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. 2020 Dec 2:29-30:100660.
doi: 10.1016/j.eclinm.2020.100660. eCollection 2020 Dec.

International values for haemoglobin distributions in healthy pregnant women

Eric O Ohuma  1 , Melissa F Young  2 , Reynaldo Martorell  2 , Leila Cheikh Ismail  3   4 , Juan Pablo Peña-Rosas  5 , Manorama Purwar  6 , Maria Nieves Garcia-Casal  5 , Michael G Gravett  7 , Mercedes de Onis  5 , QingQing Wu  8 , Maria Carvalho  9 , Yasmin A Jaffer  10 , Ann Lambert  4   11 , Enrico Bertino  12 , Aris T Papageorghiou  4   11 , Fernando C Barros  13 , Zulfiqar A Bhutta  14 , Stephen H Kennedy  4   11 , Jose Villar  4   11
Affiliations

International values for haemoglobin distributions in healthy pregnant women

Eric O Ohuma et al. EClinicalMedicine. .

Abstract

Background: Anaemia in pregnancy is a global health problem with associated morbidity and mortality.

Methods: A secondary analysis of prospective, population-based study from 2009 to 2016 to generate maternal haemoglobin normative centiles in uncomplicated pregnancies in women receiving optimal antenatal care. Pregnant women were enrolled <14 weeks' gestation in the Fetal Growth Longitudinal Study (FGLS) of the INTERGROWTH-21st Project which involved eight geographically diverse urban areas in Brazil, China, India, Italy, Kenya, Oman, United Kingdom and United States. At each 5 ± 1 weekly visit until delivery, information was collected about the pregnancy, as well as the results of blood tests taken as part of routine antenatal care that complemented the study's requirements, including haemoglobin values.

Findings: A total of 3502 (81%) of 4321 women who delivered a live, singleton newborn with no visible congenital anomalies, contributed at least one haemoglobin value. Median haemoglobin concentrations ranged from 114.6 to 121.4 g/L, 94 to 103 g/L at the 3rd centile, and from 135 to 141 g/L at the 97th centile. The lowest values were seen between 31 and 32 weeks' gestation, representing a mean drop of 6.8 g/L compared to 14 weeks' gestation. The percentage variation in maternal haemoglobin within-site was 47% of the total variance compared to 13% between sites.

Interpretation: We have generated International, gestational age-specific, smoothed centiles for maternal haemoglobin concentration compatible with better pregnancy outcomes, as well as adequate neonatal and early childhood morbidity, growth and development up to 2 years of age.

Funding: Bill & Melinda Gates Foundation Grant number 49038.

Keywords: Anaemia; Healthy pregnant women; INTERGROWTH-21st; International Haemoglobin values.

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Conflict of interest statement

ATP reports personal fees from BJOG, grants from Bill and Melinda Gates Foundation, grants from European Research Council, grants from National Institute of Health Research, grants from Grand Challenges Research Fund, outside the submitted work. JPPR and MNGC are full time staff members of the WHO. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the official position, decisions, policy or views of the World Health Organization. The WHO receives partial financial support from the Bill & Melinda Gates Foundation, and the US Centers for Disease Control and Prevention to support its work in the area of nutrition. Donors do not fund specific guidelines and do not participate in any decision related to the guideline development process. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram illustrating women enrolled in the fetal Growth Longitudinal Study.
Fig. 2
Fig. 2
Distribution of gestational ages at which haemoglobin concentration was measured.
Fig. 3
Fig. 3
Goodness-of-fit plots showing (A) fitted 3rd, 50th and 97th smoothed centile curves of maternal haemoglobin (red solid lines) and open grey circles showing empirical values for each week of gestation (top left plot); (B) normal quantile‐quantile (Q‐Q) plots of the distribution of z‐scores (top right plot), and (C) a scatter plot of z-scores according to gestational age in weeks (bottom left plot).
Fig. 4
Fig. 4
represents the smoothed, gestational age-specific, 3rd (red), 5th (blue), 10th (purple), 50th (black) 90th (purple), 95th (blue) and 97th (red) centiles for maternal haemoglobin. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 5
Fig. 5
represents smoothed, gestational age-specific, 3rd, 5th, 10th, 50th, 90th, 95th and 97th centiles for maternal haemoglobin superimposed on the current recommended WHO cut-offs for pregnant women in the second and third trimesters (black solid lines).
Fig. 6
Fig. 6
represents sensitivity analyses showing the smoothed, gestational age-specific, 3rd (red), 50th (red) and 97th (red) centiles for maternal haemoglobin from the total Fetal Growth Longitudinal Study pooled sample (n = 3502) and the fitted 3rd (blue), 50th (blue), and 97th (blue) centiles after excluding women who delivered preterm (n = 3364). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 7
Fig. 7
represents sensitivity analyses showing the smoothed, gestational age-specific, 3rd (red), 50th (red) and 97th (red) centiles for maternal haemoglobin from the total Fetal Growth Longitudinal Study pooled sample (n = 3502) and the fitted 3rd(blue), 50th (blue), and 97th (blue) centiles after excluding maternal haemoglobin data from each country in turn. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 8
Fig. 8
represents sensitivity analyses showing the smoothed, gestational age-specific, 3rd, 50th and 97th centiles for maternal haemoglobin from the total Fetal Growth Longitudinal Study using longitudinal data (n = 3502 women, 9954 observations) (red) compared to a cross-sectional random sample of haemoglobin data between 14+0 and 40+0 weeks’ gestation for each woman included in the study (n = 3502 observations) (blue). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
See this image and copyright information in PMC

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