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Am J Perinatol 2024; 41(S 01): e843-e852
DOI: 10.1055/a-1961-2425
Original Article

The Association of Prenatal C-Reactive Protein and Interleukin-8 Levels with Maternal Characteristics and Preterm Birth

Yih-Chieh S. Chen 
1   Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
2   Division of Allergy and Clinical Immunology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
,
Hooman Mirzakhani
1   Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
,
Hanna Knihtilä
1   Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
,
Raina N. Fichorova
3   Department of Obstetrics, Gynecology and Reproductive Biology, Laboratory of Genital Tract Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
,
Ngan Luu
3   Department of Obstetrics, Gynecology and Reproductive Biology, Laboratory of Genital Tract Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
,
Nancy Laranjo
1   Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
,
Anjali Jha
1   Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
,
Rachel S. Kelly
1   Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
,
Scott T. Weiss
1   Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
,
Augusto A. Litonjua‡   *
4   Division of Pediatric Pulmonary Medicine, Golisano Children's Hospital at Strong, University of Rochester Medical Center, Rochester, New York
,
Kathleen A. Lee-Sarwar‡   *
1   Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
2   Division of Allergy and Clinical Immunology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
› Author Affiliations Funding This work was supported by R01 HL091528 from National Health, Lung and Blood Institute (NHLBI) and UH3 OD023268 (NIH Office of the Director) to S.T.W. and A.A.L. R.N.F. is supported by UH3 OD023285. Y.-C.S.C. was supported by T-32 HL007427 and T-32 AI007306 from NHLBI. K.A.L.S. was supported by K08 from NHLBI (K08HL148178), and H.M. was supported by K01 from NHLBI (K01HL146977-01A1). R.S.K. was supported by K01 from NHLBI (K01 HL146980). H.K. was supported by the Jane and Aatos Erkko Foundation, the Paulo Foundation, and the Pediatric Research Foundation.
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Abstract

Objective The determinants of preterm birth remain unknown. Excessive maternal inflammation during pregnancy may play an important role in the pathogenesis of preterm birth. Our objective was to describe the association of prenatal levels of proinflammatory C-reactive protein (CRP) and interleukin-8 (IL-8) with preterm birth in participants of the Vitamin D Antenatal Asthma Reduction Trial.

Study Design Five hundred and twenty-eight patients with available samples of both first- and third-trimester plasma were included in this analysis. CRP and IL-8 were measured from maternal prenatal samples. We examined the association between prenatal CRP and IL-8 with maternal health characteristics and the outcome of preterm birth. We also described the patterns of change in CRP and IL-8 from first to third trimester and their association with preterm birth. A subgroup analysis comparing only those with a spontaneous preterm birth phenotype to those with term birth was also performed.

Results Maternal characteristics including lower educational attainment, higher prepregnancy body mass index, gestational diabetes, lower vitamin D, and an unhealthy diet were associated with elevated levels of prenatal CRP and IL-8. Higher third trimester CRP and an increase in CRP from first to third trimester were associated with an increased odds of preterm birth when compared to lower levels of CRP (adjusted odds ratio [aOR] = 1.49, 95% confidence interval: 1.02, 2.23, p = 0.04) or a decrease in CRP over pregnancy (aOR = 3.06, 95% CI = 1.31,7.55, p = 0.01), after adjusting for potential confounders. These associations were strengthened when comparing only patients with spontaneous preterm birth (n = 22) to those with term births.

Conclusion Higher levels of the proinflammatory markers CRP and IL-8 are associated with indicators of poor maternal health and preterm birth. Prenatal CRP levels may reflect maternal prenatal health status and serve as a predictor of preterm birth, especially among those with spontaneous preterm birth.

Key Points

  • Elevated prenatal CRP is associated with poor maternal health.

  • High prenatal CRP may predict premature birth, especially spontaneous premature birth phenotypes.

  • Vitamin D insufficiency may be a modifiable risk factor for prenatal inflammation.

Keywords

inflammation - preterm birth - biomarkers - maternal health - cytokine - CRP

* These authors contributed equally.


Supplementary Material



Publication History

Received: 27 January 2022

Accepted: 22 September 2022

Accepted Manuscript online:
14 October 2022

Article published online:
07 December 2022

© 2022. Thieme. All rights reserved.

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