{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T12:12:36Z","timestamp":1785499956831,"version":"3.56.0"},"reference-count":23,"publisher":"American Academy of Pediatrics (AAP)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,10,1]]},"abstract":"<jats:p>BACKGROUND. Hypocarbia and hyperoxia are risk factors for periventricular leukomalacia in low birth weight infants. The association of a cumulative index of exposure to hypocarbia and hyperoxia and periventricular leukomalacia has not been evaluated.<\/jats:p><jats:p>OBJECTIVE. Our goal was to examine the relationship between cumulative index of exposure to hypocarbia and hyperoxia and periventricular leukomalacia during the first 7 days of life in low birth weight infants.<\/jats:p><jats:p>METHODS. Blood gas results were recorded in 6-hour intervals among low birth weight infants in a prospective data registry. Cumulative index of exposure to hypocarbia was calculated as the difference between arterial carbon dioxide level and 35 mmHg multiplied by the time interval in hours for each 6-hour block in a 24-hour day for the first 7 days of life. Cumulative index of exposure to hyperoxia was calculated in the same manner for arterial oxygen level &amp;gt;80 mm Hg. The relationship between exposure to hypocarbia, hyperoxia, and periventricular leukomalacia was examined in 778 infants with blood gas and cranial sonography data.<\/jats:p><jats:p>RESULTS. Twenty-one infants had periventricular leukomalacia. Hypocarbia occurred in 489 infants and hyperoxia in 502 infants. Infants with periventricular leukomalacia were more likely to have a lower gestational age and to require delivery room resuscitation than those without periventricular leukomalacia. More infants in the highest quartile of exposure to hypocarbia had periventricular leukomalacia compared to those with no hypocarbia. Risk of periventricular leukomalacia was increased in infants with the highest quartile of exposure to hypocarbia after adjusting for maternal and neonatal variables, none to be associated with periventricular leukomalacia. Cumulative index exposure to hyperoxia was not related to periventricular leukomalacia.<\/jats:p><jats:p>CONCLUSIONS. Cumulative exposure to hypocarbia and not hyperoxia was independently related to risk of periventricular leukomalacia in low birth weight infants.<\/jats:p>","DOI":"10.1542\/peds.2005-2463","type":"journal-article","created":{"date-parts":[[2006,10,2]],"date-time":"2006-10-02T17:04:22Z","timestamp":1159808662000},"page":"1654-1659","source":"Crossref","is-referenced-by-count":110,"title":["Cumulative Index of Exposure to Hypocarbia and Hyperoxia as Risk Factors for Periventricular Leukomalacia in Low Birth Weight Infants"],"prefix":"10.1542","volume":"118","author":[{"given":"Seetha","family":"Shankaran","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Langer","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Research Triangle Institute, Research Triangle Park, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Nadya","family":"Kazzi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbot R.","family":"Laptook","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Brown Medical School, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Walsh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Case Western University, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the National Institute of Child Health and Human Development Neonatal Research Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2006,10,1]]},"reference":[{"key":"2021120822451713200_R1","doi-asserted-by":"crossref","unstructured":"Lemons JA, Bauer CR, Oh W, et al. Very low birth weight outcomes of the national institute of child health and human development neonatal research network, January 1995 through December 1996. Pediatrics.\u20082001;107:1\u20138","DOI":"10.1542\/peds.107.1.e1"},{"key":"2021120822451713200_R2","doi-asserted-by":"crossref","unstructured":"Shankaran S, Johnson Y, Langer JC, et al. Outcome of extremely-low-birth-weight infants at highest risk: gestational age \u2264 24 weeks, birth weight \u2264750g, and 1-minute Apgar \u22643. Am J Obstet Gynecol. 2004191:1084\u20131091","DOI":"10.1016\/j.ajog.2004.05.032"},{"key":"2021120822451713200_R3","doi-asserted-by":"crossref","unstructured":"Giannakopoulou C, Korakaki E, Manoura A, et al. Significance of hypocarbia in the development of periventricular leukomalacia in preterm infants. Int Pediatr.\u20082004;46:268\u2013273","DOI":"10.1111\/j.1442-200x.2004.01886.x"},{"key":"2021120822451713200_R4","doi-asserted-by":"crossref","unstructured":"Erickson SJ, Grauaug A, Gurrin L, et al. Hypocarbia in the ventilated preterm infant and its effect on intraventricular haemorrhage and brochopulmonary dysplasia. J Paediatr Child Health.\u20082002;38:560\u2013562","DOI":"10.1046\/j.1440-1754.2002.00041.x"},{"key":"2021120822451713200_R5","doi-asserted-by":"crossref","unstructured":"Okumura A, Hyakawa F, Kato T, et al. Hypocarbia in preterm infants with periventricular leukomalacia: the relation between hypocarbia and mechanical ventilation. Pediatrics.\u20082001;107:469\u2013475","DOI":"10.1542\/peds.107.3.469"},{"key":"2021120822451713200_R6","doi-asserted-by":"crossref","unstructured":"Dammann O, Allred EN, Kuban KCK, et al. for the Developmental Epidemiology Network Investigators. Hypocarbia during the first 24 postnatal index and white matter echolucencies in newborns \u2264 28 weeks gestation. Pediatr Res.\u20082001;49:388\u2013393","DOI":"10.1203\/00006450-200103000-00013"},{"key":"2021120822451713200_R7","doi-asserted-by":"crossref","unstructured":"Wiswell TE, Graziani LJ, Kornhauser MS, et al. Effects of hypocarbia on the development of periventricular leukomalacia in premature infants treated with high-frequency jet ventilation. Pediatrics.\u20081996;98:918\u2013924","DOI":"10.1542\/peds.98.5.918"},{"key":"2021120822451713200_R8","doi-asserted-by":"crossref","unstructured":"Fujimoto S, Togari H, Yamaguchi N, et al. Hypocarbia and preventricular leukomalacia in premature infants. Arch Dis Child.\u20081994;71:107\u2013110","DOI":"10.1136\/fn.71.2.F107"},{"key":"2021120822451713200_R9","doi-asserted-by":"crossref","unstructured":"Volpe JJ. Neurobiology of periventricular leukomalacia in the premature infant. Pediatr Res.\u20082001;50:553\u2013562","DOI":"10.1203\/00006450-200111000-00003"},{"key":"2021120822451713200_R10","doi-asserted-by":"crossref","unstructured":"Collins MP, Lorenz JM, Jetton JR, et al. Hypocapnia and other ventilation-related risk factors for cerebral palsy in low birth weight infants. Pediatr Res.\u20082001;50:712\u2013719","DOI":"10.1203\/00006450-200112000-00014"},{"key":"2021120822451713200_R11","doi-asserted-by":"crossref","unstructured":"Calvert SA, Hoskins EM, Forsyth SC. Etiological factors associated with the development of periventricular leukomalacia. Acta Paediatr Scand.\u20081987;76:254\u2013259","DOI":"10.1111\/j.1651-2227.1987.tb10456.x"},{"key":"2021120822451713200_R12","doi-asserted-by":"crossref","unstructured":"Wu YW, Colford JM. Chorioamnionitis as a risk factor for cerebral palsy. 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