Validity of the ESSENCE-Q neurodevelopmental screening tool in Japan.

AIM: To assess the validity of the Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations-Questionnaire (ESSENCE-Q), a simple screening tool for neurodevelopmental problems, in Japan. METHOD: Parents/caregivers completed the 11-item ESSENCE-Q for 77 612 children aged 2 years 6 months included in a national birth cohort study. Information about neurodevelopmental disorders (NDDs: autism spectrum disorder; intellectual disability and/or developmental language disorder; motor delay/motor disorder) was collected at age 3 years. Each ESSENCE-Q item was scored on a binary (0,1) scale, with a total score range of 0 to 11. Total scores and individual items were compared across children with and without NDDs. RESULTS: NDDs were recorded in 854 children (1.1%). With a total ESSENCE-Q score cut-off of ≥3, receiver operating characteristic curve analysis showed an area under the curve of 0.91, with sensitivity 84.9%, specificity 84.8%, positive predictive value 5.9%, and negative predictive value 99.8%. The proportion of parental concerns at 2 years 6 months differed significantly by NDD status for communication (89.5% vs 14.2%) and general development (80.2% vs 7.4%). ESSENCE-Q total scores were moderately negatively correlated (-0.36, p < 0.001) with Japanese Ages and Stages Questionnaire scores. INTERPRETATION: The parent/caregiver-completed ESSENCE-Q is useful as a tool for screening out children with neurotypical development at this early age. Further research into longer-term predictive validity will be possible as more NDD diagnoses are given as the children grow up.

Vitamin D deficiency associated with neurodevelopmental problems in 2-year-old Japanese boys.

AIM: While associations between vitamin D deficiency and neurodevelopmental disorders have been found, large studies on child vitamin D, neurodevelopment, and sex differences among the general population are lacking. This study aimed to investigate the association between child serum 25-hydroxyvitamin D (25(OH)D)) levels and neurodevelopmental problems (NDPs). METHODS: Serum 25(OH)D and NDPs were measured at age two among the subcohort study of the Japan Environment and Children's Study. NDPs were assessed with the Kyoto Scale of Psychological Development 2001 (Kyoto scale). Adjusted odds ratios (aORs) for the Kyoto-scale developmental quotient scores <70 were calculated, for postural-motor, cognitive-adaptive, and language-social domains and overall scores, adjusted for test month, latitude, small for gestational age, maternal age, and daycare attendance. RESULTS: Among 2363 boys and 2290 girls, boys had higher 25(OH)D levels, but scored lower in the Kyoto scale. For boys in the vitamin D deficiency (<20 ng/mL) group, aORs of scoring the Kyoto-scale DQs <70 were 2.33 (p = 0.006) for overall DQs, 1.91 (p = 0.037) for cognitive-adaptive, and 1.69 (p = 0.024) for language-social domains. For girls, results were inconclusive. CONCLUSION: Only boys showed a clear and cross-modal association between vitamin D deficiency and NDPs.

Pre-/perinatal reduced optimality and neurodevelopment at 1 month and 3 years of age: Results from the Japan Environment and Children's Study (JECS).

Neurodevelopmental disorders (NDDs) in children are associated with a complex combination of genetic and/or environmental factors. Pre-/perinatal events are major known environmental suboptimal factors, and their individual and combined contributions vary. This study investigated the association between pre-/perinatal reduced optimality and child development observed by parents at 1 month, as well as NDDs at 3 years of age (i.e., motor delay, intellectual disability, developmental language disorder, and autism spectrum disorder), in the context of the Japan Environment and Children's Study. The study also assessed whether child development at 1 month predicted NDDs at 3 years of age. Associations between 25 pre-/perinatal factors and (a) developmental concerns at 1 month of age and (b) NDDs at 3 years were analyzed (n = 71,682). Binomial regression models were used to investigate risk ratios of the developmental outcome at each time point for total pre-/perinatal reduced optimality scale scores, as well as for individual pre-/perinatal factors of the reduced optimality scale. Finally, we assessed the ability of parental observations of offspring development at 1 month to predict NDDs at 3 years. Total reduced optimality scores were positively associated with 1-month developmental concerns and 3-year NDDs, with higher scores (i.e., a reduction in optimality) associated with an increased risk of both NDDs and earlier parental concerns. Neonatal transportation, epidural analgesia, advanced maternal age, cesarean section delivery, Apgar score ≤8, and hyperbilirubinemia were identified as individual risk factors for 3-year NDDs, overlapping with 14 risk factors for 1-month developmental concerns except Apgar score ≤8. Among six developmental items assessed at 1 month of age, concerns about gross motor function and difficulty holding/trouble calming down had the strongest associations with later-diagnosed motor delay and autism spectrum disorder, respectively. Five perinatal factors and advanced maternal age were associated with NDD at 3 years of age, as were early parental developmental concerns regarding their offspring's overall development, indicating the importance of careful follow-up of offspring born with pre-/perinatal reduced optimality. The results also implicated early parental concerns, as early as 1 month, may also be a useful indicator of later NDD status.

