Association Between Individual Air Pollution (PM10, PM2.5) Exposure and Adverse Pregnancy Outcomes in Korea: A Multicenter Prospective Cohort, Air Pollution on Pregnancy Outcome (APPO) Study.

BACKGROUND: Prenatal exposure to ambient air pollution is linked to a higher risk of unfavorable pregnancy outcomes. However, the association between pregnancy complications and exposure to indoor air pollution remains unclear. The Air Pollution on Pregnancy Outcomes research is a hospital-based prospective cohort research created to look into the effects of aerodynamically exposed particulate matter (PM)10 and PM2.5 on pregnancy outcomes. METHODS: This prospective multicenter observational cohort study was conducted from January 2021 to June 2023. A total of 662 women with singleton pregnancies enrolled in this study. An AirguardK® air sensor was installed inside the homes of the participants to measure the individual PM10 and PM2.5 levels in the living environment. The time-activity patterns and PM10 and PM2.5, determined as concentrations from the time-weighted average model, were applied to determine the anticipated exposure levels to air pollution of each pregnant woman. The relationship between air pollution exposure and pregnancy outcomes was assessed using logistic and linear regression analyses. RESULTS: Exposure to elevated levels of PM10 throughout the first, second, and third trimesters as well as throughout pregnancy was strongly correlated with the risk of pregnancy problems according to multiple logistic regression models adjusted for variables. Except for in the third trimester of pregnancy, women exposed to high levels of PM2.5 had a high risk of pregnancy complications. During the second trimester and entire pregnancy, the risk of preterm birth (PTB) increased by 24% and 27%, respectively, for each 10 µg/m3 increase in PM10. Exposure to high PM10 levels during the second trimester increased the risk of gestational diabetes mellitus (GDM) by 30%. The risk of GDM increased by 15% for each 5 µg/m3 increase in PM2.5 during the second trimester and overall pregnancy, respectively. Exposure to high PM10 and PM2.5 during the first trimester of pregnancy increased the risk of delivering small for gestational age (SGA) infants by 96% and 26%, respectively. CONCLUSION: Exposure to high concentrations of PM10 and PM2.5 is strongly correlated with the risk of adverse pregnancy outcomes. Exposure to high levels of PM10 and PM2.5 during the second trimester and entire pregnancy, respectively, significantly increased the risk of PTB and GDM. Exposure to high levels of PM10 and PM2.5 during the first trimester of pregnancy considerably increased the risk of having SGA infants. Our findings highlight the need to measure individual particulate levels during pregnancy and the importance of managing air quality in residential environment.

Identification of Short-Chain Fatty Acids for Predicting Preterm Birth in Cervicovaginal Fluid Using Mass Spectrometry.

Preterm birth (PTB) refers to delivery before 37 weeks of gestation. Premature neonates exhibit higher neonatal morbidity and mortality rates than term neonates; therefore, predicting and preventing PTB are important. In this study, we investigated the potential of using short-chain fatty acid (SCFA) levels, specific vaginal microbiota-derived metabolites, as a biomarker in predicting PTB using gas chromatography/mass spectrometry. Cervicovaginal fluid (CVF) was collected from 89 pregnant women (29 cases of PTB vs. 60 controls) without evidence of other clinical infections, and SCFA levels were measured. Furthermore, the PTB group was divided into two subgroups based on birth timing after CVF sampling: delivery ≤ 2 days after sampling (n = 10) and ≥2 days after sampling (n = 19). The concentrations of propionic acid, isobutyric acid, butyric acid, valeric acid, hexanoic acid, and heptanoic acid were significantly higher in the PTB group than in the term birth (TB) group (p < 0.05). In particular, the concentrations of propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid were continuously higher in the PTB group than in the TB group (p < 0.05). In the delivery ≤ 2 days after sampling group, the propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid levels were significantly higher than those in the other groups (p < 0.05). This study demonstrated a significant association between specific SCFAs and PTB. We propose these SCFAs as potential biomarkers for the prediction of PTB.

Leber's hereditary optic neuropathy following unilateral painful optic neuritis: a case report.

