Ictal cerebral blood flow in seizures originating in the posterolateral cortex

In selecting patients for epilepsy surgery, it is important to distinguish mesial temporal seizures from seizures originating in the posterolateral cortex. We studied ictal cerebral perfusion in five patients with complex partial seizures with clear posterior EEG ictal onsets and clinical seizures semiology suggesting seizure origin in the posterolateral cortex. METHODS: Ictal SPECT was performed during video EEG monitoring using 99mTc-HMPAO as a cerebral perfusion tracer and a rotating gamma camera to acquire images. RESULTS: Three patterns of ictal hyperperfusion were seen: pattern A = temporoparieto-occipital junction extending into the lateral temporal cortex, involving the mesial temporal cortex and basal ganglia to a lesser degree and a small area of hyperperfusion in the contralateral parietal cortex (two patients); pattern B = pattern A but with no hyperperfusion of the mesial temporal cortex (one patient); and pattern C = localized hyperperfusion in the area of the temporoparieto-occipital junction (two patients). CONCLUSION: Our results suggest distinct patterns of ictal perfusion in seizures with posterolateral ictal EEG onsets. Ictal SPECT may be useful in distinguishing such seizures.     

Melatonin in relation to the antioxidative defense and immune systems: possible implications for cell and organ transplantation

Inguinal hernia (IH) is relatively common in premature newborn infants, and the timing of surgical correction is controversial. We studied 40 premature infants who developed an IH and who were initially treated in a neonatal intensive care unit. Birth weight (BW) ranged from 492 to 2,401 g; 21 infants had a BW less than 1,000 g. The weight of the infants at operation ranged from 1,000 to 4,400 g. Twenty-one patients underwent herniotomy within 2 weeks after the diagnosis (short waiting group), in which 1 case of incarceration occurred; 19 waited longer than 2 weeks between diagnosis and surgery (long waiting group). Two cases of strangulation occurred in this latter group, and in 1 of those testicular necrosis occurred. Operation time was analysed in boys with bilateral herniotomy (n = 25): the short waiting group (n = 12) showed a significantly reduced operation time compared to the long waiting group (n = 13). Patients weighing less than 1,000 g at birth (n = 21) had a longer average waiting period for surgery. In the group of male patients with bilateral herniotomy, average operation time was longer in the group weighing less than 1,000 g at birth (n = 13) than in the group over 1,000 g (n = 12). Body weight at surgery did not affect operation time. It is concluded that early hernia repair should be considered in premature infants to avoid operative difficulties and gonadal ischaemia caused by incarceration.     

Meningiomas in the region of the cavernous sinus: a review of 21 patients

OBJECTIVE: To compare the morbidities in the very low birthweight (VLBW; < 1500 g) and normal birthweight (NBW; > or = 2500 g) Malaysian infants during the first year of life. METHODOLOGY: Prospective observational cohort study of consecutive surviving VLBW infants and randomly sampled NBW infants born in the Kuala Lumpur Maternity Hospital between 1 December 1989 and 31 December 1992. Infants were followed up regularly during the first year of life, after correction for prematurity. RESULTS: Compared with NBW infants (n = 106), VLBW infants (n = 127) had significantly higher risk of failure to thrive (odds ratio [OR] = 8.0, 95% confidence intervals [CI]: 1.1 to 354.3), wheezing (OR = 3.7, 95% CI: 1.6 to 9.3), rehospitalization (OR = 2.3, 95% CI: 1.1 to 5.0), cerebral palsy (OR = 8.6, 95% CI: 2.0 to 77.6), neurosensory hearing loss (OR = 12.0, 95% CI: 1.7 to 513.6) and visual loss (7.9 vs 0%, P = 0.002). The mean mental developmental index (MDI) and mean psychomotor developmental index (PDI) at 1 year of age were significantly lower among VLBW infants (MDI 99 [SD = 28], PDI 89 [SD = 25]) than NBW infants (MDI 106 [SD = 18], PDI 101 [SD = 18]) (95% CI for difference between means being MDI: -14.1 to -1.7; and PDI: -17.6 to -6.0). Logistic regression analysis showed that among VLBW infants: (i) male sex, Malay ethnicity and bronchopulmonary dysplasia were significant risk factors associated with wheezing; (ii) longer duration of oxygen therapy during the neonatal period, seizures after the post-neonatal period and wheezing were significant risk factors associated with rehospitalization; and (iii) longer duration of oxygen therapy during the neonatal period was a significant risk factor associated with adverse neurodevelopmental outcome during the first year of life. CONCLUSIONS: Compared with NBW infants, VLBW Malaysian infants had significantly higher risks of physical and neuro-developmental morbidities.     

