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Levels of free triiodothyronine (FT3) and free thyroxine (FT4) in premature infants during the first 3 days of life — Results from the pilot study of the THORN trial (Thyroid HOrmone Replacement in Neonates)
Abstracts / Early Human Development 45 (1996) 133-165
135
Perinatal markers of intrapartum asphyxia and outcome at age 5 years EL. Yudkin a, A. Johnson b, L.M. Clover ~, K.W. Murphy c, (introduced by E Hope).
"Department of Obstetrics and Gynaecology, John Radcliffe Hospital, OX3 9DU, Oxford, J'National Perinatal Epidemiology Unit, Radcliffe Infirmary, OX2 6HE, Ox)rbrd, UK, 'Department of Obstetrics and Gynaecology, St. Mar), 's Hospital, London, UK. Background: In a geographically-based population of 11 682 livebirths, there were 30 cases of cerebral palsy (2.6 per 1000), three of which were associated with signs of intrapartum asphyxia at term.
Objectives: In a cohort of term infants with cerebral depression at delivery, to investigate the association of signs of intrapartum asphyxia (particularly abnormal fetal heart rate patterns in labour, acidaemia, and serious neonatal encephalopathy) with neurodevelopmental outcome at age 5 years.
Subjects and setting: A cohort of 184 singleton infants, born at term in a regional maternity hospital, with a l-rain Apgar score -< 3.
Main outcome measures: Neonatal death, cerebral palsy, and scores on a battery of neurodevelopmental tests at the age of five.
Results: Seven of the 184 infants in the study cohort had a cluster of perinatal signs suggestive of intrapartum asphyxia. Three of these infants died neonatally, three had spastic quadriparesis with profound developmental delay, and one was unimpaired at the age of five. Among the remaining infants no association was found between the severity of 'asphyxial' signs and test scores at the age of five. Mean test scores for the whole cohort were very similar to those recorded by a previous control group of children with normal acid-base values and l-rain Apgar score > 3.
Conclusions: Intrapartum asphyxia, identified by a cluster of abnormal perinatal signs, has a poor prognosis. If serious neonatal encephalopathy is not present, cerebral depression at birth preceded by abnormal fetal heart rate patterns in labour, or with acid-base derangement, is not predictive of later impairment.
Levels of free Triiodothyronine (FT3) and free Thyroxine (FT4) in premature infants during the first 3 days of life m Results from the pilot study of the THORN Trial (Thyroid HOrmone Replacement in Neonates) S. Biswas '~, J. Buffery b, M. Markiewicz", DN. Waiters b "Department of Child Health, Chelsea and Westminster Hospital, London, ~'Department of Child Health, St. Georges's Hospital, London, UK.
136
Abstracts / Early Human Development 45 (1996) 133-165
The THORN Trial is a planned multicentre randomised double blind placebo controlled clinical trial of Triiodothyronine (T3) and Cortisol given in replacement doses to preterm infants less than 30 weeks gestation. The purpose of this trial is to establish whether this treatment is able to reduce the incidence of lung disease and thus increase survival. As a prelude to this trial, a pilot study is in progress to determine the dose of T3 which will ensure that the plasma levels of this hormone are close to that normally seen in term infants. We measured free T3 (FT3) and free T4 (FT4) levels in three groups of preterm infants ( > 30 weeks gestation) within 5 h of age and subsequently at 24, 48, and 72 h of age. Group I (n = 10) did not receive any T3 (control group), group I1 (n = 4) received 3 ~xg/kg/day T3 as a continuous intravenous infusion for an average of 4 days, and group Ill (n = 6) received intravenous T3 at a dose of 5 p~g/kg/day continuously for 7 days.
Results Table 1. Mean FT3 levels - - pmol/l Age
Group 1 (control)
Group II (3 btg/kg/day T3)
Group 111 (5 txg/kg/day T3)
<5 h 24 h 48 h 72 h
4.3 4.3 3.6 3.8
5.7 4.9 4.4 4.6
4.25 8.9 8.5 6.25
The FT levels in groups II and III at less than 5 h of age were taken before start of T3 infusion. Table 2. Mean >~f4 levels - - pmol/1 Age
Group I (control)
Group I1 (3 btg/kg/ day T3)
Group 1II (5 btg/ kg/day T3)
<5 h 24 h 48 h 72 h
15.8 13 10.6 9.5
16.2 8.4 6.8 6.9
12 10 8.2 7
The FT4 levels in groups II and III at less than 5 h of age were taken before start of T3 infusion. Published data indicate that FT3 levels in term infants peak (to about 1200 p g / 1 0 0 ml or 18 p m o l / l ) at 24 h of age and then decline gradually thereafter. Our study suggests that in preterm infants FT3 levels remain low throughout the first 3 days of life. We were not able to raise FT3 levels significantly with 3 I x g / k g / d a y T3 but obtained levels closer to that seen in term infants by increasing the dose to 5 I x g / k g / d a y . A possible reason for needing a higher dose than anticipated may be due
Abstracts / Early Human Development 45 (1996) 133-165
137
to rapid metabolism of FT3 in preterrn infants. Our results also show that there is a gradual decay of FT4 levels in the first 3 days of life. There was no statistical difference (P > 0.05, Mann-Whitney U-test) in the mean FT4 level at 72 h between the three groups. This would suggest therefore that the administration of T3 dose not lead to significant suppression of FT4.
