{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T21:04:57Z","timestamp":1782421497223,"version":"3.54.5"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Small-for-gestational-age (SGA) preterm infants are at higher risk for oxidative stress-related complications than appropriate-for-gestational-age (AGA) preterm infants. It has been proposed that HbF may be higher in SGA than in AGA infants due to fetal hypoxia. Aim: The aim of this study was to compare postnatal changes in HbF fractions in very preterm SGA and AGA infants and in subgroups of these patients who had been transfused with red blood cells (RBCs) or not. Methods: We studied 30 SGA and 60 AGA very preterm infants with a gestational age of 27.7 \u00b1 1.6 and 27.9 \u00b1 0.7 weeks, respectively. HbF fractions were recorded daily during the first week of life, at 14 \u00b1 2, 21 \u00b1 2, and 28 \u00b1 2 days of life, and 36 weeks (\u00b13 days of life) of postmenstrual age. Results: The HbF fractions measured from the first day of life to the 36th week of postmenstrual age decreased significantly in both the groups, without differences between the groups. Transfused and non-transfused SGA infants had similar values of HbF fraction, while transfused AGA infants had lower values of HbF fraction than non-transfused infants. Conclusions: HbF fraction decreased similarly in the postnatal period in very preterm SGA and AGA infants. RBC transfusions did not affect hemoglobin fraction (HbF) values in SGA infants but were associated with a reduction in HbF in AGA infants. These findings may be due to the effect of fetal preconditioning hypoxia in very preterm SGA infants.<\/jats:p>","DOI":"10.3390\/children13010117","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T09:27:12Z","timestamp":1768296432000},"page":"117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Changes in Fetal Hemoglobin in Very Preterm Infants Born Small for Gestational Age: A Retrospective Observational Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Carlo","family":"Dani","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, 50127 Florence, Italy"},{"name":"Division of Neonatology, Careggi University Hospital of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Cipriani","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Careggi University Hospital of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ciavotta","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Careggi University Hospital of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6235-4486","authenticated-orcid":false,"given":"Giulia","family":"Remaschi","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Careggi University Hospital of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/s41433-020-0938-5","article-title":"Lower foetal haemoglobin levels at 31- and 34-weeks post menstrual age is associated with the development of retinopathy of prematurity: PacIFiHER Report No. 1 PacIFiHER Study Group (Preterm Infants and Fetal Haemoglobin in ROP)","volume":"35","author":"Jiramongkolchai","year":"2021","journal-title":"Eye"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1136\/bjophthalmol-2021-319546","article-title":"Effects of fetal haemoglobin on systemic oxygenation in preterm infants and the development of retinopathy of prematurity PacIFiHER Report No. 2","volume":"107","author":"Jiramongkolchai","year":"2023","journal-title":"Br. J. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1111\/apa.15003","article-title":"Neonatal clinical blood sampling led to major blood loss and was associated with bronchopulmonary dysplasia","volume":"109","author":"Forssell","year":"2020","journal-title":"Acta Paediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1203\/00006450-199707000-00002","article-title":"The life span of erythrocytes transfused to preterm infants","volume":"42","author":"Bard","year":"1997","journal-title":"Pediatr. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1053\/sper.2002.37313","article-title":"The effect of blood transfusion on the hemoglobin oxygen dissociation curve of very early preterm infants during the first week of life","volume":"26","author":"Truttmann","year":"2002","journal-title":"Semin. Perinatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1089\/ars.2009.2974","article-title":"The redox activity of hemoglobins: From physiologic functions to pathologic mechanisms","volume":"13","author":"Reeder","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ratanasopa, K., Strader, M.B., Alayash, A.I., and Bulow, L. (2015). Dissection of the radical reactions linked to fetal hemoglobin reveals enhanced pseudoperoxidase activity. Front. Physiol., 6.","DOI":"10.3389\/fphys.2015.00039"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.freeradbiomed.2019.03.035","article-title":"Oxygen radical disease in the newborn, revisited: Oxidative stress and disease in the newborn period","volume":"142","author":"Perez","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1136\/bjophthalmol-2020-318293","article-title":"Low fraction of fetal haemoglobin is associated with retinopathy of prematurity in the very preterm infant","volume":"106","author":"Martinsson","year":"2022","journal-title":"Br. J. