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Background: Despite the positive impact of adhering to the new antenatal care model on pregnancy outcomes and maternal health service uptake, women in resource-limited settings exhibit low levels of compliance with this recommendation. Previous studies on women's adherence to the new antenatal care recommendation have been limited to individual countries, with no evidence available at Sub-Saharan Africa (SSA) level. Therefore, this study sought to investigate compliance with the 2016 WHO's recommendation of at least eight antenatal care contacts among women in SSA countries and identify its determinants., Methods: The study utilized a weighted sample of 101,983 women who had received antenatal care during their index pregnancy, drawn from recent DHS data of sixteen SSA countries. A multilevel mixed-effect analysis was conducted to identify factors that influence compliance with new antenatal care recommendations. Model comparison was performed using deviance and log-likelihood values, and statistical significance was determined at a P-value of less than 0.05., Results: The level of compliance with the recommended antenatal care contacts among women in SSA was 9.9% (95% CI: 9.7-10.1%), with the highest rate in Sierra Leone (26.1%) and lowest in Rwanda (< 1%). A multivariable logistic regression analysis showed that age, education, employment status, household wealth, healthcare decisions, the timing of antenatal contacts, consumption of nutritional supplements, residence, community-level women illiteracy, and media exposure were the significant determinants of compliance., Conclusion: Only one in ten pregnant women in SSA countries had attended the recommended number of antenatal contacts, with Sierra Leone having the highest compliance rate and Rwanda and Senegal having the lowest. Therefore, policymakers should focus on improving access to education, especially for women and their partners, and providing exempted services for pregnant women from low-income households. Interventions that target communities with low levels of literacy and media exposure could also be effective in improving the uptake of the services., (© 2024. The Author(s).)

Despite the ongoing global vaccination campaign aimed at preventing human papillomavirus (HPV) related health issues, the uptake of the HPV vaccine remains unacceptably low in developing regions, particularly in sub-Saharan Africa (SSA). Therefore, this systematic review and meta-analysis aimed at determining the pooled prevalence and associated factors of HPV vaccine uptake among adolescent school girls in SSA. Electronic bio-medical databases were explored. Pooled prevalence, publication bias, meta-regression, sub-group, and sensitivity analysis were performed. The estimated pooled prevalence of HPV vaccine uptake was 28.53% [95% CI: (5.25, 51.81)]. Having good knowledge and a positive attitude was significantly associated with HPV vaccine uptake in SSA. Subgroup analysis revealed the highest uptake was 62.52% from Kenya and the lowest was 3.77% in Nigeria. The HPV vaccine uptake is low. It underscores the need for community education, school-based immunization, and education programs that promote the uptake of the vaccine to increase coverage.

Background: Human Immunodeficiency Virus (HIV) is a global health concern, causing over 35 million deaths, with 97% occurring in developing nations, particularly impacting Sub-Saharan Africa. While HIV testing is crucial for early treatment and prevention, existing research often focuses on specific groups, neglecting general adult testing rates. This study aims to identify predictors of HIV testing uptake among adults in Sub-Saharan Africa., Method: Data were obtained from the official Demographic and Health Survey program database, which used a multistage cluster sampling technique to collect the survey data. In this study, a weighted sample of 283,936 adults was included from thirteen Sub-Saharan African countries. Multilevel multivariable logistic regression analysis was employed to identify predictors of HIV testing uptake. Akaike's information criteria guided model selection. Adjusted odds ratios and corresponding 95% confidence intervals determined significant predictor variables., Result: Among adults in Sub-Saharan African countries, the prevalence of HIV testing uptake was 65.01% [95% CI (64.84%, 65.17%)]. Influential factors included male sex [AOR: 0.51, 95% CI (0.49,0.53)], varying odds ratios across age groups (20-24 [AOR: 3.3, 95% CI (3.21, 3.46) ], 25-29 [AOR: 4.4, 95% CI (4.23, 4.65)], 30-34 [AOR: 4.6, 95%CI (4.40, 4.87)], 35-39 [AOR: 4.0, 95%CI (3.82, 4.24)], 40-44 [AOR: 3.7, 95%CI (3.50, 3.91)], 45-49 [AOR: 2.7, 95%CI (2.55, 2.87)], 50+ [AOR: 2.7, 95%CI (2.50, 2.92)]), marital status (married [AOR: 3.3, 95%CI (3.16, 3.46)], cohabiting [AOR: 3.1, 95% CI (2.91, 3.28)], widowed/separated/divorced [AOR: 3.4, 95%CI (3.22, 3.63)]), female household headship (AOR: 1.28, 95%CI (1.24, 1.33)), education levels (primary [AOR: 3.9, 95%CI (3.72, 4.07)], secondary [AOR: 5.4, 95%CI (5.16, 5.74)], higher [AOR: 8.0, 95%CI (7.27, 8.71)]), media exposure (AOR: 1.4, 95%CI (1.32, 1.43)), wealth index (middle [AOR: 1.20, 95%CI (1.17, 1.27)], richer [AOR: 1.50, 95%CI (1.45, 1.62)]), Having discriminatory attitudes towards PLWHIV [AOR: 0.4; 95% CI (0.33, 0.37)], had multiple sexual partners [AOR: 1.2; 95% CI (1.11, 1.28)], had comprehensive knowledge about HIV [AOR: 1.6; 95% CI (1.55, 1.67)], rural residence (AOR: 1.4, 95%CI (1.28, 1.45)), and lower community illiteracy (AOR: 1.4, 95%CI (1.31, 1.50)) significantly influenced HIV testing uptake in the region., Conclusion: This study highlights the need for tailored interventions to address disparities in HIV testing uptake among adults in Sub-Saharan Africa and progress towards the achievement of 95-95-95 targets by 2030. Thus, tailored interventions addressing key factors are crucial for enhancing testing accessibility and emphasizing awareness campaigns, easy service access, and targeted education efforts to improve early diagnosis, treatment, and HIV prevention in the region., (© 2024. The Author(s).)

Background: Breastfeeding offers numerous benefits for infants, mothers, and the community, making it the best intervention for reducing infant mortality and morbidity. The World Health Organization (WHO) recommends initiating breastfeeding within one hour after birth and exclusively breastfeeding for the first six months. This study investigated the trend, spatio-temporal variation, and determinants of spatial clustering of early initiation of breastfeeding (EIBF) and exclusive breastfeeding (EBF) in Ethiopia from 2011 to 2019., Methods: Data from the Ethiopian Demographic and Health Survey (EDHS), which was conducted in 2011, 2016, and 2019, were analyzed utilizing a weighted sample of 10,616 children aged 0-23 years for EIBF and 2,881 children aged 0-5 months for EBF. Spatial autocorrelation analysis was used to measure whether EIBF and EBF were dispersed, clustered, or randomly distributed and Kriging interpolation was employed to predict the outcome variables in the unmeasured areas. Spatial scan statistics were used to identify spatial clusters with a high prevalence of cases. Both global and local regression modeling techniques were employed to examine the spatial relationships between the explanatory variables and the dependent variables., Results: The trend analysis revealed a notable increase in the prevalence of EIBF from 51.8% in 2011 to 71.9% in 2019. Similarly, the prevalence of EBF increased from 52.7% in 2011 to 58.9% in 2019. Spatial analysis demonstrated significant spatial variation in both EIBF and EBF throughout the country. Cold spots or clusters with a low prevalence of EIBF were observed consistently in the Tigray and Amhara regions, and significant cold spot areas of EBF were observed consistently in the Afar and Somali regions. Multiscale geographically weighted regression analysis revealed significant predictors of spatial variations in EIBF, including the religious affiliation of being a follower of the orthodox religion, parity of 1-2, absence of antenatal care visits, and delivery via cesarean section., Conclusions: Despite the increase in both EIBF and EBF rates over time in Ethiopia, these rates still fall below the national target. To address this issue, the government should prioritize public health programs aimed at improving maternal healthcare service utilization and maternal education. It is essential to integrate facility-level services with community-level services to achieve optimal breastfeeding practices. Specifically, efforts should be made to promote breastfeeding among mothers who have delivered via cesarean section. Additionally, there should be a focus on encouraging antenatal care service utilization and adapting maternal healthcare services to accommodate the mobile lifestyle of pastoralist communities. These steps will contribute to enhancing breastfeeding practices and achieving better outcomes for maternal and child health., (© 2024. The Author(s).)

