Thyroid function in preterm infants and neurodevelopment at 2 years.

OBJECTIVES: Postnatal thyroid dysfunction is common in preterm infants but the relationship between mild dysfunction and neurodevelopment is unclear. Our aim is to describe the relationship between thyroid function and neurodevelopment. DESIGN: Cohort analysis. PATIENTS: 1275 infants born under 31 weeks' gestation; there were no exclusion criteria. SETTING: The infants were part of a UK daily iodine supplementation trial. MAIN OUTCOMES: Thyroid-stimulating hormone, thyroid-binding globulin and total thyroxine levels were measured in dried blood spots on postnatal days 7, 14, 28 and the equivalent of 34 weeks' gestation. Neurodevelopment was measured using the Bayley-III Scales of infant development at 2 years of age. RESULTS: No infant was identified as hypothyroid through routine screening. The 3% of infants consistently in the top decile of gestationally age-adjusted thyroid-stimulating hormone levels had a reduction in cognitive score of 7 Bayley units when compared with those not in the top decile (95% CI -13 to -1). A reduction in motor composite score of 6 units (95% CI -12 to <-0.1) and fine motor score of 1 unit (95% CI -2 to -0.1) was also identified. The 0.7% of infants consistently in the bottom decile of age-adjusted thyroxine levels had a reduction in motor composite score of 14 units (95% CI -25 to -2) and its two subset scores, fine and gross motor, of 2 units (95% CI respectively -4.5 to <-0.1 and -4.3 to -0.3). CONCLUSIONS: Preterm infants with consistent 'mild' thyroid dysfunction score less on neurodevelopmental tests at 2 years of age. Many of these infants will not be detected by current clinical protocols or screening programmes.

Supplemental Iodide for Preterm Infants and Developmental Outcomes at 2 Years: An RCT.

BACKGROUND: The recommendation for enteral iodide intake for preterm infants is 30 to 40 µg/kg per day and 1 µg/kg per day for parenteral intake. Preterm infants are vulnerable to iodide insufficiency and thyroid dysfunction. The hypothesis tested whether, compared with placebo, iodide supplementation of preterm infants improves neurodevelopment. METHODS: A randomized controlled trial of iodide supplementation versus placebo in infants <31 weeks' gestation. Trial solutions (sodium iodide or sodium chloride; dose 30 µg/kg per day) were given within 42 hours of birth to the equivalent of 34 weeks' gestation. The only exclusion criterion was maternal iodide exposure during pregnancy or delivery. Whole blood levels of thyroxine, thyrotropin, and thyroid-binding globulin were measured on 4 specific postnatal days. The primary outcome was neurodevelopmental status at 2 years of age, measured by using the Bayley Scales of Infant Development-III. The primary analyses are by intention-to-treat, and data are presented also for survivors. RESULTS: One thousand two hundred seventy-three infants (637 intervention, 636 placebo) were recruited from 21 UK neonatal units. One hundred thirty-one infants died, and neurodevelopmental assessments were undertaken in 498 iodide and 499 placebo-supplemented infants. There were no significant differences between the intervention and placebo groups in the primary outcome: mean difference cognitive score, -0.34, 95% confidence interval (CI) -2.57 to 1.89; motor composite score, 0.21, 95% CI -2.23 to 2.65; and language composite score, -0.05, 95% CI -2.48 to 2.39. There was evidence of weak interaction between iodide supplementation and hypothyroxinemic status in the language composite score and 1 subtest score. CONCLUSIONS: Overall iodide supplementation provided no benefit to neurodevelopment measured at 2 years of age.

Thyroid dysfunction in preterm neonates exposed to iodine.

BACKGROUND: Infants <32 weeks' gestation should not be exposed to topical iodine and its avoidance is recommended during pregnancy and breast feeding. Exposure to contrast media and topical iodine is frequently used in many preterm neonates. AIM: To determine whether thyrotropin levels in preterm infants are affected by exposure to intrapartum/neonatal topical iodine and/or the use of iodinated contrast media. DESIGN: Infants <32 weeks' gestation were recruited. Maternal and neonatal exposures to iodinated contrast media and topical iodine were recorded; levels of thyrotropin and thyroxine were measured from blood-spot cards on postnatal days 7, 14, 28 and the equivalent of 36 weeks' gestation. RESULTS: One hundred and twenty-five infants were exposed to topical iodine/contrast media and 48 infants were unexposed. No infants were treated for hypothyroidism; three infants (exposed group) had transient hyperthyrotropinaemia. Mean thyrotropin levels were significantly higher on postnatal days 7, 14 and 28 in infants exposed to topical iodine prior to caesarean section compared to unexposed infants, a relationship which persisted after adjustment. CONCLUSIONS: In the context of this study, neonatal thyroid dysfunction was seen following exposure to iodine via caesarean section but not via exposure to contrast media.