Incidence of breakpoints in pericentric inversions of chromosome 4

Single-photon emission computed tomography (SPECT) and transcranial Doppler (TCD) ultrasonography were used to assess brain perfusion during cardiopulmonary bypass. Intravenous injections of technetium 99 m-hexamethylpropyleneamineoxime (99mTc-HMPAO) were administered before surgery and intraoperatively after the first 2 minutes in the first patient and at the end (42 minutes) of cardiopulmonary bypass in the second patient. The total middle cerebral artery territory counts were calculated using the region-of-interest method and compared to cerebellar regional counts. 99mTc-HMPAO uptake on SPECT scans was increased at the beginning and at the end of cardiopulmonary bypass, compared to baseline preoperative values (11-17%) in the presence of multiple microembolic signals on TCD (n1 = 35 and n2 = 42 for unilateral middle cerebral artery monitoring). These results indicate the feasibility of using HMPAO-SPECT to study brain perfusion changes during cardiac surgery. A combination of SPECT and TCD ultrasonography may be used to study the impact of microembolism during cardiac surgery with cardiopulmonary bypass.     

Brain perfusion imaging predicts survival in Alzheimer's disease

BACKGROUND: The variability of disease course in patients diagnosed with AD makes prediction of survival difficult, despite the identification of numerous predictors to date. This study evaluated the predictive utility of measurements of regional cerebral blood flow (rCBF) obtained with SPECT in a group of AD patients. METHODS: Fifty AD patients were studied with SPECT and followed longitudinally. SPECT measures of relative rCBF were calculated by measuring radioactivity densities in dorsolateral frontal, orbitofrontal, temporal, and parietal cortex normalized to occipital cortical radioactivity density. Subjects were classified into three tertiles of rCBF ratios for each region. These rCBF ratios were used as predictors of survival in life-table and proportional hazard models to predict survival. RESULTS: Right parietal rCBF was a significant predictor of survival in the life-table analysis, with subjects in the lowest tertile having shortest survivals. No other brain region was a significant predictor of survival. In a proportional hazards model when a variety of other potential predictors were accounted for, right parietal rCBF ratio remained a significant predictor. CONCLUSIONS: These results demonstrate that brain perfusion in the right parietal lobe is a significant predictor of survival in patients with AD even when other predictors are taken into consideration. This suggests that SPECT perfusion imaging may provide additional useful information on disease prognosis in AD.     

Evaluation of regional cerebral blood flow in massive intracerebral calcifications

Fahr's disease is histopathologically characterized by massive bilateral calcifications of the cerebral basal ganglia, the dentate nuclei of the cerebellum and both the cerebral and cerebellar cortices. We report a case of Fahr's disease in which a 99mTc-hexamethyl-propylenamine oxime (99mTc-HMPAO) brain SPECT study was used to evaluate regional cerebral blood flow to the calcified regions. There was markedly decreased perfusion to the basal ganglia bilaterally as well as decreased perfusion to the cerebral cortices that correlated well with the patient's clinical condition.     

Phylogenetic relationships of artiodactyls and cetaceans as deduced from the comparison of cytochrome b and 12S rRNA mitochondrial sequences

Functional neuroimaging studies in schizophrenia have often been confounded by various factors including medication status. To explore the effects of antipsychotic medications on relative regional cerebral perfusion, we scanned a group of 33 persons with schizophrenia twice, while receiving a stable dose of antipsychotic and after being off antipsychotics for 3 weeks, using technetium-99m hexamethyl-propyleneamine oxime single photon emission computed tomography (Tc-99m HMPAO-SPECT. We found that antipsychotic significantly increased the mean relative cerebral perfusion in the left basal ganglia. Additionally, patients receiving thiothixene (n = 9) had a significantly greater increase in relative cerebral perfusion in the basal ganglia than patients receiving haloperidol (n = 12). These findings indicate that antipsychotics lead to regional increases in cerebral perfusion and that antipsychotic status must be controlled for in functional neuroimaging studies. Functional neuroimaging techniques such as SPECT may be useful in furthering our understanding of the mechanism of antipsychotics.     