Background: Despite various interventions to combat child malnutrition in sub-Saharan Africa, wasting remains a critical public health concern for children aged 6-59 months. Wasting is a significant predictor of child survival and development, with a heightened risk of mortality among children. However, there is a lack of recent comprehensive data on the prevalence, severity level, and factors contributing to wasting in this age group., Objective: To identify the severity levels of wasting and its individual and community-level factors contributing to wasting among children aged 6-59 months in Sub-Saharan African countries., Methods: This research utilized Demographic and Health Survey data from 34 Sub-Saharan African countries, spanning the period from 2007 to 2022. The study included a weighted sample of 180,317 6-59-month-old children. We employed a multilevel proportional odds model to identify factors predicting the severity of wasting. Adjusted odds ratios and 95% confidence intervals were reported to demonstrate significant relationships ( p  < 0.05) in the final model., Results: In Sub-Saharan Africa, 7.09% of children aged 6-59 months experience wasting (95% CI: 6.97, 7.20%). Among these children, the prevalence of moderate wasting is 4.97% (95% CI: 4.90, 5.10%), while severe wasting affects 2.12% (95% CI: 2.0, 2.20%). Factors such as term/post-term babies, wealth, frequency of feeding, improved toilet facilities, water sources, employed and educated mothers, rural residence, high community maternal education, and community media exposure are strongly associated with a lower chance of experiencing severe form of wasting. Conversely, birth order, family size, breastfeeding, diarrhea, cough, and fever, high community poverty, female household heads, and all Sub-Saharan Africa regions are linked to higher levels of wasting., Conclusion: The study findings underscore the persistent challenge of wasting among Sub-Saharan Africa's children, with 7.09% affected, of which 4.97% experience moderate wasting and 2.12% severe wasting. The identified predictors of wasting highlight the complex interplay of socio-economic, environmental, and health-related determinants. To address this issue improve access to healthcare and nutrition services, enhance sanitation infrastructure, promote women's empowerment, and implement community-based education programs. Additionally, prioritize early detection through routine screening and strengthen health systems' capacity to provide timely interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Asebe, Asmare, Mare, Kase, Tebeje, Asgedom, Hailu Shibeshi, Lombebo, Sabo, Fente, Bezie and Seifu.)

Background: Anemia is the most common hematologic disorder of children worldwide. Since dietary diversity is a main requirement of children is to get all the essential nutrients, it can thus use as one of the basic indicator when assessing the child's anemia. Although dietary diversity plays a major role in anemia among children in sub-Saharan Africa, there is little evidence of an association between the dietary diversity and anemia level to identified potential strategies for prevention of anemia level in sub-Saharan Africa., Objective: To examine the association between dietary diversity and anemia levels among children aged 6-23 months in sub-Saharan Africa., Methods: The most recent Demographic and Health Surveys from 32 countries in SSA were considered for this study, which used pooled data from those surveys. In this study, a total weighted sample of 52,180 children aged 6-23 months was included. The diversity of the diet given to children was assessed using the minimum dietary diversity (MDD), which considers only four of the seven food groups. A multilevel ordinal logistic regression model was applied due to the DHS data's hierarchical structure and the ordinal nature of anemia. With a p-value of 0.08, the Brant test found that the proportional odds assumption was satisfied. In addition, model comparisons were done using deviance. In the bi-variable analysis, variables having a p-value ≤0.2 were taken into account for multivariable analysis. The Adjusted Odds Ratio (AOR) with 95% Confidence Interval (CI) was presented for potential determinants of levels of anemia in the multivariable multilevel proportional odds model., Results: The overall prevalence of minimum dietary diversity and anemia among children aged 6-23 months were 43% [95% CI: 42.6%, 43.4%] and 72.0% [95% CI: 70.9%, 72.9%] respectively. Of which, 26.2% had mild anemia, 43.4% had moderate anemia, and 2.4% had severe anemia. MDD, being female child, being 18-23 months age, born from mothers aged ≥25, taking drugs for the intestinal parasite, higher level of maternal education, number of ANC visits, middle and richer household wealth status, distance of health facility and being born in Central and Southern Africa were significantly associated with the lower odds of levels of anemia. Contrarily, being 9-11- and 12-17-months age, size of child, having fever and diarrhea in the last two weeks, higher birth order, stunting, wasting, and underweight and being in West Africa were significantly associated with higher odds of levels of anemia., Conclusion: Anemia was a significant public health issue among children aged 6-23 months in sub-Saharan Africa. Minimum dietary diversity intake is associated with reduced anemia in children aged 6 to 23 months in sub-Saharan Africa. Children should be fed a variety of foods to improve their anemia status. Reducing anemia in children aged 6-23 months can be achieved by raising mother education levels, treating febrile illnesses, and improve the family's financial situation. Finally, iron fortification or vitamin supplementation could help to better reduce the risk of anemia and raise children's hemoglobin levels in order to treat anemia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shibeshi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Even though childhood diarrhea is treated with a simple treatment solution, it continues to be one of the leading causes of under-five child mortality and malnutrition globally. In resource-limited settings such as Sub-Saharan Africa (SSA), the combination of oral rehydration salts (ORS) and zinc is regarded as an effective treatment for diarrhea; however, its utilization is very low. The purpose of this study was to determine the proportion and associated factors of co-utilization of ORS and zinc among under-five children with diarrhea in SSA., Methods: The proportion and associated factors of co-utilization of ORS and zinc among under-five children with diarrhea in SSA were determined using secondary data analysis of recent Demographic and Health Surveys (DHS) of 35 SSA countries. The study included a total of 44,341 under-five children with diarrhea in weighted samples. A generalized linear mixed-effects model with robust error variance was used. For the variables included in the final model, adjusted prevalence ratios (aPR) with 95% confidence intervals (CI) were estimated. A model with the lowest deviance value were considered as the best-fitted model., Result: The pooled proportion of co-utilization of ORS and zinc for the treatment of diarrhea among under five children in SSA countries was 43.58% with a 95% CI (43.15%, 44.01%). Sex of the child, maternal age, residence, maternal educational and employment status, wealth index, media exposure, perceived distance to health facility and insurance coverage were statistically significant determinants of ORS and Zinc co-utilization for treating diarrhea among under five children in SSA., Conclusion: Only less than half of under-five children with diarrhea in SSA were treated with a combination of ORS and zinc. Thus, strengthening information dissemination through mass media, and community-level health education programs are important to scale up the utilization of the recommended combination treatment. Furthermore, increasing health insurance coverage, and establishing strategies to address the community with difficulty in accessing health facilities is also crucial in improving the use of the treatment., (© 2024. The Author(s).)