Arterio-venous differences in cord levels of catecholamines, glucose, lactate and blood gases.

BACKGROUND: Norepinephrine (NE) and epinephrine (EPI) levels are higher in cord arterial blood relative to venous blood, consistent with active mechanisms of placental-maternal clearance. There are no contemporary studies of cord arteriovenous blood levels of sulfated and non-sulfated catechols. AIM: To assess the arteriovenous differences in cord blood levels of dopamine (DA), the sulfated catecholamines and their sulfated and non-sulfated metabolites. To correlate levels of oxygen, H+/CO2, and glucose with cord catecholamine levels. METHODS: Fifty-seven term infants, delivered by elective cesarean section, were recruited. Cord arterial and venous blood was sampled; levels of glucose, lactate, blood gases, six catechols and their sulfated conjugates were measured. RESULTS: With one exception (DOPA sulfate), mean cord arterial levels of sulfated and non-sulfated catechols were significantly higher than venous levels. Arterial lactate and glucose levels were independently associated with NE levels, but only lactate was associated with levels of EPI and DA. CONCLUSION: This study establishes that in vivo metabolic parameters of hypoxia, respiratory and metabolic acidosis are associated with catecholamine levels, a key relationship for perinatal adaptation and homeostasis, and findings that are consistent with in vitro studies of the regulators of catecholamine secretion.

Do research studies in the UK reporting child neurodevelopment adjust for the variability of assessors: a systematic review.

AIM: Neurodevelopment is a key outcome for many childhood trials and observational studies. Clinically important decisions may rest on finding relatively small differences in neurodevelopment between groups receiving complex and costly interventions. Our purpose was to determine whether studies which measure neurodevelopment report the numbers, training, and auditing of assessors and, for multiple assessor studies, whether the results were adjusted and if so by which method? METHOD: Electronic searches were conducted using Medline, Embase, Cinahl, PsycINFO, and the Cochrane Library. A study was eligible if it reported neurodevelopmental outcome in children resident in the UK, less than or equal to 18 years and was published between 2000 and 2015. Trials and observational studies were included. RESULTS: Three hundred and seven full papers were reviewed: 52% of papers did not report the number of assessors used; 21% used a single assessor; and 27% used multiple assessors. Thirty-five per cent mentioned that assessors were trained in the use of the neurodevelopmental tool; 13% of assessors were audited; and only 1% of studies adjusted statistically for the number of assessors. INTERPRETATION: At the very least, the quality of reporting the use of assessors in these research publications is poor, while at worst, the variability of assessors may mask the true relationship between an intervention/observation and neurodevelopmental outcome.

A systematic review of thyroid dysfunction in preterm neonates exposed to topical iodine.

OBJECTIVE: To determine whether maternal exposure to iodine or neonatal exposure to topical iodine-containing solutions increases the risk of transient thyroid dysfunction in neonates born <32 weeks' gestation or <1.5 kg. DESIGN: Systematic review. SEARCH STRATEGY: Electronic searches were conducted using Medline and the Cochrane Library. ELIGIBILITY CRITERIA: A study was eligible for review if it reported neonatal exposure to topical iodine or maternal iodine exposure. The key outcome measure was neonatal thyroid function. The search had no restrictions on date of publication, type of study or language. RESULTS: 794 papers were identified during the initial search; 15 studies were fully reviewed. The incidence of (transient) hypothyroidism/hyperthyrotropinaemia following exposure to topical iodine ranged from 12 to 33 per 100 infants; the incidence in non-exposed infants was 0. CONCLUSIONS: There is evidence that neonatal exposure to iodine-containing disinfectants causes thyroid dysfunction in infants born <32 weeks. None of the studies evaluated neurodevelopment. Larger scale studies are needed to determine definitively the nature of the relationship and the impact of exposure on neurodevelopment. In the meantime, it would seem prudent to restrict exposure of iodine-containing skin disinfectants in preterm infants; chlorhexidine might be a credible alternative.

