Role of maternal, fetal and placental histopathology factors in the pathogenesis of retinopathy of prematurity

Kaur, Tarandeep; Sharma, Neha; Jakati, Saumya; Bagga, Nitasha; Mitra, Sanchita; Katamtreddy, Bhargavi K; Jalali, Subhadra; Kaur, Inderjeet

doi:10.1101/2023.02.13.528236

Cited by 3 publications

(2 citation statements)

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“…Seventeen studies assessing HCA in neonates with any stage ROP compared to neonates without ROP were included, with the number of sample size ranging from 13 to 912 (Table S1) [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. HCA was detected 1.8 times as frequently in neonates with any stage ROP compared to neonates without ROP (OR 1.8; 95% CI 1.3─2.4, p=0.0004) (Figure 2).…”

Section: Hca and Any Stage Ropmentioning

confidence: 99%

Histological Chorioamnionitis and Funisitis as New Risk Factors for Retinopathy of Prematurity: A Meta-analysis

El Emrani,

Jansen,

Goeman

et al. 2023

Am J Perinatol

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Objective The role of placental inflammation in neonatal morbidities is underestimated due to lack of placental examination. This meta-analysis aims to assess the association between histological chorioamnionitis (HCA) with and without funisitis (FUN) and risk of retinopathy of prematurity (ROP). Study Design Forty-five studies reporting (unadjusted) data on HCA without FUN and HCA with FUN in neonates with ROP were included. Primary outcomes were any stage ROP and severe ROP. Potential confounders explored were gestational age (GA) at birth, birthweight, maternal steroid use, necrotizing enterocolitis, sepsis (suspected/proven) and mechanical ventilation duration. Results Neonates with HCA had increased risk for any stage ROP (odds ratio [OR] 1.8; 95% confidence interval [CI] 1.3–2.4) and severe ROP (OR 1.5; 95% CI 1.2–1.8) compared with neonates without HCA. The rates of any stage ROP (OR 1.8; 95% CI 1.4–2.2) and severe ROP (OR 1.4; 95% CI 1.1–1.6) were higher in neonates with FUN compared with neonates without FUN. Multivariate meta-regression analysis suggests that lower GA increases the effect size between FUN and severe ROP. Conclusion This meta-analysis confirms that presence of HCA and FUN are risk factors for any stage ROP and severe ROP. Structured histological placental examination of HCA and FUN may be a tool to further refine the ROP risk profile. Key Points

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Section: Hca and Any Stage Ropmentioning

confidence: 99%

Histological Chorioamnionitis and Funisitis as New Risk Factors for Retinopathy of Prematurity: A Meta-analysis

El Emrani,

Jansen,

Goeman

et al. 2023

Am J Perinatol

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“…This method can have high variability due to differences in storage and transportation temperature, transit time and exact collection methods between patients. Another common method is fecal occult blood test (FOBT) cards (29–33). In FOBT sampling fecal smears are collected at home on specialized sample cards designed to detect blood.…”