BACKGROUND: Leber's hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease, characterized by acute or subacute, painless, bilateral visual loss. LHON is often misdiagnosed as optic neuritis at an early stage because of the similarity of their clinical presentation. To date, there has been no reported case of actual optic neuritis and LHON in one patient. CASE PRESENTATION: A 40-year-old, healthy man was referred to our clinic with acute painful visual loss in the right eye for 2 weeks. In the right eye, visual acuity decreased to 20/40, and the Ishihara colour test score was 8/14 with a relative afferent pupillary defect. Optic disc swelling was found only in the right eye, and magnetic resonance imaging revealed enhancement of the the right optic nerve, consistent with optic neuritis. After receiving 1 g of intravenous methylprednisolone daily for three days, his ocular pain resolved, and visual acuity improved to 20/20 within 2 weeks. Seven months later, the patient developed acute painless visual loss in the right eye. Visual acuity decreased to 20/200 in the right eye. There was no response to the intravenous methylprednisolone therapy at that time. Eight months later, he developed subacute painless visual loss in the left eye. Genetic testing for LHON was performed and revealed the pathologic mtDNA 11778 point mutation. CONCLUSIONS: We report a case with painful unilateral optic neuritis preceding the onset of LHON. Even if a typical optic neuritis patient has completely recovered from steroid treatment once in the past, it is advisable to keep in mind the possibility of LHON if acute or subacute loss of vision subsequently or simultaneously occurs in both eyes and does not respond to steroids.

Computer-aided recognition of myopic tilted optic disc using deep learning algorithms in fundus photography.

BACKGROUND: It is necessary to consider myopic optic disc tilt as it seriously impacts normal ocular parameters. However, ophthalmologic measurements are within inter-observer variability and time-consuming to get. This study aimed to develop and evaluate deep learning models that automatically recognize a myopic tilted optic disc in fundus photography. METHODS: This study used 937 fundus photographs of patients with normal or myopic tilted disc, collected from Samsung Medical Center between April 2016 and December 2018. We developed an automated computer-aided recognition system for optic disc tilt on color fundus photographs via a deep learning algorithm. We preprocessed all images with two image resizing techniques. GoogleNet Inception-v3 architecture was implemented. The performances of the models were compared with the human examiner's results. Activation map visualization was qualitatively analyzed using the generalized visualization technique based on gradient-weighted class activation mapping (Grad-CAM++). RESULTS: Nine hundred thirty-seven fundus images were collected and annotated from 509 subjects. In total, 397 images from eyes with tilted optic discs and 540 images from eyes with non-tilted optic discs were analyzed. We included both eye data of most included patients and analyzed them separately in this study. For comparison, we conducted training using two aspect ratios: the simple resized dataset and the original aspect ratio (AR) preserving dataset, and the impacts of the augmentations for both datasets were evaluated. The constructed deep learning models for myopic optic disc tilt achieved the best results when simple image-resizing and augmentation were used. The results were associated with an area under the receiver operating characteristic curve (AUC) of 0.978 ± 0.008, an accuracy of 0.960 ± 0.010, sensitivity of 0.937 ± 0.023, and specificity of 0.963 ± 0.015. The heatmaps revealed that the model could effectively identify the locations of the optic discs, the superior retinal vascular arcades, and the retinal maculae. CONCLUSIONS: We developed an automated deep learning-based system to detect optic disc tilt. The model demonstrated excellent agreement with the previous clinical criteria, and the results are promising for developing future programs to adjust and identify the effect of optic disc tilt on ophthalmic measurements.

Intraretinal microvascular alterations in indirect traumatic optic neuropathy using optical coherence tomography angiography.

