Cooling for newborns with hypoxic ischaemic encephalopathy childbirth medicine fetal anoxia

1 H E A D E R . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 A B S T R A C T . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 P L A I N L A N G U A G E S U M M A R Y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 B A C K G R O U N D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 O B J E C T I V E S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 M E T H O D S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 R E S U L T S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 D I S C U S S I O N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 A U T H O R S ’ C O N C L U S I O N S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 A C K N O W L E D G E M E N T S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 R E F E R E N C E S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 C H A R A C T E R I S T I C S O F S T U D I E S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 D A T A A N D A N A L Y S E S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Fetal anoxia analysis 1.1. Comparison 1 therapeutic hypothermia versus standard care, outcome 1 death or major disability in s u r v i v o r s a s s e s s e d , b y q u a l i t y o f f o l l o w – u p . . . . . . . . . . . . . . . . . . . . . . . . . 2 8 analysis 1.2. Comparison 1 therapeutic hypothermia versus standard care, outcome 2 death or major disability in s u r v i v o r s a s s e s s e d , b y m e t h o d o f c o o l i n g . . . . . . . . . . . . . . . . . . . . . . . . . 2 9 analysis 1.3. C omparison 1 therapeu tic hypothermia versus sta ndard care, outcome 3 M ortality , by method of cooling. 30 analysis 1.4. Comparison 1 therapeutic hypothermia versus standard care, outcome 4 major neurodevelopmental d i s a b i l i t y , b y q u a l i t y o f f o l l o w – u p . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1 analysis 1.5.Fetal anoxia comparison 1 therapeutic hypothermia versus standard care, outcome 5 major neurodevelopmental d i s a b i l i t y i n s u r v i v o r s a s s e s s e d , b y q u a l i t y o f f o l l o w – u p . . . . . . . . . . . . . . . . . . . . . 3 2 analysis 1.6. Comparison 1 therapeutic hypothermia versus standard care, outcome 6 major neurodevelopmental d i s a b i l i t y i n s u r v i v o r s a s s e s s e d , b y m e t h o d o f c o o l i n g . . . . . . . . . . . . . . . . . . . . . 3 3 analysis 1.7. Comparison 1 therapeutic hypothermia versus standard care, outcome 7 cerebral palsy in survivors assessed, b y m e t h o d o f c o o l i n g . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 4 analysis 1.8.Fetal anoxia comparison 1 therapeutic hypothermia versus standard care, outcome 8 neuromotor delay (BSID PDI mo r e th a n 2 SD b el o w m ea n ) in s ur v i v o rs as s es s ed , b y q ua li ty o f fo ll o w- u p . . . . . . . . . . . . . 3 5 analysis 1.9. Comparison 1 therapeutic hypothermia versus standard care, outcome 9 neuromotor delay (BSID PDI m o r e t h a n 2 S D b el o w m ea n ) i n s u rv i v o r s a s s es s ed , b y m et h o d o f c o o li n g . . . . . . . . . . . . . . 3 6 analysis 1.10. Comparison 1 therapeutic hypothermia versus standard care, outcome 10 neuromotor development (BSID P D I ) i n s u r v i v o r s a s s e s s e d . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 7 analysis 1.11.Fetal anoxia comparison 1 therapeutic hypothermia versus standard care, outcome 11 developmental delay (BSID M D I mo r e th a n 2 S D be lo w me a n) i n su rv i vo rs a ss es se d, by qu al i ty o f fo ll o w -u p . . . . . . . . . . . 3 7 analysis 1.12. Comparison 1 therapeutic hypothermia versus standard care, outcome 12 developmental delay (BSID M D I mo r e th a n 2 S D be lo w me a n) i n su rv i vo rs a ss es se d, by me th o d o f co o li n g . . . . . . . . . . . . 3 8 analysis 1.13. Comparison 1 therapeutic hypothermia versus standard care, outcome 13 mental development (BSID M D I ) i n s u r v i v o r s a s s e s s e d . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 9 analysis 1.14.Fetal anoxia comparison 1 therapeutic hypothermia versus standard care, outcome 14 blindness in survivors assessed, b y m e t h o d o f c o o l i n g . