Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 1 of 22
Appendix 5. Cerebral Palsy
Study N Treatment (n/N) Controls (n/N) RR (95% CI) Dexa‐ or
betamethasone
Wong 2014(1) 17/743 9/143 0.364 (0.165‐
0.799)
Chawla 2013(2) 13/51 3/8 0.680 (0.248‐
1.867)
Carlo 2011(3) 341/3972 107/891 0.715 (0.583‐
0.877)
Dessens 2000(4) 2/61* 2/58* 0.951 (0.138‐
6.529)
Salokorpi 1997(5) 5/50 7/32 0.457 (0.159‐
1.317)
Doyle 1989(6) 3/42 2/41 1.464 (0.258‐
8.135) Collaborative
1984**(7)
9/200 16/206 0.579 (0.262‐
1.281) Pooled – REM
Fixed (M‐H)
I
2=0% 390/5119 146/1379 0.678 (0.564‐
0.815) 0.680 (0.566‐
0.817)
Dexamathasone
Lee 2008 (Dexa)(8) 29/408 10/153 1.087 (0.543‐
2.178)
Salokorpi 1997(5) 5/50 7/32 0.457 (0.159‐
1.317) Collaborative
1984**(7)
9/200 16/206 0.579 (0.262‐
1.281) Pooled – REM
Fixed (M‐H)
I
2=15% 43/658 33/391 0.726 (0.435‐
1.211) 0.743 (0.468‐
0.178)
Betamethasone
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 2 of 22
Chawla 2013(2) 13/51 3/8 0.680 (0.248‐
1.867)
Lee 2008 (Beta)(8) 30/563 10/153 0.815 (0.408‐
1.630)
Dessens 2000(4) 2/61* 2/58* 0.951 (0.138‐
6.529)
Doyle 1989(6) 3/42 2/41 1.464 (0.258‐
8.135) Pooled –REM
Fixed (M‐H)
I
2=0% 48/717 17/260 0.828 (0.491‐
1.396) 0.851 (0.502‐
1.443)
RCTs only
Dessens 2000(4) 2/61* 2/58* 0.951 (0.138‐
6.529)
Salokorpi 1997(5) 5/50 7/32 0.457 (0.159‐
1.317) Collaborative
1984**(7)
9/200 16/206 0.579 (0.262‐
1.281) Pooled –REM
FEM M‐H
I
2=0% 16/311 25/396 0.563 (0.308‐
1.029) 0.569 (0.312‐
1.037)
<28 weeks
Wong 2014(1) 17/743 9/143 0.364 (0.165‐
0.799)
Chawla 2013(2) 13/51 3/8 0.680 (0.248‐
1.867)
Carlo 2011(3) 341/3972 107/891 0.715 (0.583‐
0.877)
Doyle 1989(6) 3/42 2/41 1.464 (0.258‐
8.135) Pooled –REM
FEM (M‐H)
I
2=11% 374/4808 121/1083 0.668 (0.498‐
0.895)
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 3 of 22
0.695 (0.573‐
0.842)
28‐34 weeks
Dessens 2000(4) 2/61* 2/58* 0.951 (0.138‐
6.529)
Salokorpi 1997(5) 5/50 7/32 0.457 (0.159‐
1.317) Collaborative
1984**(7)
9/200 16/206 0.579 (0.262‐
1.281) Pooled –REM
FEM (M‐H)
I
2=0% 16/311 25/396 0.563 (0.308‐
1.029) 0.569 (0.312‐
1.037)
REM: random effects model; FEM (M‐H): Fixed effect model (Mantel‐Haenszel)
*These numbers are derived by the initial cohort reported by Schutte et al.; **hemiparesis, di‐, tetra‐, quadriplegia
1. Wong D, Abdel-Latif M, Kent A, Network N. Antenatal steroid exposure and outcomes of very premature infants: a regional cohort study. Archives of disease in childhood Fetal and neonatal edition 2014 Jan;99(1):F12-20.