Background: Stunting poses a significant health risk to adolescent girls aged 15-19 in low- and middle-income countries, leading to lower education levels, reduced productivity, increased disease vulnerability, and intergenerational malnutrition. Despite the inclusion of adolescent nutrition services in the Sustainable Development Goals, little progress has been made in addressing malnutrition among adolescent girls in several African nations. Limited evidence exists in East Africa due to small sample sizes and methodological limitations. To overcome these constraints, this study utilizes the latest Demographic and Health Survey data to estimate the prevalence and factors influencing stunting among late adolescent girls in ten East African countries., Methods: This study utilized the most recent Demographic and Health Survey (DHS) data from 10 East African countries, including a total sample weight of 22,504 late-adolescent girls. A multilevel mixed-effect binary logistic regression model with cluster-level random effects was employed to identify factors associated with stunting among these girls. The odds ratio, along with the 95% confidence interval, was calculated to determine individual and community-level factors related to stunting. A p-value less than 0.05 was considered statistically significant in determining the factors influencing stunting among late-adolescent girls., Results: The prevalence of stunting among late adolescent girls in East Africa was found to be 13.90% (95% CI: 0.13-0.14). Religion, relationship to the head, presence of under-five children in the household, lactating adolescent, marital status, Time to get water source, and country of residence were significantly associated with Stunting., Conclusion: This study highlights the complexity of stunting in East Africa and identifies key factors that need attention to reduce its prevalence. Interventions should focus on improving water access, supporting lactating girls, addressing socioeconomic disparities, promoting optimal care practices, and implementing country-specific interventions to combat stunting and improve adolescent girls' nutrition., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Asebe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Stunting is a major public health problem affecting more than one-third of under five year's old children in Ethiopia. It has short and long (irreversible) consequences, including stunted growth, never reaching physical and cognitive potential, struggles in school, and increased morbidity and mortality due to infections. Though stunting is the leading cause of child mortality in Ethiopia, evidence is scarce on the prevalence and predictors of stunting among under-five years old children in Ethiopia. Therefore, this study aimed to estimate the prevalence and predictors of stunting severity among under-5 children in Ethiopia., Materials and Methods: This study was based on 2019 Mini-Ethiopian Demographic and Health Survey (EDHS) data. A weighted total sample of 4972 under-five years old children was included in the study. Height measurement was collected for each child. Anthropometric indicator, height-for-age was determined for children using World Health Organization growth standards (Z-scores for Height-for-Age (HAZ)) to asses stunting level. Given the ordinal nature of stunting and the hierarchical nature of EDHS data, a multilevel ordinal logistic regression model was applied. Brant test was used to check the proportional odds assumption, which was satisfied (P-value ≥0.05). Moreover, deviance was used for model comparison. For the multivariable analysis, variables with a p-value ≤0.2 in the bivariable analysis were considered. The Adjusted Odds Ratio (AOR) with 95% Confidence Interval (CI) was reported as associated factor to the severity levels of stunting in the multivariable multilevel proportional odds model., Results: The overall prevalence of stunting among under-5 children in Ethiopia was 35.7% [95% CI: 34.4%, 37.1%]. Of these, 12.1% were severely stunted, and 24.9% were moderately stunted. Being male [AOR = 0.83, 95% CI: 0.74, 0.93], children aged 6-23 months [AOR = 2.38, 95% CI: 1.84, 3.07], ≥ 24 months [AOR = 4.15, 95% CI: 3.26, 5.28], children whose maternal age 15-24 years [AOR = 0.73, 95% CI: 0.58, 0.92], children from the poorest, poorer, middle, and richer household wealth were [AOR = 1.84, 95% CI: 1.32, 2.57], [AOR = 1.66, 95% CI: 1.20, 2.31], [AOR = 1.78, 95% CI: 1.29, 2.44], and [AOR = 1.62, 95% CI: 1.20, 2.17], children whose maternal educational status of no formal education and primary education had [AOR = 1.90, 95% CI: 1.28, 2.82], [AOR = 1.78, 95% CI: 1.22, 2.60], Tigray [AOR = 2.95, 95% CI: 1.78, 4.86], Afar [AOR = 1.85, 95% CI: 1.11, 3.10], Amhara [AOR = 1.90, 95% CI: 1.14, 3.14] and Harari [AOR = 1.97, 95% CI: 1.20, 3.25]regions, low community maternal education [AOR = 0.76, 95% CI: 0.62, 0.92] were significantly associated with stunting severity levelling., Conclusion: Stunting among children under five years of old in Ethiopia remains a major public health issue. Improving access to maternal education is related to appropriate child feeding practices and health, particularly in younger and uneducated mothers. Strengthening the family's wealth status is also recommended to reduce stunting. In addition, it is better to support strategies of preconception care for mothers during pregnancy to reduce stunting in the long term., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Asgedom et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Women's high-risk fertility behavior (HRFB), which is characterized by narrow birth intervals, high birth order, and younger maternal age at birth, have been scientifically reported to have detrimental effects on the mother and child's health. To date, there has been limited research into the underlying factors contributing to high-risk fertility behavior in Kenya. Thus, the aim of this study is to identify the factors associated with high-risk fertility behavior among women of reproductive age in Kenya., Method: The 2022 Kenyan Demography and Health Survey data was used for the current study. This study included 15,483 women of reproductive age. To account for the clustering effects of DHS data and the binary nature of the outcome variable, a multilevel binary logistic regression model was applied. An adjusted odds ratio with a 95% confidence interval was reported to declare the statistical significance. In addition, the model that had the lowest deviance was the one that best fit the data., Results: The overall prevalence of HRFB among Kenyan women were 70.86% (95%CI = 69.96, 71.40). Women with primary, secondary, and higher educational levels, Protestant and Muslim religion followers, women whose husbands/partners had secondary and higher educational levels, a high household wealth index, ever had a terminated pregnancy, and rural residence, all of these factors were found to be strongly associated with high-risk fertility behavior., Conclusion: As per the findings of our study, in Kenya a significant proportion of women has experienced HRFB. This is a matter of concern as it poses a significant challenge to the healthcare system. The high prevalence of HRFB indicates that there is an urgent need to take appropriate measures in order to mitigate its impact. The situation calls for a comprehensive and coordinated approach involving all stakeholders to address this issue effectively. It would benefit policymakers to create programs that consider factors like education, wealth, and residence that make women more susceptible to HRFB. Targeting women living in high HRFB-prevalence areas could help address the root causes of the issue. This approach can alleviate negative impacts and ensure effective and sustainable solutions., (© 2023. The Author(s).)

Background: Despite the implementation of different nutritional and non-nutritional interventions, 43% of reproductive-age women in Africa suffer from anemia. Recent evidence also shows that none of the Sub-Saharan African (SSA) countries are on the track to achieve the nutrition target of 50% anemia reduction by 2030. To date, information on the level of anemia and its determinants among reproductive-age women at the SSA level is limited. Thus, this study aimed to estimate the pooled prevalence of anemia level and its determinants in SSA countries., Methods: We used a pooled data of 205,627 reproductive-age women from the recent demographic and health surveys of 29 SSA countries that were conducted between 2010-2021. A multilevel mixed-effects analysis with an ordered logistic regression model was fitted to identify determinants of anemia level and the deviance value was used to select the best-fitted model. First, bivariable ordinal logistic regression analysis was done and the proportional odds assumption was checked for each explanatory variable using a Brant test. Finally, in a multivariable multilevel ordinal logistic regression model, a p-value<0.05 and AOR with the corresponding 95% CI were used to identify determinants of anemia level. All analyses were done using Stata version 17 software., Results: The pooled prevalence of anemia among women of reproductive age in SSA was 40.5% [95% CI = 40.2%-40.7%], where 24.8% [95% CI: 24.6%-25.0%], 11.1% [95% CI = 10.9%-11.2%], and 0.8% [95% CI = 0.7%-0.8%] had mild, moderate, and severe anemia, respectively. The prevalence significantly varied from the lowest of 13% in Rwanda to the highest of 62% in Mali, and anemia was found as a severe public health problem (prevalence of ≥ 40%) in 18 countries. The regression result revealed that polygamous marriage, women and husband illiteracy, poor household wealth, shorter birth interval, non-attendance of antenatal care, underweight, unimproved toilet and water facilities, and low community-level women literacy were positively linked with high anemia level. Additionally, the likelihood of anemia was lower in women who were overweight and used modern contraception., Conclusions: Overall results showed that anemia among women of reproductive age is a severe public health problem in SSA countries, affecting more than four in ten women. Thus, enhancing access to maternal health services (antenatal care and contraception) and improved sanitation facilities would supplement the existing interventions targeted to reduce anemia. Moreover, strengthening women's education and policies regulating the prohibition of polygamous marriage are important to address the operational constraints., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mare et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Trachoma is the chief cause of preventable blindness worldwide and has been earmarked for elimination as a public health problem by 2030. Despite the five-year Surgery, Antibiotics, Facial cleanliness, and Environmental improvement (SAFE)-based interventions in the Andabet district, the prevalence of trachomatous follicular (TF) was 37%. With such a high prevalence of TF, the determinant factors were not revealed. Besides, there were no reports on the overall prevalence of active trachoma (i.e.TF and or trachomatous intense (TI))., Objective: To determine the prevalence and associated factors of active trachoma among 1-9 years of age children in the Andabet district., Method: A community-based cross-sectional study was conducted among children aged under nine years from March 1-30, 2023 in Andabet district, Northwest Ethiopia. Multi-stage systematic random sampling was employed to reach 540 children. A multilevel mixed-effect logistic regression analysis was employed to assess factors associated with active trachoma. We fitted both random effect and fixed effect analysis. Finally, variables with p<0.05 in the multivariable multilevel analysis were claimed to be significantly associated with active trachoma., Result: In this study, the overall prevalence of active trachoma was 35.37% (95% CI: 31.32%, 39.41%). The prevalence of TF and TI was 31.3% and 4.07% respectively. In the multilevel logistic regression analysis ocular discharge, fly-eye contact, latrine utilization, and source of water were significantly associated with the prevalence of active trachoma., Conclusion: In this study, the prevalence of active trachoma was much higher than the World Health Organization (WHO) threshold prevalence. Ocular discharge, fly-eye contact, latrine utilization, and source of water were independent determinants of active trachoma among children (1-9 years). Therefore, paying special attention to these high-risk groups could decrease the prevalence of a neglected hyperendemic disease, active trachoma., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Asmare et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The risks of developing energy or nutrient deficits are of great concern in infants and children with the rare lymphoedema cholestasis syndrome 1 (LCS1)/Aagenaes syndrome. In adolescents and adults, it is not known whether LCS1 patients need specific dietary advice outside periods of cholestasis. The primary objective of the present study was to evaluate the progression of the liver disease and nutritional status in patients with LCS1 over a period of nine years. Dietary and biochemical data were obtained for patients and healthy controls in two cross-sectional studies, a baseline (2000) and a follow-up study (2009). Thirteen patients above 18 years of age with LCS1 (65%) were included (six females). Dietary intake and biochemical measures were stable in the patients from baseline until follow-up. Compared to healthy controls, the patients had significantly higher serum levels of alkaline phosphatase (p = .015 and p = .002), gamma-glutamyltransferase (p = .001 and p < .001), total bile acids (p = .037 and p = .016), and fibrinogen (p = .046 and p < .001) and lower albumin (p = .033 and p < .001) and α-tocopherol (p = .011 and p = .003) at baseline and follow-up. Despite stable liver function, the presence of a low grade of hepatobiliary dysfunction in these patients was suggested. Patients with LCS1 had a nutritional status similar to healthy controls, with no clinical deterioration of liver function during the nine-year period. The findings presented in this paper support that more than 50% of patients with LCS1 can expect a normal lifespan.

