Maternal one carbon metabolism and interleukin-10 &-17 synergistically influence the mode of delivery in women with Early Onset Pre-Eclampsia

• Published in: Pregnancy hypertension Vol. 24; pp. 79 - 89
• Main Authors: Kaur, Lovejeet, Puri, Manju, Pal Sachdeva, Mohinder, Mishra, Jyoti, Nava Saraswathy, Kallur
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-06-2021
• Subjects: Early onset pre-eclampsia; Interleukin 10 & 17; One carbon metabolism; IL10; One carbon metabolism; B12; Early onset pre-eclampsia; βhCG; Interleukin 10 & 17; EO-PE; OCM; IL17
• ISSN: 2210-7789; 2210-7797
• DOI: 10.1016/j.preghy.2021.02.011

•H-HCYS associated with EO-PE, in folate replete & B12 deficient North Indian population.•MTHFR 677TT genotype found only in EO-PE.•High plasma IL-17 counterbalanced by IL-10 & β-hCG in EO-PE.•Elevated homocysteine & IL-10 in EO-PE women with spontaneous vaginal deliveries.
Studies on One Carbon Metabolism (OCM), Interleukins-10 &-17 (IL-10/-17) & βhCG in pre-eclampsia and its delivery outcome (preterm birth) reveal contradictory results, attributed to clinical heterogeneity (early/late onset pre-eclampsia) or preterm/term birth. Disturbed OCM also influences IL-10 &-17 during pregnancy. We sought to investigate the synergism between OCM and IL-10/-17 mediated immune-regulation through βhCG in Early onset pre-eclampsia (EO-PE) patients, delivering preterm, among North Indian women.
Case-control study with a total of 399 pregnant women (EO-PE delivering preterm = 199; Normotensives delivering at term = 200). Maternal genotypes & biochemical estimations along with fetal genotypes on subset (n = 72) pertaining to OCM and IL-10/-17 regulation were assessed.
Association of 1) maternal plasma levels with EO-PE 2) maternal and fetal genotypes with EO-PE. 3) Effect of Hyper-homocysteinemia (surrogate of disturbed OCM) on differential immune regulation (IL10,-17, βhCG) in EO-PE and mode of delivery.
Hyper-homocysteinemia posed an increased risk of three folds for EO-PE. Both, folate and B12 deficiencies were associated with elevated homocysteine in EO-PE. Further, MTHFR 677TT homozygotes was present only in EO-PE indicating its detrimental role. However, maternal IL17-197AA genotype showed decreased risk for EO-PE. Furthermore, elevated maternal plasma IL-17 along with elevated IL-10 & βhCG were observed in EO-PE. Taken together, altered homocysteine metabolism was associated with high IL10 in EO-PE; and was more pronounced in spontaneous vaginal deliveries as compared to induced/caesarean section deliveries.
We report homocysteine mediated IL-10 &17 dysregulation and its influence on mode of delivery in EO-PE, possibly through initiation of cervical ripening. Further, these could serve potential biomarkers of EO-PE & its delivery outcome among vulnerable populations with similar nutritional & genetic predispositions.