Gestational weight gain mediates the effects of energy intake on birth weight among singleton pregnancies in the Japan Environment and Children's Study.

BACKGROUND: Extra energy intake is commonly recommended for pregnant women to support fetal growth. However, relevant data regarding variations in energy intake and expenditure, body mass index and gestational weight gain (GWG) are frequently not considered. This study aimed to investigate how energy intake during pregnancy and gestational weight gain (GWG) are associated with birth weight. METHODS: Early pregnant women were recruited into a Japanese nationwide prospective birth cohort study between 2011 and 2014. We analysed data of 89,817 mother-child pairs of live-born non-anomalous singletons after excluding births before 28 weeks or after 42 weeks. Energy intake during pregnancy was estimated from self-administered food frequency questionnaires (FFQ) and was stratified into low, medium, and high. Participants completed the FFQ in mid-pregnancy (mean 27.9 weeks) by recalling food consumption at the beginning of pregnancy. Effects of energy intake on birth weight and mediation by GWG were estimated using the Karlson-Holm-Breen method; the method separates the impact of confounding in the comparison of conditional and unconditional parameter estimates in nonlinear probability models. Relative risks and risk differences for abnormal birth size were calculated. RESULTS: Mean daily energy intake, GWG, and birth weight were 1682.1 (533.6) kcal, 10.3 (4.0) kg, and 3032.3 (401.4) g, respectively. 6767 and 9010 women had small-for-gestational-age and large-for-gestational-age infants, respectively. Relative to low energy intake, moderate and high intakes increased adjusted birth weights by 13 g and 24 g, respectively: 58 and 69% of these effects, respectively, were mediated by GWG. Compared with the moderate energy intake group, the low energy intake group had seven more women per 1000 women with a small-for-gestational-age birth, whereas the high energy intake group had eight more women per 1000 women with a large-for-gestational-age birth. CONCLUSION: GWG mediates the effect of energy intake on birth weight. All pregnant women should be given adequate nutritional guidance for optimal GWG and fetal growth.

Maternal pain during pregnancy dose-dependently predicts postpartum depression: The Japan Environment and Children's Study.

BACKGROUND: Postpartum depression (PPD) affects women during the first year after delivery. This study investigated the association between prenatal pain (maternal pain during pregnancy) and PPD. METHODS: Data were analyzed from the Japan Environment and Children's Study (JECS), a nationwide prospective birth cohort study. Information on prenatal pain was collected twice during pregnancy through self-administered questionnaires. PPD symptoms were assessed using the Edinburgh Postnatal Depression Scale at one month postpartum. Poisson regression analyses were performed to investigate the association between prenatal pain and PPD, with other putative risk factors adjusted in the model. RESULTS: Among 84,801 study subjects, 11,535 (13.6%) were screened as positive for PPD. In the present study, the occurrence of prenatal pain was 69.6 and 84.0% at the first trimester and the second/third trimester, respectively. A positive relationship between any degree of pain and PPD in both the first and the second/third trimester was observed. A significant linear dose-dependent association was also found (Ptrend < 0.001) when the subjects were divided by the severity of pain. Using participants without any pain at either point as a reference, those with persistent pain both at the first and the second/third trimesters showed the highest risk for PPD: aRR = 1.95 (95%CI: 1.76-2.15; p < 0.001). LIMITATIONS: No detailed information regarding the type or site of prenatal pain was available in the JECS questionnaires, neither did data concerning delivery and postpartum pain. CONCLUSIONS: The study results suggest that prenatal pain is a dose-dependent risk factor for the development of PPD.

Early neurodevelopmental problems and risk for avoidant/restrictive food intake disorder (ARFID) in 4-7-year-old children: A Japanese birth cohort study.