Background: The characterizations of primary lymphedemas in different hereditary diseases are often published as case reports. In this study, 17 out of 20 Norweigian adult patients with lymphedema cholestasis syndrome 1 (LCS1)/Aagenaes syndrome were examined. The patients exhibited lymphedema and sporadic cholestasis. Individual clinical variations are described., Methods and Results: Lymphedema was classified from Grade I to IV by clinical examinations and ultrasound B-mode scanning. To support the clinical findings, direct segmental multifrequency bioelectrical impedance analysis (DSM-BIA) was included and was compared to healthy matched controls. The lymphedema was similar to other hereditary lymphedemas, with more pronounced fluid retention in the lower extremities. It was generally more extensive, as it also included lymphedema in the arms, face, and trunk. Limited tissue fibrosis was observed, even after long-standing lymphedema., Conclusions: Approximately one-third of the patients had severe forms of lymphedema in the limbs (grades III and IV) and their conditions required close followup. A more frequent use of compression in the upper extremities is advised.

Background: The main treatment for phenylketonuria (PKU) is a low phenylalanine (Phe) diet, phenylalanine-free protein substitute and low-protein special foods. This study describes dietary composition and nutritional status in late-diagnosed adult patients adhering to a PKU diet., Methods: Nineteen patients, followed at Oslo University Hospital in Norway, participated; median age was 48 years (range 26-66). Subjects were mild to severely mentally retarded. Food intake, clinical data and blood analyses relevant for nutritional status were assessed., Results: Median energy intake was 2,091 kcal/day (range 1,537-3,277 kcal/day). Carbohydrates constituted 59% (range 53-70%) of the total energy, including 15% from added sugar; 26% was from fat. The total protein intake was 1.02 g/kg/day (range 0.32-1.36 g/kg/day), including 0.74 g/kg/day (range 0.13-1.07 g/kg/day) from protein substitutes. Median dietary Phe intake was 746 mg/day (range 370-1,370 mg/day). Median serum Phe was 542 μmol/L (range 146-1,310 mg/day). Fortified protein substitutes supplied the main source of micronutrients. Iron intake was 39.5 mg/day (range 24.6-57 mg/day), exceeding the upper safe intake level. Intake of folate and folic acid, calculated as dietary folate equivalents, was 1,370 μg/day (range 347-1744 μg/day), and resulted in high blood folate concentrations. Median intake of vitamin B(12) was 7.0 μg/day (range 0.9-15.1 μg/day)., Conclusions: The diet supplied adequate protein and energy. Fortification of the protein substitutes resulted in excess intake of micronutrients. The protein substitutes may require adjustment to meet nutritional recommendations for adults with PKU.

Background: We have studied the significance of the thyroxine treatment for neuropsychological functioning in young adults with congenital hypothyroidism., Subjects and Methods: This is a neuropsychological follow-up study of a three-year cohort of early treated congenital hypothyroidism in Norway (N = 49) at age 20. Siblings comprise the control group (N = 41, 21 years)., Results: The patient group performed weaker than the control group on cognitive and motor measures. They reported somewhat more psychosocial problems; fewer completed high school. A more severe hypothyroidism at the time of diagnosis was associated with a larger motor deficit at age 20. Better cognitive function in young adulthood was associated with a higher thyroxine starting dose and serum thyroxine level in the first years of life. Blood samples in young adulthood showed elevated thyrotropin levels in 45% of the patients., Interpretation: This study supports the new guidelines for treatment of congenital hypothyroidism with a higher starting dose of 10-15 microg thyroxine/kg/24 hours. The young adults are in need of better medical follow up.

Unlabelled: From the second year of life a girl showed an insidious development of clinical hypothyroidism due to a non-goitrous lymphocytic thyroiditis without traceable circulating levels of thyroid antibodies measured by routine immunoassays. The diagnostic delay of this rare variant of atrophic thyroiditis caused persistent neuropsychological deficits., Conclusion: Her difficulties with speed of processing and working memory in particular could suggest a frontal deficit, possibly in the dorsolateral prefrontal circuit. This contrasts with findings in congenital hypothyroidism, suggesting a relatively preserved frontal function, and could illustrate different neuropsychological deficits of hypothyroidism at different ages in early childhood.

Background: In congenital hypothyroidism (CH) it has been questioned whether high dose thyroxine replacement therapy has detrimental effects on memory, attention, and behaviour., Aims: To describe memory, attention, and behaviour problems in young adults with CH, and to study possible negative effects of high dose thyroxine replacement therapy., Methods: A cohort based follow up study of 49 young adults (mean age 20 years) with early treated CH, and sibling controls (n = 41)., Results: Controlled for age and sex, the CH group attained significantly lower scores than sibling controls on some tests of memory (Wechsler Logical Memory part II: 12.9 versus 17.8; difference 5.2, 95% CI 3.6 to 6.8) and attention (Wechsler Freedom From Distractibility factor: 95.6 versus 104.8; difference 9.9, 95% CI 6.4 to 13.4). They rated themselves with more behaviour problems than did sibling controls (52.7 versus 44.7; difference -7.6, 95% CI -11.2 to -4.0) on the Achenbach Self Report. A high thyroxine starting dose, high serum thyroxine treatment levels during the first six childhood years, and high levels at assessment had no adverse effects on outcome measures at age 20. On the contrary, the results suggest better outcome with higher childhood treatment levels., Conclusions: Long term outcome revealed deficits in some aspects of memory, attention, and behaviour in young adults with CH relative to sibling controls. No adverse effects of high dose thyroxine therapy were found on measures of memory, attention, and behaviour problems.

Background: Newborn screening for total homocysteine (tHcy) in blood may identify babies with vitamin B12 (B12) deficiency or homocystinuria, but data on the causes of increased tHcy in screening samples are sparse., Methods: Serum concentrations of tHcy, cystathionine, methionine, folate, and B12 and the methylenetetrahydrofolate reductase (MTHFR) 677C > T polymorphism were determined in 4992 capillary blood samples collected as part of the routine screening program in newborn children. Methylmalonic acid (MMA), gender (SRY genotyping), and the frequency of six cystathionine beta-synthase (CBS) mutations were determined in 20-27% of the samples, including all samples with tHcy > 15 micromol/L (n = 127), B12 < 100 pmol/L (n = 159), or methionine > 40 micromol/L (n = 154)., Results: The median (5th-95th percentile) tHcy concentration was 6.8 (4.2-12.8) micromol/L. B12 status, as determined by serum concentrations of B12, tHcy, and MMA, was moderately better in boys than in girls. tHcy concentrations between 10 and 20 micromol/L were often associated with low B12, whereas tHcy > 20 micromol/L (n = 43) was nearly always explained by increased methionine. tHcy did not differ according to folate concentrations or MTHFR 677C > T genotypes. None of the babies had definite CBS deficiencies, but heterozygosity led to low cystathionine, increased methionine, but normal tHcy concentrations., Conclusion: Increased tHcy is a common but not specific finding in newborns. The metabolite and vitamin profiles will point to the cause of hyperhomocysteinemia. Screening for tHcy and related factors should be further evaluated in regions with high prevalence of homocystinuria and in babies at high risk of B12 deficiency.

