Postnatal genetic and neurodevelopmental assessment in infants born at term with severely low birth weight of non‐placental origin

• Published in: Ultrasound in obstetrics & gynecology Vol. 62; no. 3; pp. 361 - 368
• Main Authors: Paz y Miño, M. F., Pauta, M., Meler, E., Matas, I., Mazarico, E., Camacho, A., Segura, M., Figueras, F., Borrell, A.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.09.2023; Wiley Subscription Services, Inc
• Subjects: Birth weight; Birth Weight - genetics; Childbirth & labor; Children; Cognitive ability; Copy number; Deoxyribonucleic acid; Disorders; DNA; DNA Copy Number Variations; exome sequencing; Female; fetal growth restriction; Fetal Growth Retardation - diagnostic imaging; Fetal Growth Retardation - genetics; Fetuses; FGR; genetic syndrome; Gestational Age; Gynecology; Humans; Impairment; Infant; Infant, Newborn; Infant, Small for Gestational Age; Infants; intrauterine growth restriction; IUGR; Low birth weight; Medical diagnosis; neurodevelopmental disorder; Neurodevelopmental disorders; Obstetrics; Placenta; Placental Insufficiency - diagnostic imaging; Placental Insufficiency - genetics; Pregnancy; prenatal diagnosis; Saliva; Syndrome; Ultrasonic imaging; Ultrasound; FGR; exome sequencing; fetal growth restriction; IUGR; neurodevelopmental disorder; intrauterine growth restriction; prenatal diagnosis; genetic syndrome
• ISSN: 0960-7692; 1469-0705
• DOI: 10.1002/uog.26188

ABSTRACT Objective To determine the frequency of genetic syndromes and childhood neurodevelopmental impairment in non‐malformed infants born at term with severely low birth weight and no evidence of placental insufficiency. Methods This case series was constructed from the data of infants delivered at term between 2013 and 2018 with severely low birth weight, defined as birth weight more than 2.5 SD below the mean, with normal maternal and fetal Doppler (umbilical artery, fetal middle cerebral artery, cerebroplacental ratio and uterine artery) and no maternal hypertensive disorder during pregnancy or fetal structural anomaly on prenatal ultrasound examination. Clinical exome sequencing and copy number variation (CNV) analysis were performed using DNA extracted from the children's saliva. Cognitive and psychomotor development was evaluated using the Bayley Scales of Infant and Toddler Development, 3rd edition or the Wechsler Intelligence Scale for Children, 5th edition tests, according to the child's age at testing. Results Among the 36 405 infants born within the study period, 274 (0.75%) had a birth weight below –2.5 SD, of whom 98 met the inclusion criteria. Among the 63 families contacted, seven (11%) reported a postnatal diagnosis of a genetic syndrome and a further 18 consented to participate in the study. Median gestational age at delivery was 38.0 (interquartile range (IQR), 37.3–38.5) weeks and median birth weight was 2020 (IQR, 1908–2248) g. All 18 children showed a normal result on clinical exome sequencing and CNV analysis, but six (33%) obtained a low score on neurodevelopmental testing. Conclusion Non‐malformed severely small term infants with no clinical or Doppler signs of placental insufficiency present a high rate of genetic syndromes and neurodevelopmental impairment during childhood. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. Linked article: There is a comment on this article by Chen and Li. Click here to view the Correspondence.