2. Chawla S, Bapat R, Pappas A, Bara R, Zidan M, Natarajan G. Neurodevelopmental outcome of extremely premature infants exposed to incomplete, no or complete antenatal steroids. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet 2013 Oct;26(15):1542-7.
3. Carlo WA, McDonald SA, Fanaroff AA, Vohr BR, Stoll BJ, Ehrenkranz RA, et al. Association of antenatal corticosteroids with mortality and neurodevelopmental outcomes among infants born at 22 to 25 weeks' gestation. JAMA : the journal of the American Medical Association 2011 Dec 7;306(21):2348-58.
4. Dessens AB, Haas HS, Koppe JG. Twenty-year follow-up of antenatal corticosteroid treatment. Pediatrics 2000 Jun;105(6):E77.
5. Salokorpi T, Sajaniemi N, Hallback H, Kari A, Rita H, von Wendt L. Randomized study of the effect of antenatal dexamethasone on growth and development of premature children at the corrected age of 2 years. Acta paediatrica 1997 Mar;86(3):294-8.
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 4 of 22
6. Doyle LW, Kitchen WH, Ford GW, Rickards AL, Kelly EA. Antenatal steroid therapy and 5- year outcome of extremely low birth weight infants. Obstetrics and gynecology 1989 May;73(5 Pt 1):743-6.
7. No_authors_listed. Effects of antenatal dexamethasone administration in the infant: long-term follow-up. The Journal of pediatrics 1984 Feb;104(2):259-67.
8. Lee BH, Stoll BJ, McDonald SA, Higgins RD, National Institute of Child H, Human Development Neonatal Research N. Neurodevelopmental outcomes of extremely low birth weight infants exposed prenatally to dexamethasone versus betamethasone. Pediatrics 2008 Feb;121(2):289-96.
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 5 of 22
Appendix 6. Severe Disability
Study N Treatment (n/N) Controls (n/N) RR (95% CI) Dexa‐ or
betamethasone
Wong 2014(1) 48/791 15/150 0.607 (0.349‐
1.055)
Chawla 2013(2) 16/51 3/8 0.837 (0.313‐
2.234)
Carlo 2011(3) 1476/3800 426/865 0.789 (0.729‐
0.853)
Salokorpi 1997(4) 3/50 3/32 0.640 (0.138‐
2.978)
Doyle 1986(5) 24/148 28/156 0.903 (0.550‐
1.485) Pooled –REM
FEM (M‐H)
I
2=0% 1567/4840 475/1211 0.787 (0.729‐
0.850) 0.786 (0.728‐
0.849)
Dexamethasone
Lee 2008 (Dexa)(6) 167/408 69/153 0.908 (0.736‐
1.120)
Salokorpi 1997(4) 3/50 3/32 0.640 (0.138‐
2.978) Pooled –REM
FEM (M‐H)
I
2=0% 170/458 72/185 0.902 (0.732‐
1.111) 0.898 (0.729‐
1.107)
Betamethasone
Chawla 2013(2) 16/51 3/8 0.837 (0.313‐
2.234)
Lee 2008 (Beta)(6) 191/563 69/153 0.752 (0.610‐
0.928)
Doyle 1986(5) 24/148 28/156 0.903 (0.550‐
1.485)
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 6 of 22
Pooled –REM FEM (M‐H)
I
2=0% 231/762 100/317 0.776 (0.642‐
0.937) 0.785 (0.647‐
0.951)
RCTs only
Salokorpi 1997(4) 3/50 3/32 0.640 (0.138‐
2.978)
Pooled N/A N/A N/A N/A
<28 weeks
Wong 2014(1) 48/791 15/150 0.607 (0.349‐
1.055)
Chawla 2013(2) 16/51 3/8 0.837 (0.313‐
2.234)
Carlo 2011(3) 1476/3800 426/865 0.789 (0.729‐
0.853) Pooled –REM
FEM (M‐H)
I
2=0% 1898/5613 513/1176 0.785 (0.726‐
0.848) 0.783 (0.724‐
0.846)
28‐34 weeks
Salokorpi 1997(4) 3/50 3/32 0.640 (0.138‐
2.978)
Doyle 1986(5) 24/148 28/156 0.903 (0.550‐
1.485) Pooled –REM
FEM (M‐H)
I
2=0% 27/198 31/188 0.875 (0.545‐
1.403) 0.872 (0.544‐
1.399)
REM: random effects model; FEM (M‐H): Fixed effect model (Mantel‐Haensel)
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 7 of 22
1. Wong D, Abdel-Latif M, Kent A, Network N. Antenatal steroid exposure and outcomes of very premature infants: a regional cohort study. Archives of disease in childhood Fetal and neonatal edition 2014 Jan;99(1):F12-20.
