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Background: The COVID-19 pandemic contact restrictions considerably changed maternal visiting contacts during the time in which breastfeeding is initiated. We wanted to know how maternity ward staff and mothers rated the conditions of starting breastfeeding under contact restrictions., Methods: In the Breastfeeding in North Rhine-Westphalia (SINA) study, Germany, 2021/22, chief physicians as well as ward staff from 41 (out of 131) maternity hospitals (82 members of the healthcare sector in total) were surveyed by telephone concerning structural and practical conditions for breastfeeding support before and during the pandemic; 192 (out of 426 eligible) mothers answered an online-questionnaire about their breastfeeding experiences at 2 weeks and 2 months after birth., Results: In almost all of the hospitals, visits were restricted due to the pandemic, with the exception of the primary support person. After more than one year of pandemic experience, the ward staff were convinced that the restrictions were mostly positive for the mothers (97.6%) and for the ward staff themselves (78.0%). A total of 80.5% of the ward staff would maintain the restrictions beyond the pandemic. The mothers themselves mostly rated the restrictions in the hospital as being just right; moreover, many mothers voluntarily maintained the restrictions at home, at least in part., Conclusions: The unprecedented visiting restrictions in hospitals during the pandemic were like an "experiment" born out of necessity. Restricting visiting arrangements may be an underestimated beneficial component for the development of the mother-infant dyad in perinatal breastfeeding care, particularly in healthcare systems where almost all births occur in the maternity hospital., Trial Registration: German Clinical Trials Register (DRKS) (DRKS00027975)., (© 2024. The Author(s).)

Early infant feeding and swallowing are complex motor processes involving numerous muscles in coordination, e.g. the orofacial muscles as well as the muscles of the pharynx, larynx and esophagus. The newborn's reflexive drinking develops into the ability to ingest pureed complementary food as infancy progresses. Finally, in the last part of the first year of life, a differentiated eating, chewing and swallowing process develops allowing the voluntary intake of different foods of the family diet. The dietary schedule for the first year of life, which describes the recommended nutrition of infants in Germany, corresponds to these milestones in eating development. Disturbances in gross motor development, sensory processing issues, and organic and behavioral problems are known to interfere with the development of eating skills. Swallowing disorders (dysphagia) in children can have a detrimental effect on food intake and pose a serious risk to growth and development. Their prevention treatment requires a multidisciplinary approach with the aim of enabling the child to eat independently in the long term., (© 2024. The Author(s).)

Introduction: Childhood asthma is a highly prevalent chronic disease. A failure to implement patient education programmes may result in increased morbidity, despite the availability of distinct diagnostic and therapeutic approaches. Patients with lower socioeconomic status (SES) tend to have a higher asthma prevalence. Moreover, the progression of asthma is significantly influenced by factors such as health literacy and the children's specific knowledge about the condition. With this trial, the primary objective is to evaluate whether asthma education enhances specific disease understanding in children with asthma (primary outcome). Secondary objectives include evaluating training effects on health literacy, retention rates of information, 'Children Asthma Control Test' (C-ACT) score, frequency of emergency room and physician visits (secondary outcomes) and whether SES influences training effects., Methods and Analysis: To address the research objectives, this study comprises two projects. The first subproject will investigate the influence of asthma training on the development of disease understanding and health literacy. The second subproject will analyse the influence of SES on the outcome of children participating in asthma training. This research is designed as a comparative, non-randomised study involving two paediatric groups between the ages of ≥7 and < 14 years. After being diagnosed with asthma, the intervention group undergoes standardised psychoeducational asthma training at a certified centre associated with paediatricians in private practice in Germany, following the recommendations of the 'Arbeitsgruppe Asthmaschulung im Kindes- und Jugendalter e.V.', a national association aiming to establish uniform and guideline-based standards for patient education in children and adolescents. The comparison group receives a significantly shorter period of education and instruction on the usage of asthma medication at outpatient clinics. Data will be collected from patients and their parents at three specific survey time points, based on standardised tools.To describe mean differences between the intervention and control group over time (subproject 1), a repeated-measures analysis of variance (ANOVA) will be conducted. In subproject 2, multivariate linear regression analysis will be used to analyse the variables determining the changes in specific disease understanding and health literacy, including SES. The sample size calculation is based on a mixed ANOVA model with two groups and two measurements resulting in a total of 126 participants., Ethics and Dissemination: All protocols and a positive ethics approval were obtained from the Witten/Herdecke University, Germany (S-159, 2023; application submission: 24 June 2023, final vote: 10 July 2023). Furthermore, the study was registered at the German Clinical Trials Register (DRKS), DRKS00032423. The application submission was on 3 August 2023, and the final approval was on 4 August 2023. The results will be disseminated among experts and participants and will be published in peer-reviewed, international journal with open access., Trial Registration Number: DRKS00032423., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

