Developmental Trends in Postnatal Thyroid Hormones and Thyroid Dysfunction in Preterm Infants Born at less than 34 weeks Gestation.

OBJECTIVES: To analyse the trends in thyroid function tests (TFT) in preterm infants, evaluate the frequency of thyroid dysfunction, and identify the factors that influence thyroid function. METHODS: The TFT results and risk factors for thyroid dysfunction in preterm infants with gestational ages (GA) between 25 and 34 weeks were analysed. RESULTS: In total, 535 infants were enrolled in this study. Thyroid hormone levels vary with gestational and postnatal age, and the total frequency of thyroid dysfunction is 50.3%. Thirty-one infants (5.8%) had delayed TSH elevation. Transient hypothyroxinaemia of prematurity remained significantly associated with both lower birth weight and GA. Congenital hypothyroidism was significantly associated with lower birth weight, 5 min Apgar score, and dopamine use. CONCLUSIONS: Thyroid hormone levels in preterm infants are related to gestation and postnatal age, the frequency of thyroid dysfunction in premature infants is high, and is negatively correlated with GA and birth weight.

Response of preterm infants with transient hypothyroxinaemia of prematurity to the thyrotropin-releasing hormone stimulation test is characterized by a delayed decrease in thyroid-stimulating hormone after the peak.

OBJECTIVES: We evaluated the response to the thyrotropin-releasing hormone (TRH) stimulation test in very low-birth weight (VLBW) infants to elucidate the aetiology of transient hypothyroxinaemia of prematurity (THOP). DESIGN AND METHODS: We performed TRH stimulation tests on 43 VLBW infants. Subjects were divided into two groups; a THOP group (N = 11; basal TSH < 15 mU/L and basal FT4 ≤ 0.8 ng/dL) and a non-THOP group (N = 32; basal TSH < 15 mU/L and basal FT4 > 0.8 ng/dL). Basal FT4 and FT3 were measured before, and TSH (0, 30, 60, 90, 120 and 180 minutes) was measured after, the administration of TRH (7 µg/kg). We calculated the ratio of TSH 180 minutes to THS 0 minute as the primary outcome. We also collected data on T3 and rT3 in this study. RESULTS: In both groups, TSH 30 minutes values were the highest. However, the ratios of TSH 180 minutes to THS 0 minutes in the non-THOP group and the THOP group were (median [IQR]) 1.3 [1.0-1.7] and 3.0 [1.5-5.3] (P < .01). No significant differences were observed in T3 (1.0 [0.8-1.3] and 0.7 [0.4-0.7] ng/mL, P = .06). However, in the THOP group, rT3 was significantly lower than that of the non-THOP group (168.0 [148.1-197.0] and 92.9 [74.7-101.6] pg/mL, P < .01). CONCLUSIONS: The delayed decrease in the TSH concentration after the peak for the TRH tests and decreased levels of rT3 suggest that the main aetiology for THOP is suppression at the level of the hypothalamus, but not inactivation of peripheral thyroid hormone metabolism.

Thyroxine Threshold Is Linked to Impaired Outcomes in Preterm Infants.

Transient hypothyroxinaemia of prematurity (THOP) presents as decreased free thyroxine without an increase in thyroid stimulating hormone. Thyroxine availability is important in case of premature birth, and THOP could be associated with impaired adaptation to extra-uterine life but the association of thyroxine level and clinical status has not yet been clearly defined. Aim: To defined a free thyroxine threshold likely associated with neonatal clinical impairment and outcomes at age three years. Methods: This retrospective cohort study included infants born before or at 28 weeks' gestation at the Regional Maternity in Nancy, France. We defined a free thyroxine threshold as a function of clinical impairment by Receiver Operating Curve analysis, validated by log likelihood iteration in binary logistic regression, in infants born from October 2008 to December 2012 and meeting neonatal clinical impairment criteria. This threshold was validated in a distinct cohort of infants born from January 2014 to December 2016. Clinical impairment was defined as assisted ventilation requirement at seven days of age plus four minor clinical disorders among heart rate, blood pressure, temperature, serum sodium and potassium, APGAR score at five minutes, vasopressor treatment and patent ductus arteriosus. The first cohort was assessed at age three years for neurodevelopmental outcomes. Results: We identified a ≤10 pmol/L threshold with 85.7% sensitivity and 51% specificity. From the first and second cohorts, 196 and 176 infants respectively had available data, and 85% (97/112) and 26% (20/78) with free thyroxine ≤10 pmol/L met clinical impairment criteria. For infants with values >10 pmol/L, 41% (35/84) and 3% (3/98) from the first and second cohorts met impairment criteria. Of 147 children with available data at age 3 years, 65% (58/89) with neonatal free thyroxine ≤10 pmol/L had adverse neurodevelopmental outcomes vs. 34% (20/58) with >10 pmol/L (OR 3.55; 95% confidence interval, 1.77-7.13; p < 0.001). Conclusion: A free thyroxine level ≤10 pmol/L in infants is associated with neonatal clinical impairment and poor outcome at age three years.

Review shows that thyroid hormone substitution could benefit transient hypothyroxinaemia of prematurity but treatment strategies need to be clarified.

AIM: Thyroid hormones are crucial for foetal and neonatal brain development. This paper provides an overview of the normal role of thyroid hormones in foetal brain development and the pathophysiology of transient hypothyroxinaemia of prematurity (THOP). It also discusses the diagnostic and therapeutic controversies around THOP and looks at directions for future research. METHODS: We used the PubMed and Embase databases to identify papers published in English from 1969 to June 2018. This identified 20 papers about the impact of THOP on neurodevelopment and seven randomised controlled trials about therapeutic approaches from 1981-2016. RESULTS: THOP has been researched for more than three decades. The impact of temporarily low thyroxine levels, without any increase in pituitary-secreted thyroid-stimulating hormone at a critical timeframe in an infant's brain development, is still debated. Heterogeneity in THOP definitions, difficulties with thyroid hormone assessment, identifying patients at risk and a clear lack of sufficiently powered studies add to the current controversy. There are indications that thyroid hormone substitution might be useful in extremely low gestational age neonates with THOP. CONCLUSION: Some preterm infants could benefit from THOP treatment, but more studies are needed to clarify further treatment strategies, including the optimal timing of initiation and duration.

The study of breast milk thyroxine / 国际儿科学杂志

Breast milk is the best food for the newborn.The effect in the development and growth of the neonate is irreplaceable.There are many hormones in the breast milk,including insulin,leptin and thyroxine.The quantity of thyroxine is low and is related to the methods of the mensuration and the duration of the lactation.Breast milk thyroxine may mitigate the transient hypothyroxinaemia of preterm and delay the infants' hypothyroidism.