Background: An overrepresentation of neurodevelopmental problems (NDPs) has been observed in individuals with avoidant/restrictive food intake disorder (ARFID). Previous studies on the association between ARFID and NDPs have been limited by cross-sectional data from clinical samples of small size. This study aimed to extend previous research by using prospectively collected data in a non-clinical child cohort. We examined the occurrence of early NDPs in 4-7-year-old children with suspected ARFID and how predictive early NDPs are of ARFID. Methods: Data were collected via parent-report a sub-sample of the Japan Environment and Children's Study (JECS) including 3728 children born 2011-2014 in Kochi prefecture. NDPs were assessed biannually between 0.5 and 3 years of age with the Ages and Stages Questionnaire-3, at age 2.5 years with the ESSENCE-Q, and at age 1 and 3 years via parent-reported clinical diagnoses. ARFID was identified cross-sectionally (at age 4-7 years) using a newly developed screening tool. Logistic regressions were used to test association of (1) a composite early NDP risk score, (2) specific early NDPs, and (3) neurodevelopmental trajectories over time with ARFID. Results: Children in the highest risk percentiles of the NDP risk score had roughly three times higher odds of having suspected ARFID; the absolute risk of later ARFID for children above the 90th percentile was 3.1%. Early NDPs (excluding early feeding problems) were more predictive of later ARFID than were early feeding problems. Specific NDPs predictive of ARFID were problems with general development, communication/language, attention/concentration, social interaction, and sleep. Neurodevelopmental trajectories of children with and without suspected ARFID started to divert after age 1 year. Conclusions: The results mirror the previously observed overrepresentation of NDPs in ARFID populations. In this non-clinical child cohort, early feeding problems were common and rarely developed into ARFID; however, our findings imply that they should be monitored closely in children with high NDP risk to prevent ARFID.

Association between nausea and vomiting of pregnancy and postpartum depression: the Japan Environment and Children's Study.

OBJECTIVE: Postpartum depression (PPD) is a global emotional distress that affects women and their offspring regardless of their culture. The association between nausea and vomiting of pregnancy (NVP) and PPD has been widely described only for the severe form of NVP. We aimed to assess the relationship between PPD and NVP with regards to its severity. METHODS: Data from the Japan Environment and Children's Study (JECS), a birth cohort study, were analyzed. PPD was assessed using the Edinburgh Postnatal Depression Scale (EPDS). Multiple logistic regression models were performed to assess the association between NVP and PPD. RESULTS: Out of the 80,396 women included in the study 14% had PPD. Among them 4,640 (42.1%) had mild NVP; 3,295 (29.9%) had moderate NVP whereas 1,481 (13.4%) had severe NVP. All forms of NVP were associated with PPD and the association gradually increased with the severity of NVP symptoms with odd ratio (OR): 1.26; 95% confidence interval (CI): 1.18-1.35 for mild, OR: 1.28; 95% CI: 1.19-1.38 for moderate and OR: 1.54; 95% CI: 1.42-1.68 for severe NVP. CONCLUSION: Japanese women with NVP were more susceptible to develop PPD and the more severe the NVP symptoms were, the greater the risk of PPD. Thus, close monitoring of NVP-affected women is recommended.

Development of a parent-reported screening tool for avoidant/restrictive food intake disorder (ARFID): Initial validation and prevalence in 4-7-year-old Japanese children.

The prevalence of avoidant/restrictive food intake disorder (ARFID) in the general child population is still largely unknown and validated screening instruments are lacking. The aims of this study were (1) to investigate the prevalence of children screening positive for ARFID in a Japanese birth cohort using a newly developed parent-reported screening tool, (2) to estimate the prevalence of children with ARFID experiencing physical versus psychosocial consequences of their eating pattern, and (3) to provide preliminary evidence for the validity of the new screening tool. Data were collected from 3728 4-7-year-old children born between 2011 and 2014 in Kochi prefecture, Japan (response rate was 56.5%); a sub-sample of the Japan Environment and Children's Study (JECS). Parents completed a questionnaire including the ARFID screener and several other measures to assess convergent validity. The point prevalence of children screening positive for ARFID was 1.3%; half of them met criteria for ARFID based on psychosocial impairment alone, while the other half met diagnostic criteria relating to physical impairment (and additional psychosocial impairment in many cases). Sensory sensitivity to food characteristics (63%) and/or lack of interest in eating (51%) were the most prevalent drivers of food avoidance. Children screening positive for ARFID were lighter in weight and shorter in height, they showed more problem behaviors related to mealtimes and nutritional intake, and they were more often selective eaters and more responsive to satiety, which together provides preliminary support for the validity of the new screening tool. This is the largest screening study to date of ARFID in children up to 7 years. Future studies should examine the diagnostic validity of the new ARFID screener using clinically ascertained cases. Further research on ARFID prevalence in the general population is needed.