High dietary phosphorus intake (P-In) and high acid loads may adversely affect kidney function. In animal models, excessive phosphorus intake causes renal injury, which, in humans, is also inducible by chronic metabolic acidosis. We thus examined whether habitually high P-In and endogenous acid production during childhood and adolescence may be early indicators of incipient renal inflammatory processes later in adulthood. P-In and acid-base status were longitudinally and exclusively determined by biomarker-based assessment in 277 healthy children, utilizing phosphate and net acid excretion (NAE) measurements in 24 h urine samples repeatedly collected between the ages of 3 and 17 years. Standard deviation scores (by sex and age) were calculated for anthropometric data and for the urinary biomarkers available within age range 3-17 years. Multivariable linear regression was used to analyze the relations of phosphate excretion and NAE with the adulthood outcome circulating interleukin-18 (IL-18), a marker of inflammation and kidney dysfunction. After adjusting for growth- and adulthood-related covariates and pro-inflammatory biomarkers to rule out confounding by non-renal inflammatory processes, regression models revealed a significant positive relationship of long-term NAE ( p = 0.01), but not of long-term phosphate excretion with adult serum IL-18. Similar significant positive regression results were obtained after replacing NAE with 24 h urinary ammonium excretion as the exposition variable. Our results suggest that even moderate elevations in renal ammonia production, as caused by habitually higher acid loading during growth, may affect the intrarenal pro-inflammatory system in the long-term, known to be boosted by acidosis-induced raised ammoniagenesis.

Objective: As global warming intensifies, residents of temperate regions will also face heat waves in the near future. Food habits are one component in addressing the global challenge of climate change. However, water, the most important food for humans, has not been adequately addressed., Design: For this commentary, on the one hand, publications on the increasing heat stress of children were consulted. On the other hand, publications on the special demands of children's temperature regulation in hot environments on fluid balance were analysed., Setting: The situation of young children in care facilities on days with heat stress is presented as a scenario. In this way, the effects of climatic changes on fluid balance can be estimated and measures to reduce heat stress and stabilise the fluid balance of children can be developed., Participants: For this analysis, first, infants will be considered in order to identify their specific fluid needs. Second, the possibilities for caregivers to improve fluid intake and train appropriate drinking habits already in infancy will be highlighted., Results: Climate change should be included in recommendations on hydration for children. The need to adapt drinking habits requires educational approaches to weather and water - starting in early childhood care., Conclusions: In the face of rapid climate change, countries must act now by protecting, preparing and prioritising the high-risk group of children. Particular focus should be placed on supporting adequate hydration.

Objectives: To show by the example of the Optimized Mixed Diet (OMD) for children and adolescents in Germany, how the different food and nutrient profiles of the traditional daily meals complement each other to achieve daily nutrient intakes that meet the Dietary References V., Methods: The 7-day menu plan of the OMD with the usual 5 daily meals in Germany was used. The total nutrient intake from all meals was compared with the nutrient references. Then the composition of the meals was optimized., Results: Although the cooked meal (lunch) provides only 25% of the daily energy intake, it is relatively rich (>25% of the daily intake) in most vitamins and minerals, which distinguishes it from the other meals. The cold main meals (breakfast, dinner) are rich in calcium and vitamin B2, due to the preferential use of milk in these meals. The two snacks each provide 12.5% of the daily energy intake., Discussion and Conclusion: People eat foods but not nutrients and they eat foods as meals; this holds especially true for children and adolescents. A well-calculated menu plan can assure the nutrient adequacy of an OMD where the different food and nutrient profiles of the meals complement each other in a modular system. Guidelines for meals could facilitate flexible coordination of family meals and meals in childcare centers and schools. Different meal types set varied stimulus patterns at different levels (neurocognition, emotion, digestion), which may open up long-term health benefits., 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 © 2022 Kersting, Kalhoff, Sinningen and Lücke.)

