrolled and divided into two groups: group B included hypotensive infants treated with plasma expanders and dopamine infusion; group A was the control group including newborns who were never treated with dopamine. The newborns were studied dynamically through blood samples taken every day till 10 days. Newborns of group B were studied during dopamine infusion and after its withdrawal. RESULTS: Among the VLBW newborns who were given dopamine, the four pituitary hormones had different dynamics: a reduction of T4, TSH, and PRL levels was noticed since the first day of treatment, and a rebound of their levels was evident since the first day after its interruption. On the contrary, the postprandial GH levels were roughly constant: GH plasma concentrations were in fact a little lower in newborns treated with dopamine, and a slight increase was observed after its withdrawal. However, observed differences were not statistically significant. CONCLUSIONS: The results suggest that dopamine infusion reduces T4, TSH, and PRL plasma levels in preterm VLBW infants and have no effect on postprandial GH rate. This hormonal suppression reverses rapidly after dopamine withdrawal. This observation suggests that the iatrogenic pituitary suppression probably cannot produce long-term injuries.     

Changes in serum concentrations of thyroid hormones and thyroid hormone-binding proteins during early infancy. Studies in healthy fullterm, small-for-gestational age and preterm infants aged 7 to 240 days.

Serum concentrations of thyrotropin (TSH), thyroxine (T4), triiodothyronine (T3), thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin (Alb) were determined in 492 blood samples from 127 fullterm (FT), 91 small-for-gestational age (SGA) and 88 preterm (PT) healthy infants aged 7 to 240 days. Serum T4 decreased about 20% during the first month of life. In infants aged 7--49 days, serum T4 concentrations were significantly lower in SGA than in FT infants, and even lower values were found in PT infants. Serum T3 increased 50--70% reaching maximal values by 50--79 days of life. Serum T3 levels were higher in FT than in SGA infants throughout the observation period. In PT infants serum T3 increased from low values to levels which exceeded those of SGA and FT infants by 120--240 days of life. Serum TSH level did not change with age and was less than or equal to 5 mU/l in all infants. Serum TBG values were high compared to normal adult values and did not change significantly with age. Comparable serum TBG values were found in FT, SGA and PT infants. Serum TBPA increased with age. Serum TBPA increased gradually in FT infants. In SGA infants serum TBPA increased from low values to levels which by 120--240 days of life exceeded those of PT and FT infants. In PT infants a decrease in serum TBPA appeared before the rise commenced. Serum Alb increased gradually in FT, SGA and PT infants during the observation period. Serum Alb in PT infants aged 30--119 days was lower than those in FT infants with similar ages. These physiological changes in serum concentrations of thyroid hormones and hormone-binding proteins during early infancy should be considered when interpreting thyroid function tests in infants with various maturity.     

Energy expenditure in very low birth weight newborns: a comparison between small and appropriate‐for‐gestational‐age

Aims: To compare resting energy expenditure (REE) in small‐ and appropriate‐for‐gestational‐age very low birth weight newborns after reaching corrected at‐term age. Methods: Observational study that included all clinically stable very low birth weight newborns admitted to a neonatal intensive care unit. The newborns were classified as small‐for‐gestational‐age (SGA) and appropriate‐for‐gestational‐age (AGA). Resting energy expenditure was measured using indirect calorimetry when the newborns reached at‐term age. Results: A total of 51 newborns, of which 23 were SGA and 28 AGA, were included. There was no statistically significant difference in REE between the two groups, although the observed levels were higher than the reference values. Conclusion: There is no statistical difference in resting expenditure energy between SGA and AGA infants when they reached term. The higher energy expenditure found in both groups may be explained by other factors related to prematurity and its complications and requires further investigation.     

Serum concentrations of thyroxine-binding globulin, prealbumin and albumin in healthy fullterm, small-for-gestational age and preterm newborn infants.

Simultaneous serum concentrations of thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin (Alb) were measured in 130 fullterm, 32 small-for-gestational age and 25 preterm infants during their first six days of life. In all infants serum concentrations of TBG were higher and serum TBPA and Alb were lower than in male adults. Even higher serum TBG levels were found in the mothers. There was no correlation between serum concentrations in paired maternal and cord sera. In infants with birth weights appropriate for gestation serum TBG, TBPA, and Alb concentrations increased progressively with gestational age. In small-for-gestational age infants born at term serum concentrations of TBG and Alb were lower than those in fullterm, but higher than those in premature newborns. Serum TBPA in small-for-gestational age babies was even lower than seen in prematures. A positive correlation was found between thyroid hormones and TBG concentrations, not between serum TBPA and thyroid hormones. The ratios between serum concentration of thyroid hormones and proteins might indicate that more thyroid hormonebinding sites are occupied in fullterm than in low birth-weight newborns. However, the main reason for the different serum levels of thyroid hormones in fullterm, small-for-gestational age and preterm babies is probably the various serum TBG concentrations demonstrated in these infants.     