In human liver, unconjugated bile acids can be formed by the action of bile acid-CoA thioesterases (BACTEs), whereas bile acid conjugation with taurine or glycine (amidation) is catalyzed by bile acid-CoA:amino acid N-acyltransferases (BACATs). Both pathways exist in peroxisomes and cytosol. Bile acid amidation facilitates biliary excretion, whereas the accumulation of unconjugated bile acids may become hepatotoxic. We hypothesized that the formation of unconjugated and conjugated bile acids from their common substrate bile acid-CoA thioesters by BACTE and BACAT is regulated via the peroxisome proliferator-activated receptor alpha (PPARalpha). Livers from wild-type and PPARalpha-null mice either untreated or treated with the PPARalpha activator WY-14,643 were analyzed for BACTE and BACAT expression. The total liver capacity of taurochenodeoxycholate and taurocholate formation was decreased in WY-14,643-treated wild-type mice by 60% and 40%, respectively, but not in PPARalpha-null mice. Suppression of the peroxisomal BACAT activity was responsible for the decrease in liver capacity, whereas cytosolic BACAT activity was essentially unchanged by the treatment. In both cytosol and peroxisomes, the BACTE activities and protein levels were upregulated 5- to 10-fold by the treatment. These effects caused by WY-14,643 treatment were abolished in PPARalpha-null mice. The results from this study suggest that an increased formation of unconjugated bile acids occurs during PPARalpha activation.

Serious complications of homocystinuria caused by cystathionine beta-synthase deficiency can be prevented by early intervention. We determined the prevalence of 6 specific mutations in 1133 newborn blood samples. Our results suggest that homocystinuria is more common than previously reported. Newborn screening for homocystinuria through mutation detection should be further considered.

Objective: To describe intellectual, motor, and school-associated outcome in young adults with early treated congenital hypothyroidism (CH) and to study the association between long-term outcome and CH variables acting at different points in time during early development (CH severity and early L-thyroxine treatment levels [0-6 years])., Methods: Neuropsychological tests were administered to all 49 subjects with CH identified during the first 3 years of the Norwegian neonatal screening program (1979-1981) at a mean age of 20 years and to 41 sibling control subjects (mean age: 21 years)., Results: The CH group attained significantly lower scores than control subjects on intellectual, motor, and school-associated tests (total IQ: 102.4 [standard deviation: 13] vs 111.4 [standard deviation: 13]). Twelve (24%) of the 49 CH subjects had not completed senior high school, in contrast to 6% of the control subjects. CH severity (pretreatment serum thyroxine [T4]) correlated primarily with motor tests, whereas early L-thyroxine treatment levels were related to verbal IQ and school-associated tests. In multiple regression analysis, initial L-thyroxine dose (beta = 0.32) and mean serum T4 level during the second year (beta = 0.48) predicted Verbal IQ, whereas mean serum T4 level during the second year (beta = 0.44) predicted Arithmetic., Conclusions: Long-term outcome revealed enduring cognitive and motor deficits in young adults with CH relative to control subjects. Verbal functions and Arithmetic were associated with L-thyroxine treatment variables, suggesting that more optimal treatment might be possible. Motor outcome was associated with CH severity, indicating a prenatal effect.

Peroxisomes function in beta-oxidation of very long and long-chain fatty acids, dicarboxylic fatty acids, bile acid intermediates, prostaglandins, leukotrienes, thromboxanes, pristanic acid, and xenobiotic carboxylic acids. These lipids are mainly chain-shortened for excretion as the carboxylic acids or transported to mitochondria for further metabolism. Several of these carboxylic acids are slowly oxidized and may therefore sequester coenzyme A (CoASH). To prevent CoASH sequestration and to facilitate excretion of chain-shortened carboxylic acids, acyl-CoA thioesterases, which catalyze the hydrolysis of acyl-CoAs to the free acid and CoASH, may play important roles. Here we have cloned and characterized a peroxisomal acyl-CoA thioesterase from mouse, named PTE-2 (peroxisomal acyl-CoA thioesterase 2). PTE-2 is ubiquitously expressed and induced at mRNA level by treatment with the peroxisome proliferator WY-14,643 and fasting. Induction seen by these treatments was dependent on the peroxisome proliferator-activated receptor alpha. Recombinant PTE-2 showed a broad chain length specificity with acyl-CoAs from short- and medium-, to long-chain acyl-CoAs, and other substrates including trihydroxycoprostanoyl-CoA, hydroxymethylglutaryl-CoA, and branched chain acyl-CoAs, all of which are present in peroxisomes. Highest activities were found with the CoA esters of primary bile acids choloyl-CoA and chenodeoxycholoyl-CoA as substrates. PTE-2 activity is inhibited by free CoASH, suggesting that intraperoxisomal free CoASH levels regulate the activity of this enzyme. The acyl-CoA specificity of recombinant PTE-2 closely resembles that of purified mouse liver peroxisomes, suggesting that PTE-2 is the major acyl-CoA thioesterase in peroxisomes. Addition of recombinant PTE-2 to incubations containing isolated mouse liver peroxisomes strongly inhibited bile acid-CoA:amino acid N-acyltransferase activity, suggesting that this thioesterase can interfere with CoASH-dependent pathways. We propose that PTE-2 functions as a key regulator of peroxisomal lipid metabolism.

Background: There is a need for systematic evaluation of methods before their release to the market. We addressed this problem in novel homocysteine assays as part of an European Demonstration Project involving six centers in four countries., Methods: Two immunological methods for measurement of plasma total homocysteine (P-tHcy), the fluorescence polarization immunoassay (FPIA) and the enzyme immunoassay (EIA), were compared with two comparison methods, HPLC and gas chromatography-mass spectrometry (GC-MS). All laboratories performed the following procedures: (a) familiarization; (b) determination of linearity and precision by analyzing five plasma samples with interrelated concentrations for 20 days; (c) correlation using patients' samples; and (d) assessment of long-term performance., Results: Both immunological methods were linear for P-tHcy between 5 and 45 micromol/L. The intralaboratory imprecision (CV) was <5% for FPIA and <9% for EIA used with a sample processor. The bias was -2% to 3% for FPIA and 2-4% for EIA used with a sample processor., Conclusions: The immunological methods provide results with little bias compared with HPLC and GC-MS. The imprecision of the assays must be considered in the context of their intended use(s).

To extend our knowledge of how the synthesis of free bile acids and bile salts is regulated within the hepatocyte, bile acid-CoA:amino acid N-acyltransferase and bile acid-CoA thioesterase activities were measured in subcellular fractions of human liver homogenates. Some bile acids, both conjugated and unconjugated, have been reported to be natural ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. The conversion of [(14)C]choloyl-CoA and [(14)C]chenodeoxycholoyl-CoA into the corresponding tauro- and glyco-bile acids or the free bile acids was measured after high-pressure liquid radiochromatography. There was an enrichment of the N-acyltransferase in the cytosolic and the peroxisomal fraction. Bile acid-CoA thioesterase activities were enriched in the cytosolic, peroxisomal, and mitochondrial fractions. The highest amidation activities of both choloyl-CoA and chenodeoxycholoyl-CoA were found in the peroxisomal fraction (15-58 nmol/mg protein/min). The K(m) was higher for glycine than taurine both in cytosol and the peroxisomal fraction.These results show that the peroxisomal de novo synthesis of bile acids is rate limiting for peroxisomal amidation, and the microsomal bile acid-CoA synthetase is rate limiting for the cytosolic amidation. The peroxisomal location may explain the predominance of glyco-bile acids in human bile. Both a cytosolic and a peroxisomal bile acid-CoA thioesterase may influence the intracellular levels of free and conjugated bile acids.

In human liver homogenate the formation of bile acid-CoA thioesters is localized both to the microsomal fraction catalysed by an ATP-dependent synthetase and to the peroxisomal fraction catalysed by the thiolase in the last step of the beta-oxidative cleavage of the 5beta-cholestanoyl side chain. The cytosolic bile acid-CoA:amino acid N-acyltransferase catalyse the conjugation of the CoA-activated bile acids with taurine or glycine prior to secretion into bile. The formation of bile acid-CoA esters is considered the rate-limiting step in bile acid amidation. So far, a bile acid-CoA cleaving activity has not been assessed in the research of bile acid amidation in human liver. In this work, a bile acid-CoA cleaving activity has been demonstrated at a rate that may influence the concentration of bile acid-CoA thioesters, free bile acids and amidated bile acids within the hepatocyte. Recently, it was shown that free chenodeoxycholic acid, formed by the thioesterase, is the physiological ligand of the farnesoid X receptor. A multiorganelle distribution of the bile acid-CoA hydrolytic activity was found. In the postnuclear fraction of human liver homogenate, apparent Km and Vmax for the cleavage of choloyl-CoA were 7.7 x 10-5 mol/L and 3.6 nmol x mg-1 x min-1 respectively. The corresponding values for chenodeoxycholoyl-CoA cleavage were 7.1 x 10-5 mol/L and 4.8 nmol x mg-1 x min-1. Hydrolytic activities were detected in the microsomal and the peroxisomal fractions where the bile acid-CoA esters are formed as well as in cytosol housing the N-acyltransferase activity. Compared to the bile acid-CoA synthetase activities, the hydrolytic activities were considerably higher, both in the postnuclear fraction and in the microsomal fraction. The thioesterase activities were in the same range as detected for the N-acyltransferase activities both in the postnuclear fraction and in the cytosolic fraction. The mere presence of thioesterase in microsomes, peroxisomes and cytosol seems counterproductive to bile acid amidation. The thioesterases may have an indirect regulatory function on the bile acid synthesis and are important for the regulation of bile acid synthesis by providing free chenodeoxycholic acid, the most potent activator of the farnesoid X receptor.