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1136\/archdischild-2020-319181","article-title":"Fetal haemoglobin and bronchopulmonary dysplasia in neonates: An observational study","volume":"106","author":"Martinsson","year":"2021","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3478","DOI":"10.4103\/IJO.IJO_274_23","article-title":"Role of fetal hemoglobin in the development and progression of retinopathy of prematurity in preterm infants","volume":"71","author":"Prasad","year":"2023","journal-title":"Indian J. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1007\/s00431-017-2957-1","article-title":"Neonatal outcome of small for gestational age preterm infants","volume":"176","author":"Nobile","year":"2017","journal-title":"Eur. J. Pediatr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/apa.12888","article-title":"Perinatal conditions related to growth restriction and inflammation are associated with an increased risk of bronchopulmonary dysplasia","volume":"104","author":"Eriksson","year":"2015","journal-title":"Acta Paediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1136\/archdischild-2019-316976","article-title":"Association of small for gestational age with retinopathy of prematurity: A systematic review and meta-analysis","volume":"105","author":"Razak","year":"2020","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2279017","DOI":"10.1080\/14767058.2023.2279017","article-title":"Small for gestational age at preterm birth identifies adverse neonatal outcomes more reliably than antenatal suspicion of fetal growth restriction","volume":"36","author":"Alda","year":"2023","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Malhotra, A., Allison, B.J., Castillo-Melendez, M., Jenkin, G., Polglase, G.R., and Miller, S.I. (2019). Neonatal morbidities of fetal growth restriction: Pathophysiology and impact. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00055"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.braindev.2015.07.008","article-title":"Extremely preterm infants small for gestational age are at risk for motor impairment at 3 years corrected age","volume":"38","author":"Kato","year":"2016","journal-title":"Brain Dev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1001\/jamapediatrics.2020.1097","article-title":"Association of Intrauterine growth restriction and small for gestational age status with childhood cognitive outcomes: A systematic review and meta-analysis","volume":"174","author":"Sacchi","year":"2020","journal-title":"JAMA Pediatr."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Motte-Signoret, E., Shankar-Aguilera, S., Brailly-Tabard, S., Soreze, Y., Dell\u2019Orto, V., Ben Ammar, R., De Luca, D., and Boileau, P. (2021). Small for gestational age preterm neonates exhibit defective GH\/IGF1 signaling pathway. Front. Pediatr., 9.","DOI":"10.3389\/fped.2021.711400"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/S0140-6736(16)00384-6","article-title":"INTERGROWTH-21st very preterm size at birth reference charts","volume":"387","author":"Villar","year":"2016","journal-title":"Lancet"},{"key":"ref_21","first-page":"359","article-title":"Relationship between platelet count and volume and spontaneous and pharmacological closure of ductus arteriosus in preterm infants","volume":"30","author":"Dani","year":"2013","journal-title":"Am. J. Perinatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1542\/peds.2005-0249","article-title":"Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia","volume":"116","author":"Ehrenkranz","year":"2005","journal-title":"Pediatrics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0022-3476(78)80282-0","article-title":"Incidence and evolution of the sub-ependymal intraventricular hemorrhage; a study of infants weighing less than 1500 grams","volume":"92","author":"Papile","year":"1978","journal-title":"J. Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/00000658-197801000-00001","article-title":"Neonatal necrotizing enterocolitis: Therapeutic decisions based upon clinical staging","volume":"187","author":"Bell","year":"1978","journal-title":"Ann. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"International Committee for the Classification of Retinopathy of Prematurity (2005). The International Classification of Retinopathy of Prematurity revisited. Arch. Ophthalmol., 123, 991\u2013999.","DOI":"10.1001\/archopht.123.7.991"},{"key":"ref_26","first-page":"484","article-title":"Recommendations for transfusion therapy in neonatology","volume":"13","author":"Girelli","year":"2015","journal-title":"Blood Transfus."