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International gestational age-specific centiles for umbilical artery Doppler indices: a longitudinal prospective cohort study of the INTERGROWTH-21st Project.

Drukker, L; Staines-Urias, E; Villar, J; Barros, FC; Carvalho, M; Munim, S; McGready, R; Nosten, F; Berkley, JA; Norris, SA; et al. Drukker, L; Staines-Urias, E; Villar, J; Barros, FC; Carvalho, M; Munim, S; McGready, R; Nosten, F; Berkley, JA; Norris, SA; Uauy, R; Kennedy, SH; Papageorghiou, AT (2020) International gestational age-specific centiles for umbilical artery Doppler indices: a longitudinal prospective cohort study of the INTERGROWTH-21st Project. Am J Obstet Gynecol, 222 (6). 602.e1-602.e15. ISSN 1097-6868 https://doi.org/10.1016/j.ajog.2020.01.012
SGUL Authors: Papageorghiou, Aris

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Abstract

BACKGROUND: Reference values for umbilical artery Doppler indices are used clinically to assess fetal well-being. However, many studies that have produced reference charts have important methodologic limitations, and these result in significant heterogeneity of reported reference ranges. OBJECTIVES: To produce international gestational age-specific centiles for umbilical artery Doppler indices based on longitudinal data and the same rigorous methodology used in the original Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project. STUDY DESIGN: In Phase II of the INTERGROWTH-21st Project (the INTERBIO-21st Study), we prospectively continued enrolling pregnant women according to the same protocol from 3 of the original populations in Pelotas (Brazil), Nairobi (Kenya), and Oxford (United Kingdom) that had participated in the Fetal Growth Longitudinal Study. Women with a singleton pregnancy were recruited at <14 weeks' gestation, confirmed by ultrasound measurement of crown-rump length, and then underwent standardized ultrasound every 5±1 weeks until delivery. From 22 weeks of gestation umbilical artery indices (pulsatility index, resistance index, and systolic/diastolic ratio) were measured in a blinded fashion, using identical equipment and a rigorously standardized protocol. Newborn size at birth was assessed using the international INTERGROWTH-21st Standards, and infants had detailed assessment of growth, nutrition, morbidity, and motor development at 1 and 2 years of age. The appropriateness of pooling data from the 3 study sites was assessed using variance component analysis and standardized site differences. Umbilical artery indices were modeled as functions of the gestational age using an exponential, normal distribution with second-degree fractional polynomial smoothing; goodness of fit for the overall models was assessed. RESULTS: Of the women enrolled at the 3 sites, 1629 were eligible for this study; 431 (27%) met the entry criteria for the construction of normative centiles, similar to the proportion seen in the original fetal growth longitudinal study. They contributed a total of 1243 Doppler measures to the analysis; 74% had 3 measures or more. The healthy low-risk status of the population was confirmed by the low rates of preterm birth (4.9%) and preeclampsia (0.7%). There were no neonatal deaths and satisfactory growth, health, and motor development of the infants at 1 and 2 years of age were documented. Only a very small proportion (2.8%-6.5%) of the variance of Doppler indices was due to between-site differences; in addition, standardized site difference estimates were marginally outside this threshold in only 1 of 27 comparisons, and this supported the decision to pool data from the 3 study sites. All 3 Doppler indices decreased with advancing gestational age. The 3rd, 5th 10th, 50th, 90th, 95th, and 97th centiles according to gestational age for each of the 3 indices are provided, as well as equations to allow calculation of any value as a centile and z scores. The mean pulsatility index according to gestational age = 1.02944 + 77.7456*(gestational age)-2 - 0.000004455*gestational age3. CONCLUSION: We present here international gestational age-specific normative centiles for umbilical artery Doppler indices produced by studying healthy, low-risk pregnant women living in environments with minimal constraints on fetal growth. The centiles complement the existing INTERGROWTH-21st Standards for assessment of fetal well-being.

Item Type: Article
Additional Information: © 2020 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Keywords: Doppler, INTERBIO, INTERGROWTH-21(st) ultrasound, antepartum testing, fetal growth restriction, fetal well-being, longitudinal study, multinational study, perinatal morbidity, perinatal mortality, placenta, pulsatility index, reference ranges, resistance index, systolic/diastolic ratio, umbilical artery, Obstetrics & Reproductive Medicine, 1114 Paediatrics and Reproductive Medicine
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Clinical Education (INMECE )
Journal or Publication Title: Am J Obstet Gynecol
ISSN: 1097-6868
Language: eng
Dates:
DateEvent
June 2020Published
16 January 2020Published Online
8 January 2020Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
49038Bill and Melinda Gates Foundationhttp://dx.doi.org/10.13039/100000865
PubMed ID: 31954701
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/111829
Publisher's version: https://doi.org/10.1016/j.ajog.2020.01.012

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