mentioning

confidence: 99%

S-Wipe: stool sample collection for metabolomic gut health tracking

Melnik,

Pobozhev,

Lotfi

et al. 2024

Preprint

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Microbiome is increasingly recognized as a key factor in health. Intestinal microbiota modulates gut homeostasis via a range of diverse metabolites. Molecules such as short chain fatty acids (SCFAs), the microbial fermentation products of dietary fiber, have been established to be reflective of microbiome and/or dietary shifts and have been linked to multiple gastrointestinal disorders from cancer to colitis, and thus present an excellent diagnostic target. Yet, technical bottlenecks preclude broad translation of such established biomarkers into routine medical practice. In particular, easily accessible, reproducible and robust sampling of stool remains challenging. Here we present Stool Wipe (S-Wipe), an ultra low cost, simplified fecal specimen collection approach designed to overcome key translational barriers without compromising analytical rigor. This sampling approach harnesses lint-free mass spectrometry-compatible cellulose wipes used as a regular toilet paper. The collected stool specimens are then preserved in ethanol solution, do not require refrigeration and can be shipped via regular mail. Using mass spectrometry, we have demonstrated a broad range of captured metabolites, both volatile and non-volatile. The reproducibility and stability of the method was validated for a panel of molecules of particular diagnostic interest, including SCFAs and p-cresol. We demonstrate sensitivity as well as stability and reproducibility of various metabolites collected with S-Wipe. We further demonstrate that S-Wipe is equivalent to the direct stool collection and thus could be used interchangeably and compared to other studies where stool is collected directly. This methodology is ideally suited and is scalable for broad population-based studies, longitudinal tracking such as therapeutic interventions and personalized medicine.IMPORTANCEGut microbiome and intestinal metabolome present invaluable diagnostic and therapeutic targets. However, conventional stool testing has several barriers limiting bioassessment from populations. Routine, high temporal resolution monitoring of stool metabolome, including validated biomarkers such as SCFAs, is not implemented due to relatively high cost and inconvenience of sampling, possible need for clinical setting for sample collection, difficulty to collect samples reproducibly, especially due to possible user errors, requirement for freezer storage and maintaining cold chain during shipment. We present a sampling strategy specifically designed to overcome these obstacles. This method can enable capturing accurate molecular snapshots at massive scales, at ultra low cost. The approach collapses complex medical-grade collection into easy self-administration. Individuals can thereby self-monitor therapeutic responses through routine metabolome tracking, including the volatilome, otherwise hindered by infrastructure restrictions. Ultimately, this sampling approach is intended to enable participatory wellness transformation through practical high frequency self-sampling.

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Arachidonic acid metabolism regulates the development of retinopathy of prematurity among preterm infants

Kumar,

Patnaik,

Joshi

et al. 2024

Journal of Neurochemistry

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Extremely preterm infants are at risk of developing retinopathy of prematurity (ROP), characterized by neovascularization and neuroinflammation leading to blindness. Polyunsaturated fatty acid (PUFA) supplementation is recommended in preterm infants to lower the risk of ROP, however, with no significant improvement in visual acuity. Reasonably, this could be as a result of the non‐consideration of PUFA metabolizing enzymes. We hypothesize that abnormal metabolism of the arachidonic acid (AA) pathway may contribute to severe stages of ROP. The present study investigated the AA‐metabolizing enzymes in ROP pathogenesis by a targeted gene expression analysis of blood (severe ROP = 70, No/Mild = 56), placenta (preterm placenta = 6, full term placenta = 3), and human primary retinal cell cultures and further confirmed at the protein level by performing IHC in sections of ROP retina. The lipid metabolites were identified by LC–MS in the vitreous humor (VH; severe ROP = 15, control = 15). Prostaglandins D2 (p = 0.02), leukotrienes B5 (p = 0.0001), 11,12‐epoxyeicosatrienoic acid (p = 0.01), and lipid‐metabolizing enzymes of the AA pathway such as CYP1B1, CYP2C8, COX2, and ALOX15 were significantly upregulated while EPHX2 was significantly (0.04) downregulated in ROP cases. Genes involved in hypoxic stress, angiogenesis, and apoptosis showed increased expression in ROP. An increase in the metabolic intermediates generated from the AA metabolism pathway further confirmed the role of these enzymes in ROP, while metabolites for EPHX2 activity were low in abundance. Inflammatory lipid intermediates were higher compared to anti‐inflammatory lipids in VH and showed an association with enzyme activity. Both the placenta of preterm infants who developed ROP and hypoxic retinal cultures showed a reduced expression of EPHX2. These findings suggested a strong involvement of EPHX2 in regulating retinal neovascularization and inflammation. The study results underscore the role of arachidonic acid metabolism in the development of ROP and as a potential target for preventing vision loss among preterm‐born infants.image

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Role of maternal, fetal and placental histopathology factors in the pathogenesis of retinopathy of prematurity

Cited by 3 publications

References 53 publications

Histological Chorioamnionitis and Funisitis as New Risk Factors for Retinopathy of Prematurity: A Meta-analysis

Histological Chorioamnionitis and Funisitis as New Risk Factors for Retinopathy of Prematurity: A Meta-analysis

S-Wipe: stool sample collection for metabolomic gut health tracking

Arachidonic acid metabolism regulates the development of retinopathy of prematurity among preterm infants

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