PURPOSE: To quantitatively evaluate macular and peripapillary microvascular alterations in patients with indirect traumatic optic neuropathy (TON) compared to normal controls using optical coherence tomography angiography (OCT-A) and determine their associations with other ocular parameters. METHODS: We enrolled 33 eyes of 33 patients with TON and 34 eyes of 34 healthy controls. OCT-A was used to generate microvascular structure images of the superficial retinal capillary plexus (SRCP), deep retinal capillary plexus (DRCP), and radial peripapillary capillary (RPC) segment in the macula and peripapillary area. Functional and structural parameters such as best-corrected visual acuity, visual field, peripapillary retinal nerve fibre layer (pRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, OCT-A variables were compared between TON patients and controls. Age, gender, and spherical equivalent refractive errors were statistically adjusted for the analysis. RESULTS: OCT-A revealed a significant reduction of the average vessel density in the RPC segment in TON patients compared to controls (48.5% ± 6.28 vs. 57.88% ± 3.06%, P < 0.0001, corrected P < 0.0001). When comparing sectors, the vessel density of the RPC segment in TON patients was also significantly lower in all four quadrants compared to healthy controls. The inferior sector vessel density of the RPC segment was significantly associated with visual field defects (P = 0.0253) and visual acuity (P = 0.0369). The temporal sector vessel density of DRCP was also associated with visual field defects (P = 0.0377). The RPC segment in the superior and inferior sector vessel density displayed a significant association with the corresponding regional pRNFL thickness (P = 0.0248 and <0.0001, respectively). CONCLUSIONS: Patients with indirect TON exhibit significant microvascular alterations compared to controls. This study confirms that TON can induce intraretinal microvascular changes and suggests that OCT-A may serve as a useful biomarker for assessing visual functional and structural changes.

Dysbiotic Vaginal Microbiota Induces Preterm Birth Cascade via Pathogenic Molecules in the Vagina.

Dysbiotic vaginal microbiota (DVM) disturb the vaginal environment, including pH, metabolite, protein, and cytokine profiles. This study investigated the impact of DVM on the vaginal environment in 40 Korean pregnant women and identified predictable biomarkers of birth outcomes. Cervicovaginal fluid (CVF) samples were collected in the third trimester using vaginal swabs, examined for pH, and stored at -80 °C for further analysis. The samples were grouped as full-term (FTB, n = 20) and preterm (PTB, n = 20) births. The microbiota was profiled in the V1-V9 regions. The levels of targeted metabolites, TLR-4, and cytokines were determined. The pH of CVF from PTB (>4.5) was significantly higher than that of the CVF from FTB (>3.5) (p < 0.05). Neonatal gestational age at delivery, birth weight, and Apgar score differed significantly between groups. The relative abundances of beneficial Lactobacillus spp., such as Lactobacillus gasseri, Lactobacillus jensenii, and Bifidobacterium, were higher in FTB, whereas those of pathogenic Enterococcus faecalis, Staphylococcus, Prevotella, Ureaplasma parvum, and Corynebacterium spp. were higher in PTB. Acetate, methanol, TLR-4, and TNF-α levels were negatively correlated with gestational age at delivery and birth weight. Moreover, ethanol, methanol, TLR-4, IL-6, IL-1ß, and TNF-α levels were positively correlated with succinate, acetate, acetoacetate, formate, and ammonia. Overall, DVM induces preterm birth via pathogenic molecules in the vagina.

Urinary metabolite biomarkers of pregnancy complications associated with maternal exposure to particulate matter.

Particulate matter 2.5 (PM2.5) is associated with reproductive health and adverse pregnancy outcomes. However, studies evaluating biological markers of PM2.5 are lacking, and identifying biomarkers for estimating prenatal exposure to prevent pregnancy complications is essential. Therefore, we aimed to explore urine metabolites that are easy to measure as biomarkers of exposure. In this matched case-control study based on the PM2.5 exposure, 30 high PM2.5 group (>15 µg/m3) and 30 low PM2.5 group (<15 µg/m3) were selected from air pollution on pregnancy outcome (APPO) cohort study. We used a time-weighted average model to estimate individual PM exposure, which used indoor PM2.5 and outdoor PM2.5 concentrations by atmospheric measurement network based on residential addresses. Clinical characteristics and urine samples were collected from participants during the second trimester of pregnancy. Urine metabolites were quantitatively measured using gas chromatography-mass spectrometry following multistep chemical derivatization. Statistical analyses were conducted using SPSS version 21 and MetaboAnalyst 5.0. Small for gestational age and gestational diabetes (GDM) were significantly increased in the high PM2.5 group, respectively (P = 0.042, and 0.022). Fifteen metabolites showed significant differences between the two groups (P < 0.05). Subsequent pathway enrichment revealed that four pathways, including pentose and glucuronate interconversion with three pentose sugars (ribose, arabinose, and xylose; P < 0.05). The concentration of ribose increased preterm births (PTB) and GDM (P = 0.044 and 0.049, respectively), and the arabinose concentration showed a tendency to increase in PTB (P = 0.044). Therefore, we identified urinary pentose metabolites as biomarkers of PM2.5 and confirmed the possibility of their relationship with pregnancy complications.