References [1] renberg, A., Phelps, D.L., Lam, R. and Fisher, D.A. (1974): Pediatrics, 53(2), 211. [2] Eggermont, E.. Vanderschueren Loderwyckx, M., De Nayer, R, Smeets, E., Vanacker, Y., Cornette, C., Jaeker, J., Devlieger, H., Eeckels, R. and Beckers. C. (1984): Heir. Paediatr. Acta, 39(3), 209-222.
Lipid peroxidation in sick preterm infants J. Nycyk, J. Drury, R.W.I. Cooke
Department of Child Health, Universio' of Liverpool, Liverpool Women's Hospital, Crown Street, Liverpool L8 7SS, UK. Many complications of the management of respiratory distress syndrome in preterm infants are believed to be related to oxygen derived free radical (ODFR) injury. Not only are the conditions for increased ODFR generation present, but there is an immaturity of some antioxidant systems. Knowledge of the relative importance of these factors would help with the development of protective strategies. We estimated ODFR injury in 15 ventilated preterm infants (24-33 weeks gestation) during the first 7 days of life by measuring pentane in their expired breath using gas chromatography with thermal desorption and cryofocussing. Pentane is generated by lipid peroxidation of linoleic and related fatty acids. Pentane levels were lowest on day 0 (median 3.9 pmol/kg/min) and peaked on day 3 (median 13.1 pmol/kg/min) and were highest in those infants with poor outcomes such as the need for supplemental oxygen on day 28, and intracranial haemorrhage.
Fetal haemoglobin fraction is more important than total haemoglobin concentration in determining oxygen extraction in the peripheral circulation of neonates E.M. Winter, C.W. Yoxall, A.M. Weindling Department of Child Health, UniversiO, of Liverpool, Neonatal Intensive Care Unit, Liverpool Womens Hospital, Crown Street. Liverpool, L8 7SS, UK.
Background: There are guidelines, based on total haemoglobin concentration ([Hb]) and clinical condition, to help us decide when neonates should be transfused. However these guidelines do not have a sound scientific basis. One reason for blood
135
Perinatal markers of intrapartum asphyxia and outcome at age 5 years EL. Yudkin a, A. Johnson b, L.M. Clover ~, K.W. Murphy c, (introduced by E Hope).
"Department of Obstetrics and Gynaecology, John Radcliffe Hospital, OX3 9DU, Oxford, J'National Perinatal Epidemiology Unit, Radcliffe Infirmary, OX2 6HE, Ox)rbrd, UK, 'Department of Obstetrics and Gynaecology, St. Mar), 's Hospital, London, UK. Background: In a geographically-based population of 11 682 livebirths, there were 30 cases of cerebral palsy (2.6 per 1000), three of which were associated with signs of intrapartum asphyxia at term.
Objectives: In a cohort of term infants with cerebral depression at delivery, to investigate the association of signs of intrapartum asphyxia (particularly abnormal fetal heart rate patterns in labour, acidaemia, and serious neonatal encephalopathy) with neurodevelopmental outcome at age 5 years.
Subjects and setting: A cohort of 184 singleton infants, born at term in a regional maternity hospital, with a l-rain Apgar score -< 3.
Main outcome measures: Neonatal death, cerebral palsy, and scores on a battery of neurodevelopmental tests at the age of five.
Results: Seven of the 184 infants in the study cohort had a cluster of perinatal signs suggestive of intrapartum asphyxia. Three of these infants died neonatally, three had spastic quadriparesis with profound developmental delay, and one was unimpaired at the age of five. Among the remaining infants no association was found between the severity of 'asphyxial' signs and test scores at the age of five. Mean test scores for the whole cohort were very similar to those recorded by a previous control group of children with normal acid-base values and l-rain Apgar score > 3.
Conclusions: Intrapartum asphyxia, identified by a cluster of abnormal perinatal signs, has a poor prognosis. If serious neonatal encephalopathy is not present, cerebral depression at birth preceded by abnormal fetal heart rate patterns in labour, or with acid-base derangement, is not predictive of later impairment.
Levels of free Triiodothyronine (FT3) and free Thyroxine (FT4) in premature infants during the first 3 days of life m Results from the pilot study of the THORN Trial (Thyroid HOrmone Replacement in Neonates) S. Biswas '~, J. Buffery b, M. Markiewicz", DN. Waiters b "Department of Child Health, Chelsea and Westminster Hospital, London, ~'Department of Child Health, St. Georges's Hospital, London, UK.