2. Chawla S, Bapat R, Pappas A, Bara R, Zidan M, Natarajan G. Neurodevelopmental outcome of extremely premature infants exposed to incomplete, no or complete antenatal steroids. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet 2013 Oct;26(15):1542-7.
3. Carlo WA, McDonald SA, Fanaroff AA, Vohr BR, Stoll BJ, Ehrenkranz RA, et al. Association of antenatal corticosteroids with mortality and neurodevelopmental outcomes among infants born at 22 to 25 weeks' gestation. JAMA : the journal of the American Medical Association 2011 Dec 7;306(21):2348-58.
4. Salokorpi T, Sajaniemi N, Hallback H, Kari A, Rita H, von Wendt L. Randomized study of the effect of antenatal dexamethasone on growth and development of premature children at the corrected age of 2 years. Acta paediatrica 1997 Mar;86(3):294-8.
5. Doyle LW, Kitchen WH, Ford GW, Rickards AL, Lissenden JV, Ryan MM. Effects of antenatal steroid therapy on mortality and morbidity in very low birth weight infants. The Journal of
pediatrics 1986 Feb;108(2):287-92.
6. Lee BH, Stoll BJ, McDonald SA, Higgins RD, National Institute of Child H, Human Development Neonatal Research N. Neurodevelopmental outcomes of extremely low birth weight infants exposed prenatally to dexamethasone versus betamethasone. Pediatrics 2008 Feb;121(2):289-96.
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 8 of 22
Appendix 7. Mental Developmental Index (MDI) <70
Study N Treatment (n/N) Controls (n/N) RR (95% CI) Dexa‐ or
betamethasone
Wong 2014(1) 34/699 12/131 0.531 (0.282‐
0.998)
Chawla 2013(2) 14/51 3/8 0.732 (0.269‐
1.989)
Carlo 2011(3) 1125/2867 328/753 0.901 (0.821‐
0.989) Collaborative
1984(4)
8/211 13/219 0.639 (0.270‐
1.510) Pooled –REM
FEM (M‐H)
I
2=0% 1181/3828 356/1111 0.840 (0.692‐
1.020) 0.880 (0.803‐
0.964)
Dexamethasone
Lee 2008 (Dexa)(5) 135/408 58/153 0.873 (0.683‐
1.115) Collaborative
1984(4)
8/211 13/219 0.639 (0.270‐
1.510) Pooled –REM
FEM (M‐H)
I
2=0% 143/619 71/372 0.853 (0.673‐
1.079) 0.842 (0.664‐
1.069)
Betamethasone
Chawla 2013(2) 14/51 3/8 0.732 (0.269‐
1.989)
Lee 2008 (Beta)(5) 163/563 58/153 0.764 (0.600‐
0.971) Pooled –REM
FEM (M‐H)
I
2=0% 177/614 61/161 0.762 (0.603‐
0.963) 0.762 (0.603‐
0.963)
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 9 of 22
RCTs only
Collaborative 1984(4)
8/211 13/219 0.875 (0.804‐
0.952)
Pooled N/A N/A
<28 weeks
Wong 2014(1) 34/699 12/131 0.531 (0.282‐
0.998)
Chawla 2013(2) 14/51 3/8 0.732 (0.269‐
1.989)
Carlo 2011(3) 1125/2867 328/753 0.901 (0.821‐
0.989) Pooled –REM
FEM (M‐H)
I
2=2% 1173/3617 343/892 0.806 (0.596‐
1.090) 0.886 (0.808‐
0.971)
28‐34 weeks
Collaborative 1984(4)
8/211 13/219 0.875 (0.804‐
0.952)
Pooled N/A N/A
REM: random effects model; FEM (M‐H): Fixed effects model (Mantel‐Haenszel)
1. Wong D, Abdel-Latif M, Kent A, Network N. Antenatal steroid exposure and outcomes of very premature infants: a regional cohort study. Archives of disease in childhood Fetal and neonatal edition 2014 Jan;99(1):F12-20.