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 0 analysis 1.15. Comparison 1 therapeutic hypothermia versus standard care, outcome 15 deafness in survivors assessed, b y m e t h o d o f c o o l i n g . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1 an aly sis 1.1 6. Co mpa ris on 1 the rap eut ic hypo ther mia ver sus sta nda rd ca re, out co me 16 si nus bra dy car dia . . . . 42 analysis 1.17. Comparison 1 therapeutic hypothermia versus standard care, outcome 17 hypotensi on requiring inotropic s u p p o r t . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 3 analysis 1.18.Fetal anoxia comparison 1 therapeutic hypothermia versus standard care, outcome 18 arrhythmia requiring medical t r e a t m e n t . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 4 analysis 1.19. Comparison 1 therapeutic hypothermia versus standard care, outcome 19 anaemia requirning t r a n s f u s i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 5 an aly sis 1.2 0. Co mpa ris on 1 the rap eut ic hypo ther mia ver sus sta nda rd ca re, out co me 20 leu kop aen ia. . . . . . 45 ana lysis 1.21. Comp aris on 1 thera peuti c hypot hermia versu s stan dard car e, outc ome 21 throm bocy topa enia. . . 46

Analysis 1.22. Comparison 1 therapeutic hypothermia versus standard care, outcome 22 coagulopathy resulting in major t h r o m b o s i s o r h a e m o r r h a g e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 6 an aly sis 1.2 3.Fetal anoxia co mpa ris on 1 the rap eut ic hypo ther mia ver sus sta nda rd ca re, out co me 23 hy po gly cae mia . . . . . 47 an aly sis 1.2 4. Co mpa ris on 1 the rap eut ic hypo ther mia ver sus sta nda rd ca re, out co me 24 hy po kal aem ia . . . . . 48 A na ly si s 1. 25 . Co mp ar is on 1 th er ap eu ti c hyp ot her mi a ve rs us st an da rd ca re , ou tc om e 25 ol ig ur ia . . . . . . . 48 A na ly si s 1. 26 . Co mp ar is on 1 th er ap eu ti c hyp ot her mi a ve rs us st an da rd ca re , ou tc om e 26 se ps is . . . . . . . . 49 A na ly si s 1. 27 . Co mp ar is on 1 th er ap eu ti c hyp ot her mi a ve rs us st an da rd ca re , ou tc om e 27 se iz ur es . . . . . . . 49 analysis 2.1. Comparison 2 therapeutic hypothermia versus standard care in infants with severe e ncephalopathy , outcome 1 D e a t h o r m a j o r d i s a b i l i t y i n s u r v i v o r s a s s e s s e d . . . . . . . . . . . . . . . . . . . . . . . 5 0 analysis 2.2.Fetal anoxia comparison 2 therapeutic hypothermia versus standard care in infants with severe e ncephalopathy , outcome 2 M o r t a l i t y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1 analysis 2.3. Comparison 2 therapeutic hypothermia versus standard care in infants with severe e ncephalopathy , outcome 3 M a j o r d i s a b i l i t y i n s u r v i v o r s a s s e s s e d . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1 analysis 3.1. Comparison 3 therapeutic hypothermia versus standard care in infants with moderate encephalopathy, O u t c o m e 1 D e a t h o r m a j o r d i s a b i l i t y i n s u r v i v o r s a s s e s s e d . . . . . . . . . . . . . . . . . . . 5 2 analysis 3.2.Fetal anoxia comparison 3 therapeutic hypothermia versus standard care in infants with moderate encephalopathy, O u t c o m e 2 M o r t a l i t y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 2 analysis 3.3. Comparison 3 therapeutic hypothermia versus standard care in infants with moderate encephalopathy, O u t c o m e 3 M a j o r d i s a b i l i t y i n s u r v i v o r s a s s e s s e d . . . . . . . . . . . . . . . . . . . . . . 5 3 53 W H A T ’ S N E W . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 H I S T O R Y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 C O N T R I B U T I O N S O F A U T H O R S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 D E C L A R A T I O N S O F I N T E R E S T . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 S O U R C E S O F S U P P O R T . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 I N D E X T E R M S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Fetal anoxia