Human milk contains more than 150 different oligosaccharides, which together are among to the quantitatively predominant solid components of breast milk. The oligosaccharide content and composition of human milk show large inter-individual differences. Oligosaccharide content is mostly influenced by genetic variants of the mother's secretor status. Oligosaccharides in human milk are utilized by infants' intestinal bacteria, affecting bacterial composition and metabolic activity. Maternal secretor status, and respective differing fucosylated oligosaccharide content, has been associated both with reduced and increased risk of infection in different populations of breastfed infants, possibly due to environmental conditions and the infant's genotype. There are no safety concerns regarding the addition of previously approved oligosaccharides to infant formula; however, no firm conclusions can be drawn about clinically relevant benefits either. Therefore, infant formulas with synthetic oligosaccharide additives are currently not preferentially recommended over infant formulas without such additives. We consider the use of terms such as "human milk oligosaccharides" and corresponding abbreviations such as "HMO" in any advertising of infant formula to be an inappropriate idealization of infant formula. Manufacturers should stop this practice, and such marketing practices should be prevented by responsible supervisory authorities. Pediatricians should inform families that infant formulas supplemented with synthetic oligosaccharides do not resemble the complex oligosaccharide composition of human milk., (© 2022. The Author(s).)

Recently, the European Food Safety Authority (EFSA) issued a tolerable daily intake (TDI) for erucic acid, which is mainly found in rapeseed oil. Infants may be exposed to erucic acid from rapeseed oil indirectly through maternal consumption via breastmilk or the fat component in formula, and directly as a part of complementary feeding (CF). To check the safety of infant nutrition, scenarios for erucic acid exposure were calculated based on the daily food amounts of the German dietary guidelines. Information on erucic acid concentrations in foods was obtained from European studies for breastmilk, from EFSA samples for formula powder, and from a representative analysis of rapeseed oil samples in the German retail market. 6 scenarios were calculated for the early milk feeding phase (4 formula feeding, 2 breastfeeding) and 8 scenarios for the later CF phase (5 CF +formula feeding, 3 CF +breastfeeding). Out of the 14 scenarios, only 3 resulted in exposures that were definitively below the TDI (range 4.4.-6.0 mg/kg bodyweight; BW). Assuming either high consumption or high concentration led to high exceedances (range 7.5-26.2 mg/kg BW), especially in case of the new EU limits for formula or vegetable oils (33.6 and 43.2 mg/kg BW, respectively). In our scenarios, high erucic acid exposures occurred during a particularly sensitive developmental period. To definitively weigh the potential risks from erucic acid in infants against nutritional benefits of the dietary recommendations, reliable, timely data on erucic acid in breast milk and formula are needed, similar to those from rapeseed oil in Germany., (© 2021 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

A recent study concerning the "Impact of COVID-19 on the Interrelation of Physical Activity, Screen Time and Health-Related Quality of Life in Children and Adolescents in Germany" was investigated by Wunsch et al. [...].

A lower 24-h urine pH (24h-pH), i.e., a higher renal excretion of free protons, at a given acid load to the body, denotes a reduction in the kidney's capacity for net acid excretion (NAE). There is increasing evidence, not only for patients with type 2 diabetes but also for healthy individuals, that higher body fatness or waist circumference (WC) has a negative impact on renal function to excrete acids (NAE). We hypothesized that adiposity-related inflammation molecules might mediate this relation between adiposity and renal acid excretion function. Twelve biomarkers of inflammation were measured in fasting blood samples from 162 adult participants (18-25 yr old) of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study who had undergone anthropometric measurements and collected 24-h urine samples. Both Baron and Kenny's (B&K's) steps to test mediation and causal mediation analysis were conducted to examine the potential mediatory roles of biomarkers of inflammation in the WC-24-h pH relationship after strictly controlling for laboratory-measured NAE. In B&K's mediation analysis, leptin, soluble intercellular adhesion molecule 1 (sICAM-1), and adiponectin significantly associated with the outcome 24-h pH and attenuated the WC-pH relation. In agreement herewith, causal mediation analysis estimated the "natural indirect effects" of WC on 24-h pH via leptin ( P = 0.01) and adiponectin ( P = 0.03) to be significant, with a trend for sICAM-1 ( P = 0.09). The calculated proportions mediated by leptin, adiponectin, and sICAM-1 were 64%, 23%, and 12%, respectively. Both mediation analyses identified an inflammatory cytokine (leptin) and an anti-inflammatory cytokine (adiponectin) along with sICAM-1 as being potentially involved in mediating adiposity-related influences on renal acid excretion capacity.