2. Chawla S, Bapat R, Pappas A, Bara R, Zidan M, Natarajan G. Neurodevelopmental outcome of extremely premature infants exposed to incomplete, no or complete antenatal steroids. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet 2013 Oct;26(15):1542-7.
3. Carlo WA, McDonald SA, Fanaroff AA, Vohr BR, Stoll BJ, Ehrenkranz RA, et al. Association of antenatal corticosteroids with mortality and neurodevelopmental outcomes among infants born at 22 to 25 weeks' gestation. JAMA : the journal of the American Medical Association 2011 Dec 7;306(21):2348-58.
4. No_authors_listed. Effects of antenatal dexamethasone administration in the infant: long-term follow-up. The Journal of pediatrics 1984 Feb;104(2):259-67.
5. Lee BH, Stoll BJ, McDonald SA, Higgins RD, National Institute of Child H, Human Development Neonatal Research N. Neurodevelopmental outcomes of extremely low birth weight infants exposed prenatally to dexamethasone versus betamethasone. Pediatrics 2008 Feb;121(2):289-96.
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 10 of 22
Appendix 8. Psychomotor Developmental Index (PDI) <70
Study N Treatment (n/N) Controls (n/N) RR (95% CI) Dexa‐ or
betamethasone
Carlo 2011(1) 776/2843 246/751 0.833 (0.740‐
0.938) Collaborative
1984(2)
7/206 12/218 0.617 (0.248‐
1.537) Pooled –REM
FEM (M‐H)
I
2=0% 783/3049 258/969 0.829 (0.737‐
0.933) 0.827 (0.735‐
0.931)
Dexamethasone
Lee 2008 (Dexa)(3) 98/408 31/153 1.185 (0.828‐
1.697) Collaborative
1984(2)
7/206 12/218 0.850 (0.761‐
0.950) Pooled –REM
FEM (M‐H)
I
2=41% 105/614 43/371 0.984 (0.553‐
1.753) N/A
Betamethasone
Lee 2008 (Beta)(3) 107/563 31/153 0.923 (0.591‐
1.444)
Pooled N/A N/A
RCTs only
Collaborative 1984(2)
7/206 12/218 0.850 (0.761‐
0.950)
Pooled N/A N/A
<28 weeks
Carlo 2011(1) 776/2843 246/751 0.833 (0.740‐
0.938)
Pooled N/A N/A
28‐34 weeks
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 11 of 22
Collaborative 1984(2)
7/206 12/218 0.850 (0.761‐
0.950)
Pooled N/A N/A
REM: random effects model; FEM (M‐H): fixed effects model (Mantel‐Haenszel)
1. Carlo WA, McDonald SA, Fanaroff AA, Vohr BR, Stoll BJ, Ehrenkranz RA, et al. Association of antenatal corticosteroids with mortality and neurodevelopmental outcomes among infants born at 22 to 25 weeks' gestation. JAMA : the journal of the American Medical Association 2011 Dec 7;306(21):2348-58.
2. No_authors_listed. Effects of antenatal dexamethasone administration in the infant: long-term follow-up. The Journal of pediatrics 1984 Feb;104(2):259-67.
3. Lee BH, Stoll BJ, McDonald SA, Higgins RD, National Institute of Child H, Human Development Neonatal Research N. Neurodevelopmental outcomes of extremely low birth weight infants exposed prenatally to dexamethasone versus betamethasone. Pediatrics 2008 Feb;121(2):289-96.