136
Abstracts / Early Human Development 45 (1996) 133-165
The THORN Trial is a planned multicentre randomised double blind placebo controlled clinical trial of Triiodothyronine (T3) and Cortisol given in replacement doses to preterm infants less than 30 weeks gestation. The purpose of this trial is to establish whether this treatment is able to reduce the incidence of lung disease and thus increase survival. As a prelude to this trial, a pilot study is in progress to determine the dose of T3 which will ensure that the plasma levels of this hormone are close to that normally seen in term infants. We measured free T3 (FT3) and free T4 (FT4) levels in three groups of preterm infants ( > 30 weeks gestation) within 5 h of age and subsequently at 24, 48, and 72 h of age. Group I (n = 10) did not receive any T3 (control group), group I1 (n = 4) received 3 ~xg/kg/day T3 as a continuous intravenous infusion for an average of 4 days, and group Ill (n = 6) received intravenous T3 at a dose of 5 p~g/kg/day continuously for 7 days.
Results Table 1. Mean FT3 levels - - pmol/l Age
Group 1 (control)
Group II (3 btg/kg/day T3)
Group 111 (5 txg/kg/day T3)
<5 h 24 h 48 h 72 h
4.3 4.3 3.6 3.8
5.7 4.9 4.4 4.6
4.25 8.9 8.5 6.25
The FT levels in groups II and III at less than 5 h of age were taken before start of T3 infusion. Table 2. Mean >~f4 levels - - pmol/1 Age
Group I (control)
Group I1 (3 btg/kg/ day T3)
Group 1II (5 btg/ kg/day T3)
<5 h 24 h 48 h 72 h
15.8 13 10.6 9.5
16.2 8.4 6.8 6.9
12 10 8.2 7
The FT4 levels in groups II and III at less than 5 h of age were taken before start of T3 infusion. Published data indicate that FT3 levels in term infants peak (to about 1200 p g / 1 0 0 ml or 18 p m o l / l ) at 24 h of age and then decline gradually thereafter. Our study suggests that in preterm infants FT3 levels remain low throughout the first 3 days of life. We were not able to raise FT3 levels significantly with 3 I x g / k g / d a y T3 but obtained levels closer to that seen in term infants by increasing the dose to 5 I x g / k g / d a y . A possible reason for needing a higher dose than anticipated may be due
Abstracts / Early Human Development 45 (1996) 133-165
137
to rapid metabolism of FT3 in preterrn infants. Our results also show that there is a gradual decay of FT4 levels in the first 3 days of life. There was no statistical difference (P > 0.05, Mann-Whitney U-test) in the mean FT4 level at 72 h between the three groups. This would suggest therefore that the administration of T3 dose not lead to significant suppression of FT4.
References [1] renberg, A., Phelps, D.L., Lam, R. and Fisher, D.A. (1974): Pediatrics, 53(2), 211. [2] Eggermont, E.. Vanderschueren Loderwyckx, M., De Nayer, R, Smeets, E., Vanacker, Y., Cornette, C., Jaeker, J., Devlieger, H., Eeckels, R. and Beckers. C. (1984): Heir. Paediatr. Acta, 39(3), 209-222.
Lipid peroxidation in sick preterm infants J. Nycyk, J. Drury, R.W.I. Cooke
Department of Child Health, Universio' of Liverpool, Liverpool Women's Hospital, Crown Street, Liverpool L8 7SS, UK. Many complications of the management of respiratory distress syndrome in preterm infants are believed to be related to oxygen derived free radical (ODFR) injury. Not only are the conditions for increased ODFR generation present, but there is an immaturity of some antioxidant systems. Knowledge of the relative importance of these factors would help with the development of protective strategies. We estimated ODFR injury in 15 ventilated preterm infants (24-33 weeks gestation) during the first 7 days of life by measuring pentane in their expired breath using gas chromatography with thermal desorption and cryofocussing. Pentane is generated by lipid peroxidation of linoleic and related fatty acids. Pentane levels were lowest on day 0 (median 3.9 pmol/kg/min) and peaked on day 3 (median 13.1 pmol/kg/min) and were highest in those infants with poor outcomes such as the need for supplemental oxygen on day 28, and intracranial haemorrhage.
Fetal haemoglobin fraction is more important than total haemoglobin concentration in determining oxygen extraction in the peripheral circulation of neonates E.M. Winter, C.W. Yoxall, A.M. Weindling Department of Child Health, UniversiO, of Liverpool, Neonatal Intensive Care Unit, Liverpool Womens Hospital, Crown Street. Liverpool, L8 7SS, UK.
Background: There are guidelines, based on total haemoglobin concentration ([Hb]) and clinical condition, to help us decide when neonates should be transfused. However these guidelines do not have a sound scientific basis. One reason for blood