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Inflammation throughout pregnancy and fetal growth restriction in rural Nepal

  • Michael W. Sauder (a1), Sun Eun Lee (a2), Kerry J. Schulze (a2), Parul Christian (a2) (a3), Lee S. F. Wu (a2), Subarna K. Khatry (a4), Steven C. LeClerq (a2) (a4), Ramesh K. Adhikari (a4), John D. Groopman (a5) and Keith P. West (a2) (a4)...

Abstract

Maternal systemic inflammation during pregnancy may restrict embryo−fetal growth, but the extent of this effect remains poorly established in undernourished populations. In a cohort of 653 maternal−newborn dyads participating in a multi-armed, micronutrient supplementation trial in southern Nepal, we investigated associations between maternal inflammation, assessed by serum α1-acid glycoprotein and C-reactive protein, in the first and third trimesters of pregnancy, and newborn weight, length and head and chest circumferences. Median (IQR) maternal concentrations in α1-acid glycoprotein and C-reactive protein in the first and third trimesters were 0.65 (0.53–0.76) and 0.40 (0.33–0.50) g/l, and 0.56 (0.25–1.54) and 1.07 (0.43–2.32) mg/l, respectively. α1-acid glycoprotein was inversely associated with birth size: weight, length, head circumference and chest circumference were lower by 116 g (P = 2.3 × 10−6), and 0.45 (P = 3.1 × 10−5), 0.18 (P = 0.0191) and 0.48 (P = 1.7 × 10−7) cm, respectively, per 50% increase in α1-acid glycoprotein averaged across both trimesters. Adjustment for maternal age, parity, gestational age, nutritional and socio-economic status and daily micronutrient supplementation failed to alter any association. Serum C-reactive protein concentration was largely unassociated with newborn size. In rural Nepal, birth size was inversely associated with low-grade, chronic inflammation during pregnancy as indicated by serum α1-acid glycoprotein.

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Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

