Inflammation Increases Risk of Adverse Birth Outcomes in Women Living With, Without HIV

The inflammatory markers interleukin (IL) 17A and IL-1β as measured during the third pregnancy trimester were associated with adverse pregnancy- and birth-related outcomes among a cohort of pregnant patients living with or without HIV who received antenatal care at Byramjee Jeejeebhoy Government Medical College (a referral center for HIV care) in Pune, India. This indicates a need for interventions that aim to ameliorate pregnancy-related inflammatory pathways and improve birth-related and infant growth outcomes, the authors emphasized.

These findings were published in December in JAMA Network Open.

“Pregnancy is characterized by major changes in maternal immunity, with an immunosuppressive and anti-inflammatory profile in midpregnancy to late pregnancy compared with a more proinflammatory profile during labor,” the authors wrote. “Alterations to this profile have been associated with adverse pregnancy and birth outcomes.” Specifically, they noted that although much is known of the influence of IL-6, tumor necrosis factor (TNF), IL-1β, and C-reactive protein (CRP) on pregnancy-related outcomes, few data exist on how other inflammation biomarkers may affect these outcomes.

After analyzing data on 218 mother-infant pairs (mean [interquartile] mother age, 23 [21-27] years; gestation, 13-34 weeks at enrollment) from pregnancy through 1 year post partum, who received care between June 27, 2016, and December 9, 2019, they found the following:

• 12% of the women delivered preterm birth (PTB) infants
• Biomarker levels were measured at a median 29.3 weeks gestation
• IL-17A and IL-1β levels were higher among women with PTB vs term births:
  • IL-17A: 2.56 vs 2.27 pg/mL (P = .008)
  • IL-1β: 4.55 vs 2.40 pg/mL (P = .002)
• Women with higher levels of IL-17A had a 162% greater risk of delivering a PTB infant, before 37 weeks gestation (adjusted odds ratio [aOR], 2.62; 95% CI, 1.11-6.17) and an 81% greater risk of delivering a low-birthweight (LBW; < 2500g) infant (aOR, 1.81; 95% CI, 1.04-3.15)
• Women with higher levels of IL-1β had a 47% greater risk of delivering a PTB infant (aOR, 1.47; 95% CI, 1.15-1.89)
• Women with higher levels of IL-1β were more likely to deliver infants with demonstrated lower weight and length:
  • Lower length-for-age z score: adjusted β, −0.10 (95% CI, −0.18 to −0.01)
  • Lower weight-for-age z score: adjusted β, −0.07 (95% CI, −0.14 to 0.001)

The inflammatory markers indicated above—in addition to soluble CD163, soluble CD14 intestinal fatty acid–binding protein, CRP, alpha 1-acid glycoprotein, interferon β, interferon γ, IL-1β, IL-6, interleukin 13, IL-17A, and TNF were also performed on these—were chosen because they are known to influence birth outcomes and HIV status, the authors noted, with the aORs noted above including influences of maternal age, mid upper arm circumference (MUAC), smoking status, HIV status, parity, and PTB history.

Additional findings show that 34% of the women lived below India’s poverty line, 24% had an educational level of primary school or less, 28% were classified as undernourished based on their MUAC, and 8% had a history of PTB.

Primary outcomes for this longitudinal cohort study were PTB delivery, with secondary outcomes being LBW and measures of infant growth (length-for-age, weight-for-age, and weight-for-length z scores) taken at delivery and 6 weeks and 3, 6, and 12 months post partum. Of the entire patient cohort, 69 of the mothers were living with HIV. In addition, ultrasonography confirmed gestational age of pregnancy.

“These results suggest a need for future studies to test whether modulating specific inflammatory pathways (eg, those associated with the inflammasome pathway or the TH17 pathway) could be associated with birth outcomes and growth deficits,” the authors wrote. “If these findings are confirmed, future studies should identify and test such an intervention for improved maternal-infant health outcomes.”

Additional future studies, they determined, should investigate the influence of circulating levels of IL-17A on PTB and LBW, as well as the ability of infants born with lower length-for-age and lower weight-for-age z scores to mothers living with HIV to partially recover from those deficits.

“This study examines multiple inflammatory markers, providing insights into different inflammatory pathways associated with general inflammation, monocyte activation, gut integrity, and inflammasome activation,” the authors concluded. “As most existing research on some of these inflammatory markers and PTB have been conducted in Western countries, our study provides valuable data from India with its unique immune, metabolic, and nutritional profile.”

Reference

Shafiq M, Mathad JS, Naik S, et al.Association of maternal inflammation during pregnancy with birth outcomes and infant growth among women with or without HIV in India. JAMA Netw Open. Published online December 22, 2021. doi:10.1001/jamanetworkopen.2021.40584