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 12 of 22
Appendix 9. Intact Survival
Study N Treatment (n/N) Controls (n/N) RR (95% CI) Dexa‐ or
betamethasone
Wong 2014(1) 554/791 97/150 1.083 (0.954‐
1.229)
Chawla 2013(2) 22/70 3/23 2.410 (0.794‐
7.315)
Lee 2008(3) 331/971 32/153 1.630 (1.183‐
2.245)
Schaap 2001(4) 51/53 40/47 1.131 (0.992‐
1.289)
Salokorpi 1997(5) 26/50 11/32 1.513 (0.875‐
2.616)
Doyle 1986(6) 98/148 90/156 1.148 (0.962‐
1.370) Pooled –REM
FEM (M‐H)
I
2=39% 1082/2083 273/561 1.186 (1.056‐
1.332) 1.219 (1.110‐
1.338)
Dexamethasone
Lee 2008 (Dexa)(3) 106/408 32/153 1.242 (0.876‐
1.761)
Salokorpi 1997(5) 26/50 11/32 1.513 (0.875‐
2.616) Pooled –REM
FEM (M‐H)
I
2=0% 132/458 43/185 1.315 (0.980‐
1.765) 1.303 (0.969‐
1.751)
Betamethasone
Chawla 2013(2) 22/70 3/23 2.410 (0.794‐
7.315)
Lee 2008 (Beta)(3) 225/563 32/153 1.911 (1.382‐
2.643)
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 13 of 22
Schaap 2001(4) 51/53 40/47 1.131 (0.992‐
1.289)
Doyle 1986(6) 98/148 90/156 1.148 (0.962‐
1.370) Pooled –REM
FEM (M‐H)
I
2=71% 396/834 165/379 1.329 (1.047‐
1.686) N/A
RCTs only
Salokorpi 1997(5) 26/50 11/32 1.513 (0.875‐
2.616)
Pooled N/A N/A
<28 weeks
Wong 2014(1) 554/791 97/150 1.083 (0.954‐
1.229)
Chawla 2013(2) 22/70 3/23 2.410 (0.794‐
7.315)
Lee 2008(3) 331/971 32/153 1.630 (1.183‐
2.245) Pooled –REM
FEM (M‐H)
I
2=72% 907/1832 132/326 1.377 (0.934‐
2.029) N/A
28‐34 weeks
Schaap 2001(4) 51/53 40/47 1.131 (0.992‐
1.289)
Salokorpi 1997(5) 26/50 11/32 1.513 (0.875‐
2.616)
Doyle 1986(6) 98/148 90/156 1.148 (0.962‐
1.370) Pooled –REM
FEM (M‐H)
I
2=0% 175/251 141/235 1.148 (1.036‐
1.273) 1.177 (1.036‐
1.337)
REM: random effects model; FEM (M‐H): fixed effect model (Mantel‐Haenszel)
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 14 of 22
1. Wong D, Abdel-Latif M, Kent A, Network N. Antenatal steroid exposure and outcomes of very premature infants: a regional cohort study. Archives of disease in childhood Fetal and neonatal edition 2014 Jan;99(1):F12-20.
2. Chawla S, Bapat R, Pappas A, Bara R, Zidan M, Natarajan G. Neurodevelopmental outcome of extremely premature infants exposed to incomplete, no or complete antenatal steroids. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet 2013 Oct;26(15):1542-7.
3. Lee BH, Stoll BJ, McDonald SA, Higgins RD, National Institute of Child H, Human Development Neonatal Research N. Neurodevelopmental outcomes of extremely low birth weight infants exposed prenatally to dexamethasone versus betamethasone. Pediatrics 2008 Feb;121(2):289-96.
4. Schaap AH, Wolf H, Bruinse HW, Smolders-De Haas H, Van Ertbruggen I, Treffers PE.
Effects of antenatal corticosteroid administration on mortality and long-term morbidity in early preterm, growth-restricted infants. Obstetrics and gynecology 2001 Jun;97(6):954-60.
