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Meta-Analysis
. 2007 Jan 24;2007(1):CD005948.
doi: 10.1002/14651858.CD005948.pub2.

Prophylactic postnatal thyroid hormones for prevention of morbidity and mortality in preterm infants

D A Osborn  1 , R W Hunt
Affiliations
Meta-Analysis

Prophylactic postnatal thyroid hormones for prevention of morbidity and mortality in preterm infants

D A Osborn et al. Cochrane Database Syst Rev. .

Abstract

Background: Observational studies have shown an association between transiently low thyroid hormone levels in preterm infants in the first weeks of life (transient hypothyroxinaemia) and abnormal neurodevelopmental outcome. Thyroid hormone replacement might prevent this.

Objectives: To determine whether prophylactic thyroid hormones given to preterm infants without congenital hypothyroidism result in clinically important changes in neonatal and long term outcomes.

Search strategy: The standard search strategy of the Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966 - March 2006), EMBASE, PREMEDLINE, and searches of abstracts of conference proceedings, citations of published articles and expert informants.

Selection criteria: All trials using random or quasi-random patient allocation in which prophylactic thyroid hormone treatment was compared to control in premature infants.

Data collection and analysis: Assessment of trial quality, data extraction and synthesis of data, using relative risk (RR) and weighted mean difference (WMD), were performed using standard methods of the Cochrane Collaboration and its Neonatal Review Group.

Main results: Four studies enrolling 318 infants were included. All studies enrolled preterm infants on the basis of gestational age criteria. All studies commenced treatment in the first 48 hours, but used different regimens, dose and durations of treatment. All four studies used thyroxine (T4). Valerio 2004 incorporated one arm with an early short course of T3, then T4 for 6 weeks. Only two studies with neurodevelopmental follow-up were of good methodology (van Wassenaer 1997; Vanhole 1997). All studies were small with the largest (van Wassenaer 1997) enrolling 200 infants.No significant difference was found in neonatal morbidity, mortality or neurodevelopmental outcome in infants who received thyroid hormones compared to control. van Wassenaer 1997 reported no significant difference in abnormal mental development at 6, 12, 24 months (RR 0.67, 95% CI 0.28, 1.56) or five years (RR 0.66, 95% CI 0.22, 1.99) or cerebral palsy assessed at five years (RR 0.72, 95% CI 0.28, 1.84). Meta-analysis of two studies (van Wassenaer 1997, Vanhole 1997) found no significant difference in the Bayley MDI (WMD -1.14, 95% CI -5.46, 3.19) and PDI (WMD 0.22, 95% CI -4.80, 5.24) at 7 - 12 months. van Wassenaer 1997 reported no significant difference in the Bayley MDI (MD -3.50, 95% CI -11.21, 4.21) and PDI (MD 3.10, 95% CI -3.31, 9.51) at 24 months, IQ scores at 5 years (MD -2.10, 95% CI -7.91, 3.71) and children in special schooling at 10 years (RR 0.88, 95% CI 0.43, 1.83). Meta-analysis of all four trials found no significant difference in mortality to discharge (typical RR 0.76, 95% CI 0.46 to 1.24). van Wassenaer 1997 reported no significant difference in death or cerebral palsy at five years (RR 0.70, 95% CI 0.43 to 1.14). No significant differences were reported for neonatal morbidities, including the need for mechanical ventilation, duration of mechanical ventilation, air leak, CLD in survivors at 28 days or 36 weeks, intraventricular haemorrhage, severe intraventricular haemorrhage, periventricular leucomalacia, patent ductus arteriosus, sepsis, necrotising enterocolitis or retinopathy of prematurity.

Authors' conclusions: This review does not support the use of prophylactic thyroid hormones in preterm infants to reduce neonatal mortality, neonatal morbidity or improve neurodevelopmental outcomes. An adequately powered clinical trial of thyroid hormone supplementation with the goal of preventing the postnatal nadir of thyroid hormone levels seen in very preterm infants is required.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

