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      Incidence, clinical features and perinatal outcome in anomalous fetuses with late‐onset growth restriction: cohort study

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          ABSTRACT

          Objective

          To describe the incidence, clinical features and perinatal outcome of late‐onset fetal growth restriction (FGR) associated with genetic syndrome or aneuploidy, structural malformation or congenital infection.

          Methods

          This was a retrospective multicenter cohort study of patients who attended one of four tertiary maternity hospitals in Italy. We included consecutive singleton pregnancies between 32 + 0 and 36 + 6 weeks' gestation with either fetal abdominal circumference (AC) or estimated fetal weight < 10 th percentile for gestational age or a reduction in AC of > 50 percentiles from the measurement at an ultrasound scan performed between 18 and 32 weeks. The study group consisted of pregnancies with late‐onset FGR and a genetic syndrome or aneuploidy, structural malformation or congenital infection (anomalous late‐onset FGR). The presence of congenital anomalies was ascertained postnatally in neonates with abnormal findings on antenatal investigation or detected after birth. The control group consisted of pregnancies with structurally and genetically normal fetuses with late‐onset FGR. Composite adverse perinatal outcome was defined as the presence of at least one of stillbirth, 5‐min Apgar score < 7, admission to the neonatal intensive care unit (NICU), need for respiratory support at birth, neonatal jaundice and neonatal hypoglycemia. The primary aims of the study were to assess the incidence and clinical features of anomalous late‐onset FGR, and to compare the perinatal outcome of such cases with that of fetuses with non‐anomalous late‐onset FGR.

          Results

          Overall, 1246 pregnancies complicated by late‐onset FGR were included in the study, of which 120 (9.6%) were allocated to the anomalous late‐onset FGR group. Of these, 11 (9.2%) had a genetic syndrome or aneuploidy, 105 (87.5%) had an isolated structural malformation, and four (3.3%) had a congenital infection. The most frequent structural defects associated with late‐onset anomalous FGR were genitourinary malformations (28/105 (26.7%)) and limb malformation (21/105 (20.0%)). Compared with the non‐anomalous late‐onset FGR group, fetuses with anomalous late‐onset FGR had an increased incidence of composite adverse perinatal outcome (35.9% vs 58.3%; P < 0.01). Newborns with anomalous, compared to those with non‐anomalous, late‐onset FGR showed a higher frequency of need for respiratory support at birth (25.8% vs 9.0%; P < 0.01), intubation (10.0% vs 1.1%; P < 0.01), NICU admission (43.3% vs 22.6%; P < 0.01) and longer hospital stay (median, 24 days (range, 4–250 days) vs 11 days (range, 2–59 days); P < 0.01).

          Conclusions

          Most pregnancies complicated by anomalous late‐onset FGR have structural malformations rather than genetic abnormality or infection. Fetuses with anomalous late‐onset FGR have an increased incidence of complications at birth and NICU admission and a longer hospital stay compared with fetuses with isolated late‐onset FGR. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

          Abstract

          Linked article: There is a comment on this article by Li and Lei. Click here to view the Correspondence.

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          Most cited references39

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          Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.

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            Consensus definition of fetal growth restriction: a Delphi procedure.

            To determine, by expert consensus, a definition for early and late fetal growth restriction (FGR) through a Delphi procedure.
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              Update on the diagnosis and classification of fetal growth restriction and proposal of a stage-based management protocol.

              Small fetuses are defined as those with an ultrasound estimated weight below a threshold, most commonly the 10th centile. The first clinically relevant step is the distinction of 'true' fetal growth restriction (FGR), associated with signs of abnormal fetoplacental function and poorer perinatal outcome, from constitutional small-for-gestational age, with a near-normal perinatal outcome. Nowadays such a distinction should not be based solely on umbilical artery Doppler, since this index detects only early-onset severe forms. FGR should be diagnosed in the presence of any of the factors associated with a poorer perinatal outcome, including Doppler cerebroplacental ratio, uterine artery Doppler, a growth centile below the 3rd centile, and, possibly in the near future, maternal angiogenic factors. Once the diagnosis is established, differentiating into early- and late-onset FGR is useful mainly for research purposes, because it distinguishes two clear phenotypes with differences in severity, association with preeclampsia, and the natural history of fetal deterioration. As a second clinically relevant step, management of FGR and the decision to deliver aims at an optimal balance between minimizing fetal injury or death versus the risks of iatrogenic preterm delivery. We propose a protocol that integrates current evidence to classify stages of fetal deterioration and establishes follow-up intervals and optimal delivery timings, which may facilitate decisions and reduce practice variability in this complex clinical condition.
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                Author and article information

                Contributors
                andrea.dallasta@unipr.it
                Journal
                Ultrasound Obstet Gynecol
                Ultrasound Obstet Gynecol
                10.1002/(ISSN)1469-0705
                UOG
                Ultrasound in Obstetrics & Gynecology
                John Wiley & Sons, Ltd. (Chichester, UK )
                0960-7692
                1469-0705
                01 November 2022
                November 2022
                : 60
                : 5 ( doiID: 10.1002/uog.v60.5 )
                : 632-639
                Affiliations
                [ 1 ] Department of Medicine and Surgery, Obstetrics and Gynecology Unit University of Parma Parma Italy
                [ 2 ] Unit of Fetal Medicine and Prenatal Diagnosis Institute for Maternal and Child Health IRCCS Burlo Garofolo Trieste Italy
                [ 3 ] Department of Medicine, Surgery and Health Sciences University of Trieste Trieste Italy
                [ 4 ] Department of Biomedical, Experimental and Clinical Sciences, Division of Obstetrics and Gynecology University of Florence Florence Italy
                [ 5 ] Department of Obstetrics and Gynecology, University Hospital Rechts der Isar Technical University of Munich Munich Germany
                [ 6 ] Department of Clinical and Experimental Sciences, Section of Maternal and Child Health University of Brescia Brescia Italy
                [ 7 ] Division of Maternal and Fetal Medicine University of Rome Tor Vergata Rome Italy
                Author notes
                [*] [* ] Correspondence to: Prof. A. Dall'Asta, Department of Medicine and Surgery, Obstetrics and Gynecology Unit, University of Parma, Via Gramsci 14, 43126 Parma, Italy (e‐mail: andrea.dallasta@ 123456unipr.it )
                Author information
                https://orcid.org/0000-0001-7201-0206
                https://orcid.org/0000-0001-7706-3016
                https://orcid.org/0000-0002-8681-4501
                https://orcid.org/0000-0002-9273-505X
                https://orcid.org/0000-0002-7368-0823
                https://orcid.org/0000-0002-5525-4353
                https://orcid.org/0000-0001-7793-714X
                Article
                UOG24961 UOG-2022-0189.R1
                10.1002/uog.24961
                9827976
                35638182
                fcdaf33a-2682-4f77-85c9-6c64b150fae9
                © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 05 May 2022
                : 02 March 2022
                : 17 May 2022
                Page count
                Figures: 1, Tables: 4, Pages: 8, Words: 4889
                Categories
                Original Paper
                Original Papers
                Custom metadata
                2.0
                November 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.3 mode:remove_FC converted:09.01.2023

                Obstetrics & Gynecology
                aneuploidy,cgh‐array,congenital malformation,fetal growth restriction,perinatal outcome,respiratory complication

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