The rights of children in hospitals in Norway are protected by regulations based on Norwegian legislation. These regulations cover matters such as teaching of hospitalized children, housing of parents, economic rights of parents, and information. We did a questionnaire study among hospitalized children and their parents about their views on how hospitals complied with these regulations. 90 of 131 questionnaires (69%) were returned. There was a considerable gap between what the law demands of continuance in health care during treatment, schooling and information, and what children and parents actually experience. The study shows that the present regulations concerning children's rights in hospitals should be changed. The health authorities should demand documentation from the hospitals as to how the rights of children are ensured in hospitals.

High levels of bile acids in the colon may correlate with an increased risk of colon cancer, but the underlying mechanisms are not known. Proteoglycan structures have been shown to change when human colon cells differentiate in vitro. The expression of [(35)S]sulphated molecules was used as a phenotypic marker to study the effects of bile acids on the human-colon-carcinoma cell line CaCo-2. [(35)S]sulphated compounds were isolated from the medium of cell fractions of cells metabolically labelled with [(35)S]sulphate in the absence and presence of cholic acid, deoxycholic acid, chenodeoxycholic acid and lithocholic acid (LA). Labelled molecules were analysed by gel chromatography, HPLC and SDS/PAGE in combination with chemical and enzymic methods. The expression of (35)S-labelled proteoglycans was not affected by any of the bile acids tested. However, the level of sulphated metabolites increased 7-18-fold in different experiments during a 22 h labelling period in the presence of an LA concentration of 10 microg/ml (26.6 nmol/ml) compared with controls. Further analyses showed that this was due, at least in part, to the sulphation of LA itself. This sulphation of LA was a rapid process followed by secretion back to the medium. Brefeldin A did not reduce the sulphation of LA, indicating that this conversion takes place in the cytosol, rather than in the Golgi apparatus of the CaCo-2 cells. LA in colon may be sulphated efficiently by the colonocytes to reduce the toxic effects of this particular bile acid. Sulphation may possibly be an important protective mechanism in the colon.

The rights of children in hospitals in Norway are protected by regulations based on the hospital statute: Regulations covering children in hospital, signed in 1989. These regulations cover matters such as the schooling of hospitalized children, the housing of parents, the economic rights of parents and information. We interviewed hospital management at two different levels of administration to find out how they put these regulations into practice. We found a certain gap between what the law demands and what the hospitals actually provide e.g. with regard to children on adult wards, firm point of contact, activity areas and provisions for education, clarification of parents' duties and respite facilities, reimbursement of expenses and issue of regulations. We conclude that the time has come for hospitals to report on the actions taken to ensure children's rights and for amendment to the law.

Length/height was studied from birth to 6 years of age in 103 children with congenital hypothyroidism identified by the Norwegian or Swedish screening programs. We used the "infancy-childhood-puberty (ICP) growth model". This model describes normal linear growth during the first 3 years of life by an infancy component with the addition of a childhood component, the latter acting from the second half of the first year. In comparison with reference children, children with hypothyroidism had reduced growth from 6 to 12 months, and increased growth after 12 months of age. Mean onset of the childhood component of growth was delayed from 8.1 months (SD 1.9) to 10.4 months (SD 2.2) in girls, and from 8.9 months (SD 2.0) to 11.0 months (SD 2.1) in boys. Age at onset of the childhood component was correlated with age at start of treatment (r = 0.24), and in children with more severe hypothyroidism (pretreatment serum thyroxine < 40 nmol/l) inversely correlated with the L-thyroxine dose at start of treatment (r = -0.40). Change in height standard deviation score from 1 to 3 years of age was correlated with the serum thyroxine concentration at age 1 year (r = 0.30). The delay in the onset of the childhood component of growth and the association with age at start of treatment and initial L-thyroxine dose indicate that thyroid hormones during the first months of life are essential for normal onset of the childhood component of growth, which otherwise is assumed to be growth hormone-dependent.

Up till now, errors of phytanic acid metabolism in children with peroxisomal disorders have been estimated by measuring 14CO2 formation from 1-14C-labelled phytanic acid in different systems. In the present work we have incubated both 1-14C- and U-3H-labelled phytanic acid and U-3H-labelled pristanic acid with cultured fibroblasts from healthy children as well as from children with peroxisomal disorders. In cultured fibroblasts from healthy children, [U-3H]-pristanic acid was degraded at a rate 60 times that of [U-3H]-phytanic acid, indicating that the initial degradation of phytanic acid into pristanic acid is the rate-limiting step in the overall conversion. In cultured fibroblasts from children with the Zellweger syndrome and infantile Refsum disease, the degradation of both phytanic acid and pristanic acid, was severely impaired (10-40 and 10-30 times, respectively), but the degradation of pristanic acid was still more than 20 times higher than that of phytanic acid in these disorders. In fibroblasts from a child with rhizomelic chondrodysplasia punctata the rate of degradation of U-3H- and 1-14C-labelled phytanic acid was markedly reduced whereas the rate of degradation of U-3H-labelled pristanic acid was normal. No evidence was obtained for elongation of phytanic or pristanic acid in the different fibroblastic cultures. It is concluded that both the degradation of phytanic acid and pristanic acid may be affected in peroxisomal disorders. The possibility that phytanic acidaemia in these disorders is due to product inhibition of accumulated pristanic acid seems to be excluded. The pristanic acidaemia sometimes seen is likely to be due to dietary pristanic acid rather than to de novo synthesized pristanic acid from accumulated phytanic acid.

The Centre for Rare Disorders at the National Hospital is a trial project in connection with the Government's Plan of Action for the disabled. The intention is to establish nationwide facilities which in cooperation with local resources can provide both medical, pedagogical and social services for persons with rare disorders and their families. The work at the centre is based on a life span perspective and the goal is improved coping, independence and better quality of life. The centre gathers, adapts and spreads information on 15 rare disorders. Representatives from the user organisations ensure that the users have a strong influence on the management of the centre. It is hoped that systematic evaluation of the centre's activities will give an answer to the Government and to the host hospital as to whether the intentions and goals will be fulfilled or not during the project period.

We have identified the mutations in the iduronate-2-sulfatase (IDS) gene of five unrelated Norwegians with Hunter syndrome by reverse transcription-polymerase chain reaction (RT-PCR) analysis of IDS mRNA followed by single strand conformation polymorphism (SSCP) analysis and cDNA sequencing. One patient had a 5-bp deletion, located at the intron 5/exon 6 junction, that created a new alternative splice site. This expanded the deletion to 9 bp in mRNA, an in-frame deletion of the first 3 codons of exon 6 of the IDS gene. In two patients point mutations were identified, the S333L mutation, which has been reported previously, and A346D (a C-->A transversion at nucleotide 1161/exon 8), which is novel. Two patients had large 3' mRNA rearrangements. The A346D mutation was associated with the mild phenotype, all others with the severe form.

Serum thyrotropin concentrations are frequently elevated during treatment of children with congenital hypothyroidism. It is unclear if elevated thyrotropin during early treatment indicates non-optimal treatment. In a cohort of 49 children with congenital hypothyroidism, we studied the decline in serum thyrotropin concentration after initiating L-thyroxine treatment, the relationship between elevated thyrotropin and treatment variables, and non-compliance with the treatment as a possible cause of elevated thyrotropin. The initial mean dose of thyroxine was 8.5 (SD 3.3) micrograms/kg body weight/day: 71% of the serum samples obtained 15-21 days after the start of treatment had serum thyrotropin concentrations < 10 mU/l. Six children had no samples with serum thyrotropin < 10 mU/l during the first 3 months of treatment. These children had a lower thyroxine dose prescribed, and serum thyrotropin was normalized when the dose was sufficiently increased. During treatment, from 6 weeks of age, serum thyrotropin > 10 mU/l was related to a lower dose of thyroxine and lower serum thyroxine, and was not due to non-compliance with treatment.

