Efficacy and Safety of Different Maintenance Doses of Caffeine Citrate for Treatment of Apnea in Premature Infants: A Systematic Review and Meta-Analysis

<table class="fixed-width table-group" id="tab2"><tr><td><table class="table"><colgroup><col style="width:3.26em"/><col style="width:5.99em"/><col style="width:4.62em"/><col style="width:4.62em"/><col style="width:4.62em"/><col style="width:4.62em"/><col style="width:2.53em"/><col style="width:6.52em"/><col style="width:7.40em"/><col style="width:2.99em"/></colgroup><tr><td class="thead-hr" colspan="10"><hr/></td></tr><tr class="thead"><td class="align_left"> </td><td class="align_center">No. of trials</td><td class="align_center" colspan="2"> HD</td><td class="align_center" colspan="2"> LD</td><td class="align_center">I<sup>2</sup></td><td class="align_center">Effect-Model</td><td class="align_center">Outcomes</td><td class="align_center">P</td></tr><tr class="thead"><td class="align_left"> </td><td class="align_center"> </td><td class="align_center">case</td><td class="align_center">total</td><td class="align_center">case</td><td class="align_center">total</td><td class="align_center"> </td><td class="align_center"> </td><td class="align_center"> </td><td class="align_center"> </td></tr><tr><td class="thead-hr" colspan="10"><hr/></td></tr><tr><td class="align_left">ROP</td><td class="align_center">6</td><td class="align_center">42</td><td class="align_center">340</td><td class="align_center">61</td><td class="align_center">361</td><td class="align_center">0%</td><td class="align_center">Fixed</td><td class="align_center">0.74<svg height="11.439pt" id="M1" style="vertical-align:-2.15067pt" version="1.1" viewbox="-0.0498162 -9.28833 57.7881 11.439" width="57.7881pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M290 -163V-135C183 -126 181 -122 181 -44V583C181 662 184 666 290 675V703H120V-163H290Z"></path></g><g transform="matrix(.013,0,0,-0.013,4.485,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,10.725,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,13.689,0)"><path d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"></path></g><g transform="matrix(.013,0,0,-0.013,19.929,0)"><path d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"></path></g><g transform="matrix(.013,0,0,-0.013,26.169,0)"><path d="M95 130C70 130 46 113 46 88C46 72 54 64 59 64C93 55 121 33 121 -3C121 -41 93 -68 44 -88L55 -117C117 -98 186 -56 186 22C186 91 131 130 95 130Z"></path></g><g transform="matrix(.013,0,0,-0.013,31.312,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"></path></g><g transform="matrix(.013,0,0,-0.013,37.552,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,40.516,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,46.756,0)"><path d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"></path></g><g transform="matrix(.013,0,0,-0.013,52.997,0)"><path d="M226 -163V703H56V676C162 667 165 662 165 584V-43C165 -122 162 -126 56 -136V-163H226Z"></path></g></svg></td><td class="align_center">0.09</td></tr><tr><td class="align_left">NEC</td><td class="align_center">4</td><td class="align_center">10</td><td class="align_center">239</td><td class="align_center">19</td><td class="align_center">247</td><td class="align_center">0%</td><td class="align_center">Fixed</td><td class="align_center">0.54<svg height="11.439pt" id="M2" style="vertical-align:-2.15067pt" version="1.1" viewbox="-0.0498162 -9.28833 57.7881 11.439" width="57.7881pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M290 -163V-135C183 -126 181 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-12C362 -12 447 89 447 209C447 311 374 393 267 393C247 393 226 386 204 376L137 343ZM227 337C318 337 361 256 361 173C361 105 336 22 258 22C176 22 126 120 126 240C126 266 127 291 132 310C155 323 189 337 227 337Z"></path></g><g transform="matrix(.013,0,0,-0.013,26.169,0)"><path d="M95 130C70 130 46 113 46 88C46 72 54 64 59 64C93 55 121 33 121 -3C121 -41 93 -68 44 -88L55 -117C117 -98 186 -56 186 22C186 91 131 130 95 130Z"></path></g><g transform="matrix(.013,0,0,-0.013,31.312,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"></path></g><g transform="matrix(.013,0,0,-0.013,37.552,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,40.516,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"></path></g><g transform="matrix(.013,0,0,-0.013,46.756,0)"><path d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"></path></g><g