Neonatal Thyroid Status Research Articles

Delivery factors and neonatal thyroid hormone levels: a systematic review.

Postnatal thyroid hormone changes enable the neonate to be adapted for postnatal life. Several factors can affect this adaption. In this review, we summarized the studies that reported the association among the delivery factors and neonatal thyroid hormones and thyroid stimulating hormone. A comprehensive literature search was performed in PubMed, Web of Science, and Scopus up to March 2020, to identify the studies investigating the relationship between delivery factors, especially the mode of delivery and labor pain, and neonatal thyroid hormones and TSH. Finally, in this review study, of 157 articles obtained in the initial search, 25 eligible studies were reviewed. Various maternal, fetal/neonatal, and obstetric factors affected neonatal TSH and thyroid hormones. Among various influencing factors, mode of delivery, labor pains, and duration of labor have a strong relationship with neonatal thyroid hormones and need to be considered for interpretation of neonatal thyroid status. The majority of the studies revealed that vaginal deliveries (instrumental or natural) lead to higher levels of cord TSH compared to elective cesarean section. This can be explained by the increased secretion of catecholamine during labor. It has been suggested that blood TSH and thyroid hormone levels are affected by perinatal stress events such as maternal anxiety, labor pains, fetal distress, and other stimulants of the catecholamine response. These changes may act as the trigger to increase thyroid hormone levels for adapting of neonates in the first hours after birth. This assumption needs to be re-evaluated by performing comprehensive and well-designed studies.

Impact of maternal thyroid disease on neonatal thyroid status.

Prevalence of Maternal and congenital hypothyroidism is on the rise. To present the thyroid stimulating hormone screening results in babies born to hypothyroid mothers and assess the burden, aetiology of hypothyroidism in these babies. All antenatal mothers attending our hospital during the study period were enrolled into the study. Group I includes 249 term babies born to hypothyroid mothers and group II comprises 2154 newborns born to mothers who are euthyroid. Heel prick thyroid stimulating hormone was done for all newborns on day 3 for both groups. Confirmatory venous testing was done for all for babies in group I and screen positives belonging to group II. Evaluation and therapy done as per standard guidelines. Thyroid stimulating hormone values in the two groups are presented. There was significant correlation between peak maternal thyroid stimulating hormone and neonatal day 3 heel prick in group I (r=0.7, P<0.05). The prevalence of positive screening test in groups I and II was 3.8 and 1.03% (p<0.05) whereas corresponding values for confirmed disease was 4.3 and 0.6%, respectively (p<0.05). Aetiological evaluation revealed both transient hypothyroidism (33.3%) and permanent hypothyroidism (66.6%). 4.3% of babies born to hypothyroid mothers develop congenital hypothyroidism; aetiology being both transient and permanent. A venous test by 3weeks is helpful in these babies to improve case identification.

Who needs thyroid function testing at birth?

There have been notable advances in terms of what biochemistry laboratories can measure, how quickly they can measure and how much sample is required to do the measuring. This has...

Do maternal factors influence neonatal thyroid status in the extreme premature infant?

Background: In early pregnancy, maternal transfer of thyroxine (T4) significantly contributes to the foetal T4 requirements. Interruption of the maternal transfer of T4 may lead to inadequate T4 exposure, potentially leading to neurodevelopmental deficits.Aim: To determine if maternal factors are associated with the thyroid hormone status of extremely premature infants during the first five days of life.Method: This prospective study looked at 117 mothers and their extremely premature babies (born before 28 weeks’ gestation). The relationship between neonatal thyroid hormone status and maternal factors (gestation, route of delivery, exogenous maternal glucocorticoid administration, maternal free T4 (FT4), presence or absence of maternal chorioamnionitis, maternal smoking status, maternal body mass index (BMI) index, maternal thyroid peroxidase antibody status (TPO) and maternal haemoglobin levels) were evaluated. Multiple linear regression was used to study independent factors affecting neonatal thyroid function.Results: Mean gestational age was 25+5 ± 1.3 weeks (range 22+0 to 27+6). Neonatal FT4 strongly correlated with gestation, with a greater severity of hypothyroxinaemia associated with lower gestation (r = 0.6, p < 0.0001). Multiple regression found gestation to be the only independent factors affecting thyroid status (beta coefficient = 0.08, p = 0.01), and no maternal factors were found to be associated with neonatal thyroid status.Conclusion: Neonatal thyroid status in extreme preterm infants is independently affected by gestation and not maternal factors such as route of delivery, exogenous maternal glucocorticoid administration, third trimester maternal FT4, presence or absence of chorioamnionitis, smoking status, BMI, TPO status or haemoglobin levels. The severity of neonatal hypothyroxinaemia increases with lower gestational age.

