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The magnitude rather than the rate of decline in fetal growth is a stronger risk factor for perinatal mortality in term infants

  • Mads Langager Larsen
    Affiliations
    Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

    Department of Obstetrics and Gynecology, Copenhagen University Hospital – Amager-Hvidovre, Hvidovre, Denmark

    Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

    Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia
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  • Veronika Schreiber
    Affiliations
    Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia

    Faculty of Medicine, University of Queensland, Mater Mother's Hospital, Brisbane, Queensland, Australia
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  • Lone Krebs
    Affiliations
    Department of Obstetrics and Gynecology, Copenhagen University Hospital – Amager-Hvidovre, Hvidovre, Denmark

    Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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  • Christina Engel Hoei-Hansen
    Affiliations
    Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

    Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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  • Sailesh Kumar
    Correspondence
    Corresponding author: Professor Sailesh Kumar, Mater Research Institute - University of Queensland, Level 3, Aubigny Place, Raymond Terrace, South Brisbane, Queensland 4101, Australia. Phone: +61 7 31638844
    Affiliations
    Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia

    Faculty of Medicine, University of Queensland, Mater Mother's Hospital, Brisbane, Queensland, Australia

    Centre for Maternal and Fetal Medicine, Mater Mother's Hospital, Brisbane, Queensland, Australia

    NHMRC Centre for Research Excellence in Stillbirth, Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia
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Published:October 20, 2022DOI:https://doi.org/10.1016/j.ajogmf.2022.100780

      Highlights

      • ≥50 centile fetal growth decline is associated with late fetal growth restrictions
      • ≥50 centile fetal growth decline is strongly associated with perinatal mortality
      • The risk of fetal demise is related to magnitude of decline and not rate of decline
      • Neonatal morbidity is not significantly associated with fetal growth decline
      • Magnitude of fetal growth decline is important when determining the timing of birth

      Abstract

      Background

      Prenatal diagnosis of an infant suspected of having fetal growth restriction (FGR) is important due to its strong association with perinatal mortality and morbidity. The current Delphi consensus criteria include a decline >50 centiles in fetal growth when diagnosing late FGR; however, the evidence underpinning this criterion is limited.

      Objectives

      To analyze the relationships between the magnitude of decline in fetal growth and stillbirth, perinatal mortality and adverse neonatal outcomes.

      Study Design

      This cohort study of 15,861 pregnancies was conducted at the Mater Mother's Hospital in Brisbane, Australia. Decline in fetal growth was calculated as a drop in either estimated fetal weight (EFW) or abdominal circumference (AC) centiles between two ultrasound scans performed after 18+0 weeks of gestation. Relationships between declining fetal growth and the outcomes were, firstly, analyzed as a continuous variable and, if significant, further assessed with the rate of decline and different magnitudes of decline, compared to the referent category (change in growth of +/- 10 centiles between scans). The three categories of growth decline were >10 – <25 centiles, ≤25 – <50 centiles and ≥50 centiles. Associations were analyzed by logistic regressions. The primary study outcomes were stillbirth and perinatal mortality (composite of stillbirth and neonatal death). Secondary outcomes were birth of an SGA infant (birthweight <10th centile for gestation), emergency cesarean section (CS) for non-reassuring fetal status (NRFS), and composite severe neonatal morbidity.

      Results

      The risks of stillbirth and perinatal mortality increased significantly by 2.6% (0.4%–4.6%) and 2.8% (1.0%–4.5%), respectively, per one centile decline in fetal growth. Additionally, the odds of stillbirth (adjusted odds ratio (aOR) 3.68 (95% CI 1.32–10.24)) and perinatal mortality (aOR 4.44 (1.82–10.84)) compared with the referent group were significantly increased only when the decline was ≥50 centiles, regardless of birth weight. Furthermore, none of the primary outcomes were significantly associated with the rate of growth decline. The risk of a small for gestational age infant increased by 2.4% (2.2%–2.7%) for every centile decline. Conversely, reduced fetal growth was not associated with emergency CS for NRFS or severe neonatal morbidity.