Maternal and umbilical cord levels of T4, FT4, TSH, TPOAb, and TgAb in term infants and neurodevelopmental outcome at 5.5 years.

CONTEXT: Relatively little is known in euthyroid populations about the changes in maternal thyroid hormones during pregnancy, the nature of the relationship to cord thyroid hormone levels, and subsequent infant neurodevelopment. OBJECTIVES: The aim of the study was to describe the relationship between maternal and cord thyroid hormone parameters and to describe their associations with neurodevelopment at 5.5 years. DESIGN: We conducted a follow-up of women and their children born at or over 37 weeks' gestation. MAIN OUTCOMES: We measured maternal levels of TSH, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), T(4), and free T(4) (FT(4)) at 10 and 34 weeks and at delivery, and cord levels of T(4), FT(4), TPOAb, and TgAb. The association of cord thyroid hormone parameters with McCarthy scale scores adjusted for the major confounders of neurodevelopment. RESULTS: Fifteen percent of the women were TPOAb-positive, and 12% were TgAb-positive; the proportion of women with mildly elevated TSH levels increased during pregnancy with the maximum (14%) at delivery. Lower perceptual performance and motor scores were found with TgAb-positive women and lower perceptual performance scores with TgAb-positive cord levels; otherwise, unadjusted maternal levels of TPOAb, TgAb, and TSH and unadjusted cord levels of FT(4), TPOAb, and TgAb were not associated with neurodevelopment at 5.5 years. Low cord T(4) levels were associated with significant increments in four McCarthy scales: General Cognitive Index, Verbal, Quantitative, and Memory scales-increments that persisted after adjustment at 11.4, 7.8, 7.6, and 7.8 points, respectively. CONCLUSIONS: Lower levels of cord T(4) were associated with increments in the McCarthy scales in the domains that tested cognitive and verbal abilities at 5.5 years.

A survey on public knowledge and perceptions of methicillin-resistant Staphylococcus aureus.

OBJECTIVES: The aim of the study was to establish knowledge and understanding of methicillin-resistant Staphylococcus aureus (MRSA) among patients, visitors and members of the general public accessing health services and to identify public education needs in relation to MRSA. PARTICIPANTS AND METHODS: Survey participants were recruited through 15 general practice surgeries across Tayside and through a young people's health and information project in Dundee city centre and at a health information facility at Ninewells Hospital and Medical School, Dundee. RESULTS: There were 1000 responses. The majority (86%) had heard of MRSA, 59% knew that it is a bacterium and 47% were aware that a healthy person can have MRSA without feeling ill. Those who knew someone who had had MRSA (32%) showed greater knowledge but greater worry about getting MRSA if admitted to hospital. Knowledge of possible treatments was variable, with 7% of respondents thinking of MRSA as untreatable. Across all groups, most estimates of MRSA prevalence were much higher than actual prevalence. CONCLUSIONS: Public awareness of MRSA and its treatment was higher than expected, mainly gained through the media, but with considerable gaps in knowledge. Knowing someone with MRSA makes the individual more likely to be knowledgeable about MRSA in general, but more likely to think it is untreatable and almost twice as likely to be worried about contracting MRSA if admitted to hospital. The findings of this survey will inform the development of educational packages for the general public, as well as patients entering hospital and their visitors.

Perinatal factors affecting thyroid hormone status in extreme preterm infants.

Pragmatic criteria are required for defining transient hypothyroxinemia and to permit entry to clinical trials of thyroxine substitution of only those extreme preterm infants who are hypothyroxinemic. The purpose of this article is to suggest that transient hypothyroxinemia is defined by postnatal serum T(4) levels, which are cord levels corrected to an equivalent gestational age had the fetuses remained in utero, and that those levels are adjusted for the significant prenatal and intrapartum factors. Lowered serum FT(4) levels are not a consistent pathognomonic feature of transient hypothyroxinemia as postnatal FT(4) levels in this large series of preterm infants are within or above the cord values of equivalent gestational age, irrespective of severity of illness. Although serum T(3) and thyroid-stimulating hormone levels do not contribute to the diagnosis of transient hypothyroxinemia, measurement of their levels is nevertheless required for trial monitoring involving thyroxine substitution to avoid inadvertent suppression of the developing hypothalamic-pituitary-thyroid axis by excess T(4) substitution.

Some simple tests for spatial effects around putative sources of health risk.