Hyperthyroidism during pregnancy--the role of measuring maternal TSH receptor antibodies and foetal ultrasound monitoring.

To evaluate the usefulness of measuring maternal anti-TSH receptor antibodies (TRAbs) and foetal ultrasound (US) monitoring in cases of current or past maternal hyperthyroidism. 77 pregnant women suffering from hyperthyroidism or with a history of Graves' hyperthyroidism were observed prospectively. Maternal serum TSH, fT4, fT3, TRAbs, and foetal US were performed at baseline and repeated every 2-4 weeks when needed. Neonatal thyroid status was assessed based on serum TSH, fT4 and fT3 obtained in the first days of life. 35 women were diagnosed with gestational hyperthyroidism and 42 with Graves' disease; among them 26 had current and 16 past hyperthyroidism. Foetal and neonatal thyroid dysfunction occurred only in cases of maternal Graves' disease: nine (21%) and three (7%), respectively. Active maternal Graves' hyperthyroidism and TRAbs elevated at least five times above the upper normal limit predisposed to foetal hyperthyroidism. Maternal anti-thyroid drug therapy (ATD) and low TRAbs and fT4 were the risk factors of foetal hypothyroidism. Abnormal foetal thyroid sonogram was the only sign of foetal thyroid dysfunction. Four patients (9.5%) had high TRAbs in the 3rd trimester (10.8-29.9 IU/mL), but neither foetal nor neonatal thyroid dysfunctions were noted. In the cases of maternal Graves' disease, foetal thyroid dysfunction occurs more often than commonly assumed. Foetal thyroid US is a valuable tool in early diagnosis and monitoring of the foetal thyroid status in pregnancy complicated by maternal Graves' disease. The evaluation of biological activity of maternal TRAbs may be helpful in prenatal diagnosis in some cases.

The influence of diffuse toxic goiter on the course and outcome of pregnancy

We have studied peculiarities of pregnancy, delivery and neonatal thyroid status in 58 women with diffuse toxic goiter. During pregnancy patients received thyreostatic therapy (imidazole and thiouracil derivates). Examination consisted of assessment of levels of free thyroxin, TSH, autoantibodies to TSH-receptors and autoantibodies to thyroperoxidasis in the blood of pregnant women and in umbilical cord blood. The group of comparison consisted of 58 women without thyroid pathology and 111 women with autoimmune thyroiditis. In women with diffuse toxic goiter preeclampsia, chronic placental insufficiency, preterm rupture of membranes, fetal hypotrophy and hypoxia were observed more frequently. 17 % of newborns of mothers with diffuse toxic goiter had subclinical hyperthyroidism and 54% of newborns — subclinical hypothyroidism, depending of transplacental pass of thyreostatic medications

Thyroid autoantibodies: adverse effects on pregnancy outcomes and child development and its intervention

Thyroid autoantibodies (TAA) in euthyroid women were associated with several adverse pregnancy outcomes,such as miscarriage,preterm birth.Maternal TAA frequently results in transient mild elevation of serum TSH above the normal reference value in women during pregnancy and in infants born in the first month of life,and may affect neuropsychological development of their offspring.The cause is still unclear.Medical interventions on TAA involve levothyroxine or selenium supplementation. The article reviews the effects of maternal thyroid autoantibodies on pregnancy outcomes,as well as on neonatal thyroid status,and neuropsychological development of the fetus and neonate,and summarizes therapeutic strategies used to intervene maternal thyroid autoimmunity. Key words: Thyroid autoantibodies; Autoimmunity; Pregnancy outcomes; Intervention

Psychomotor Development of Children from an Iodine-Deficient Region

To assess the psychomotor development of the progeny of women from a moderately iodine-deficient area for whom thyroid function during pregnancy was measured. The development of 86 children was assessed by the Bayley Scale of Infant Development at 12, 18, and 24 months. Maternal serum free thyroxine (FT(4)) levels in the first trimester of pregnancy were the major determinant of psychomotor development at 18 and 24 months. Children born from mothers with FT(4) levels <25th percentile (<10 pg/mL) had an OR of 2.1 for mild-to-severe delay. Furthermore, alterations in behavior were already observed at 12 months and were related to subsequent changes in development. Neonatal thyroid status did not influence development. This study highlights the need to implement active measures of iodine supplementation periconceptionally and during pregnancy and lactation because the negative effects on development and behavior might be prevented through preemptive action.

