Prenatal humid heat exposure and cord blood extracellular vesicle microRNA profiles in a Ghanaian Pregnancy Cohort: GRAPHS

Abstract Humid heat exposures over pregnancy impact birth outcomes but mechanisms are poorly described. We leveraged the Ghana Randomized Air Pollution and Health Study (GRAPHS) to examine associations between maximum shaded wet bulb globe temperature (WBGT) and cord blood extracellular vesicle (EV)-associated microRNA. We also considered heat index (HI) and dry air temperature as secondary exposures. Cord blood was collected at delivery and EVs isolated and RNAs sequenced and small RNA libraries constructed. We assigned participants’ trimester and whole pregnancy average heat exposures using satellite reanalysis heat exposures at the level of participant community of residence. We then performed linear regression to examine associations between prenatal heat exposures and log2-transformed miRNA counts and considered significance with an unadjusted P-value ≤ .01 and |beta| > 0.2. In 44 participants, we identified 91 microRNAs that were detected in at least 70% of samples. We identified that miR-146b-5p (β = 0.94 [95% CI = 0.27, 1.6], per 1-degree increase in WBGT); miR-381-3p (β = 2.23 [1.3, 3.15]), miR-378a-3p (β = −1.4, [−2.42, −0.39]), and miR-744-5p (β = 1.51 [0.46, 2.57]); and miR-126-3p (β = −0.75 [−1.2, −0.29]) were associated with first-, second-, and third-trimester WBGT, respectively. miR-1307-3p (β = 2.27 [0.61, 3.94] per 1-degree increase in WBGT) was associated with WBGT averaged over the whole pregnancy. Similar findings were observed with HI. In the GRAPHS cohort, we identified that humid-heat exposure over pregnancy alters the cord blood EV-associated miRNA profiles.