High resolution sonographic determination of the normal dimensions of the intracranial extraaxial compartment in the newborn infant

Prominence of the extraaxial space occasionally is encountered in infants referred for ultrasonography to exclude hydrocephalus. The interpretation of this finding can be problematic. We examined the width of the extraaxial compartment in 82 normal newborn infants. Scanning technique was optimized for viewing the near field, and the extraaxial space was measured over the cerebral convexities. Correlation was made with demographic variables. Measurements varied from 0 to 3.3 mm (mean, 1.6 mm), with slight negative linear relationship to gestational age. We conclude that small amounts of extraaxial fluid, up to 3.3 mm in width on scans, are common and normal in newborn infants.     

HMPAO SPECT in Parkinson's disease before and after levodopa: correlation with dopaminergic responsiveness

Regional cerebral perfusion was evaluated by SPECT with technetium 99m hexamethylpropyleneamine oxime (99mTc HMPAO) as a tracer in 21 patients presenting with Parkinson's disease and in 11 normal controls. In the parkinsonian patients, scans were performed both off treatment, and after levodopa, and clinical dopaminergic responsiveness was evaluated. Uptake of HMPAO by the basal ganglia was significantly decreased in the parkinsonian subjects, compared with normal controls. This reduction was seen in both responders (n = 14) and non-responders (n = 7) to dopaminergic treatment. Uptake of HMPAO by the basal ganglia rose after treatment with levodopa, but the change was similar in both responders and non-responders. By contrast a striking difference in cortical HMPAO uptake was found between responders and non-responders, with significantly lower uptake in the medial temporal and posterior parietal cortex in the non-responders. This reduction was symmetrical. Basal ganglia perfusion assessed by this technique is unlikely to be of use in the diagnosis of Parkinson's disease that is responsive to dopaminergic treatment. The presence of extensive cortical involvement on a baseline scan correlates with a lack of dopaminergic responsiveness, however, and this may be useful diagnostically.     

1,25-Dihydroxyvitamin D3 regulates the expression of VDR and NGF gene in Schwann cells in vitro

OBJECTIVES: In mild Alzheimer's disease, SPECT imaging of regional cerebral blood flow has highlighted deficits in the posterior association cortex, and later in the disease process, the deficit spreads to involve the frontal cortex. The sigma4 allele of apolipoprotein E is a risk factor for Alzheimer's disease. The effect of apolipoprotein E polymorphism on cerebral perfusion was studied. The hypothesis was that those patients with Alzheimer's disease who carry the sigma4 allele would have more severe cerebral hypoperfusion. METHODS: Thirty one patients with Alzheimer's disease and eight age and sex matched control subjects were examined in a three year longitudinal study. Patients with Alzheimer's disease were divided into subgroups according to their number of sigma4 alleles. Regional cerebral blood flow ratios referred to the cerebellum were examined by 99mTc-HMPAO SPECT. Apolipoprotein E genotypes were determined by digestion of polymerase chain reaction products with the restriction enzyme Hha1. RESULTS: All patients with Alzheimer's disease had bilateral temporoparietal hypoperfusion compared with control subjects. The two sigma4 allele subgroups had the lowest ratios at the baseline assessment in the parietal and occipital cortices, and at the follow up in the temporal, parietal, and occipital cortices. They had the highest reduction in percentage terms in the temporal and occipital cortices compared with the other subgroups. However, the global clinical severity did not differ at the baseline or follow up examinations between the subgroups. CONCLUSION: Apolipoprotein E polymorphism is involved in the pathogenesis and heterogeneity of Alzheimer's disease as the most severe cerebral hypoperfusion was found in the sigma4 allele subgroups. This might have implications for therapeutic approaches in Alzheimer's disease.     

Thyroxine values from newborn screening of 919 infants born before 29 weeks' gestation

OBJECTIVES: Severe transient hypothyroxinemia in premature infants is associated with cerebral palsy and mental retardation: this study assessed its prevalence in very premature infants. METHODS: Congenital hypothyroidism screening programs in three states provided thyroxine values for 919 newborn infants younger than 29 weeks who were enrolled in a multicenter study. RESULTS: Thyroxine values were lower than 4.0 micrograms/dL in 21% of survivors and increased each week by 0.6 microgram/dL (95% confidence interval [CI] = 0.4, 0.7). At tests done 1 to 2 days after birth, levels were 2.5 micrograms/dL higher (95% CI = 1.8, 3.3) than at tests done at 8 to 14 days. In New York, levels were 1.0 microgram/dL higher (95% CI = 0.3, 1.6) than elsewhere. The levels of infants who died were 1.3 micrograms/dL lower (95% CI = 0.6, 2.0) than those of survivors. CONCLUSIONS: Severe transient hypothyroxinemia is common in very premature infants and deserves further study.     