Neonatal thyroid status in an area of iodine sufficiency

Iodine deficiency constitutes a public health problem in many countries worldwide. Fetal neurodevelopment is affected by maternal iodine intake. The aim of present study was to assess urinary iodine excretion (UIE) in the 3 trimesters of pregnancy and evaluate its association with newborn thyroid function in Tehran, an area of iodine sufficiency. Based on median urinary iodine in 3 trimesters, 138 pregnant women were divided into 2 groups with UIE<150 (group I) and UIE ≥ 150 μg/l (group II). Cord blood samples of their newborns were evaluated for serum concentrations of TSH, T3, T4, free T4 (FT4), and thyroglobolin. Quartiles of UIE were also determined. Correlations between mothers' UIE and newborns' thyroid function in both groups were investigated. Fifty-two pregnant women (38%) had median UIE<150 μg/l and 86 had (62%) UIE ≥ 150 μg/l. Median UIE in groups I and II in the 1st, 2nd, and 3rd trimesters were 125 and 212 μg/l, 97 and 213 μg/l, 93 and 227 μg/l, respectively. No significant difference was seen in thyroid function of newborns in the 2 groups. Mean concentrations of T4, T3, FT4, and TSH of newborn did not show significant difference in median UIE of mothers in various quartiles. This study shows that newborns, irrespective of mothers' UIE, in an area with a sustained iodine supplementation program, may not be at risk of alterations in thyroid functions.

Effect of prenatal or perinatal nicotine exposure on neonatal thyroid status and offspring growth in rats

Smoking during pregnancy causes intrauterine growth retardation and low birth weight of the offspring. However, it is unclear whether nicotine, rather than other compounds from a cigarette, would mediate long-term growth retardation. There is a body of evidence suggesting that optimal thyroid status is important for the normal development of the fetus. Therefore, these studies examined whether developmental nicotine exposure would interfere with the growth of the offspring and alter the thyroid status of neonates. Pregnant Sprague-Dawley rats were given 0, 15 or 25 mg nicotine pellets throughout pregnancy. Some offspring continued to receive 1 or 2 mg/kg/day nicotine during early postnatal period. The remaining offspring received no further treatment after birth. The body weight of all offspring was monitored until adulthood. Additionally, the neonatal thyroid status from all treatment groups was assessed from the serum of 10-day-old pups. Regardless of the timing of nicotine exposure, the nicotine treatment significantly increased the body weight in female offspring starting on postnatal day (PD) 35 and such an increase persisted into adulthood (PD 91). However, this nicotine exposure paradigm led to a transient increase in male offspring body weight on PD 35. Furthermore, current nicotine exposure regimens did not alter the total T4 level, T3 uptake and the calculated Free T4 index. The present findings are in agreement with some clinical studies reporting a higher body weight among children born to mothers who smoked during pregnancy. Furthermore, the data on thyroid status suggest that cigarette smoking-induced alterations in thyroid status might be mediated through compounds in cigarettes other than nicotine.

Effects of hypergravity exposure on the developing central nervous system: possible involvement of thyroid hormone.

The present study examined the effects of hypergravity exposure on the developing brain and specifically explored the possibility that these effects are mediated by altered thyroid status. Thirty-four timed-pregnant Sprague-Dawley rats were exposed to continuous centrifugation at 1.5 G (HG) from gestational Day 11 until one of three key developmental points: postnatal Day (P) 6, P15, or P21 (10 pups/dam: 5 males/5 females). During the 32-day centrifugation, stationary controls (SC, n = 25 dams) were housed in the same room as HG animals. Neonatal body, forebrain, and cerebellum mass and neonatal and maternal thyroid status were assessed at each time point. The body mass of centrifuged neonates was comparatively lower at each time point. The mass of the forebrain and the mass of the cerebellum were maximally reduced in hypergravity-exposed neonates at P6 by 15.9% and 25.6%, respectively. Analysis of neonatal plasma suggested a transient hypothyroid status, as indicated by increased thyroid stimulating hormone (TSH) level (38.6%) at P6, while maternal plasma TSH levels were maximally elevated at P15 (38.9%). Neither neonatal nor maternal plasma TH levels were altered, suggesting a moderate hypothyroid condition. Thus, continuous exposure of the developing rats to hypergravity during the embryonic and neonatal periods has a highly significant effect on the developing forebrain and cerebellum and neonatal thyroid status (P < 0.05, Bonferroni corrected). These data are consistent with the hypothesized role of the thyroid hormone in mediating the effect of hypergravity in the developing central nervous system and begin to define the role of TH in the overall response of the developing organism to altered gravity.