Correction: Park et al. Effect of Particulate Matter 2.5 on Fetal Growth in Male and Preterm Infants through Oxidative Stress. Antioxidants 2023, 12, 1916.

In the original publication [...].

Deep learning-based optic disc classification is affected by optic-disc tilt.

We aimed to determine the effect of optic disc tilt on deep learning-based optic disc classification. A total of 2507 fundus photographs were acquired from 2236 eyes of 1809 subjects (mean age of 46 years; 53% men). Among all photographs, 1010 (40.3%) had tilted optic discs. Image annotation was performed to label pathologic changes of the optic disc (normal, glaucomatous optic disc changes, disc swelling, and disc pallor). Deep learning-based classification modeling was implemented to develop optic-disc appearance classification models with the photographs of all subjects and those with and without tilted optic discs. Regardless of deep learning algorithms, the classification models showed better overall performance when developed based on data from subjects with non-tilted discs (AUC, 0.988 ± 0.002, 0.991 ± 0.003, and 0.986 ± 0.003 for VGG16, VGG19, and DenseNet121, respectively) than when developed based on data with tilted discs (AUC, 0.924 ± 0.046, 0.928 ± 0.017, and 0.935 ± 0.008). In classification of each pathologic change, non-tilted disc models had better sensitivity and specificity than the tilted disc models. The optic disc appearance classification models developed based all-subject data demonstrated lower accuracy in patients with the appearance of tilted discs than in those with non-tilted discs. Our findings suggested the need to identify and adjust for the effect of optic disc tilt on the optic disc classification algorithm in future development.

Retinal and peripapillary vascular deformations in prematurely born children aged 4-12 years with a history of retinopathy of prematurity.

In this study, foveal, parafoveal, peripapillary anatomical, and microvascular anomalies in prematurely born children aged 4-12 years with a history of retinopathy of prematurity (ROP) were evaluated. Seventy-eight eyes of 78 prematurely born children ([tROP]: ROP with laser treatment, [srROP]: spontaneously regressed ROP) and 43 eyes of 43 healthy children were included. Foveal and peripapillary morphological parameters (including ganglion cell and inner plexiform layer (GCIPL) thickness, peripapillary retinal nerve fiber layer (pRNFL) thickness) and vasculature parameters (including foveal avascular zone area, vessel density from superficial retinal capillary plexus (SRCP), deep retinal capillary plexus (DRCP), and radial peripapillary capillary (RPC) segments) were analyzed. Foveal vessel densities in SRCP and DRCP were increased and parafoveal vessel densities in SRCP and RPC segments vessel density were decreased in both ROP groups compared with those of control eyes. The best-corrected visual acuity was negatively correlated with pRNFL thickness in the tROP group. Refractive error was negatively correlated with vessel density of RPC segments in the srROP group. In children born preterm with a history of ROP, it was found that foveal, parafoveal, and peripapillary structural and vascular anomalies and redistribution were accompanied. These retinal vascular and anatomical structure anomalies showed close relationships with visual functions.

Risk of optic neuritis in type 2 diabetes mellitus: A nationwide cohort study.