1.1
1.1. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 1 Abnormal mental development in survivors at 2 years (Bayley MDI > 2sd below mean).
1.2
1.2. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 2 Abnormal mental development in survivors at 5 years (RAKIT IQ score > 2sd below mean).
1.3
1.3. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 3 Cerebral palsy in survivors.
1.4
1.4. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 4 Bayley MDI in survivors at 7‐12 months.
1.5
1.5. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 5 Bayley PDI in survivors at 7‐12 months.
1.6
1.6. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 6 Bayley MDI in survivors at 24 months.
1.7
1.7. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 7 Bayley PDI in survivors at 24 months.
1.8
1.8. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 8 RAKIT IQ score in survivors at 5 years.
1.9
1.9. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 9 Special schooling at 9‐12 years.
1.10
1.10. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 10 Clinically significant Child Behaviour Checklist score in survivors at 2 years.
1.11
1.11. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 11 Clinically significant Child Behaviour Checklist score in survivors at 5 years.
1.12
1.12. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 12 Clinically significant Teacher Report Form score in survivors at 5 years.
1.13
1.13. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 13 Neonatal mortality.
1.14
1.14. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 14 Mortality to discharge.
1.15
1.15. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 15 Death or cerebral palsy.
1.16
1.16. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 16 Duration of mechanical ventilation (days).
1.17
1.17. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 17 CLD in survivors (oxygen at 28 days).
1.18
1.18. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 18 CLD in survivors (oxygen at 36 weeks).
1.19
1.19. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 19 Intraventricular haemorrhage ‐ any grade.
1.20
1.20. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 20 Intraventricular haemorrhage ‐ grade 3 or 4.
1.21
1.21. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 21 Periventricular leucomalacia.
1.22
1.22. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 22 Patent ductus arteriosus.
1.23
1.23. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 23 Sepsis.
1.24
1.24. Analysis
Comparison 1 Prophylactic thyroid hormones versus no thyroid hormones, Outcome 24 Retinopathy of prematurity (any grade) in survivors.
2.1
2.1. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 1 Abnormal mental development in survivors at 2 years (Bayley MDI >2sd below mean).
2.2
2.2. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 2 Abnormal mental development in survivors at 5 years (RAKIT IQ score >2sd below mean).
2.3
2.3. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 3 Cerebral palsy in survivors.
2.4
2.4. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 4 Bayley MDI in survivors at 7‐12 months.
2.5
2.5. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 5 Bayley PDI in survivors at 7‐12 months.
2.6
2.6. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 6 Bayley MDI in survivors at 24 months.
2.7
2.7. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 7 Bayley PDI in survivors at 24 months.
2.8
2.8. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 8 RAKIT IQ score in survivors at 5 years.
2.9
2.9. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 9 Clinically significant Child Behaviour Checklist score in survivors at 2 years.
2.10
2.10. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 10 Clinically significant Child Behaviour Checklist score in survivors at 5 years.
2.11
2.11. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 11 Clinically significant Teacher Report Form score in survivors at 5 years.
2.12
2.12. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 12 Neonatal mortality.
2.13
2.13. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 13 Mortality to discharge.
2.14
2.14. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 14 Death or cerebral palsy.
2.15
2.15. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 15 Duration of mechanical ventilation (days).
2.16
2.16. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 16 CLD in survivors (oxygen at 28 days).
2.17
2.17. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 17 CLD in survivors (oxygen at 36 weeks).
2.18
2.18. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 18 Patent ductus arteriosus.
2.19
2.19. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 19 Intraventricular hemorrhage ‐ any grade.
2.20
2.20. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 20 Intraventricular hemorrhage ‐ grade 3 or 4.
2.21
2.21. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 21 Periventricular leukomalacia.
2.22
2.22. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 22 Retinopathy of prematurity (any grade) in survivors.
2.23
2.23. Analysis
Comparison 2 Prophylactic thyroid hormones versus no thyroid hormones according to thyroid hormone dosing strategy, Outcome 23 Sepsis.
3.1
3.1. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 1 Abnormal mental development in survivors at 2 years (Bayley MDI > 2sd below mean).
3.2
3.2. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 2 Abnormal mental development in survivors at 5 years (RAKIT IQ score > 2sd below mean).
3.3
3.3. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 3 Cerebral palsy in survivors.
3.4
3.4. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 4 Bayley MDI in survivors at 7‐12 months.
3.5
3.5. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 5 Bayley PDI in survivors at 7‐12 months.
3.6
3.6. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 6 Bayley MDI in survivors at 24 months.
3.7
3.7. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 7 Bayley PDI in survivors at 24 months.
3.8
3.8. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 8 RAKIT IQ score in survivors at 5 years.
3.9
3.9. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 9 Special schooling at 9‐12 years.
3.10
3.10. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 10 Clinically significant Child Behaviour Checklist score in survivors at 2 years.
3.11
3.11. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 11 Clinically significant Child Behaviour Checklist score in survivors at 5 years.