Early and late effect of neonatal hypo- and hyperthyroidism on coronary capillary geometry and long-term heart function in rat.

The aim of the present study was two-fold: (1) to examine the effect of hyper- and hypothyroidism on the developing coronary capillary network in neonatal rats, and (2) to determine in adult rats that had re-established euthyroid status whether long-term changes in capillary geometry or cardiac function had been induced by either neonatal thyroid condition. Two-day-old rats were treated every other day for 12 or 28 days with either 3,3'5-triiodo-l-thyronine or 0.05% 6-n-propylthiouracil. After this time, treatment was stopped and in two-thirds of the rats morphometric examination of capillary geometry and immunohistochemical detection of proliferating cell nuclear antigen (PCNA) expression in endothelial cell nuclei were conducted. Remaining rats were weaned and grew to 80 days of age, at which time persistent changes in capillary geometry, PCNA expression, and cardiac function were assessed. Neonatal hyperthyroidism induced cardiomegaly (P < 0.01), whereas neonatal hypothyroidism attenuated cardiac growth (P < 0.01). Capillary numerical density, capillary segment lengths and PCNA-labelling analysis indicated marked capillary growth in hyperthyroid rats (P < 0.05), but attenuated capillary growth in hypothyroid rats. The elicited capillary growth response appeared to be more dependent on altered tissue maturation than on cardiac growth rate. After discontinuing treatment both neonatal thyroid conditions induced a deficit in left ventricular growth (P < 0.01). Furthermore, neonatal hyperthyroidism appeared to inhibit subsequent capillary growth in distal regions of the capillary bed in addition to inducing lasting positive chronotropic and inotropic effects on cardiac function (P < 0.05). Neonatal hypothyroidism did not produce any lasting changes in capillarization or in cardiac function. Results suggest that neonatal thyroid status influences early growth and development of the coronary capillary network, possibly by regulating tissue maturation, as well as inducing lasting effects on subsequent cardiac and capillary growth and heart function.

Effect of neonatal thyroid hormone alterations on CNS ethanol sensitivity in adult LS and SS mice

LS and SS mice develop their differential sensitivity to the motor-incoordinating and hypothermic effects of ethanol at 10–16 days after birth, when thyroid hormones (T 4) show a transient peak. This rise in thyroid hormones is an important element in the normal development of monoaminergic systems and thyroid hormones reach a significantly higher level in the less ethanol-sensitive SS mice than in the more ethanol-sensitive LS mice. Previous investigations have suggested the differential ethanol response of brain monoaminergic neuronal systems in adult LS and SS mice may be related to this development difference in thyroid status. To test the hypothesis that neonatal thyroid status can influence adult. CNS ethanol sensitivity, LS and SS mice were treated neonatally with thyrotropin-releasing hormone (TRH) and propylthiouracil (PTU) to enhance of diminish, respectively, thyroid status at this critical developmental period. The subsequent effect on adult CNS ethanol sensitivity was then determined. Contrary to expectations, both PTU and TRH administration attenuated the transient rise in plasma T 4 levels at postnatal days 10–16 in LS mice and in both instances this was associated with decreased CNS ethanol sensitivity (sleep time and hypothermia) in adults. In SS mice, PTU treatment attenuated the postnatal rise in T 4 levels as expected, whereas TRH treatment had no significant effect. However, neither neonatal treatment altered CNS ethanol sensitivity in adult SS mice. The decrease in ethanol-induced sleep times and hypothermia of neonatally treated LS mice was associated with an attenuation of ethanol-induced decreases in in vivo tyrosine and tryptophan hydroxylase activity that was not seen in the SS mice. These findings are consistent with the notion that the response of monoaminergic neuronal systems to ethanol is an important determinant of behavioral intoxication. However, the observation that neonatal administration of both TRH and PTU blunted the postnatal rise in thyroid levels in LS mice, yet both treatments resulted in a decrease in adult ethanol sensitivity in LS mice, that the relationship between postnatal thyroid development and CNS ethanol sensitivity is more complex than originally hypothesized.