      Conclusions

      Our results support the use of a ≥50 centile decline in fetal growth as a criterion for identifying infants at risk of late fetal growth restriction. This cut-off also identifies fetuses at high risk of perinatal mortality regardless of birth weight and rate of growth decline. Our findings may guide obstetric practice by alerting clinicians to the importance of incorporating the magnitude of fetal growth decline into antenatal counselling and decisions regarding timing of birth.

      Keywords

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      References

        • Zhang J
        • Merialdi M
        • Platt LD
        • Kramer MS.
        Defining normal and abnormal fetal growth: promises and challenges.
        American Journal of Obstetrics and Gynecology. 2010; 202: 522-528https://doi.org/10.1016/j.ajog.2009.10.889
      1. Mifsud W, Sebire NJ. Placental Pathology in Early-Onset and Late-Onset Fetal Growth Restriction. Fetal Diagnosis and Therapy. 2014;36(2):117-128. doi:10.1159/000359969

        • Gordijn SJ
        • Beune IM
        • Thilaganathan B
        • et al.
        Consensus definition of fetal growth restriction: a Delphi procedure.
        Ultrasound in Obstetrics & Gynecology. 2016; 48: 333-339https://doi.org/10.1002/uog.15884
        • Martins JG
        • Biggio JR
        • Abuhamad A.
        Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction: (Replaces Clinical Guideline Number 3, April 2012).
        American Journal of Obstetrics and Gynecology. 2020; 223: B2-B17https://doi.org/10.1016/j.ajog.2020.05.010
        • Lees CC
        • Stampalija T
        • Baschat AA
        • et al.
        ISUOG Practice Guidelines: diagnosis and management of small-for-gestational-age fetus and fetal growth restriction.
        Ultrasound in Obstetrics & Gynecology. 2020; 56: 298-312https://doi.org/10.1002/uog.22134
        • Melamed N
        • Baschat A
        • Yinon Y
        • et al.
        FIGO (International Federation of Gynecology and Obstetrics) initiative on fetal growth: Best practice advice for screening, diagnosis, and management of fetal growth restriction.
        International Journal of Gynecology & Obstetrics. 2021; 152: 3-57https://doi.org/10.1002/ijgo.13522
        • Mendez-Figueroa H
        • Truong VTT
        • Pedroza C
        • Khan AM
        • Chauhan SP.
        Small-for-gestational-age infants among uncomplicated pregnancies at term: a secondary analysis of 9 Maternal-Fetal Medicine Units Network studies.
        American Journal of Obstetrics and Gynecology. 2016; 215 (628.e1-628.e7)https://doi.org/10.1016/j.ajog.2016.06.043
        • Madden J V
        • Flatley CJ
        • Kumar S.
        Term small-for-gestational-age infants from low-risk women are at significantly greater risk of adverse neonatal outcomes.
        American Journal of Obstetrics and Gynecology. 2018; 218 (525.e1-525.e9)https://doi.org/10.1016/j.ajog.2018.02.008
        • Yu J
        • Flatley C
        • Greer RM
        • Kumar S.
        Birth-weight centiles and the risk of serious adverse neonatal outcomes at term.
        Journal of Perinatal Medicine. 2018; 46: 1048-1056https://doi.org/10.1515/jpm-2017-0176
        • Meher S
        • Hernandez-Andrade E
        • Basheer SN
        • Lees C.
        Impact of cerebral redistribution on neurodevelopmental outcome in small-for-gestational-age or growth-restricted babies: a systematic review.
        Ultrasound in Obstetrics & Gynecology. 2015; 46: 398-404https://doi.org/10.1002/uog.14818
        • Hadlock FP
        • Harrist RB
        • Sharman RS
        • Deter RL
        • Park SK.