Author for correspondence: Keith P. West, Jr, E-mail: kwest@jhsph.edu

References

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1.WHO. Comprehensive implementation plan on maternal, infant and young child nutrition. Available at http://www.who.int/nutrition/publications/CIP_document/en/ (Accessed 22 August 2019).
2.Levels and Trends in Child Mortality Report 2017 − Estimates Developed by the UN Inter-agency Group for Child Mortality Estimation. Available at https://www.unicef.org/publications/index_101071.html (Accessed 22 August 2019).
3.Blencowe, H et al. (2012) National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet (London, England) 379, 21622172.
4.Lee, AC et al. (2013) National and regional estimates of term and preterm babies born small for gestational age in 138 low-income and middle-income countries in 2010. The Lancet Global Health 1, 26.
5.Ergaz, Z, Avgil, M and Ornoy, A (2005) Intrauterine growth restriction-etiology and consequences: what do we know about the human situation and experimental animal models? Reproductive Toxicology (Elmsford, N.Y.) 20, 301322.
6.Romero, R et al. (2007) The role of inflammation and infection in preterm birth. Seminars in Reproductive Medicine 25, 2139.
7.Reinebrant, HE et al. (2018) Making stillbirths visible: a systematic review of globally reported causes of stillbirth. BJOG: an International Journal of Obstetrics and Gynaecology 125, 212224.
8.Raiten, DJ et al. (2015) Inflammation and Nutritional Science for Programs/Policies and Interpretation of Research Evidence (INSPIRE). The Journal of Nutrition 145, 1108S.
9.King, AE et al. (2007) Innate immune defences in the human uterus during pregnancy. Placenta 28, 10991106.
10.Larsson, A et al. (2008) Reference values for alpha1-acid glycoprotein, alpha1-antitrypsin, albumin, haptoglobin, C-reactive protein, IgA, IgG and IgM during pregnancy. Acta Obstetricia et Gynecologica Scandinavica 87, 10841088.
11.Hindle, LJ et al. (2006) Effect of multiple micronutrient supplementation during pregnancy on inflammatory markers in Nepalese women. The American Journal of Clinical Nutrition 84, 10861092.
12.Christian, P et al. (2003) Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster-randomized trial in Nepal. The American Journal of Clinical Nutrition 78, 11941202.
13.Christian, P et al. (2006) Antenatal supplementation with micronutrients and biochemical indicators of status and subclinical infection in rural Nepal. The American Journal of Clinical Nutrition 83, 788794.
14.West, KP et al. (1999) Double blind, cluster randomised trial of low dose supplementation with vitamin A or beta carotene on mortality related to pregnancy in Nepal. The NNIPS-2 Study Group. BMJ (Clinical Research ed.) 318, 570575.
15.Christian, P et al. (2003) Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomised community trial. BMJ (Clinical Research ed.) 326, 571.
16.Jiang, T et al. (2005) Micronutrient deficiencies in early pregnancy are common, concurrent, and vary by season among rural Nepali pregnant women. The Journal of Nutrition 135, 11061112.
17.Thurnham, DI, McCabe, GP and World Health Organization (2012) Influence of infection and inflammation on biomarkers of nutritional status with an emphasis on vitamin A and iron. Report: priorities in the assessment of Vitamin A and iron status in populations, Panama City, Panama, 15–17 September 2010. Geneva: World Health Organization, pp. 6380.
18.Christian, P et al. (2013) Risk of childhood undernutrition related to small-for-gestational age and preterm birth in low- and middle-income countries. International Journal of Epidemiology 42, 13401355.
19.Romero, R, Chaiworapongsa, T and Espinoza, J (2003) Micronutrients and intrauterine infection, preterm birth and the fetal inflammatory response syndrome. The Journal of Nutrition 133, 1673S.
20.Honda, M et al. (1990) Quantitative analysis of serum alpha 1-acid glycoprotein levels in normal and diabetic pregnancy. Diabetes Research and Clinical Practice 10, 147152.
21.Siddiqua, TJ et al. (2016) Vitamin B12 supplementation during pregnancy and postpartum improves B12 status of both mothers and infants but vaccine response in mothers only: a randomized clinical trial in Bangladesh. European Journal of Nutrition 55, 281293.
22.Bahizire, E et al. (2017) Malaria is more prevalent than iron deficiency among anemic pregnant women at the first antenatal visit in Rural South Kivu. The American Journal of Tropical Medicine and Hygiene 97, 15511560.
23.Luo, Z et al. (2015) Orosomucoid, an acute response protein with multiple modulating activities. Journal of Physiology and Biochemistry 71, 329340.
24.Hochepied, T et al. (2003) Alpha(1)-acid glycoprotein: an acute phase protein with inflammatory and immunomodulating properties. Cytokine & Growth Factor Reviews 14, 2534.
25.Lainé, E et al. (1990) Modulation of human polymorphonuclear neutrophil functions by alpha 1-acid glycoprotein. Inflammation 14, 19.
26.Mestriner, FLAC et al. (2007) Acute-phase protein alpha-1-acid glycoprotein mediates neutrophil migration failure in sepsis by a nitric oxide-dependent mechanism. Proceedings of the National Academy of Sciences of the United States of America 104, 1959519600.
27.Ceciliani, F and Pocacqua, V (2007) The acute phase protein alpha1-acid glycoprotein: a model for altered glycosylation during diseases. Current Protein & Peptide Science 8, 91108.
28.Van Dijk, W and Poland, DCW (2003) Anti-inflammatory properties of specific glycoforms of human alpha1-acid glycoprotein. Advances in Experimental Medicine and Biology 535, 251256.
29.Muchitsch, EM, Auer, W and Pichler, L (1998) Effects of alpha 1-acid glycoprotein in different rodent models of shock. Fundamental & Clinical Pharmacology 12, 173181.
30.Thomas, T et al. (1989) The expression of alpha(1)-acid glycoprotein mRNA during rat development. High levels of expression in the decidua. The Journal of Biological Chemistry 264, 57845790.
31.Thomas, T (1993) Distribution of alpha 2-macroglobulin and alpha 1-acid glycoprotein mRNA shows regional specialization in rat decidua. Placenta 14, 417428.
32.Seta, N et al. (1991) Changes in alpha 1-acid glycoprotein serum concentrations and glycoforms in the developing human fetus. Clinica Chimica Acta; International Journal of Clinical Chemistry 203, 167175.
33.Sacks, GP et al. (2004) Maternal C-reactive protein levels are raised at 4 weeks gestation. Human Reproduction (Oxford, England) 19, 10251030.
34.Kim, EN et al. (2015) Placental deposition of C-reactive protein is a common feature of human pregnancy. Placenta 36, 704707.
35.Maged, AM et al. (2017) Association of biochemical markers with the severity of pre-eclampsia. International Journal of Gynaecology and Obstetrics: The Official Organ of the International Federation of Gynaecology and Obstetrics 136, 138144.
36.Pitiphat, W et al. (2005) Plasma C-reactive protein in early pregnancy and preterm delivery. American Journal of Epidemiology 162, 11081113.
37.Erkenekli, K et al. (2015) Levels of neopterin and C-reactive protein in pregnant women with fetal growth restriction. Journal of Obstetrics and Gynaecology: The Journal of the Institute of Obstetrics and Gynaecology 35, 225228.
38.Haedersdal, S et al. (2013) Inflammatory markers in the second trimester prior to clinical onset of preeclampsia, intrauterine growth restriction, and spontaneous preterm birth. Inflammation 36, 907913.
39.de Oliveira, LC et al. (2017) Maternal C-reactive protein concentrations during pregnancy and birth weight in a prospective cohort in Rio de Janeiro, Brazil. The Journal of Maternal-Fetal & Neonatal Medicine: The Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 30, 23462353.
40.Lee, SE et al. (2015) Plasma proteome biomarkers of inflammation in school aged children in Nepal. PLoS One 10, e0144279.

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Inflammation throughout pregnancy and fetal growth restriction in rural Nepal

  • Michael W. Sauder (a1), Sun Eun Lee (a2), Kerry J. Schulze (a2), Parul Christian (a2) (a3), Lee S. F. Wu (a2), Subarna K. Khatry (a4), Steven C. LeClerq (a2) (a4), Ramesh K. Adhikari (a4), John D. Groopman (a5) and Keith P. West (a2) (a4)...

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