Treatment of hyper- and hypothyroidism in pregnancy.

In healthy subjects there are changes in thyroid function during pregnancy consequent on the increased synthesis of TBG and the thyroid stimulating effect of hCG. Serum thyroid hormones are elevated in the first trimester but fall during the latter half of pregnancy. Iodine deficiency may accentuate these changes. Hyperemesis gravidarum is associated with elevated thyroid hormone values due to high hCG levels in a third of patients. Hyperthyroidism in pregnancy is usually due to Graves' disease and is best managed with doses of antithyroid drugs sufficient to maintain euthyroidism. There is no evidence of damage to the fetus by this regime and breast feeding can be allowed. Beta adrenoreceptor blocking agents should not be used on a long-term basis. Hypothyroidism in pregnancy is associated with an adverse outcome in fetal health as well as an increase in obstetric complications. While treatment is eventually the same as for a non-pregnant person, there is evidence that the dose of L-thyroxine may require adjustment during pregnancy. Increasing L-thyroxine requirements, based on measurements of maternal L-T4 values have been noted by some but not all investigators. Women presenting in pregnancy with untreated hypothyroidism should be allowed to continue to term preferably with L-T4 replacement. The neonatal thyroid status should be assessed carefully in babies from mothers who have had either hyper- or hypothyroidism in pregnancy. Transplacental passage of maternal antibodies may cause neonatal hyperthyroidism or be associated with transient neonatal hypothyroidism.

Effect of congenital renal disease and neonatal thyroid status on urinary human epidermal growth factor concentrations.

We have previously demonstrated that changes in urinary epidermal growth factor/creatinine ratios relate to gestational age and gender. It is unclear what controls this developmental pattern although chronic renal disease and thyroid aberrations have significant effects on epidermal growth factor and creatinine excretion in childhood and in adults. Therefore, we chose to explore the effects of these disease states on epidermal growth factor excretion during the perinatal time period. We collected urine samples from 8 infants with congenital renal disease and 45 infants with low T4 and normal TSH values who 'failed' the newborn screen. In addition, 2 infants with hypothyroidism and 2 infants with neonatal Grave's disease had urine samples examined. Values were compared with the epidermal growth factor and creatinine excretion from 190 infants. We demonstrated that epidermal growth factor excretion increased earlier in gestation than does creatinine excretion. In infants with renal disease or hypothyroidism, epidermal growth factor excretion was decreased while hyperthyroidism enhanced excretion. Epidermal growth factor excretion increased with relief of an obstruction but still remained low and creatinine excretion was unchanged. We confirm that in preterm infants as in childhood there are similar effects of thyroid and renal diseases on epidermal growth factor excretion.

Thyroid hormone concentrations and free thyroxine status in neonatal venous and capillary serum pairs.

The levels of thyroid hormones in paired venous and capillary serum samples taken from 68 healthy full-term neonates were determined by radioimmunoassay. Compared with capillary values, total thyroxine (T4), thyrotropin (TSH) and thyroxine-binding globulin (TBG) each showed a significant decrease in venous serum. The mean venous and capillary concentrations of tri-iodothyronine (T3), reverse tri-iodothyronine (rT3) and free thyroxine (fT4) were not significantly different; however, in each case the fitted linear relationship suggested that venous and capillary values were not concordant (P less than 0.02, P less than 0.01, P less than 0.05 respectively). Both the T3 uptake test and the free thyroxine index (FTI) were significantly higher in venous serum, while the ratios of T4 to TBG in paired samples were equivalent. These results suggest that consistent sample collection and assay methods should be applied when assessing neonatal thyroid status, particularly if comparison of results is intended.

Amniotic fluid concentrations of iodothyronines and thyrotropin do not reliably predict fetal thyroid status in pregnancies complicated by maternal thyroid disorders or anencephaly.

In this study we report measurements of amniotic fluid (AF) concentrations of iodothyronines and TSH in 69 normal and 16 complicated pregnancies. The latter group included 2 women with untreated hyperthyroidism, 1 patient with untreated hypothyroidism, 5 hyperthyroid patients who received propylthiouracil (3 with Graves' disease, 1 with a multinodular goiter, and 1 with chronic thyroiditis), 3 women with Graves' disease who were hypothyroid after treatment, but who were receiving replacement therapy, and 5 anencephalic pregnancies. AF hormone levels could not be correlated with either maternal or cord serum values, neonatal serum measurements, and/or the clinical status of the infant. AF TSH and T4 levels were markedly elevated in 1 patient with Graves' disease and severe Rh isoimmunization and in 2 pregnancies complicated by anencephaly without identifiable pituitary tissue in the fetus. We conclude that measurements of AF concentrations of thyroid hormones and TSH do not reliably predict fetal or neonatal thyroid status.