        Estimation of fetal weight with the use of head, body, and femur measurements - A prospective study.
        Am J Obstet Gynecol. 1985; 151: 333-337
        • Westerway SC
        • Davison A
        • Cowell S.
        Ultrasonic fetal measurements: new Australian standards for the new millennium.
        Australian and New Zealand Journal of Obstetrics and Gynaecology. 2000; 40: 297-302https://doi.org/10.1111/j.1479-828X.2000.tb03338.x
        • Flatley C
        • Kumar S
        • Greer RM.
        Reference centiles for the middle cerebral artery and umbilical artery pulsatility index and cerebro-placental ratio from a low-risk population - a Generalised Additive Model for Location, Shape and Scale (GAMLSS) approach.
        The journal of maternal-fetal & neonatal medicine. 2019; 32: 2338-2345
        • Joseph FA
        • Hyett JA
        • Schluter PJ
        • et al.
        New Australian birthweight centiles.
        Medical Journal of Australia. 2020; 213: 79-85https://doi.org/10.5694/mja2.50676
        • Akaike H.
        Information Theory and an Extension of the Maximum Likelihood Principle.
        in: Kotz S Johnson NL Breakthroughs in Statistics. Springer Series in Statistics, Springer New York1991: 610-624
        • Core Team R
        R: A Language and Environment for Statistical Computing.
        R Foundation for Statistical Computing. 2020; (Published online)
        • Chatzakis C
        • Papaioannou GK
        • Eleftheriades M
        • Makrydimas G
        • Dinas K
        • Sotiriadis A.
        Perinatal outcome of appropriate-weight fetuses with decelerating growth.
        The Journal of Maternal-Fetal & Neonatal Medicine. 2021; 34: 3362-3369https://doi.org/10.1080/14767058.2019.1684470
        • Pacora P
        • Romero R
        • Jung E
        • et al.
        Reduced fetal growth velocity precedes antepartum fetal death.
        Ultrasound in Obstetrics & Gynecology. 2021; 57: 942-952https://doi.org/10.1002/uog.23111
        • de Jong CLD
        • Francis A
        • van Geijn HP
        • Gardosi J
        Fetal growth rate and adverse perinatal events.
        Ultrasound in Obstetrics & Gynecology. 1999; 13: 86-89https://doi.org/10.1046/j.1469-0705.1999.13020086.x
        • Smith-Bindman R
        • Chu PW
        • Ecker JL
        • Feldstein VA
        • Filly RA
        • Bacchetti P.
        US Evaluation of Fetal Growth: Prediction of Neonatal Outcomes.
        Radiology. 2002; 223: 153-161https://doi.org/10.1148/radiol.2231010876
        • Danielian PJ
        • Allman ACJ
        • Steer PJ.
        Is obstetric and neonatal outcome worse in fetuses who fail to reach their own growth potential?.
        BJOG: An International Journal of Obstetrics & Gynaecology. 1992; 99: 452-454
        • Stratton JF
        • Ni Scanaill S
        • Stuart B
        • Turner MJ
        Are babies of normal birth weight who fail to reach their growth potential as diagnosed by ultrasound at increased risk?.
        Ultrasound in Obstetrics & Gynecology. 1995; 5: 114-118https://doi.org/10.1046/j.1469-0705.1995.05020114.x
        • Damodaram MS
        • Story L
        • Kulinskaya E
        • Rutherford M
        • Kumar S.
        Early adverse perinatal complications in preterm growth-restricted fetuses.
        Australian and New Zealand Journal of Obstetrics and Gynaecology. 2011; 51: 204-209https://doi.org/10.1111/j.1479-828X.2011.01299.x
        • Chang TC
        • Robson SC
        • Spencer JAD
        • Gallivan S.
        Prediction of perinatal morbidity at term in small fetuses: comparison of fetal growth and Doppler ultrasound.
        BJOG. 1994; 101: 422-427
        • Barker ED
        • McAuliffe FM
        • Alderdice F
