Maternal, placental and cord blood cytokines and the risk of adverse birth outcomes among pregnant women infected with Schistosoma japonicum in the Philippines

Ajibola I Abioye, Emily A McDonald, Sangshin Park, Ayush Joshi, Jonathan D Kurtis, Hannah Wu, Sunthorn Pond-Tor, Surendra Sharma, Jan Ernerudh, Palmera Baltazar, Luz P Acosta, Remigio M Olveda, Veronica Tallo, Jennifer F Friedman, Ajibola I Abioye, Emily A McDonald, Sangshin Park, Ayush Joshi, Jonathan D Kurtis, Hannah Wu, Sunthorn Pond-Tor, Surendra Sharma, Jan Ernerudh, Palmera Baltazar, Luz P Acosta, Remigio M Olveda, Veronica Tallo, Jennifer F Friedman

Abstract

Background: The objectives of this study were to 1) evaluate the influence of treatment with praziquantel on the inflammatory milieu in maternal, placental, and cord blood, 2) assess the extent to which proinflammatory signatures in placental and cord blood impacts birth outcomes, and 3) evaluate the impact of other helminths on the inflammatory micro environment.

Methods/findings: This was a secondary analysis of samples from 369 mother-infant pairs participating in a randomized controlled trial of praziquantel given at 12-16 weeks' gestation. We performed regression analysis to address our study objectives. In maternal peripheral blood, the concentrations of CXCL8, and TNF receptor I and II decreased from 12 to 32 weeks' gestation, while IL-13 increased. Praziquantel treatment did not significantly alter the trajectory of the concentration of any of the cytokines examined. Hookworm infection was associated with elevated placental IL-1, CXCL8 and IFN-γ. The risk of small-for-gestational age increased with elevated IL-6, IL-10, and CXCL8 in cord blood. The risk of prematurity was increased when cord blood sTNFRI and placental IL-5 were elevated.

Conclusions: Our study suggests that fetal cytokines, which may be related to infectious disease exposures, contribute to poor intrauterine growth. Additionally, hookworm infection influences cytokine concentrations at the maternal-fetal interface.

Clinical trial registry number and website: ClinicalTrials.gov (NCT00486863).

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Flowchart of sample collection and…
Fig 1. Flowchart of sample collection and biomarker testing.
Fig 2. Maternal cytokine concentrations at 32…
Fig 2. Maternal cytokine concentrations at 32 weeks' gestation, by praziquantel treatment status.
Cytokine concentrations were modeled using linear regression models. Praziquantel treatment did not significantly modify cytokine concentrations.
Fig 3. Relationship of elevated placental cytokines…
Fig 3. Relationship of elevated placental cytokines with coinfection with hookworm at 12 weeks' gestation.
Cytokines were regarded as elevated if they exceeded the 90th percentile. P-values obtained from models adjusted for praziquantel treatment, fetal sex, maternal age, parity, underweight, and infection with any of T. trichuria and A. lumbricoides at 12 weeks' gestation. There were no other significant associations with other cytokines or with coinfection with T. trichuria or A. lumbricoides.
Fig 4. Relationship of elevated cord blood…
Fig 4. Relationship of elevated cord blood cytokines with SGA risk.
Cytokines were regarded as elevated if they exceeded the 90th percentile. P values obtained from models adjusted for praziquantel treatment, fetal sex, maternal age, parity, underweight, and infection with any of T. trichuria, A. lumbricoides and hookworm at 12 weeks' gestation.
Fig 5. Relationship of cord blood sTNFRI…
Fig 5. Relationship of cord blood sTNFRI and placental IL-5 with the risk of preterm birth.
Cytokines were regarded as elevated if they exceeded the 90th percentile. P-values obtained from models adjusted for praziquantel treatment, fetal sex, maternal age, parity, underweight, and infection with any of T. trichuria, A. lumbricoides and hookworm at 12 weeks' gestation.

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