Publication: International gestational age-specific centiles for umbilical artery Doppler indices: a longitudinal prospective cohort study of the INTERGROWTH-21<sup>st</sup> Project
Issued Date
2020-01-01
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ISSN
10976868
00029378
00029378
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2-s2.0-85079864902
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Mahidol University
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SCOPUS
Bibliographic Citation
American Journal of Obstetrics and Gynecology. (2020)
Suggested Citation
Lior Drukker, Eleonora Staines-Urias, José Villar, Fernando C. Barros, Maria Carvalho, Shama Munim, Rose McGready, Francois Nosten, James A. Berkley, Shane A. Norris, Ricardo Uauy, Stephen H. Kennedy, Aris T. Papageorghiou International gestational age-specific centiles for umbilical artery Doppler indices: a longitudinal prospective cohort study of the INTERGROWTH-21<sup>st</sup> Project. American Journal of Obstetrics and Gynecology. (2020). doi:10.1016/j.ajog.2020.01.012 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/53878
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Title
International gestational age-specific centiles for umbilical artery Doppler indices: a longitudinal prospective cohort study of the INTERGROWTH-21<sup>st</sup> Project
Other Contributor(s)
The Aga Khan University Hospital
Wellcome Trust Research Laboratories Nairobi
Aga Khan Hospital Nairobi
London School of Hygiene & Tropical Medicine
Green Templeton College
University of Oxford
Universidade Catolica de Pelotas
University of Witwatersrand
Universidade Federal de Pelotas
Mahidol University
Universidad de Chile
Wellcome Trust Research Laboratories Nairobi
Aga Khan Hospital Nairobi
London School of Hygiene & Tropical Medicine
Green Templeton College
University of Oxford
Universidade Catolica de Pelotas
University of Witwatersrand
Universidade Federal de Pelotas
Mahidol University
Universidad de Chile
Abstract
© 2020 The Author(s) 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.