Birth month and infant gross motor development: Results from the Japan Environment and Children's Study (JECS).

The association between birth month and neurodevelopmental or psychiatric disorders has been investigated in a number of previous studies; however, the results have been inconsistent. This study investigated the association between birth month and child gross motor development at 6 and 12 months of age in a large cohort of infants (n = 72,203) participating in the Japan Environment and Children's Study (JECS). Gross motor development was assessed using the Ages and Stages Questionnaire (ASQ-3). At 6 months and 12 months, 20.7% and 14.2%, respectively, had ASQ-3 indications of gross motor problems. Birth month was strongly associated with gross motor development at both time points, particularly at 6 months. Summer-born infants had the worst outcomes at both 6 months and 12 months of age. This outcome applied to the ASQ-3 score itself and to the adjusted Relative Risk (aRR), with the highest aRRs (relative to January-born) among August-born (aRR 2.51; 95%CI 2.27-2.78 at 6 months), and June-born (aRR 1.84; 95%CI 1.63-2.09 at 12 months). Boys had better scores than girls both at 6 and 12 months of age. We speculate that seasonal factors-such as maternal vitamin D deficiency and influenza infection-affecting the fetus in early pregnancy might account for the findings.

Biomass energy, particulate matter (PM2.5), and the prevalence of chronic obstructive pulmonary disease (COPD) among Congolese women living near of a cement plant, in Kongo Central Province.

This study investigated whether the individual and combined effects of using biomass energy and living in the neighborhood of a cement plant were associated with the risk of COPD and respiratory symptoms among Congolese women. A total of 235 women from two neighborhood communities of a cement plant participated in this cross-sectional study. Participants were classified into the more exposed group (MEG = 137) and a less exposed group (LEG = 98), as well as into biomass users (wood = 85, charcoal = 49) or electricity users (101 participants). Participants completed a questionnaire including respiratory symptoms, sociodemographic factors, medical history, lifestyle, and household characteristics. In addition to spirometry performance, outdoor PM2.5 (µg/m3) was measured. Afternoon outdoor PM2.5 concentration was significantly higher in MEG than LEG (48.8 (2.5) µg/m3 vs 42.5 (1.5) µg/m3). Compared to electricity users, wood users (aOR: 2.6, 95%CI 1.7; 5.9) and charcoal users (aOR: 2.9, 95%CI 1.4; 10.7) were at risk of developing airflow obstruction. Combined effects of biomass use and living in the neighborhood of a cement plant increased the risk of COPD in both wood users (aOR: 4, 95%CI 1.3; 12.2) and charcoal users (aOR: 3.1, 95%CI 1.7; 11.4). Exposure to biomass energy is associated with an increased risk of COPD. In addition, combined exposure to biomass and living near a cement plant had additive effects on COPD.

Prevalence of chronic obstructive pulmonary disease (COPD) among Congolese cement workers exposed to cement dust, in Kongo Central Province.

Chronic exposure to cement dust may induce adverse health effects, including a significant decrease in lung function. The study investigated whether the prevalence of COPD and respiratory symptoms was associated with working at different tasks exposed to varying levels of cement dust. The cross-sectional study was carried out among 223 exposed and 156 less exposed workers from two cement factories from November 20 to December 15, 2016 in DRC. Workers completed a questionnaire and spirometry was performed. Multivariate analysis was performed to evaluate the association between occupation exposed to cement dust, COPD, and respiratory symptoms, after adjustment for confounders. Morning cough and cough on most days for as much as 3 months each year were significantly higher in the exposed group (p < 0.05) (p = 0.001) than in the less exposed group. As compared to the less exposed group, the prevalence of COPD was higher among the exposed group, 28.2 and 9.6% respectively (p < 0.001). A significant association with COPD, aOR 14.49 (5.33; 39.40), aOR 3.37 (1.44; 7.89), and aOR 3.09 (1.58; 6.05) was found among cleaning, transportation, and production workers, respectively. Working at certain tasks exposed to cement dust is associated with the higher prevalence of COPD and respiratory symptoms. A greater risk is being among cleaning, transportation, and production workers. This suggests the necessity to prioritize the quality of preventive measures in each work area.

Nausea and vomiting during pregnancy associated with lower incidence of preterm births: the Japan Environment and Children's Study (JECS).