Rabbit and human atherosclerotic lesions contain IgG that recognizes epitopes of oxidized LDL

In the management of major cerebral artery obstruction, cerebral perfusion reserve is key to introducing cerebral revascularization surgery. The purpose of this study was to evaluate the feasibility of assessing cerebral perfusion reserve by consecutive 99mTc-hexamethyl-propyleneamine oxime (99mTc-HMPAO) SPECT with 5% carbon dioxide (CO2) inhalation. METHODS: The CO2 inhalation and consecutive 99mTc-HMPAO SPECT study was performed on 30 chronic ischemic cerebrovascular disease patients with unilateral major cerebral artery obstruction and on 27 patients without. CO2 reactivity was expressed as the percent increase of 99mTc-HMPAO accumulation from the baseline (%Change) and as a constant k' that was the ratio of 99mTc-HMPAO accumulation per 1 mmHg change of end-tidal CO2 tension by exponential curve fitting. RESULTS: The mean %Change and k' in the middle cerebral artery (MCA) territory on the side without an obstructive lesion or in the cerebellum ranged from 10.0% to 11.1% and from 0.98% to 1.13% per mmHg, respectively. In the MCA territory, an obstructive lesion was noted in 5.9% versus 0.54% per mmHg in the contralateral MCA territory (p < 0.01). Eleven of 30 patients with major cerebral artery obstruction revealed significant asymmetry in the k' value between bilateral MCA territories. CONCLUSION: The results showed compromised cerebral perfusion reserve in the obstructed major cerebral artery territory. The present method was proven clinically useful for evaluating cerebral perfusion reserve in patients with unilateral major cerebral artery obstruction.     

ACR presidential address: Rheum for more. American College of Rheumatology

Regional brain injury in three neonates with hypoglycemic encephalopathy are presented using serial 99mTc-hexamethyl propyleneamine oxime (HMPAO) SPECT and, for comparison, MRI. During the acute stage, both 99mTc-HMPAO SPECT and MRI reveal abnormalities in the posterior cerebrum. Technetium-99m-HMPAO SPECT reveals further areas of insult, for example the frontal lobes. The degree of hypoperfusion correlates with the clinical severity of hypoglycemia during the neonatal period and subsequent neurological sequelae. Follow-up with HMPAO SPECT several months after insult demonstrates persistent hypoperfusion in some areas, mainly in the occipital and posterior parietal regions. MRI can depict morphological changes with superior resolution. Because morphological change generally follows slowly after functional change, MRI is less sensitive than HMPAO SPECT in detecting and predicting the extent of hypoglycemic cerebral injury during the acute phase. HMPAO SPECT during the acute stage is a valuable tool for evaluating the extent and severity of brain injury in neonates with hypoglycemic encephalopathy.     

Our policy in diagnosis and treatment of hydrocephalus

The authors present the policy they have worked out for hydrocephalus patients with special reference to the pressure measurement and test methods and to rCBF, SPECT and transcranial Doppler sonography (TDC) studies. For diagnosis, the protocol proposed by Gjerris and Borgesen was followed in 75 cases: besides other methods (CT, radionuclide cisternography, MRI) the intracranial pressure waves routinely recorded and analyzed by means of ventricular catheters for 24 h. The patients were roughly divided into groups in terms of diagnosis, baseline pressure, compliance, results of infusion tests and of surgery. In 13 patients the investigations were supplemented by rCBF SPECT and in 42 patients by TCD studies before and after CSF shunting or withdrawal to analyze the acute effects on cerebral circulation. Clinical follow-up shows that need for shunting was indicated fairly well by the common results of baseline ICP, compliance and infusion loading. The rCBF SPECT studies revealed a significant increase of the cerebral perfusion at the basal ganglia after shunting while, on the basis of CBF velocity changes three types of vasoregulatory response could be defined with TCD. In our hands, monitoring of the pressure and craniospinal capacity has proved to be a valuable aid in decisions on surgery; however, for a more precise (and beneficial) appreciation of whether surgery is indicated the vasoregulatory responses should also be taken into account in future.     