The need for tests dealing with different features of small area health data is less important with the increase in computation speed of computers and the access to MCMC methods. However there are many situations where exploratory testing could be useful and where MCMC methods are not readily usable or available. In this paper, a number of simple tests are derived for the logistic model for case events. This model assumes that a control disease is available and that the events have a binary label relating to case or control state. The tests are derived from likelihood considerations and Monte Carlo critical regions are examined. A simulated evaluation of the tests is presented in terms of Monte Carlo power. A data example is considered.

A population based study of respiratory function in motor neuron disease patients living in Tayside and North East Fife, Scotland.

Respiratory failure is a major cause of morbidity and the principal cause of death in motor neuron disease; non-invasive ventilation is increasingly used worldwide to palliate the respiratory symptoms. This observational study was designed to evaluate the prevalence of respiratory insufficiency within the motor neuron disease population of Tayside and North East Fife, Scotland. Twenty-six patients were identified, their diagnosis confirmed according to agreed criteria and subjected to the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, the Epworth Sleepiness questionnaire; spirometry, sniff nasal inspiratory pressure and nocturnal pulse oximetry measurements.Twenty-two (84.6%) patients reported one or more symptoms of respiratory insufficiency, 19 patients (73%) had forced vital capacity <80% of predicted in the sitting position and 10 (38.5%) had oxygen saturation <90% for >5% of night. On this basis a potential 10 patients required consideration for ventilation. As well as probable improvement in quality of life and survival for those patients this potential increase in workload has major educational, management and resource implications for health care providers.

Transient hypothyroxinaemia in preterm infants.

Thyroid hormones are required for normal development of the brain. Transient hypothyroxinaemia is the most common thyroid dysfunction in preterm infants and is defined by temporary low levels of T4, T3 and normal or low TSH. Low T4 levels in preterm infants are associated with persistent neurodevelopmental deficits in cognitive and motor function. Thyroid hormone substitution trials to date are underpowered and show inconsistent results; the question remains -- are low T4 levels simply an epiphenomenon? The aetiology of transient hypothyroxinaemia is multifactorial and the components amenable to correction form the basis of the therapeutic strategy: rectification of iodine deficiency in parenteral nutrition; a reduction of non-thyroidal illnesses and attenuation of their severity; and substitution of drugs that interfere with the hypothalamic-pituitary-thyroid axis. Thyroxine substitution therapy should only be done in the context of clinical trials and only in those infants who are hypothyroxinaemic.

Serum thyroid hormones in preterm infants: associations with postnatal illnesses and drug usage.

CONTEXT: Transient hypothyroxinemia is common in infants less than 30 wk gestation and is associated with neurodevelopmental deficits. Reductions in T4 and T3 levels with TSH unchanged are the key features of severe illness using surrogate indices of overall severity of illness, but these do not inform the impact of individual disease conditions or drug use. OBJECTIVE: Our objective was to investigate the contribution of postnatal factors to the variations in serum levels of iodothyronines, thyroid-binding globulin, and TSH. DESIGN: We recruited a cohort of infants (23-34 wk gestation; n = 780) between January 1998 and September 2001. SETTING AND PATIENTS: The study involved 11 level III Scottish neonatal intensive care units and included cohorts of infants delivered at 23-34 wk gestation. MAIN OUTCOME: We assessed serum levels of iodothyronines, thyroid-binding globulin, and TSH at 7, 14, and 28 d adjusted for the potentially significant postnatal influences (n = 31). RESULTS: Serum levels of TSH, free T4, T3, and T4 are variably but significantly associated with bacteremia, endotracheal bacterial cultures, persistent ductus arteriosus, necrotizing enterocolitis, cerebral ultrasonography changes, oxygen dependence at 28 d, and the use of aminophylline, caffeine, dexamethasone, diamorphine, and dopamine. CONCLUSIONS: There are many more associations of postnatal factors with transient hypothyroxinemia than had previously been considered in preterm infants. Alternative strategies should be considered for correction of hypothyroxinemia rather than sole reliance on the direct therapy of hormone replacement. A more oblique preventative approach may be necessary through reduction in the incidence or severity of individual illness(es). Similarly, alternatives to those drugs that interfere with the hypothalamic-pituitary-thyroid axis should be evaluated (e.g. other inotropics instead of dopamine).