BACKGROUND/PURPOSE: This study aimed to investigate the association between the time course of type 2 diabetes mellitus (DM) and the development of optic neuritis (ON) in the Korean population aged 20 years and older. METHODS: A total of 10,069,044 subjects were included in this study, which utilized stratified random sampling from the national cohort. The hazard ratios (HRs) for incident ON were compared between subjects with normal fasting glucose (NFG) levels, impaired fasting glucose (IFG) levels, patients with new-onset DM, diabetes duration of fewer than 5 years (early DM), and diabetes duration of 5 years or more (late DM). In addition, the HR for incident ON was assessed and stratified into 20 fasting glucose levels. RESULTS: The cumulative incidence and HR for ON demonstrated a significant increase across the time course of diabetes (adjusted hazard ratio [aHR] = 1.05, 95% confidence interval [CI]: 1.00 to 1.10 for IFG; aHR = 1.31, 95% CI: 1.19 to 1.44 for new-onset DM; aHR = 1.46, 95% CI: 1.32 to 1.60 for early DM; and aHR = 1.92, 95% CI: 1.77 to 2.08 for late DM). Moreover, the HR for ON was 1.71-fold higher in individuals with fasting glucose levels of 132 mg/dL or more compared to those with levels below 75 mg/dL. CONCLUSION: In this nationwide cohort study, the risk of ON was found to increase with the time course of diabetes and elevated glucose levels. These results suggest that efforts to regulate glucose levels and prevent DM progression could reduce the risk of ON.

A genome-wide and candidate gene association study of preterm birth in Korean pregnant women.

Preterm birth (PTB) refers to delivery before 37 weeks of gestation. Premature neonates exhibit higher neonatal morbidity and mortality rates than term neonates; therefore, it is crucial to predict and prevent PTB. Advancements enable the prediction and prevention of PTB using genetic approaches, especially by investigating its correlation with single nucleotide polymorphisms (SNPs). We aimed to identify impactive and relevant SNPs for the prediction of PTB via whole-genome sequencing analyses of the blood of 31 pregnant women with PTB (n = 13) and term birth (n = 18) who visited the Ewha Womans University Mokdong Hospital from November 1, 2018 to February 29, 2020. A genome-wide association study was performed using PLINK 1.9 software and 256 SNPs were selected and traced through protein-protein interactions. Moreover, a validation study by genotyping was performed on 60 other participants (preterm birth, n = 30; term birth, n = 30) for 25 SNPs related to ion channel binding and receptor complex pathways. Odds ratios were calculated using additive, dominant, and recessive genetic models. The risk of PTB in women with the AG allele of rs2485579 (gene name: RYR2) was significantly 4.82-fold increase, and the risk of PTB in women with the AG allele of rs7903957 (gene name: TBX5) was significantly 0.25-fold reduce. Our results suggest that rs2485579 (in RYR2) can be a genetic marker of PTB, which is considered through the association with abnormal cytoplasmic Ca2+ concentration and dysfunctional uterine contraction due to differences of RYR2 in the sarcoplasmic reticulum.

Predicting visual outcomes after decompression of pituitary tumours based on stratified inner-retinal layer thickness and age.

PURPOSE: The purpose of the study was to evaluate the potential role of stratified preoperative optical coherence tomography (OCT) measurements and age in predicting postoperative visual field (VF) improvement among adult patients with chiasmal compression due to pituitary tumours after decompression surgery. METHODS: Postoperative visual outcomes were analysed using mean deviation of the VF test. Eyes were divided into three groups based on preoperative OCT parameters including peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness: groups 1, 2 and 3 with pRNFL thickness <65 µm, 65 µm or more but <85 µm, and 85 µm or more, respectively. The GCIPL thickness was also divided into three groups based on values ranging from 55 to 77 µm. Each group was further categorized according to age: 20 years or older but younger than 40 years, 40 years or older but younger than 60, and 60 years or older. RESULTS: This study included 197 eyes of 197 patients with chiasmal compression due to pituitary tumours. No patient showed complete VF recovery in group 1 with a preoperative pRNFL thickness <65 µm or a GCIPL thickness <55 µm regardless of age. These groups showed the worst VF outcome (pRNFL, p = 0.0001; GCIPL, p < 0.0001). However, a significant recovery in VF (greater than 2 dB) was observed in 45% of group 1 patients based on pRNFL thickness and in 61.54% of group 1 patients according to GCIPL thickness. In groups 2 and 3 with a preoperative pRNFL thickness of 65 µm or more and a GCIPL thickness of 55 µm or more, the rate of complete VF recovery decreased as subjects' ages increased. Group 3 with a preoperative pRNFL thickness of 85 µm or more and a GCIPL thickness of 77 µm or more were 2.5-fold and 4.0-fold more likely to completely recover VF, respectively, compared with group 2. CONCLUSIONS: Stratified preoperative pRNFL and GCIPL thicknesses measured via OCT in different age categories are effective biomarkers for predicting visual functional outcomes.