BACKGROUND: Nausea and vomiting during pregnancy (NVP) is considered to be associated with favorable fetal outcomes, such as a decreased risk for spontaneous abortion. However, the relationship between NVP and preterm births remains unknown. This study was conducted to evaluate the association between NVP and the risk of preterm births. METHODS: The dataset of a birth cohort study, the Japan Environment and Children's Study (JECS), was retrospectively reviewed. Participants' experience of NVP prior to 12 gestational weeks were evaluated by a questionnaire administered from 22 weeks of pregnancy to 1 month before delivery. NVP responses were elicited against four choices based on which the study population was divided into four subcohorts. Preterm birth was the main study outcome. Logistic regression analysis was used to quantify an association between NVP and risk of preterm birth. RESULTS: Of 96,056 women, 79,460 (82.7%) experienced some symptoms of NVP and 10,518 (10.9%) experienced severe NVP. Compared to those who did not experience NVP, women with severe NVP had lower odds for preterm birth [adjusted odds ratio (aOR) 0.84, 95% confidence interval (95% CI) 0.74-0.95]. An even lower OR was found among very preterm birth and extremely preterm birth (aOR 0.44, 95% CI 0.29-0.65). CONCLUSION: An inverse association exists between NVP and preterm births, especially, very preterm births and extremely preterm births.

Development of a new screening tool for neuromotor development in children aged two - the neuromotor 5 min exam 2-year-old version (N5E2).

OBJECTIVE: As a new screening tool for neuromotor development in children aged two, we developed the Neuromotor 5 min Exam 2-year-old version (N5E2), which can be easily administered by pediatricians or primary care physicians. In this study, as an initial attempt to examine the utility of the N5E2, the inter-rater reliability on scoring for the individual items in this scale was assessed. METHODS: The participants of the study were 29 children (aged 1-5 years, mean age = 2.79) diagnosed with a variety of neuromotor/developmental disorders/high-risk conditions. Inter-rater reliability was examined on the following 11 items in the N5E2: (1) Retrieving a rolling ball, (2) Gait, (3) Toe-walking, (4) Asymmetries of posture and/or movement, (5) Age at unsupported walking, (6) Speaking in two-word understandable sentences, (7) Hypotonus, (8) Hypertonus, (9) Eye movement, (10) Vision problem, (11) Hearing problem. The items were administered to children by two pediatricians with different expertise and clinical experience, separately. RESULTS: The results showed that among the eleven items in the N5E2 examined, a high level of agreement (κ ≥ 0.60) was found on 4 items, and a moderate level of agreement (0.40 ≤ κ < 0.60) was found on 5 items. The level of agreement somewhat improved after the dichotomization of the score; using this format, a high level of rater agreement (κ ≥ 0.60) was found on 6 out of 11 items. The analyses also revealed high inter-rater reliability on the sum score of the 11 items (r = 0.84). CONCLUSIONS: The results suggest the possibility that this brief screening tool could be feasible in settings where clinicians' experience varies, based on its inter-rater reliability on individual items between the clinicians with different expertise and amount of clinical experiences.

Occupation exposed to road-traffic emissions and respiratory health among Congolese transit workers, particularly bus conductors, in Kinshasa: a cross-sectional study.

OBJECTIVES: Road-traffic emissions (RTE) induce adverse health effects, notably respiratory symptoms and respiratory diseases, as a result of pollutants deposited into the respiratory tract. The aim of this study was to evaluate the association between occupation groups of Congolese transit workers exposed to RTE, particularly bus conductors and respiratory health, in Kinshasa. METHODS: A cross-sectional study was conducted from 2015 April 20th to May 14th, whose participants were bus conductors (n = 110), bus drivers (n = 107), taxi-motorcyclists (n = 102) and high school teachers (control group; n = 106). Subjects had completed the American Thoracic Society respiratory symptom questionnaire. Lung function test was performed by spirometry. Air pollutants levels of PM2.5, NO2 and SO2 were measured between 7:30 and 8:30 and 16:30-17:30 using a portable gas monitor. Multivariate analysis was performed to evaluate the association between occupation exposed to RTE and impaired pulmonary function, after adjustment by plausible confounders. RESULTS: The prevalence of mixed syndrome was 21.9% for bus conductors, 10.9% for bus drivers, 15.4% for taxi-motorcyclists and 7.1% for high school teachers with (p < 0.05). The risk of developing a mixed syndrome was seven times higher among bus conductors [OR = 7.64; 95% CI: 1.83-31.67; p < 0.05] than other groups. Additionally, the prevalence of respiratory syndromes increased with the duration of exposure. CONCLUSIONS: Occupation exposed to RTE is associated with impaired pulmonary function and the prevalence of respiratory symptoms among transit workers, especially bus conductors. Furthermore, this association increases with the duration of exposure suggesting the necessity to regulate these categories of occupations and to apply preventives measures.