Fetal growth regulation and intrauterine growth retardation

Gestational age and neonatal anthropometric parameters are currently used to evaluate fetal growth and are predictive factors of perinatal and postnatal morbidity and mortality. We performed a retrospective analysis of neonatal anthropometric parameters (weight, vertex-heel length and head circumference) in 1,470 live preterm neonates born between 1997 and 2002 and a prospective analysis of the same parameters in 1,786 live newborns of both sexes born in 2001 and 2002, products of single 37-42 week uncomplicated pregnancies in healthy Spanish Caucasian mothers. A progressive increase in these parameters with gestational age and sexual dimorphism were observed from the 30th week of gestational age onwards, with statistically-significant differences (p<0.05) at 38-42 weeks of gestational age. An increase in weight and length values in relation to previous Spanish studies was also documented in preterm newborns. It is estimated that 10-15% of children born small for gestational age (SGA) do not experience catch-up growth by the age of 3 years and may have short stature in adulthood. Preliminary data of a cross-sectional study on spontaneous growth in boys and girls born SGA without postnatal catch-up growth show that their +2 SD values of height are similar to -2 SD values of our normal control population of children born with adequate weight and length for gestational age (AGE). However, weight +2 SD values are similar to mean values of control children born AGE. In summary, our data show sexual dimorphism in neonatal anthropometric growth parameters and that these parameters change with time and may be updated. In addition children born SGA without postnatal catch-up are shorter and have higher weight than age-, height- and sex-matched controls born AGE.     

Dopamine infusion: a possible cause of undiagnosed congenital hypothyroidism in preterm infants.

OBJECTIVE: To describe the possibility that dopamine infusion can prevent early diagnosis of congenital hypothyroidism. DESIGN: Case report. SETTING: Medical neonatal intensive care unit of a tertiary academic medical center. PATIENTS: We report four preterm newborns affected by transient primary congenital hypothyroidism who showed low serum thyroxine and normal thyroid-stimulating hormone concentrations on primary screening performed during treatment with dopamine. INTERVENTIONS: Thyroid reevaluation screening after dopamine discontinuation. MEASUREMENTS AND MAIN RESULTS: Thyroid reevaluation showed elevated thyroid-stimulating hormone levels. CONCLUSION: We emphasize that dopamine capacity to suppress thyroid-stimulating hormone could prevent early diagnosis of congenital hypothyroidism. We suggest all newborns to be tested simultaneously for thyroid-stimulating hormone and thyroxine values at primary screening. A reevaluation of thyroid hormones after dopamine discontinuation is advisable in patients treated with dopamine.     

Effect of perinatal asphyxia on thyroid hormones

OBJECTIVE: To verify the effect of perinatal asphyxia on thyroid hormone levels in term newborn infants. METHODS: We carried out a case-control study with 17 term and asphyxiated (A) and 17 term and control (N) newborn infants at the Hospital de Clínicas de Porto Alegre. Patients were paired according to color of skin, sex, type of delivery, gestational age, and weight at birth. We collected umbilical cord plasma T4, T3, free T4, reverse T3, and TSH after 18 to 24 hours of life and from asphyxiated and control newborn infants. RESULTS: There were no differences in thyroid hormones of cord blood, with the exception of reverse T3, which was higher in A than in controls [median (25th-75th percentile): A= 2(1.4-2); N= 1.41 (1.13-1.92); P=0.037)]. Thyroid hormone levels were lower in A than in controls on samples collected within 18-24 hours after birth, except for reverse T3, which was similar in both groups [average -/+ SD: T4 A= 9.79 -/+ 2.59; N=14.68 -/+ 3.05; P<0.001; median T3 A= 40.83 (37.4-80.4); N= 164 (56.96-222.5); P=0.003; average -/+ SD: free T4 A=1.85 -/+ 0.92; N= 2.8 -/+ 0.74; P=0.004; median: reverse T3 A=1.54 (1.16-1.91); N=1.31(0.87-2); P=0.507; TSH A=9.1 (6.34-12.95); N=14.5(12.9-17.85); P=0.008]. CONCLUSIONS: Our data suggest that lower T4, free T4, and T3 levels are secondary to lower TSH levels in asphyxiated newborns; also, peripheral metabolism of T4 in asphyxiated infants can be altered due to low T3 and normal reverse T3 levels.     