Effects of changes in neonatal thyroid status on the development of neuropeptide systems in the rat brain

The effects of neonatal thyroid deficiency or hyperthyroidism on the development of neurones containing certain neuropeptides was examined in the brains of rats killed at two weeks of age. Five brain areas were dissected and extracted for radioimmunoassay measurement of vasoactive intestinal polypeptide (VIP), somatostatin, cholecystokinin octapeptide (CCK), substance P and neurotensin, whilst corresponding immunocytochemical data were obtained from a quantitative morphological analysis of cell bodies in the cingulate cortex. The two methods of analysis did not always agree, but in hypothyroidism both the concentration of VIP and the number of cells containing VIP-like immunoreactivity were significantly decreased in the anterior and posterior cingulate cortex. In contrast to these effects on the late maturing VIP neurones, the earlier developing somatostatin system was relatively unaffected, whilst neuropeptides localized in cortical fibres rather than cell bodies (such as substance P and neurotensin) were found by radioimmunoassay to be elevated. Hyperthyroidism had less marked effects than neonatal thyroidectomy, although the concentration of CCK (but not the number of immunostained cells) was significantly increased in the cingulate cortex. Radioimmunoassay results from three subcortical areas showed a decrease in VIP concentration in the hypothyroid hypothalamus, and in hyperthyroidism significant elevations of VIP in the basal ganglia, somatostatin in the hypothalamus and CCK in the hippocampus. It appears that in the brain areas studied thyroid disorders result in dis-synchronous shifts in the developmental patterns of the different neuropeptides, and that the effects of thyroid hormone on peptides as on other transmitters are critically dependent on the developmental profile of the system in question.

Neonatal thyroid function in fullterm, small-for-gestational-age and premature newborns

A two-year experience in screening for congenital hypothyroidism has shown new problems concerning evaluation of borderline values especially in prematures. In order to elucidate neonatal thyroid status we examined TSH, T4, T3,reverse T3(rT3) and TBG in 80 full-term(FT),20 small-for-gestational-age(SGA) and 70 pre-mature(P) newborns. Approved by our local ethical committee, blood was drawn together with clinically indicated blood examinations between 5th and 30th day of life.RESULTS: TSH(2,9 uU/ml)did not differ from FT in SGA and P. T4,T3,rT3 and TBG-levels rose with gestational age: T4 89-120ng/ml; T3 1,4-1,7ng/ml; rT3 0,54 - 1,38ng/ml; TBG 23,7-27,3mg/l. FT-values were reached by P at a “gestational” age of 40-42 weeks. There is no difference between SGA and FT. CONCLUSION: Relatively low TBG-levels and a supposed immaturity of thyroid gland seem to account for lowered peripheral thyroid hormones in P. This assumption is supported by the absence of TSH-stimulation of thyroid gland developmentin P in spite of low circulating thyroid hormones.

Cord blood reverse T3 in normal, premature, euthyroid low T4, and hypothyroid newborns.

To assess whether 3,3’,5’-triiodothyronine (reverse T3, rT3) can predict neonatal thyroid status we have determined rT3,thyroxine (T4), thyrotropin (TSH), and rT3 /T4 (X1000) ratio in 57 full-term normal (group N), 32 premature (group P) with birth weights 1048 to 2430 g and gestation ages 28 to 37 weeks, 95 hypothyroxinemic (T4 70 /AJ/ml in all. In group H rT3 was low in 50% (of 6) and infants with normal rT3 (false negative) values had iodide-induced myxedema, sepsis, or lingual thyroid. Low rT3 (false positives) were noted in 3.5% N, 3.1% P, and 12.6% L. These observations suggested that (a) an increased rT3/T4 ratio indicates prematurity, (b) a normal rT3 in the hypothyroid infant may indicate either a less severe degree of hypothyroidism or co-existing prematurity and systemic illness, (c) because rT3 varies with fetal maturity and available T4 precursor, rT3 is of limited value in screening for hypothyroidism.