An experimental study on the occurrence of brain edema after retrograde cerebral perfusion

To assess the safety of retrograde cerebral perfusion, the occurrence of brain edema after this procedure was investigated. Twenty-eight adult mongrel dogs were divided into three groups that underwent the following treatments: antegrade perfusion (group 1, n = 9); retrograde perfusion alone (group 2, n = 11); or tetrograde perfusion with drugs (manuitol, thiopental sodium, and methylprednisolone; group 3, n = 8). After 90 minutes of cerebral perfusion at 20 degrees C of the pharyngeal temperature, evans blue (EB) was administered to check for disruptions of the blood-brain-barrier (BBB) and brain tissue water content was measured. Intracranial pressure after cerebral perfusion was markedly higher in group 2 than in group 1 (26.4 +/- 9.4 vs. 11.2 +/- 3.6 mmHg), and brain tissue water content was also significantly higher in group 2 than in group 1 (80.7 +/- 2.0 vs. 77.8 +/- 0.9%). These data suggested that brain edema was more prominent after retrograde perfusion than after antegrade perfusion. The extent of EB to brain tissue was greater in group 2 than in group 1 (169.8 +/- 97.7 vs. 54.7 +/- 31.5 micrograms/dl). The BBB was highly disrupted in group 2 and vasogenic edema appeared after retrograde cerebral perfusion. Maximum intracranial pressure, brain tissue water content and EB concentration were significantly lower in group 3 than in group 2, and did not differ significantly between group 3 and 1. Administration of pharmacologic agents suppressed edema formation and extravasation of EB. We conclude that 90 minutes of retrograde cerebral perfusion at 20 degrees C of the pharyngeal temperature causes brain edema and disrupts the BBB in a manner different from that associated with antegrade perfusion. Mannitol, thiopental sodium, and methylprednisolone prevent these phenomena, indicating that pharmacologic intervention may improve the safety of retrograde cerebral perfusion.     

A mouse model of embolic focal cerebral ischemia

We developed a mouse model of embolic focal cerebral ischemia, in which a fibrin-rich clot was placed at the origin of the middle cerebral artery (MCA) in C57BL/6J mice (n = 31) and B6C3 mice (n = 10). An additional three non-embolized C57BL/6J mice were used as a control. Embolus induction, cerebral vascular perfusion deficit, and consequent ischemic cell damage were confirmed by histopathology, immunohistochemistry, laser confocal microscopy, and regional cerebral blood flow (rCBF) measurements. Reduction in rCBF and cerebral infarct were not detected in the control animals. An embolus was found in all C57BL/6J and B6C3 mice at 24 hours after injection of a clot. Regional CBF in the ipsilateral parietal cortex decreased to 23% (P < 0.05) and 17% (P < 0.05) of preembolization levels immediately and persisted for at least 1 hour in C57BL/6J mice (n = 6) and in B6C3 mice (n = 3), respectively. A significant decrease of rCBF was accompanied by a corresponding reduction of plasma perfusion in the ipsilateral MCA territory. Neurons exhibited marked reduction in microtubule-associated protein-2 immunostaining coincident with the area of perfusion deficit. The percent infarct volume was 30.3% +/- 13.4% for C57BL/6J mice (n = 17), and 38.3% +/- 15.3% for B6C3 mice (n = 7) at 24 hours after embolization. This model of embolic ischemia is relevant to thromboembolic stroke in humans and may be useful to investigate embolic cerebral ischemia in the genetically altered mouse and for evaluation of antiembolic therapies.     

Evaluation of an automated auditory brainstem response infant hearing screening method in at risk neonates

An automated auditory brainstem response (ABR) method-the ALGO-1 Plus- has been developed for hearing screening in healthy neonates. The aim of this study was to test the validity of this automated ABR screening method in at-risk neonates in a neonatal intensive care unit. Two hundred and fifty at-risk neonates were selected for screening according to the criteria of the American Joint Commerce on Infant Hearing. All 250 neonates were screened with the ALGO-1 Plus for bilateral hearing loss. When two consecutive screenings pointed to bilateral hearing loss ("refer") further audiological investigations were performed and where necessary therapeutic measures were taken. All children who "passed" the screening unilateral or bilateral enrolled in a nationwide behavioural screening programme at the age of 9 months as well as in a 6-monthly follow up programme documenting speech and language development. A total of 245 (98%) neonates passed the ALGO-1 screening, 230 (92%) at the first attempt and 15 (6%) at the second attempt. Five (2%) were referred with bilateral hearing loss. One of these died of congenital rubella shortly after screening and bilateral congenital hearing loss of > 35 dB was confirmed in the other 4. None of the infants who passed the screening were discovered to have moderate to severe bilateral hearing loss (> 40 dB) with behavioural screening (n = 183/233) or at follow up (n = 233/233). In this study, all at-risk neonates with bilateral congenital hearing loss were detected with ALGO-1 Plus screening. No false-negatives were discovered. CONCLUSION: The ALGO-1 Plus infant hearing screener can be used as a valid automated ABR-screener to detect hearing loss in at-risk neonates in a neonatal intensive care setting.     