Pureed complementary feeding products packed in squeezable plastic pouches, usually with a spout and a screw cap, have been increasingly marketed. The Committee on Nutrition recommends that infants and young children should not suck pureed or liquid complementary foods from baby food pouches. Complementary foods should be offered with a spoon or should be fed as finger foods. Infants and young children should be given the opportunity to get to know a variety of foods and food textures including pieces of foods, supported by responsive feeding between the child and their parents or caregivers. Complementary foods marketed in baby food pouches often have a high energy density and are predominantly extremely high in sugar content, with up to almost 90% of the total energy content. Regular consumption bears the risks of imbalanced nutrient provision and increased risks for dental caries and overweight. Complementary foods for infants and young children should have a balanced composition following the recommendations of the German Society of Pediatrics and Adolescent Medicine (DGKJ) and should contain only limited amounts of sugar. We discourage the feeding of pureed complementary foods from baby food pouches.

Flavonoids have been implicated in the prevention of cardiovascular diseases (CVD). In a prospective approach, we investigated whether habitual flavonoid intake from fruit, vegetables and juices (FlavFVJ) during adolescence is associated with adult levels of serum lipids, one of the main CVD risk factors. This analysis included healthy participants from the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study, who had provided a fasting blood sample in adulthood (aged 18-39 years), data on FlavFVJ intake during adolescence (females: 9-15 years, males: 10-16 years)-estimated either from multiple 3-day weighed dietary records ( n = 257), or from validated biomarker hippuric acid (uHA) excretion from multiple 24-h urine samples ( n = 233)-together with information on relevant covariates. In multivariable linear regression analyses, a higher FlavFVJ intake during adolescence was independently associated with higher serum high-density lipoprotein cholesterol (HDL-C) levels among males ( P trend = 0.038); however, the inclusion of adult waist circumference attenuated this association ( P trend = 0.053). FlavFVJ was not associated with triglycerides (TG), total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C; all P trend ≥ 0.1), nor was uHA excretion with any serum lipid outcome among males (all P trend ≥ 0.5). Neither FlavFVJ intake nor uHA excretion was associated with serum lipids among women (all P trend ≥ 0.1). However, a higher flavonoid intake from fruit and vegetables was independently related to lower LDL-C levels ( P trend = 0.021), while a higher intake from juices was associated with higher LDL-C levels ( P trend = 0.016) among females. In conclusion, a higher flavonoid intake from fruit, vegetables and/or juices during adolescence may be linked to cholesterol levels in early adulthood in a sex- and food source-specific manner., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Nonalcoholic fatty liver disease (NAFLD), frequently already present in young subjects, has been linked to reduced growth hormone levels and signaling. Similar hormonal changes occur during metabolic acidosis (MA), which may thus contribute to an increased NAFLD risk. Because subclinical MA can be diet induced, we aimed to examine whether a higher diet-dependent acid load during adolescence is prospectively associated with several currently used NAFLD surrogates in young adulthood. Dietary acidity during adolescence (boys:10-15 y, girls: 9-14 y) was calculated as potential renal acid load (PRAL) from at least three 3-d weighed dietary records according to a published algorithm considering dietary protein and minerals in 145 healthy participants. Routine measurements derived from blood analysis and anthropometric data in participants' young adulthood (18-25 y) were used to determine the NAFLD surrogates alanine-aminotransferase (ALT), hepatic steatosis index (HSI), and fatty liver index (FLI). Sex-stratified linear regression models, adjusted for dietary fiber, saturated fat, protein, and adolescent BMI SD scores, were run with PRAL as the independent variable. Dietary PRAL during puberty was positively associated with ALT (P = 0.02), HSI (P = 0.002), and FLI (P = 0.005) in adult females but not males. Females with an adolescent dietary acid load in the highest tertile had 3.5, 4.4, and 4.5 higher values of ALT, HSI, and FLI as adults, respectively, compared to females with the lowest PRAL. The present findings suggest that higher dietary acidity in adolescence may be prospectively associated with hepatic lipid accumulation in females. Whether this relationship is due to the higher proton load or rather represents an unhealthy dietary pattern requires further investigation.