Lactobacillus Probiotics Improve Vaginal Dysbiosis in Asymptomatic Women.

Vaginal dysbiosis can lead to serious infections in asymptomatic women. Lactobacillus probiotics (LBPs) are being investigated as a promising therapy for reversing vaginal microbiota dysbiosis. This study aimed to investigate whether administering LBPs could improve vaginal dysbiosis and facilitate the colonization of Lactobacillus species in asymptomatic women. 36 asymptomatic women were classified based on the Nugent score as Low-NS (n = 26) and High-NS (n = 10) groups. A combination of Lactobacillus acidophilus CBT LA1, Lactobacillus rhamnosus CBT LR5, and Lactobacillus reuteri CBT LU4 was administered orally for 6 weeks. The study found that among women with a High-NS, 60% showed improved vaginal dysbiosis with a Low-NS after LBP intake, while four retained a High-NS. Among women with a Low-NS, 11.5 % switched to a High-NS. Genera associated with vaginal dysbiosis were positively correlated with the alpha diversity or NS, while a negative correlation was observed between Lactobacillus and the alpha diversity and with the NS. Vaginal dysbiosis in asymptomatic women with an HNS improved after 6 weeks of LBP intake, and qRT-PCR revealed the colonization of Lactobacillus spp. in the vagina. These results suggested that oral administration of this LBP could improve vaginal health in asymptomatic women with an HNS.

Effect of Particulate Matter 2.5 on Fetal Growth in Male and Preterm Infants through Oxidative Stress.

Particulate matter 2.5 (PM2.5) levels are associated with adverse pregnancy outcomes. In this retrospective cohort study, we examined whether the concentration of indoor PM2.5 affected pregnancy outcomes. Additionally, we evaluated biomarkers of pregnancy-related complications caused by fine dust. We collected clinical information and data based on residential addresses from the Air Korea database to assess PM2.5 exposure levels. As a multicenter prospective cohort study, we measured the indoor PM2.5 concentration and inflammatory and oxidative stress markers. The PM2.5 concentration of the low-birth-weight (LBW) delivery group was 27.21 µg/m3, which was significantly higher than that of the normal-birth-weight (NBW) group (26.23 µg/m3) (p = 0.02). When the newborns were divided by sex, the PM2.5 concentration of the LBW group was 27.89 µg/m3 in male infants, which was significantly higher than that of the NBW group (26.26 µg/m3) (p = 0.01). In the prospective study, 8-hydroxy-2-deoxyguanosine significantly increased in the high-concentration group (113.55 ng/mL, compared with 92.20 ng/mL in the low-concentration group); in the high-concentration group, the rates of preterm birth (PTB) and small size for gestational age significantly increased (p < 0.01, p = 0.01). This study showed an association between PM2.5, oxidative stress, and fetal growth, with the PTB group being more vulnerable.

Personal exposure of PM2.5 and metabolic syndrome markers of pregnant women in South Korea: APPO study.