transform="matrix(.013,0,0,-0.013,52.996,0)"><path d="M226 -163V703H56V676C162 667 165 662 165 584V-43C165 -122 162 -126 56 -136V-163H226Z"></path></g></svg></td><td class="align_center">0.10</td></tr><tr><td class="align_left">IVH</td><td class="align_center">7</td><td class="align_center">86</td><td class="align_center">422</td><td class="align_center">92</td><td class="align_center">438</td><td class="align_center">0%</td><td class="align_center">Fixed</td><td class="align_center">0.98<svg height="11.439pt" id="M3" style="vertical-align:-2.15067pt" version="1.1" viewbox="-0.0498162 -9.28833 57.7881 11.439" width="57.7881pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M290 -163V-135C183 -126 181 -122 181 -44V583C181 662 184 666 290 675V703H120V-163H290Z"></path></g><g transform="matrix(.013,0,0,-0.013,4.485,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,10.725,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,13.689,0)"><path d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"></path></g><g transform="matrix(.013,0,0,-0.013,19.931,0)"><path d="M137 343C167 482 260 545 321 574C357 591 397 603 429 609L423 641C382 634 335 622 295 608C189 570 37 457 37 238C37 84 125 -12 242 -12C362 -12 447 89 447 209C447 311 374 393 267 393C247 393 226 386 204 376L137 343ZM227 337C318 337 361 256 361 173C361 105 336 22 258 22C176 22 126 120 126 240C126 266 127 291 132 310C155 323 189 337 227 337Z"></path></g><g transform="matrix(.013,0,0,-0.013,26.172,0)"><path d="M95 130C70 130 46 113 46 88C46 72 54 64 59 64C93 55 121 33 121 -3C121 -41 93 -68 44 -88L55 -117C117 -98 186 -56 186 22C186 91 131 130 95 130Z"></path></g><g transform="matrix(.013,0,0,-0.013,31.315,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"></path></g><g transform="matrix(.013,0,0,-0.013,37.555,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,40.519,0)"><path d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"></path></g><g transform="matrix(.013,0,0,-0.013,46.759,0)"><path d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"></path></g><g transform="matrix(.013,0,0,-0.013,53.001,0)"><path d="M226 -163V703H56V676C162 667 165 662 165 584V-43C165 -122 162 -126 56 -136V-163H226Z"></path></g></svg></td><td class="align_center">0.89</td></tr><tr><td class="align_left">PVL</td><td class="align_center">3</td><td class="align_center">12</td><td class="align_center">119</td><td class="align_center">9</td><td class="align_center">120</td><td class="align_center">0%</td><td class="align_center">Fixed</td><td class="align_center">1.35<svg height="11.439pt" id="M4" style="vertical-align:-2.15067pt" version="1.1" viewbox="-0.0498162 -9.28833 57.7881 11.439" width="57.7881pt" xmlns="http://www.w3.org/2000/svg" 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transform="matrix(.013,0,0,-0.013,19.929,0)"><path d="M244 635C114 635 38 519 38 422C38 317 111 240 217 240C236 240 255 244 277 256L345 292C311 140 203 39 59 15L64 -15C89 -15 150 -5 204 17C339 72 440 202 440 386C440 521 368 635 244 635ZM228 602C326 602 352 479 352 390C352 370 351 347 348 324C327 308 293 296 258 296C174 296 124 369 124 458C124 517 152 602 228 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,26.17,0)"><path d="M95 130C70 130 46 113 46 88C46 72 54 64 59 64C93 55 121 33 121 -3C121 -41 93 -68 44 -88L55 -117C117 -98 186 -56 186 22C186 91 131 130 95 130Z"></path></g><g transform="matrix(.013,0,0,-0.013,31.314,0)"><path d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"></path></g><g transform="matrix(.013,0,0,-0.013,37.554,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,40.518,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,46.758,0)"><path d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"></path></g><g transform="matrix(.013,0,0,-0.013,53,0)"><path d="M226 -163V703H56V676C162 667 165 662 165 584V-43C165 -122 162 -126 56 -136V-163H226Z"></path></g></svg></td><td class="align_center">0.47</td></tr><tr class="table-tr"><td colspan="10"><hr class="tbody-hr"/></td></tr></table></td></tr></table>

BioMed Research International

tab2

Table 2

Table 2: Efficacy and Safety of Different Maintenance Doses of Caffeine Citrate for Treatment of Apnea in Premature Infants: A Systematic Review and Meta-Analysis 

Table 2 | Efficacy and Safety of Different Maintenance Doses of Caffeine Citrate for Treatment of Apnea in Premature Infants: A Systematic Review and Meta-Analysis 