5. Salokorpi T, Sajaniemi N, Hallback H, Kari A, Rita H, von Wendt L. Randomized study of the effect of antenatal dexamethasone on growth and development of premature children at the corrected age of 2 years. Acta paediatrica 1997 Mar;86(3):294-8.
6. Doyle LW, Kitchen WH, Ford GW, Rickards AL, Lissenden JV, Ryan MM. Effects of antenatal steroid therapy on mortality and morbidity in very low birth weight infants. The Journal of
pediatrics 1986 Feb;108(2):287-92.
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 15 of 22
Appendix 10. Minor Disability
Study N Treatment (n/N) Controls (n/N) RR (95% CI) Dexa‐ or
betamethasone
Wong 2014(1) 108/791 21/150 0.975 (0.632‐
1.505)
Salokorpi 1997(2) 21/50 17/32 0.791 (0.499‐
1.253)
Doyle 1986(3) 26/148 38/156 0.721 (0.462‐
1.126) Pooled –REM
FEM (M‐H)
I
2=0% 155/989 76/338 0.826 (0.638‐
1.068) 0.833 (0.641‐
1.083)
Dexamethasone
Salokorpi 1997(2) 21/50 17/32 0.791 (0.499‐
1.253)
Pooled N/A N/A
Betamethasone
Doyle 1986(3) 26/148 38/156 0.721 (0.462‐
1.126)
RCTs only
Salokorpi 1997(2) 21/50 17/32 0.791 (0.499‐
1.253)
Pooled N/A N/A
<28 weeks
Wong 2014(1) 108/791 21/150 0.975 (0.632‐
1.505)
Pooled N/A N/A
28‐34 weeks
Salokorpi 1997(2) 21/50 17/32 0.791 (0.499‐
1.253)
Doyle 1986(3) 26/148 38/156 0.721 (0.462‐
1.126)
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 16 of 22
Pooled –REM FEM (M‐H)
I
2=0% 47/198 55/188 0.754 (0.547‐
1.038) 0.746 (0.537‐
1.036)
REM: random effects model; FEM (M‐H): fixed effect model (Mantel‐Haenszel)
1. Wong D, Abdel-Latif M, Kent A, Network N. Antenatal steroid exposure and outcomes of very premature infants: a regional cohort study. Archives of disease in childhood Fetal and neonatal edition 2014 Jan;99(1):F12-20.
2. Salokorpi T, Sajaniemi N, Hallback H, Kari A, Rita H, von Wendt L. Randomized study of the effect of antenatal dexamethasone on growth and development of premature children at the corrected age of 2 years. Acta paediatrica 1997 Mar;86(3):294-8.
3. Doyle LW, Kitchen WH, Ford GW, Rickards AL, Lissenden JV, Ryan MM. Effects of antenatal steroid therapy on mortality and morbidity in very low birth weight infants. The Journal of
pediatrics 1986 Feb;108(2):287-92.