The aim of this investigation was to study if bone age development (assessed by the Greulich & Pyle atlas) was related to L-thyroxine treatment in 47 children with congenital hypothyroidism, treated early and according to general recommendations. In spite of frequent delay in skeletal maturation at diagnosis, the delay in mean bone age at a mean chronological age of 1.5 years was slight (0.5 months), and 30% of the variation in bone age SD score (SDS) at 1.5 years was accounted for by the dose of L-thyroxine and serum thyroxine during the first year. The children with a bone age within +/- 1 SDS had a prescribed mean dose of L-thyroxine per kg body weight from 3 to 12 months of age of 5.4 +/- 1.7 micrograms/kg/day, and their mean serum thyroxine concentration during the first year was 175 +/- 29 nmol/l. We conclude that bone age at 1.5 years of age was positively correlated with the dose of L-thyroxine and the serum thyroxine concentrations during the first year. This supports the general use of bone age assessments as a complement to other treatment variables in the follow-up of children with congenital hypothyroidism.

By focusing the consequences of loading platelets with the fluorescent calcium indicator, fura-2, in buffer or plasma the influences of plasma constituents on calcium responses in blood platelets has been worked out. Proteins were removed from the pre-incubation medium before agonist stimulation and measurement of intracellular calcium concentration [Ca2+]i. We found that moderate amounts (1-33%, v/v) of plasma added to the buffer during pre-incubation stimulated the mobilization of cytoplasmic calcium, delta[Ca2+]i, and reduced the time from agonist stimulation to peak level of [Ca2+]i in platelets stimulated with ADP or arginine vasopressin A8VP. With the buffer used, calcium response was restored by addition of 33% (v/v) plasma to the same level as found for unwashed platelets in the platelet rich plasma (cf. methods). The presence of human serum albumin during the pre-incubation also influenced the calcium response, but not to the same extent as plasma. From a resting level of 73 +/- 10 nmol l-1, addition of 0.4 mumol l-1 ADP increased the [Ca2+]i by 24 +/- 13 nmol l-1 (n = 20), 65 +/- 30 nmol l-1 (n = 5), and 144 +/- 44 nmol l-1 (n = 22) in platelets pre-incubated with buffer, 5 gl-1 albumin, and 33% (v/v) plasma, respectively. The corresponding values after stimulation with 0.05 mumol l-1 A8VP were 49 +/- 34 nmol l-1, 105 +/- 27 nmol l-1, and 170 +/- 39 nmol l-1, (n = 7). In platelets incubated in buffer only, the delta t from stimulation with 0.4 mumol l-1 ADP was 18.9s.(ABSTRACT TRUNCATED AT 250 WORDS)

We have shown that rat liver peroxisomes can chain-shorten prostaglandins to dinor- and tetranor-metabolites. In a recent in vivo study we could demonstrate that peroxisomes are of major importance for chain-shortening of prostaglandin F2 alpha in humans (1991, Diczfalusy et al. J. Clin. Invest. 88:978-984). This was shown by identifying the major urinary metabolites of radiolabeled prostaglandin F2 alpha given intravenously to a patient lacking functional peroxisomes (Zellweger syndrome). In the present investigation we have studied the peroxisomal chain-shortening of thromboxane B2, a compound structurally related to prostaglandins. Isolated rat liver peroxisomes oxidized thromboxane B2 to a chain-shortened metabolite in an NAD(+)-dependent reaction. The metabolite was identified as 9,11,15-trihydroxy-2,3,4,5-tetranor-thromb-13-enoic acid (tetranor-thromboxane B1). The urinary excretion of the major beta-oxidized metabolites of thromboxane B2 and prostacyclin was determined in three Zellweger patients and six age-matched controls. The controls excreted on an average 1.7 and 1.1 ng/mg creatinine of 2,3-dinorthromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha, respectively. In none of the three Zellweger patients could these dinor-metabolites be detected, i.e., the urinary excretion was less than 0.2 ng/mg creatinine. This shows that peroxisomes play an important role in the degradation of the carboxyl side chain of thromboxane B2 in vivo.

Cross-sectional and retrospective data on growth and anthropometric outcome, feeding problems and dietary intake are presented for 10 girls between three and 16 years of age with Rett syndrome. All girls had birth weight and length within the normal range for gestational age and development was considered normal until six to 24 months of age. The girls presented a fall off in linear growth during the first two years of life and at the time of study, all but one had height and/or weight for height below the 2.5th percentile of healthy children. The girls had good appetite but could not eat by themselves and oral-motor dysfunctions were common. The mean energy intake was 66.9% of the US recommendations according to age and 107.8% of the recommendations according to body weight. The intakes of thiamin, vitamin D, calcium and iron were considered low. None was anaemic. Different nutritional intervention strategies should be investigated to reduce and, if possible, prevent malnutrition and wasting in girls with Rett syndrome.

Cross-sectional data on growth outcome, upper-arm measurements and energy intake have been analysed according to the presence or absence of early feeding problems and poor appetite in 40 children (0.9-13 years) with congenital heart disease (CHD). At the time of study, refusal to eat or poor appetite was reported as a significant problem in 19 children and subnormal height and/or weight were recorded in 11 children. The children ate considerably less calories than recommended for healthy children. The cross-sectional analyses showed that children with poor appetite had significantly (P less than 0.05 and P less than 0.01) lower outcome values of growth and upper-arm measurements than their disabled counterparts with no feeding problems and good appetite. Children with feeding problems also tended to eat less than children without feeding problems. For most parents (65%) feeding of infants and children with CHD involves difficulties, time and anxiety. This study has shown that the parents' experience about feeding problems may be a good predictor for low growth outcome and low voluntary food intake of the child. Whenever feeding problems are reported, nutritional intervention should be offered in order to increase the caloric intake of the child and to develop a sound feeding relationship in the family.

We examined the effect of feeding problems and alternative feeding practices on the energy and nutrient intakes of disabled children. Subjects were 221 disabled children aged 1 to 16 years from seven diagnostic groups: a 4-day food record was obtained for 166 children. The children's energy and nutrient intakes were examined in relation to the presence or absence of four feeding problems (gross motor/self-feeding impairment, oral-motor dysfunction, lack of appetite, food aversions) and two alternate feeding practices (prolonged assisted feeding and use of pureed foods). Cross-sectional analyses showed that children with feeding problems or alternative feeding practices had lower energy and nutrient intakes than did children without these factors. The presence of oral-motor dysfunction or prolonged assisted feeding significantly reduced relative energy intake. In general, differences in energy and nutrient intakes between children with and without other feeding problems or practices were small, and few statistically significant differences were found. The findings indicate that some feeding problems may reduce food intake in disabled children, although this effect is lessened by the conscientious efforts of parents. Parents and families of disabled children should receive dietary counseling to prevent deteriorative effects on the physical growth and health of children with long-standing feeding problems.

Retrospective data on growth and cross-sectional data on growth outcome, anthropometric measurements and energy intake have been analysed according to the presence or absence of feeding problems in 42 children with cerebral palsy (CP) between 1 and 13 years of age. The mean age for boys and girls was 5.1 and 5.9 years, respectively. The study revealed a high frequency of feeding problems (50%) and growth retardation (48%) in the group. The results of weight for height, triceps skinfold thickness and energy intake indicate that 15% of the children were undernourished at the time of study. The cross-sectional analyses showed that children with feeding problems at the time of study (n = 22) had significantly lower height for age, weight for height, triceps skinfold thickness and upper-arm circumference than children without problems (P less than 0.05). Children with feeding problems also tended to have lower energy intake, but the differences were not significant. The feeding problems were most frequent among the severely disabled children. This study has shown that the presence of feeding problems is one important predictor of low growth outcome in children with CP. When parents report on feeding problems, feeding evaluation, training and nutritional intervention should be offered immediately. This is important for alleviating the heavy care-load for parents and health-workers and for some children it may be necessary to maintain an acceptable nutritional state.