Impact of vector control on a dengue fever outbreak in Trinidad, West Indies, in 1998

In 1998, Trinidad experienced its first major outbreak of dengue haemorrhagic fever. Data from the Trinidad Public Health Laboratory, the National Surveillance Unit and Insect Vector Control Division, Ministry of Health, Trinidad and Tobago were analysed to determine the impact of vector control measures on the dengue outbreak. Geographical Information Systems (GIS)/Global Positioning Systems (GPS) were used to map cases and to distinguish epidemiological clusters. The Aedes aegypti population densities were higher than the 5% transmission threshold in all counties. The spatial distribution of dengue fever cases was significantly correlated with the heavily populated east-west corridor in the north and several distinctly separate clusters in the western part of the island. The temporal distribution patterns showed significantly more dengue fever cases occurring during the rainy season than during the dry season. This study documents the importance of vector control in the prevention of dengue transmission since no vaccine is currently available, and emphasizes the urgent need to understand better the environmental factors which contribute to the proliferation of this disease vector Ae. aegypti.

Impact of vector control on a dengue fever outbreak in Trinidad, West Indies, in 1998.

In 1998, Trinidad experienced its first major outbreak of dengue haemorrhagic fever. Data from the Trinidad Public Health Laboratory, the National Surveillance Unit and Insect Vector Control Division, Ministry of Health, Trinidad and Tobago were analysed to determine the impact of vector control measures on the dengue outbreak. Geographical Information Systems (GIS)/Global Positioning Systems (GPS) were used to map cases and to distinguish epidemiological clusters. The Aedes aegypti population densities were higher than the 5% transmission threshold in all counties. The spatial distribution of dengue fever cases was significantly correlated with the heavily populated east-west corridor in the north and several distinctly separate clusters in the western part of the island. The temporal distribution patterns showed significantly more dengue fever cases occurring during the rainy season than during the dry season. This study documents the importance of vector control in the prevention of dengue transmission since no vaccine is currently available, and emphasizes the urgent need to understand better the environmental factors which contribute to the proliferation of this disease vector Ae. aegypti.

Transient hypothyroxinemia in preterm infants: the role of cord sera thyroid hormone levels adjusted for prenatal and intrapartum factors.

CONTEXT: Transient hypothyroxinemia is common in infants less than 30 wk gestation and is associated with neurodevelopmental deficits; it has no consensus definition. We previously suggested that appropriate ranges for postnatal serum T4 values are at least cord levels corrected to an equivalent gestational age if the fetuses had remained in utero. OBJECTIVE: The study objective is to investigate the contribution of prenatal and intrapartum factors (n = 27) to the variations in cord levels of iodothyronines, T4-binding globulin, and TSH, and to provide an appropriate definition of transient hypothyroxinemia. DESIGN: The study design is a cohort study (n = 620) in 11 Scottish neonatal intensive care units. PATIENTS: Infants were delivered at 23- to 42-wk gestation and recruited between January 1998 and September 2001. RESULTS: Using -2 SD of adjusted T4 cord levels applied to postnatal d-7 values of equivalent gestational age, 14% of the 23- to 27-wk group, 1% of the 28- to 30-wk group, and 3% of the 31- to 34-wk group are hypothyroxinemic; using -1 SD, the respective figures are 41, 23, and 12%. CONCLUSIONS: In the absence of neurodevelopmental follow-up studies to quantify transient hypothyroxinemia, a pragmatic criterion is necessary for selection of extreme preterm infants into clinical trials of T4 supplementation. We suggest the use of serum T4 levels on postnatal d 7 that are below -1 SD of adjusted cord T4 levels of equivalent gestational age. This criterion avoids over-recruitment of the more mature infants in whom universal T4 supplementation is detrimental to neurodevelopmental outcome, but still allows selection of the least mature entrants on whom universal T4 supplementation is beneficial.

Glucose homeostasis in the newborn.

Hepatic glucose production by glycogenolysis and gluconeogenesis is essential to maintain blood glucose levels, and the glucose-6-phosphatase system catalyses the terminal step of both pathways. Developmental delays in the postnatal up-regulation of hepatic glucose-6-phosphatase enzyme activity are common in preterm infants. Two groups of infants have been identified with failure of developmental regulation of glucose homeostasis. Firstly, up to 20% of preterm infants about to be discharged home are at risk of hypoglycaemia if a feed is delayed. Cortisol, corticotrophin and epinephrine levels are higher in the infants with severe and persistent hypoglycaemia, but insulin, glucagon and human growth hormone do not differ from normoglycaemic infants. Secondly, preterm infants with an inadequate glycaemic response to glucagon (30% at the time of discharge home) have relative fasting hyperglycaemia, hyperinsulinaemia, increased insulin:glucagon ratios and a lower insulin sensitivity index. Hormonal dysfunctions in preterm infants may contribute to failures in postnatal expression of hepatic enzymes.