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Dani, C., Remaschi, G., Ulivi, M., Monti, N., and Pratesi, S. (2025). Fetal hemoglobin in preterm infants after resuscitation with immediate cord clamping, delayed cord clamping, or cord milking. Children, 12.","DOI":"10.3390\/children12050627"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"434","DOI":"10.18203\/2349-3291.ijcp20210522","article-title":"tudy of fetal hemoglobin with different gestational age and birth weight of the newborn","volume":"8","author":"Roy","year":"2021","journal-title":"Int. J. Contemp. Pediatr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ebiom.2016.11.032","article-title":"Postnatal prediction of gestational age using newborn fetal hemoglobin levels","volume":"15","author":"Wilson","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1203\/00006450-199408000-00018","article-title":"The reactivation of fetal hemoglobin synthesis during anemia of prematurity","volume":"36","author":"Bard","year":"1994","journal-title":"Pediatr. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1542\/peds.86.2.193","article-title":"Elevated levels of fetal hemoglobin synthesis in infants with bronchopulmonary dysplasia","volume":"86","author":"Bard","year":"1990","journal-title":"Pediatrics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1172\/JCI107360","article-title":"Postnatal fetal and adult hemoglobin synthesis in early preterm newborn infants","volume":"52","author":"Bard","year":"1973","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1542\/peds.45.5.766","article-title":"The relative rates of synthesis of hemoglobins A and F in immature red cells of newborn infants","volume":"45","author":"Bard","year":"1970","journal-title":"Pediatrics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"211","DOI":"10.5858\/2001-125-0211-TRBNHF","article-title":"The relation between newborn hemoglobin F fractions and risk factors for sudden infant death syndrome","volume":"125","author":"Cowan","year":"2001","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_35","first-page":"919","article-title":"The changes of fetal hemoglobin in preterm and small for gestational age newborn infants","volume":"36","author":"Park","year":"1993","journal-title":"J. Korean Pediatr. Soc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1182\/blood.2023022190","article-title":"Elevating fetal hemoglobin: Recently discovered regulators and mechanisms","volume":"144","author":"Khandros","year":"2024","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1056\/NEJMra2405260","article-title":"The fetal-to-adult hemoglobin switch-mechanism and therapy","volume":"392","author":"Orkin","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/s41586-022-05312-w","article-title":"Activation of \u03b3-globin expression by hypoxia-inducible factor 1\u03b1","volume":"610","author":"Feng","year":"2022","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"121","DOI":"10.4103\/2249-4847.119995","article-title":"Assessment of iron status and red cell parameters in healthy full term small for gestational age neonates at birth","volume":"2","author":"Patidar","year":"2013","journal-title":"J. Clin. Neonatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1203\/00006450-199205000-00015","article-title":"Effect of hypoxemia on fetal hemoglobin synthesis during late gestation","volume":"31","author":"Bard","year":"1992","journal-title":"Pediatr. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.nbd.2011.04.021","article-title":"Hypoxic-preconditioning induces neuroprotection against hypoxia-ischemia in newborn piglet brain","volume":"43","author":"Ara","year":"2011","journal-title":"Neurobiol. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10020","DOI":"10.1007\/s12035-025-04896-4","article-title":"Preconditioning and posttreatment strategies in neonatal hypoxic-ischemic encephalopathy: Recent advances and clinical challenges","volume":"62","author":"Deng","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1111\/j.1471-0528.2004.00273.x","article-title":"Fetal responses to placental insufficiency: An update","volume":"111","author":"Baschat","year":"2004","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"102","DOI":"10.3345\/kjp.2018.06653","article-title":"Iron status in small for gestational age and appropriate for gestational age infants at birth","volume":"62","author":"Kim","year":"2019","journal-title":"Korean J. Pediatr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1111\/apa.15152","article-title":"Determinants and effects of fluid status changes in caesarean delivered neonates","volume":"109","author":"Zanardo","year":"2020","journal-title":"Acta Paediatr."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/1\/117\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T09:46:58Z","timestamp":1768297618000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/1\/117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,13]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["children13010117"],"URL":"https:\/\/doi.org\/10.3390\/children13010117","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,13]]}}}