Lung function measurements play an essential role in early diagnosis and monitoring of bronchial asthma in children. For clinical evaluation, measurements are commonly compared to reference values. However, these reference values are calculated based on measurements performed in groups of mostly older children and young adults two or three decades ago. In the present, cross-sectional study, lung function measurements were performed in 518 children (241 boys and 277 girls; mean age 6.0+/-0.3 years) at a regular medical check prior to school enrollment. Spirometry was done using the MasterScreen IOS (Cardinal Health, Wurzburg). We recorded forced vital capacity (FVC), forced expiratory volume in one second (FEV(1)), maximal expiratory flow (PEF), and maximal expiratory flow at 75, 50, and 25% of vital capacity (MEF(75), MEF(50), MEF(25)). We found that FEV(1) and FVC corresponded to reference values (101.0+/-14.9% and 95.4+/-13.6%, in boys and girls, respectively). In maneuvers satisfying ATS/ERS criteria (T(E) >1 sec), forced expiratory (parameters (PEF, MEF(50)) reached only 68.9+/-13.6 and 75.9+/-26.6% of reference values, in boys and girls, respectively). There was no significant correlation of lung function parameters to BMI. In conclusion, the hitherto reference values largely overestimate the maximal flow rates of preschool children performing a forced spirometry with T(E) >1 sec. At the age of 6, forced expiratory flow values are not (yet) impaired by an increased BMI. Standardized spirometry starting in preschool children allows closely evaluating the individual development of lung function during follow-up measurements.

Theory predicts respiratory instabilities at elevated system loop gain (G), determined by such factors as ventilatory CO(2) sensitivity, set-point PCO(2), and metabolic rate. In anesthetized rabbits, the effects on G of carbonic anhydrase (CA) inhibitors and of different sodium/proton exchanger type 3 (NHE3) inhibitors were studied. Acetazolamide significantly reduced G by 42.0 +/- 9.3% and methazolamide by 35.0 +/- 9.5% (each n = 7, P<0.01). Irrespective of the substance, NHE3 inhibition reduced G by 33.0 +/- 7.8% (n = 10, P<0.01) at 35.5 +/- 1.6 mmHg PaCO(2) (mean +/-SE), but not at lower arterial CO(2) levels (n=5). Since high baseline PCO(2) coincides with elevated brainstem NHE3 mRNA expression, this may also account for a higher risk of sleep apnea (or even occurrence of sudden infant death). Therefore, NHE3 inhibitors may gain similar therapeutic importance in the treatment of irregular breathing as CA inhibitors. Generally, effective treatment should aim at a low system loop gain, by reducing respiratory chemosensitivity, improving blood gases and preventing low metabolic rates.

Alkali-enriched diets are recommended for humans to diminish the net acid load of their usual diet. In contrast, herbivores have to deal with a high dietary alkali impact on acid-base balance. Here we explore the role of nutritional alkali in experimentally induced chronic metabolic acidosis. Data were collected from healthy male adult rabbits kept in metabolism cages to obtain 24-h urine and arterial blood samples. Randomized groups consumed rabbit diets ad libitum, providing sufficient energy but variable alkali load. One subgroup (n = 10) received high-alkali food and approximately 15 mEq/kg ammonium chloride (NH4Cl) with its drinking water for 5 d. Another group (n = 14) was fed low-alkali food for 5 d and given approximately 4 mEq/kg NH4Cl daily for the last 2 d. The wide range of alimentary acid-base load was significantly reflected by renal base excretion, but normal acid-base conditions were maintained in the arterial blood. In rabbits fed a high-alkali diet, the excreted alkaline urine (pH(u) > 8.0) typically contained a large amount of precipitated carbonate, whereas in rabbits fed a low-alkali diet, both pH(u) and precipitate decreased considerably. During high-alkali feeding, application of NH4Cl likewise decreased pH(u), but arterial pH was still maintained with no indication of metabolic acidosis. During low-alkali feeding, a comparably small amount of added NH4Cl further lowered pH(u) and was accompanied by a significant systemic metabolic acidosis. We conclude that exhausted renal base-saving function by dietary alkali depletion is a prerequisite for growing susceptibility to NH4Cl-induced chronic metabolic acidosis in the herbivore rabbit.