Examination of Infant Brain Maturation Using Ultra Low Field MRI

ABSTRACT. The brains of 42 newborn infants were examined with MRI at 0.02 T field, and regional variations of T1 relaxation time were measured from the images. There were three groups: 1. full term infants (9), 2. preterm infants (10) and 3. SGA (= small for gestational age) infants (20). Relaxation times showed a correlation to myelination of the brain. The brain of SGA infants showed a large variation in their T1 values.     

Adrenal and thyroid axis function in preterm ventilated baboons

Cortisol and thyroid hormones are critical to normal fetal development and neonatal transition, and baseline values and stimulation tests are abnormal after preterm birth. To evaluate cortisol and thyroxine (T4) responses that are not influenced by uncontrolled antenatal events associated with human preterm labor, we measured cortisol and T4 after standard-dose adrenocorticotropin (ACTH) and corticotropin-releasing hormone (CRH) stimulation tests, as well as high-dose CRH and thyrotropin-releasing hormone stimulation tests in baboons that were delivered for 3 separate protocols at 125 days of gestation (term is 186 days). The animals were surfactant treated and ventilated for up to 14 days. Some fetuses were exposed to fetal or maternal betamethasone, and some newborns were treated with 10 microg/kg T4 for 9 days after birth. Baseline cortisol levels were in a stress range of 30-60 microg/dl by day 5. Cortisol did not increase consistently until day 11 in response to a high CRH dose or ACTH. T4 treatment for 9 days after birth suppressed the cortisol responses and subsequent baseline T4 levels. The hypothalamic-pituitary-adrenal (HPA) axis was unresponsive to standard dose stimulation tests until 11 days of age in preterm baboons, indicating HPA immaturity.     

Maternal iron intake during pregnancy and the risk of small for gestational age

Studies of iron and its association with the risk of small for gestational age (SGA) show inconsistent results. Consuming iron supplements during pregnancy is controversial because of possible risks. This study assessed the association between iron intake and the risk of having an SGA newborn and whether iron intake is associated with gestational diabetes. A case–control study of 518 pairs of Spanish women who were pregnant and attending five hospitals was conducted. Groups were matched 1:1 for age (±2 years) and hospital. Cases were women with an SGA newborn at delivery. Controls were women with normal‐sized newborns at delivery. Data were gathered on demographic characteristics, socio‐economic status, adverse habits (like smoking), and diet. A 137‐item food frequency questionnaire was completed. Iron intakes were categorized in quintiles (Q1–Q5). Crude odds ratios (ORs) and adjusted ORs (aORs) with 95% confidence intervals (CIs) were estimated by conditional logistic regression. No significant relationship was found between dietary iron intake and SGA. A protective association was found for women receiving iron supplementation >40 mg/day and SGA versus women not taking supplements (aOR = 0.64, 95% CI [0.42, 0.99]). This association was identified in mothers both with (aOR = 0.57, 95% CI [0.40, 0.81]) and without (aOR = 0.64, 95% CI [0.64, 0.97]) anaemia. In women in the control group without anaemia, iron supplementation >40 mg/day was positively associated with gestational diabetes (aOR = 6.32, 95% CI [1.97, 20.23]). Iron supplementation in pregnancy may prevent SGA independently of existing anaemia but may also increase the risk of gestational diabetes.     

Serum free T4 and thyroid stimulating hormone levels in preterm infants and relationship between these levels and respiratory distress syndrome

BACKGROUND: There have been few studies of the thyroid stimulating hormone (TSH) surge in extremely low-birthweight (ELBW) infants, and the relationship between thyroid hormones and respiratory distress syndrome (RDS) has yet to be clarified. The present study sought to determine the serum levels of free T4 (fT4) and TSH in ELBW infants and to examine the relationship between these levels and the development of RDS. METHODS: The authors measured serum fT4 and TSH levels soon after birth in 449 preterm infants, who were born at 22-36 weeks of gestation, and determined the associations between these levels, the incidence of RDS, and the recognized clinical factors associated with RDS. RESULTS: Serum fT4 and TSH levels, and the fT4/TSH ratio, in the group at 22-24 weeks of gestation were significantly lower than those in the group at 28-36 weeks. The levels and ratio increased significantly with increasing gestational age. There were significant correlations between the serum fT4 level and the birthweight, Apgar score, and gender, and between the serum TSH level and the gestational age, mode of delivery, and birthweight. No significant relationship between the incidence of RDS and the serum levels of fT4 and TSH was observed. CONCLUSION: The authors' results suggest that the serum levels of fT4 and TSH in ELBW infants are very low, and that these levels are not correlated with the occurrence of RDS.