Preconception gynecological risk factors of postpartum depression among Japanese women: The Japan Environment and Children's Study (JECS).

BACKGROUND: Postpartum depression is one of the major causes of disability among women who are on their childbearing years. Identifying people at risk of postpartum depression may improve its management. The objective of this study was to determine the probable association between postpartum depression and some preconception gynecological morbidities. METHODS: Data from a nationwide birth cohort study, the Japan Environment and Children's study (JECS), up to one month of postpartum were analyzed. To assess postpartum depression, the Edinburgh Postnatal Depression Scale (EPDS) was used; 11 preconception gynecological morbidities were considered as risk factors. Covariates included psychiatric illness history, psychosocial factors, some pregnancy adverse outcomes, birth outcomes, socio-demographic and health behavioral factors. RESULTS: Except for the prevalence of previous miscarriage, leiomyoma and polycystic ovarian syndrome, depressive women had more gynecological morbidities compared to non-depressive ones. In logistic regression model, endometriosis (OR, 1.27; 95%CI: 1.15-1.41), dysmenorrhea (OR, 1.13; 95%CI: 1.06-1.21) and abnormal uterine bleeding (OR, 1.21; 95%CI: 1.15-1.29) were associated with postpartum depression. LIMITATIONS: CONCLUSION: Women with endometriosis and menstrual problems were at risk of developing postpartum depression. This study suggests a perinatal mental health screening for predisposed women.

Infant Motor Delay and Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations in Japan.

BACKGROUND: Abnormalities of early motor development have been reported in autism spectrum disorder, attention-deficit/hyperactivity disorder, intellectual developmental disorder, developmental coordination disorder, and other Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations (ESSENCE). However, few studies have been conducted with a view to following up a clinically representative cohort of children coming for assessment of motor delay before age two years. We performed a prospective clinical cohort study to examine whether or not early motor delay is often an indication of ESSENCE. METHODS: The sample comprised a one-year cohort of all children who came to a Japanese neurodevelopmental center before their second birthday because of delayed or abnormal gross motor development. The children were followed up from the ESSENCE viewpoint. RESULTS: Of the 30 children, 28 (18 boys and 10 girls) (93%) were given diagnoses subsumed under the ESSENCE umbrella. Of the 15 children with an identified or strongly suspected etiology, 13 (8 boys and 5 girls) (87%) had ESSENCE disorders or symptoms. Of the 15 children without a known etiology, all had ESSENCE disorders or symptoms. CONCLUSION: This study indicated that the vast majority of children with motor delay or abnormality in the first two years of life meet criteria for a disorder within the group of ESSENCE at follow-up; this means that young children, presenting with motor problems always need a broad clinical assessment, not just related to motor function, and systematic follow-up.

Development of automated conjunctival hyperemia analysis software.

Conjunctival hyperemia is observed in a variety of ocular inflammatory conditions. The evaluation of hyperemia is indispensable for the treatment of patients with ocular inflammation. However, the major methods currently available for evaluation are based on nonquantitative and subjective methods. Therefore, we developed novel software to evaluate bulbar hyperemia quantitatively and objectively. First, we investigated whether the histamine-induced hyperemia of guinea pigs could be quantified by image analysis. Bulbar conjunctival images were taken by means of a digital camera, followed by the binarization of the images and the selection of regions of interest (ROIs) for evaluation. The ROIs were evaluated by counting the number of absolute pixel values. Pixel values peaked significantly 1 minute after histamine challenge was performed and were still increased after 5 minutes. Second, we applied the same method to antigen (ovalbumin)-induced hyperemia of sensitized guinea pigs, acquiring similar results except for the substantial upregulation in the first 5 minutes after challenge. Finally, we analyzed human bulbar hyperemia using the new software we developed especially for human usage. The new software allows the automatic calculation of pixel values once the ROIs have been selected. In our clinical trials, the percentage of blood vessel coverage of ROIs was significantly higher in the images of hyperemia caused by allergic conjunctival diseases and hyperemia induced by Bimatoprost, compared with those of healthy volunteers. We propose that this newly developed automated hyperemia analysis software will be an objective clinical tool for the evaluation of ocular hyperemia.