{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T22:18:54Z","timestamp":1774563534302,"version":"3.50.1"},"reference-count":21,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,2,3]],"date-time":"2017-02-03T00:00:00Z","timestamp":1486080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJOG"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To study the relationship between neonatal morbidity (<jats:styled-content style=\"fixed-case\">NNM<\/jats:styled-content>) and two\u2010year neurodevelopmental impairment (<jats:styled-content style=\"fixed-case\">NDI<\/jats:styled-content>) in surviving children after early fetal growth restriction (<jats:styled-content style=\"fixed-case\">FGR<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Secondary analysis of a European randomised trial (<jats:styled-content style=\"fixed-case\">TRUFFLE<\/jats:styled-content>) of delivery for very preterm fetuses dependent on venous Doppler or cardiotocographic criteria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Tertiary perinatal centres, participants in <jats:styled-content style=\"fixed-case\">TRUFFLE<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Population<\/jats:title><jats:p>402 surviving children after early <jats:styled-content style=\"fixed-case\">FGR<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Prospective data were collection from the recognition of <jats:styled-content style=\"fixed-case\">FGR<\/jats:styled-content> until the corrected age of two years. We studied the association between <jats:styled-content style=\"fixed-case\">NNM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">NDI<\/jats:styled-content>, retaining trial allocation in all statistical models. <jats:styled-content style=\"fixed-case\">NNM<\/jats:styled-content> included any of bronchopulmonary dysplasia, brain injury, sepsis or necrotising enterocolitis. <jats:styled-content style=\"fixed-case\">NDI<\/jats:styled-content> was a composite of Bayley cognitive score &lt;\u00a085, cerebral palsy or severe sensory impairment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main outcome measure<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">NDI<\/jats:styled-content> in relation to <jats:styled-content style=\"fixed-case\">NNM<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">NNM<\/jats:styled-content> occurred in 104 cases (26%) and was more frequent in 17 of 39 infants with <jats:styled-content style=\"fixed-case\">NDI<\/jats:styled-content> (44%) than in the 87 of 363 infants with normal outcome (24%) [odds ratio 2.5 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>, 1.3\u20134.8); <jats:italic>P<\/jats:italic>\u00a0=\u00a00.01]. In 22 of 39 <jats:styled-content style=\"fixed-case\">NDI<\/jats:styled-content> cases (56%) there was no preceding <jats:styled-content style=\"fixed-case\">NNM<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">NNM<\/jats:styled-content> was inversely related to gestational age, but <jats:styled-content style=\"fixed-case\">NDI<\/jats:styled-content> did not vary by gestational age. In multivariable analyses, cerebral ultrasound abnormalities were most strongly associated with <jats:styled-content style=\"fixed-case\">NDI<\/jats:styled-content>, together with trial group allocation, birthweight ratio, infant sex and Apgar score.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>With the exception of cerebral ultrasound abnormalities, commonly used <jats:styled-content style=\"fixed-case\">NNM<\/jats:styled-content>s are poor markers of later\u00a0<jats:styled-content style=\"fixed-case\">NDI<\/jats:styled-content> and should not be used as surrogate outcomes for <jats:styled-content style=\"fixed-case\">NDI<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Tweetable abstract<\/jats:title><jats:p>Neonatal morbidities cannot be used as surrogate outcomes for neurodevelopmental impairment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1471-0528.14511","type":"journal-article","created":{"date-parts":[[2017,2,3]],"date-time":"2017-02-03T17:51:42Z","timestamp":1486144302000},"page":"1072-1078","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["The association of neonatal morbidity with long\u2010term neurological outcome in infants who were growth restricted and preterm at birth: secondary analyses from <scp>TRUFFLE<\/scp> (Trial of Randomized Umbilical and Fetal Flow in Europe)"],"prefix":"10.1111","volume":"124","author":[{"given":"AG","family":"Van Wassenaer\u2010Leemhuis","sequence":"first","affiliation":[{"name":"Department of Neonatology Academic Medical Center Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Marlow","sequence":"additional","affiliation":[{"name":"Department of Academic Neonatology Institute for Women's Health University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Lees","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Imperial College London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Academic Medical Center Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the TRUFFLE investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,2,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1479-828X.2011.01299.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c7087"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22489"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2014.01.046"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.7694"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2431-14-279"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000353631"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2014-1143"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2010.10.915"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)62049-3"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2010.05.002"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.13190"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-0705.1995.06030168.x"},{"key":"e_1_2_6_15_1","volume-title":"Bayley Scales of Infant and Toddler Development","author":"Bayley N","year":"2006"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.09.047"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000128983.54614.7E"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c1471"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2015-308667"},{"key":"e_1_2_6_20_1","first-page":"510","article-title":"Outcome at 4.5\u00a0years of age born after expectant management of early\u2010onset hypertensive disorders of pregnancy","volume":"204","author":"van WA","year":"2011","journal-title":"AJOG"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2010-1821"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.4042"}],"container-title":["BJOG: An International Journal of Obstetrics &amp; 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