3.12
3.12. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 12 Clinically significant Teacher Report Form score in survivors at 5 years.
3.13
3.13. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 13 Neonatal mortality.
3.14
3.14. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 14 Mortality to discharge.
3.15
3.15. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 15 Death or cerebral palsy.
3.16
3.16. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 16 Duration of mechanical ventilation (days).
3.17
3.17. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 17 CLD in survivors (oxygen at 28 days).
3.18
3.18. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 18 CLD in survivors (oxygen at 36 weeks).
3.19
3.19. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 19 Intraventricular haemorrhage ‐ any grade.
3.20
3.20. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 20 Intraventricular haemorrhage ‐ grade 3 or 4.
3.21
3.21. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 21 Periventricular leucomalacia.
3.22
3.22. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 22 Patent ductus arteriosus.
3.23
3.23. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 23 Sepsis.
3.24
3.24. Analysis
Comparison 3 Prophylactic thyroid hormones versus no thyroid hormones according to timing, Outcome 24 Retinopathy of prematurity (any grade) in survivors.
4.1
4.1. Analysis
Comparison 4 Prophylactic thyroid hormones versus no thyroid hormones according to gestational strata, Outcome 1 Mortality to discharge.
4.2
4.2. Analysis
Comparison 4 Prophylactic thyroid hormones versus no thyroid hormones according to gestational strata, Outcome 2 Duration of mechanical ventilation (days).
4.3
4.3. Analysis
Comparison 4 Prophylactic thyroid hormones versus no thyroid hormones according to gestational strata, Outcome 3 CLD in survivors (oxygen at 28 days).
4.4
4.4. Analysis
Comparison 4 Prophylactic thyroid hormones versus no thyroid hormones according to gestational strata, Outcome 4 Intraventricular haemorrhage ‐ grade 3 or 4.
4.5
4.5. Analysis
Comparison 4 Prophylactic thyroid hormones versus no thyroid hormones according to gestational strata, Outcome 5 Periventricular leucomalacia.
4.6
4.6. Analysis
Comparison 4 Prophylactic thyroid hormones versus no thyroid hormones according to gestational strata, Outcome 6 Sepsis.
5.1
5.1. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 1 Abnormal mental development in survivors at 2 years (Bayley MDI > 2sd below mean).
5.2
5.2. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 2 Abnormal mental development in survivors at 5 years (RAKIT IQ score > 2sd below mean).
5.3
5.3. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 3 Cerebral palsy in survivors.
5.4
5.4. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 4 Bayley MDI in survivors at 7‐12 months.
5.5
5.5. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 5 Bayley PDI in survivors at 7‐12 months.
5.6
5.6. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 6 Bayley MDI in survivors at 24 months.
5.7
5.7. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 7 Bayley PDI in survivors at 24 months.
5.8
5.8. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 8 RAKIT IQ score in survivors at 5 years.
5.9
5.9. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 9 Clinically significant Child Behaviour Checklist score in survivors at 2 years.
5.10
5.10. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 10 Clinically significant Child Behaviour Checklist score in survivors at 5 years.
5.11
5.11. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 11 Clinically significant Teacher Report Form score in survivors at 5 years.
5.12
5.12. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 12 Neonatal mortality.
5.13
5.13. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 13 Mortality to discharge.
5.14
5.14. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 14 Death or cerebral palsy.
5.15
5.15. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 15 Duration of mechanical ventilation (days).
5.16
5.16. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 16 CLD in survivors (oxygen at 28 days).
5.17
5.17. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 17 CLD in survivors (oxygen at 36 weeks).
5.18
5.18. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 18 Intraventricular haemorrhage ‐ any grade.
5.19
5.19. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 19 Intraventricular haemorrhage ‐ grade 3 or 4.
5.20
5.20. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 20 Periventricular leucomalacia.
5.21
5.21. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 21 Patent ductus arteriosus.
5.22
5.22. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 22 Sepsis.
5.23
5.23. Analysis
Comparison 5 Prophylactic thyroid hormones versus no thyroid hormones (studies with adequate methodology), Outcome 23 Retinopathy of prematurity (any grade) in survivors.
6.1
6.1. Analysis
Comparison 6 Prophylactic T3 and T4 versus T4 alone, Outcome 1 Mortality to discharge.
6.2
6.2. Analysis
Comparison 6 Prophylactic T3 and T4 versus T4 alone, Outcome 2 Duration of mechanical ventilation (days).
6.3
6.3. Analysis
Comparison 6 Prophylactic T3 and T4 versus T4 alone, Outcome 3 CLD in survivors (oxygen at 28 days).
6.4
6.4. Analysis
Comparison 6 Prophylactic T3 and T4 versus T4 alone, Outcome 4 Intraventricular haemorrhage ‐ grade 3 or 4.
6.5
6.5. Analysis
Comparison 6 Prophylactic T3 and T4 versus T4 alone, Outcome 5 Periventricular leucomalacia.
6.6
6.6. Analysis
Comparison 6 Prophylactic T3 and T4 versus T4 alone, Outcome 6 Sepsis.
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Update of

References

References to studies included in this review

Smith 2000 {published data only}
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Valerio 2004 {published data only}
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van Wassenaer 1997 {published and unpublished data}
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References to studies excluded from this review

Amato 1988 {published data only}
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Amato 1989 {published data only}
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Schonberger 1981 {published data only}
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Golombek {unpublished data only}
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References to other published versions of this review

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