Serum thyroid hormones in preterm infants and relationships to indices of severity of intercurrent illness.

The purpose of this study was to relate severity of illness at 1, 7, 14, and 28 postnatal days in preterm infants groups, 23-27 (n = 73), 28-30 (n = 160), and 31-34 (n = 208) wk gestation, to the corresponding sera levels of T(4), free T(4), T(4)-binding globulin, TSH, T(3), rT(3), and T(4) sulfate. The British Association of Perinatal Medicine and Neonatal Nurses Association 1992 scoring categories (published elsewhere) were used as an index of illness severity: level 1 (maximal intensive care) was compared with level 2 (high-dependency intensive care) combined with level 3 (special care); infants were scored on 1, 7, 14, and 28 postnatal days. In level 1 infants, there were significant reductions in T(3) at 7 d (28-30 wk), 14, and 28 d (23-27 and 28-30 wk); T(4) at 7, 14, and 28 d (23-27 wk); at 14 and 28 d (28-30 wk); and at 7 d (31-34 wk); and free T(4) at 14 d (23-27 wk). TSH was unchanged in all groups at all ages and with reductions in T(4) and T(3) being the key features of severe illness in extreme preterm infants.

Plasma catecholamines and the counterregulatory responses to hypoglycemia in infants: a critical role for epinephrine and cortisol.

The purpose of this study was to define plasma catecholamine responses as part of the counterregulatory hormonal reaction to hypoglycemia in infants after a regular 3- to 4-h feed was omitted. Hormone levels were assessed once, at the end of the fast or at hypoglycemia. The 121 infants were subdivided into three groups for analysis: normoglycemia (n = 94, 78%); transient hypoglycemia (n = 11, 9%); or severe and persistent hypoglycemia (n = 16, 13%). The severe and persistent hypoglycemic group had significantly higher levels of cortisol and epinephrine than the normoglycemic group. Norepinephrine and glucagon levels did not differ between the groups. Human GH levels were higher in the transiently hypoglycemic group but not in the severe and persistent hypoglycemic group. Prefeed blood lactate levels differed significantly among the groups and were highest in the severe and persistent groups. Multiple regression analysis showed that cortisol levels were significantly higher in infants who had severe and persistent hypoglycemia. The counterregulatory hormonal response in infants to severe and persistent hypoglycemia was limited to elevations in only cortisol and epinephrine levels but did not involve glucagon or human GH. This limited hormonal response may also contribute to the frequent occurrence of hypoglycemia in these infants.

Developmental trends in cord and postpartum serum thyroid hormones in preterm infants.

The purpose of this study was first to clarify postnatal trends in sera T(4), free T(4) (FT(4)), T(4)-binding globulin, TSH, T(3), rT(3), and T(4) sulfate levels in cord and at 7, 14, and 28 d in groups of preterm infants at 23-27 wk (n = 101), 28-30 wk (n = 196), and 31-34 (n = 253) wk gestation, and second to compare these trends to those of term infants and also with cord sera levels of equivalent gestational ages (n = 812; 23-42 wk gestation). In all preterm groups, TSH and rT(3) decrease to below, T(4)-binding globulin increases to within, and T(3) and T(4) sulfate increase to above cord levels of equivalent gestational age. Term infants are hyperthyroxinemic relative to cord and nonpregnant adult levels of T(4). Postnatal T(4) increases are attenuated in 31- to 34-wk infants, absent in 28- to 30-wk infants (although levels are equivalent to gestational age), and crucially reversed in 23- to 27-wk infants. This immature group is hypothyroxinemic relative to other groups and to cord levels of equivalent gestational age. Compared with term infants, postnatal FT(4) increases are lower in 31- to 34-wk infants, attenuated in 28- to 30-wk infants, and absent in 23- to 27-wk infants. The 23- to 27-wk group is distinctive; they are hypothyroxinemic on T(4) levels, yet FT(4) levels are within the cord levels of equivalent gestational age.