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 17 of 22
Appendix 11. Cognitive Development‐ Wechsler Scales of Intelligence: Verbal Intelligence Quotient – VIQ
Study N steroids/control Treatment mean (SD)
Controls mean (SD)
SMD (95% CI)
Dexa‐ or
betamethasone
Liu 2012(1) 1011/286 92.9 (5.2) 93.5 (4.7) ‐0.118 (‐
0.249 to 0.014) Dalziel 2005(2) 87/105 97.6 (11.9) 98.3 (12.8) ‐0.056 (‐
0.340 to 0.228)
Doyle 2000(3) 69/61 96.4 (16.4) 91.4 (16.6) 0.301 (‐0.045 to 0.648) Schmand 1990(4) 54/36 95.6 (13.9) 96.9 (11.4) ‐0.099 (‐
0.521 to 0.323) Pooled –REM
FEM (IV)
I
2=39% ‐0.027 (‐
0.199 to 0.323)
‐0.066 (‐
0.175 to 0.043)
Dexamethasone
Liu 2012(1) 92.9 (5.2) 93.5 (4.7) ‐0.118 (‐
0.249 to 0.014)
Pooled N/A N/A
Betamethasone
Dalziel 2005(2) 87/105 97.6 (11.9) 98.3 (12.8) ‐0.056 (‐
0.340 to
0.228)
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 18 of 22
Doyle 2000(3) 69/61 96.4 (16.4) 91.4 (16.6) 0.301 (‐0.045 to 0.648) Schmand 1990(4) 54/36 95.6 (13.9) 96.9 (11.4) ‐0.099 (‐
0.521 to 0.323) Pooled –REM
FEM (IV)
I
2=34% 0.051 (‐0.194
to 0.296) 0.048 (‐0.147 to 0.243)
RCTs only
Dalziel 2005(2) 97.6 (11.9) 98.3 (12.8) ‐0.056 (‐
0.340 to 0.228) Schmand 1990(4) 95.6 (13.9) 96.9 (11.4) ‐0.099 (‐
0.521 to 0.323) Pooled –REM
FEM (IV)
N/A N/A
<28 weeks
The mean gestational age at birth was >28 weeks in all four studies
SMD: standardized mean difference; REM: random effects model; FEM (IV): fixed effect model (inverse variance)
1. Liu J, Feng ZC, Li J, Wang Q. Antenatal dexamethasone has no adverse effects on child physical and cognitive development: a long-term cohort follow-up investigation. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet 2012 Nov;25(11):2369-71.
2. Dalziel SR, Lim VK, Lambert A, McCarthy D, Parag V, Rodgers A, et al. Antenatal exposure to betamethasone: psychological functioning and health related quality of life 31 years after inclusion in randomised controlled trial. Bmj 2005 Sep 24;331(7518):665.
3. Doyle LW, Ford GW, Rickards AL, Kelly EA, Davis NM, Callanan C, et al. Antenatal corticosteroids and outcome at 14 years of age in children with birth weight less than 1501 grams. Pediatrics 2000 Jul;106(1):E2.
4. Schmand B, Neuvel J, Smolders-de Haas H, Hoeks J, Treffers PE, Koppe JG. Psychological development of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome. Pediatrics 1990 Jul;86(1):58-64.
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 19 of 22
Appendix 12. Cognitive Development‐ Wechsler Scales of Intelligence: Performance Intelligence Quotient – PIQ
Study N Treatment mean
(SD)
Controls mean (SD)
SMD (95% CI)
Dexa‐ or
betamethasone
Liu 2012(1) 1011/286 94.1 (5.9) 94.5 (4.8) ‐0.070 (‐0.202 to 0.061) Dalziel 2005(2) 87/105 107.2 (13.8) 108.3 (14.7) ‐0.077 (‐0.361
to 0.208) Doyle 2000(3) 69/61 100.7 (15.0) 94.4 (16.6) 0.397 (0.049
to 0.745) Schmand 1990(4) 54/36 94.8 (14.6) 97.8 (13.5) ‐0.210 (‐0.633
to 0.213) Pooled –FEM
REM (IV)
I
2=57% 0.000 (‐0.209
to 0.210) N/A
Dexamethasone
Liu 2012(1) 94.1 (5.9) 94.5 (4.8) ‐0.070 (‐0.202
to 0.061)
Pooled N/A N/A
Betamethasone
Dalziel 2005(2) 107.2 (13.8) 108.3 (14.7) ‐0.077 (‐0.361 to 0.208) Doyle 2000(3) 100.7 (15.0) 94.4 (16.6) 0.397 (0.049
to 0.745) Schmand 1990(4) 94.8 (14.6) 97.8 (13.5) ‐0.210 (‐0.633
to 0.213) Pooled –FEM
REM (IV)
I
2=67% 0.043 (‐0.306
to 0.393) N/A
RCTs only
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 20 of 22
Dalziel 2005(2) 107.2 (13.8) 108.3 (14.7) Schmand 1990(4) 94.8 (14.6) 97.8 (13.5) Pooled –FEM
REM (IV)
I
2=0% ‐0.118 (‐0.354
to 0.118)
‐0.118 (‐0.354 to 0.118)
<28 weeks
The mean gestational age at birth was >28 weeks in all studies
REM: random effects model; FEM (IV): fixed effect model (inverse variance)*Liu: Wechsler Preschool and Primary Scale of Intelligence Revised (WPPSI‐R)
* Schmand: Wechsler Intelligence Scale of Children Revised (WISC‐R)
*Doyle : Wechsler Intelligence Scale of Children –III (WISC‐III)
*Dalziel:Wechsler Abbreviated Scale of Intelligence
1. Liu J, Feng ZC, Li J, Wang Q. Antenatal dexamethasone has no adverse effects on child physical and cognitive development: a long-term cohort follow-up investigation. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet 2012 Nov;25(11):2369-71.