We have recently shown in vitro that the peroxisomal fraction of a rat liver homogenate has the highest capacity to beta-oxidize prostaglandins. In order to evaluate the relative importance of peroxisomes for this conversion also in vivo, we administered [3H]prostaglandin F2 alpha to an infant suffering from Zellweger syndrome, a congenital disorder characterized by the absence of intact peroxisomes. As a control, labeled compound was administered to two healthy volunteers. Urine was collected, fractionated on a SEP-PAK C18 cartridge, and subjected to reversed-phase high-performance liquid chromatography. The Zellweger patient was found to excrete prostaglandin metabolites considerably less polar than those of the control subjects. The major urinary metabolite in the control subjects was practically absent in the urine from the Zellweger patient. The major urinary prostaglandin F2 alpha metabolite from the Zellweger patient was identified as an omega-oxidized C20-prostaglandin, 9,11-dihydroxy-15-oxoprost-5-ene-1,20-dioic acid. The major urinary prostaglandin F2 alpha metabolite from the control subjects had chromatographic properties of a tetranor (C16) prostaglandin, in accordance with earlier published data. The present results, in combination with our previous in vitro data, indicate that peroxisomal beta-oxidation is of major importance for in vivo chain shortening of prostaglandins.

The synthesis of pristanic acid from phytanic acid, and a simple reversed-phase high-pressure liquid chromatographic (HPLC) method for the separation and purification of these acids, is described. A base-line separation of [U-3H]phytanic and [U-3H]pristanic acid is achieved with a graphitized carbon column. The isoprenoid metabolites formed after incubation of cultured fibroblasts with phytanic or pristanic acids are extracted with a Sep-Pak C18 cartridge and separated from the substrates by the same reversed-phase HPLC used for substrate purification. The methods are suitable for studies on the mechanisms for degradation of phytanic acid. Recently, different inborn errors with accumulation of phytanic acid have been defined. The present method will be a useful tool in our efforts to define these metabolic defects and their subcellular localization.

The relationship between the treatment serum thyroxine level and intellectual development at 2 and 6 years was investigated in 46 Norwegian children with congenital hypothyroidism identified by neonatal screening. The level of serum thyroxine during the first 2 years was positively correlated with the Mental Development Index at 2 years of age (Bayley Scales of Infant Development) and the Verbal IQ at 6 years of age (Wechsler Preschool and Primary Scale of Intelligence). Children with a mean serum thyroxine level greater than 180 nmol/L (14 micrograms/dl) during the first year had a significantly higher Mental Development Index at 2 years and Verbal IQ at 6 years than children with serum thyroxine values less than 129 nmol/L (10 micrograms/dl). Boys had a lower Mental Development Index at 2 years of age than girls (86.9 vs 105.1; p less than 0.001) and a higher frequency of elevated serum levels of thyroid-stimulating hormone during the first year (p = 0.001). No signs of toxic effects of a high hormone level at the time of IQ assessment were detected. However, high serum levels of thyroxine at ages 2 to 4 years in girls were related to lower Performance IQ at age 6 years. The results demonstrate that the serum level of thyroxine is of importance in relation to intellectual development. Thyroxine levels above the upper reference range during the first 2 years were related to best intellectual development at 2 and 6 years.

Two hundred and twenty-one disabled children from seven diagnostic groups have been examined with respect to height, weight and prevalence of four different feeding problems. Retarded growth and feeding problems were common in children with cerebral palsy, mental retardation, congenital heart disease and deaf-blindness, but rare in children with esophagus atresia, cystic fibrosis and epilepsy. Mean relative height and weight were significantly lower (p much less than 0.01) in children with mechanical feeding problems, such as impairment of self-feeding skills and oral-motor dysfunction, than in children without these problems, regardless of diagnostic group. Mean relative weight was also significantly lower in children with poor appetite than in children with good appetite. Feeding problems contribute to short stature and underweight in severely disabled children.

Infantile Zellweger syndrome belongs to the group of peroxisomal disorders that lack peroxisomes. Both trihydroxycoprostanic acid (THCA), the precursor to cholic acid, and dihydroxycoprostanic acid (DHCA), the precursor to chenodeoxycholic acid, accumulate in this disease. In previous studies, we have shown that liver peroxisomes are required for the conversion of THCA into cholic acid both in vitro and in vivo by measuring a defective conversion in infants with Zellweger syndrome. In our present study, the conversion of DHCA into chenodeoxycholic acid has been measured in an infant with Zellweger syndrome to evaluate the importance of liver peroxisomes for the formation of chenodeoxycholic acid. Coprostanic acidemia was present from the second day of life with high levels of THCA and only trace amounts of DHCA. The conversion of i.v. administered [3H]DHCA into chenodeoxycholic acid was only 7% compared with the 80% conversion in an analogous study in an adult. There was, however, a rapid incorporation of 3H into biliary THCA and, after a lag phase, the 3H was incorporated into biliary cholic acid. After 72 h, 15% of [3H]DHCA was converted to cholic acid. The pool size of DHCA was 1.2 mg/m2 and the pool size of both cholic acid and chenodeoxycholic acid was markedly reduced. The renal excretion of cholic acid was more efficient than that of the less polar chenodeoxycholic acid. More polar metabolites of DHCA and THCA are formed in alternative metabolic pathways facilitating renal excretion of these toxic intermediates. We conclude that liver peroxisomes are essential for a normal conversion of DHCA into chenodeoxycholic acid.

Peroxisomes play an essential role in a number of different metabolic reactions, and the last few years have seen an enormous increase in our knowledge about peroxisomes and peroxisomal disorders. These disorders are caused by impairment of one or more peroxisomal functions. This article briefly reviews the clinical and biochemical aspects of peroxisomal disorders.

A boy with psychomotor retardation and Leber congenital amaurosis, sensory hearing loss, and hepatomegaly is reported. Accumulation of bile acid precursors and very long chain fatty acids together with impaired biosynthesis of plasmalogens in cultured fibroblasts (similar to those in the cerebrohepatorenal syndrome of Zellweger) were detected, but the clinical picture was distinctly different. Defective oxidation of phytanic acid was measured in fibroblasts. The virtual lack of peroxisomes in a liver biopsy specimen lends further support to the contention that at least some patients with Leber congenital amaurosis may have one of the recently defined "peroxisomal disorders." The biochemical findings indicate the possibility of prenatal diagnosis.

Infantile Refsum's disease (IRD) is a peroxisomal deficiency disease which is closely related to neonatal adrenoleukodystrophy (NALD) and the Zellweger syndrome (ZS). Recent observations suggest that NALD and ZS are separate genetic disorders but the delimitation towards IRD remains uncertain. We present here the first autopsy report of a patient who was clinically and biochemically diagnosed as having IRD, and we compare the findings with those from NALD and ZS. The main gross and microscopic findings comprised micronodular liver cirrhosis, small hypoplastic adrenals without degenerative changes, and large groups of lipid macrophages in liver, lymph nodes and certain areas of the cerebral white matter. The brain showed no malformations except for a severe hypoplasia of the cerebellar granule layer and ectopic location of the Purkinje cells in the molecular layer. A mild and diffuse reduction of axons and myelin was found in the corpus callosum and periventricular white matter, the corticospinal tracts, and the optic nerves. Large numbers of perivascular macrophages were present in the same areas but there was no active demyelination. The retina and cochlea showed severe degenerative changes. Peripheral nerves, skeletal system and kidneys were normal. Electron microscopy showed characteristic cytoplasmic inclusions with bilamellar profiles in macrophages in the liver, lymph nodes and brain but not in the adrenals. Similar inclusions were found in liver cells and astrocytes. The findings differ from ZS which shows cortical renal cysts, skeletal changes, liver changes, cerebral micropolygyria, neuronal heterotopias, and demyelination of the white matter. Cases with NALD show mild cerebral malformations, active demyelination, degenerative changes of the adrenals, liver changes, and bilamellar electromicroscopic inclusions in macrophages. Our cases thus resembled NALD but lacked active demyelination, cerebral cortical malformations and adrenal degenerative changes. Further autopsy studies will be necessary to determine whether these changes are consistent findings in IRD.

This study describes the nutritional intake, growth, and early food habits of 10 Norwegian children born deaf and blind. They were 1 girl and 9 boys aged 8 to 23 years. A 4-day dietary record, anthropometric measurements, and interviews with the parents were obtained. The children had energy intakes below or in the lower range of the reference values given in the Recommended Dietary Allowances (RDAs). Intakes of vitamins and minerals were acceptable when supplements were taken into account. Despite low physical activity, all pupils were thin. The interviews with the parents revealed early and serious feeding problems that arose at weaning. At the same time, growth retardation was registered for a majority of the pupils. All pupils were described as strikingly thin while growing up. We conclude that the early feeding problems were so pronounced that malnutrition may be considered a contributing factor to the growth retardation.