        • et al.
        The role of growth trajectories in classifying fetal growth restriction.
        Obstetrics and Gynecology. 2013; 122: 248-254
        • Caradeux J
        • Eixarch E
        • Mazarico E
        • Basuki TR
        • Gratacos E
        • Figueras F.
        Longitudinal growth assessment for prediction of adverse perinatal outcome in fetuses suspected to be small-for-gestational age.
        Ultrasound in Obstetrics & Gynecology. 2018; 52: 325-331https://doi.org/10.1002/uog.18824
        • Larose TL
        • Turner SW
        • Hutcheon JA
        • et al.
        Longitudinal Ultrasound Measures of Fetal Growth and Offspring Outcomes.
        Current Epidemiology Reports. 2017; 4: 98-105https://doi.org/10.1007/s40471-017-0103-2
        • Dall'Asta A
        • Stampalija T
        • Mecacci F
        • et al.
        Ultrasound prediction of adverse perinatal outcome at diagnosis of late-onset fetal growth restriction.
        Ultrasound in Obstetrics & Gynecology. 2022; 59: 342-349https://doi.org/10.1002/uog.23714
        • Unterscheider J
        • Daly S
        • Geary MP
        • et al.
        Optimizing the definition of intrauterine growth restriction: the multicenter prospective PORTO Study.
        American Journal of Obstetrics and Gynecology. 2013; 208 (290.e1-290.e6)https://doi.org/10.1016/j.ajog.2013.02.007
        • Chang TC
        • Robson SC
        • Spencer JAD
        • Gallivan S.
        Identification of fetal growth retardation : comparison of Doppler waveform indices and serial ultrasound measurements of abdominal circumference and fetal weight.
        Obstetrics and Gynecology. 1993; 82: 230-236
        • Larsen T
        • Greisen G
        • Petersen S.
        Prediction of birth weight by ultrasound-estimated fetal weight: a comparison between single and repeated estimates.
        European Journal of Obstetrics & Gynecology and Reproductive Biology. 1995; 60: 37-40https://doi.org/10.1016/0028-2243(95)02079-9
        • Sovio U
        • White IR
        • Dacey A
        • Pasupathy D
        • Smith GCS.
        Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study.
        The Lancet. 2015; 386: 2089-2097https://doi.org/10.1016/S0140-6736(15)00131-2
        • Hiersch L
        • Melamed N.
        Fetal growth velocity and body proportion in the assessment of growth.
        American Journal of Obstetrics and Gynecology. 2018; 218 (S700-S711.e1.)https://doi.org/10.1016/j.ajog.2017.12.014
        • Bardien N
        • Whitehead CL
        • Tong S
        • Ugoni A
        • McDonald S
        • Walker SP.
        Placental Insufficiency in Fetuses That Slow in Growth but Are Born Appropriate for Gestational Age: A Prospective Longitudinal Study.
        PLoS One. 2016; 11https://doi.org/10.1371/journal.pone.0142788
        • MacDonald TM
        • Hui L
        • Tong S
        • et al.
        Reduced growth velocity across the third trimester is associated with placental insufficiency in fetuses born at a normal birthweight: a prospective cohort study.
        BMC Medicine. 2017; 15: 164https://doi.org/10.1186/s12916-017-0928-z
        • Kennedy LM
        • Tong S
        • Robinson AJ
        • et al.
        Reduced growth velocity from the mid-trimester is associated with placental insufficiency in fetuses born at a normal birthweight.
        BMC Medicine. 2020; 18: 395https://doi.org/10.1186/s12916-020-01869-3
        • Owen P
        • Maharaj S
        • Khan KS
        • Howie PW.
        Interval between fetal measurements in predicting growth restriction.
        Obstetrics & Gynecology. 2001; 97: 499-504https://doi.org/10.1016/S0029-7844(00)01155-8