2. Dalziel SR, Lim VK, Lambert A, McCarthy D, Parag V, Rodgers A, et al. Antenatal exposure to betamethasone: psychological functioning and health related quality of life 31 years after inclusion in randomised controlled trial. Bmj 2005 Sep 24;331(7518):665.
3. Doyle LW, Ford GW, Rickards AL, Kelly EA, Davis NM, Callanan C, et al. Antenatal corticosteroids and outcome at 14 years of age in children with birth weight less than 1501 grams. Pediatrics 2000 Jul;106(1):E2.
4. Schmand B, Neuvel J, Smolders-de Haas H, Hoeks J, Treffers PE, Koppe JG. Psychological development of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome. Pediatrics 1990 Jul;86(1):58-64.
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 21 of 22
Appendix 13. Cognitive Development‐ Wechsler Scales of Intelligence: Full Intelligence Quotient
Study N Treatment mean
(SD)
Controls mean (SD)
OR (95% CI)
Betamethasone
Dalziel 2005(1) 87/105 102.6 (12.5) 103.7 (13.5) ‐0.084 (‐0.368 to 0.200) Doyle 2000(2) 69/61 98.2 (15.5) 92 (15.1) 0.403 (0.066
to 0.740) Schmand 1990(3) 54/36 94.9 (13.5) 96.8 (12.5) ‐0.144 (‐0.566
to 0.279) Pooled –FEM
REM (IV)
I
2=66% 0.064 (‐0.276
to 0.404) N/A
RCTs only
Dalziel 2005(1) 102.6 (12.5) 103.7 (13.5) ‐0.084 (‐0.368 to 0.200) Schmand 1990(3) 94.9 (13.5) 96.8 (12.5) ‐0.144 (‐0.566
to 0.279) Pooled –FEM
REM (IV)
I
2=0% ‐0.103 (‐0.338
to 0.133)
‐0.103 (‐0.338 to 0.133)
<28 weeks
The mean gestational age at birth was >28 weeks for all studies
REM: random effects model; FEM (IV):fixed effect model (inverse variance)
1. Dalziel SR, Lim VK, Lambert A, McCarthy D, Parag V, Rodgers A, et al. Antenatal exposure to betamethasone: psychological functioning and health related quality of life 31 years after inclusion in randomised controlled trial. Bmj 2005 Sep 24;331(7518):665.
2. Doyle LW, Ford GW, Rickards AL, Kelly EA, Davis NM, Callanan C, et al. Antenatal corticosteroids and outcome at 14 years of age in children with birth weight less than 1501 grams. Pediatrics 2000 Jul;106(1):E2.
Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in preterm infants: a systematic review and meta-analysis. Obstet Gynecol 2015;125.
The authors provided this information as a supplement to their article.
© Copyright 2015 American College of Obstetricians and Gynecologists. Page 22 of 22
3. Schmand B, Neuvel J, Smolders-de Haas H, Hoeks J, Treffers PE, Koppe JG. Psychological development of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome. Pediatrics 1990 Jul;86(1):58-64.