We examined the association between exposure to PM2.5, focused on individual exposure level, and metabolic dysfunction during pregnancy. APPO study (Air Pollution on Pregnancy Outcome) was a prospective, multicenter, observational cohort study conducted from January 2021 to March 2023. Individual PM2.5 concentrations were calculated using a time-weighted average model. Metabolic dysfunction during pregnancy was assessed based on a modified definition of metabolic syndrome and its components, accounting for pregnancy-specific criteria. Exposure to PM2.5 during pregnancy was associated with worsened metabolic parameters especially glucose metabolism. In comparison to participants exposed to the low PM2.5 group, those exposed to high PM2.5 levels exhibited increased odds of gestational diabetes mellitus (GDM) after adjusting for confounding variables in different adjusted models. Specifically, in model 1, the adjusted odds ratio (aOR) was 3.117 with a 95% confidence interval (CI) of 1.234-7.870; in model 2, the aOR was 3.855 with a 95% CI of 1.255-11.844; in model 3, the aOR was 3.404 with a 95% CI of 1.206-9.607; and in model 4, the aOR was 2.741 with a 95% CI of 0.712-10.547. Exposure to higher levels of PM2.5 during pregnancy was associated with a tendency to worsen metabolic dysfunction markers specifically in glucose homeostasis. Further research is needed to investigate the mechanisms underlying the effects of ambient PM2.5 on metabolic dysfunction during pregnancy.

The introduction to air pollution on pregnancy outcome (APPO) study: a multicenter cohort study.

OBJECTIVE: The air pollution on pregnancy outcome (APPO) study is a prospective hospital-based cohort study designed to investigate the maternal and fetal effects of a particulate matter with an aerodynamic below 10 µm (PM10) and PM2.5 (below 2.5 µm) exposure. This study aims to analyze a relationship between particulate matter and adverse pregnancy outcomes and to find related biomarkers and develop management guidelines. METHODS: About 1,200 pregnant women are recruited for 3 years (from January 2021 to December 2023) from seven university hospitals to investigate the effects of particulate matter on pregnancy complications and adverse pregnancy outcomes. We collect biological samples by 5 mL of maternal venous blood and 15 mL of urine in each trimester of pregnancy, and 5 mL of umbilical cord blood and 2×2×2 cm of placental tissue are collected after delivery. In addition, by applying PM10 and PM2.5 concentration values and time-activity patterns from the time weighted average model, the individual predicted exposure of air pollution for the pregnant women are obtained. RESULTS: The average exposure of PM10 and PM2.5 of the participants in the entire period of pregnancy, was exceeded the World Health Organization air quality guidelines (an annual level, PM10 >15 µg/m3, PM2.5 >5 µg/m3). Moreover, it was revealed that the PM concentration was increasing toward the 3rd trimester of pregnancy. CONCLUSION: The APPO study will be able to identify the degree of exposure to air pollution in pregnant women and use it as basic data for estimating individual exposure to particulate matter. And the results of the APPO study will facilitate in the development of health management for pregnant women against air pollution.

Neuroretinitis after the second injection of a SARS-CoV-2-vaccine: A case report.

Purpose: We report the first case of neuroretinitis after administration of a second dose of a messenger RNA vaccine for coronavirus disease-2019 (COVID-19). Observations: An 83-year-old healthy woman presented with subacute, painless, and progressive visual loss in the right eye that started 2 days after the second injection of the COVID-19 vaccine (Comirnaty®) from Pfizer (New York, NY, USA) and BioNTech (Mainz, Germany). Visual acuities were hand motion perception in the right eye and 20/30 in the left eye. There was optic nerve head swelling in the right eye and subretinal fluid and disruption of the photoreceptor layers in both eyes. Magnetic resonance imaging revealed an enhancement of the right optic nerve, consistent with optic neuritis. She was treated with intravenous corticosteroids, and the optic nerve swelling in the right eye resolved promptly. However, the amount of subretinal fluid worsened for 1 month and did not improve until 6 months from onset. Her visual acuity was slightly improved to finger count perception in the right eye and 20/20 in the left eye during an examination 6 months from onset. Conclusions and Importance: Considering the temporal relation between the second dose of vaccination and the symptom onset in our patient, the ophthalmic symptoms here reported might be considered a rare adverse effect of the Comirnaty® COVID-19 vaccine. Although a causal relationship is not established, to our knowledge, this is the first report of neuroretinitis after vaccination with Comirnaty®, and any further similar cases should be examined in detail.