Airway resistance (Raw) decreases with an increase of lung volume (ITGV) during body-growth. In asthmatic subjects, an increase of Raw may be modified by hyperinflation. In this study thirty five asthmatic children underwent histamine challenges with the monitoring of changes of Raw and ITGV. Control measurements (after withhold of spasmolytic medication) showed increased values of ITGV and Raw with high interindividual variability. Histamine challenge resulted in a further increase of both ITGV and Raw in 18 patients (normal pattern). Twelve patients showed an increase predominantly of Raw (obstructive pattern), 5 patients an increase predominantly of ITGV (hyperinflatory pattern). On provocation and after bronchospasmolysis, all subjects presented the expected inverse relation between ITGV and Raw. The variability of ITGV-Raw patterns in children with asthma may agree with the concomitantly established role for vagal reflex mechanisms in prolonged inspiratory diaphragmatic innervation during experimentally induced bronchoconstriction in animals. In children with asthma the ITGV-Raw pattern may point to different risk profiles.

Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disease characterized by thymine-uraciluria in homozygous deficient patients. Cancer patients with a partial deficiency of DPD are at risk of developing severe life-threatening toxicities after the administration of 5-fluorouracil. Thus, identification of novel disease-causing mutations is of the utmost importance to allow screening of patients at risk. In eight patients presenting with a complete DPD deficiency, a considerable variation in the clinical presentation was noted. Whereas motor retardation was observed in all patients, no patients presented with convulsive disorders. In this group of patients, nine novel mutations were identified including one deletion of two nucleotides [1039-1042delTG] and eight missense mutations. Analysis of the crystal structure of pig DPD suggested that five out of eight amino acid exchanges present in these patients with a complete DPD deficiency, Pro86Leu, Ser201Arg, Ser492Leu, Asp949Val and His978Arg, interfered directly or indirectly with cofactor binding or electron transport. Furthermore, the mutations Ile560Ser and Tyr211Cys most likely affected the structural integrity of the DPD protein. Only the effect of the Ile370Val and a previously identified Cys29Arg mutation could not be readily explained by analysis of the three-dimensional structure of the DPD enzyme, suggesting that at least the latter might be a common polymorphism. Our data demonstrate for the first time the possible consequences of missense mutations in the DPD gene on the function and stability of the DPD enzyme.

Inogranic pyrophosphate (PPi) inhibits hydroxyapatite deposition, and mice deficient in the PPi-generating nucleoside triphosphate pyrophosphohydrolase (NTPPPH) Plasma cell membrane glycoprotein-1 (PC-1) develop peri-articular and arterial calcification in early life. In idiopathic infantile arterial calcification (IIAC), hydroxyapatite deposition and smooth muscle cell (SMC) proliferation occur, sometimes associated with peri-articular calcification. Thus, we assessed PC-1 expression and PPi metabolism in a 25-month-old boy with IIAC and peri-articular calcifications. Plasma PC-1 was <1 ng/ml by enzyme-linked immunosorbent assay in the proband, but 10 to 30 ng/ml in unaffected family members and controls. PC-1 functioned to raise extracellular PPi in cultured aortic SMCs. However, PC-1 was sparse in temporal artery lesion SMCs in the proband, unlike the case for SMCs in atherosclerotic carotid artery lesions of unrelated adults. Proband plasma and explant-cultured dermal fibroblast NTPPPH and PPi were markedly decreased. The proband was heterozygous at the PC-1 locus, and sizes of PC-1 mRNA and polypeptide, and the PC-1 mRNA-coding region sequence were normal in proband fibroblasts. However, immunoreactive PC-1 protein was relatively sparse in proband fibroblasts. In conclusion, deficient extracellular PPi and a deficiency of PC-1 NTPPPH activity can be associated with human infantile arterial and peri-articular calcification, and may help explain the sharing of certain phenotypic features between some IIAC patients and PC-1-deficient mice.