Estimate of clinical dynamic in periventricular leukomalacia

Clinical observations of 68 preterm and term newborns with ultrasonographically diagnosed PVL treated in the Infant Department of the Child Health Center in Warsaw from January 1985 to December 1990 are presented. The most frequent clinical sign in newborns was hypotonia of the lower extremities. Tremors were significantly more frequent in preterms. During the infant period, more clinical signs occurred in connection with cerebral atrophy (ventriculomegaly and subdural space enlargement). Observations were carried from the neonatal period to the age of 6 years. Development of 42 (61.8%) children was normal. In 26 (38.2%) infants from 6 to 12 months old, cerebral palsy (most frequently diplegia) was diagnosed. No significant differences in the frequency of cerebral palsy between terms and preterms were found. Epilepsy and minimal brain dysfunctions were also present.     

Relations between neuropsychological findings and lateral asymmetries of cerebral blood flow measured by SPECT in dementia of Alzheimer type

We studied 16 right-handed patients clinically diagnosed as dementia of Alzheimer type (6 men, 10 women; aged 63-85, mean 72.8 years). The average duration of symptoms was 2.7 years. Dementia ranged from mild to moderately severe. None had clinical or laboratory evidence of cerebrovascular disease (Hachinski ischemic scores for all patients were 4 or below 4). All received the Wechsler Adult Intelligence Scale (WAIS), Mini-mental State Test (MMS) and Western Aphasia Battery (WAB, First Japanese edition, 1986). Regional cerebral blood flow (rCBF) was evaluated by single photon emission CT (SPECT) with 123I-N-isopropyl-p-iodoamphetamine (123I-IMP), using the Matsuda's quantitative method (Am J Physiol Imag 1: 186, 1986). Regional tracer uptake was measured in regions of interests (ROIs) over right and left frontal, temporal, parietal and occipital cortical regions; basal ganglia; and cerebellar hemispheres. The subjects were divided into three groups on the basis of lateral asymmetries in the temporal and parietal cortexes of rCBF (left < right, n = 5; right < left, n = 3; left = right, n = 8). We decided that lateral asymmetry was present when rCBF for each ROI between left and right sides differs by more than 10%. General score (MMS, T-IQ) was not correlated with asymmetry of cerebral blood flow. Verbal IQ in patients with predominant hypoperfusion of left temporal and parietal lobe was significantly lower than other group, while performance IQ and WAB constructive scores were lower in those with right hemispheric hypoperfusion (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Are perinatal risk factors helpful in predicting and optimizing treatment strategies for transient hypothyroxinemia in very-low-birth-weight infants?

Transient hypothyroxinemia is common in premature infants and has been associated with intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), poor neurodevelopmental outcomes, and mortality. Recent trials have failed to show that supplemental thyroid hormone improves overall neurodevelopmental outcome. The objective of this article is too determine perinatal risk factors for transient hypothyroxinemia (TH). We studied a cohort of infants born between July 1993 and July 2000 who were less than 1500 g and who received a newborn screening for thyroid function ( n = 932). Total serum thyroxine (T(4)) was collected routinely on the fifth day of life. T (4) was correlated with gestational age (R = 0.59, p < 0.01). After controlling for potential confounding variables, gestational age, dopamine, and mechanical ventilation were found to be independently associated with low T (4) (overall model: r(2) = 0.41, p < 0.01). Number needed to treat (NNT) analysis showed treating all infants less than 27 weeks would lead to treating 6.3 infants for every one with a subsequent T(4) < 5 microg/dL. By combining gestational age and need for dopamine support, NNT = 2.4 for every one infant with subsequent T(4) < 5 microg/dL. Low gestational age, mechanical ventilation, and need for dopamine were associated with low T(4) levels and may be helpful in optimizing treatment strategies for TH.