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Unlabelled: Sleep duration has been identified as risk factor for obesity already in children. Besides investigating the role of fat mass (FM), this study addressed the question whether endocrine mechanisms act as intermediates in the association between sleep duration and overweight/obesity. Within the framework of the IDEFICS study, the present research was conducted in 609 German resident children aged 2-9 years with information on fasting insulin, C-reactive protein and cortisol levels next to anthropometric measurements and parental questionnaires. Emphasising methodological aspects, an age-specific measure of sleep duration was derived to account for alteration in sleep duration during childhood/period of growth. Multivariate linear regression and quantile regression models confirmed an inverse relationship between sleep duration and measures of overweight/obesity. The estimate for the association of sleep duration and body mass index (BMI) was approximately halved after adjustment for FM, but remained significant. The strength of this association was also markedly attenuated when adjusting for insulin mainly for the upper BMI quantiles (Q80, β = -0.36 vs. β = -0.26; Q95, β = -0.87 vs. β = -0.47). Adjustment for cortisol and CrP did not yield this attenuation.Conclusion: The inverse relationship between sleep duration and BMI is mainly explained by the association between sleep duration and FM. Insulin may explain part of this association, in particular at the upper tail of the BMI distribution. [ABSTRACT FROM AUTHOR]

Higher levels of factor VIII: C and factor VIII R: Ag were found in healthy newborns (n = 60) as compared to adults. This could be explained as a stress reaction due to birth and the adaptation to extrauterine life. A further stress factor is disease. The highest values for factor VIII R: Ag were found in ill (n = 32) and in severely ill newborns (n = 21). The large ranges of factor VIII: C and of the ratio of factor VIII: C/VIII R: Ag in healthy newborns can be explained by an increased turnover of coagulation factors. Diseases in the newborn period lead to an increase of this process, resulting in even larger ranges of factor VIII: C and of the ratio of factor VIII: C/VIII R: Ag in ill and extremely ill newborns. Consumption of factor VIII: C with a low ratio of factor VIII: C/VIII R: Ag predominates in extremely ill newborns. The ratio of factor VIII: C/VIII R: Ag is more valuable than factor VIII: C for diagnosis of DIC in newborns. A diagnosis of hemophilia and von Willebrand's disease cannot be established with certainty in severely ill newborns. Stress and DIC may influence the characteristic changes of laboratory parameters. [ABSTRACT FROM AUTHOR]

Neisseria meningitidis infection may present as meningitis or as severe, fulminant sepsis. In order to classify individual patients early according to the expected course of the disease, we developed a score named Neisseria sepsis index [NESI]. The NESI was defined using the parameters heart rate, mean arterial blood pressure, base excess and presence of acute subcutaneous bleeding and/or skin necroses (minimal value [= no evidence for sepsis] NESI 0; maximum value [= most severe sepsis] NESI 8). Seventeen patients with documented, systemic N. meningitidis infection were prospectively assessed for the terminal complement complex (TCC), serum tumour necrosis factor alpha (TNF alpha) levels (as laboratory parameters for severity of sepsis) and NESI score. The evaluation was immediately performed when the patients were admitted to the hospital. The 17 patients showed the following distribution of data: NESI 0 (n = 4), NESI 1 (n = 6), NESI 2 (n = 0), NESI 3 (n = 1), NESI 4 (n = 2), NESI 5 (n = 2), NESI 6 (n = 0), NESI 7 (n = 1), NESI 8 (n = 1). Mortality was 4/17 patients, all had NESI > or = 5. TCC values ranged from 647-6461 ng/ml (normal range: 130-360 ng/ml); and was not correlated to NESI. TNF alpha values ranged from 10-910 pg/ml and were correlated to NESI (r2 = 0.71, n = 17, P < 0.001). In patients with fatal outcome, TNF alpha was 600 +/- 160 pg/ml (mean +/- SEM) and in surviving patients 130 +/- 50 pg/ml (mean +/- SEM). TNF alpha was increased in 15/17 patients when compared to normal controls (< 27 pg/ml). CONCLUSION. The NESI is based on few clinical, objective data, that are available in every hospital. NESI appears to offer an instrument: (1) for making decisions in regard to appropriate monitoring and treatment of vital organ function; and (2) for assessing the quality of care for this life-threatening infection. [ABSTRACT FROM AUTHOR]

Vitamin K has regained paediatric interest due to a recurrence of bleeding caused by deficiency of the vitamin in newborns and young infants. Increasing awareness of these clinical problems, the development of new methods for the detection of vitamin K deficiency and the direct measurement of vitamin K in tissues have stimulated research. Much new data obtained from these studies has proved helpful to the understanding of vitamin K deficiency in infancy. For example low concentrations of vitamin K have been found in fetal and neonatal livers. The implications of these findings with respect to manifest vitamin K deficiency and to new methods for detection of subclinical vitamin K deficiency are discussed. Breast-feeding is a major risk factor for classical haemorrhagic disease of the newborn and for late onset bleeding due to vitamin K deficiency in young infants. The interdependencies between breast-feeding and vitamin K deficiency are discussed on the basis of new data obtained from direct measurement of vitamin K in maternal milk. The review further focuses on pathophysiological concepts of bleeding due to vitamin K deficiency in infancy and current concepts of vitamin K prophylaxis. [ABSTRACT FROM AUTHOR]

The incidence of acarboxy-prothrombin and the clotting activity of factors II and VII were evaluated on the fifth day of life in 183 healthy newborns, who had received no vitamin K prophylaxis. Acarboxy-prothrombin was detected in 93/183 newborns. All acarboxy-prothrombin-negative babies had factors II and VII clotting activities above 25% whereas a great variability was observed in acarboxy-prothrombin-positive babies: 21/93 had factor II and 14/93 had factor VII activities below 25%. Seventy-two of the acarboxy-prothrombin-positive babies had normal factor II and VII clotting times on the fifth day of life. These babies must be suspected to have had vitamin K deficiency on one of the first 4 days, as acarboxy-prothrombin has a 50% disappearance rate of 50 h. Acarboxy-prothrombin was mainly observed in breast-fed infants (84/122) and only rarely detectable in infants receiving supplementary (7/44) or exclusive formula feeding (2/17). The type of milk feeding however might be less important for the babies' vitamin K supply than the actual milk intake. All acarboxy-prothrombin-positive babies had received small amounts of milk on the first 4 days of life. In those with low factor II and VII clotting activities the milk intake was low throughout the first 4 days of life, whereas babies with acarboxy-prothrombin and and normal clotting activities had increased their milk intake to more than 100 ml on the third and fourth day of life. Recommendations for vitamin K prophylaxis in newborns should be given with regard to the feeding on the first days of life. [ABSTRACT FROM AUTHOR]

A 2-year-old boy with cardiomyopathy and clinical signs of cardiac failure presented with an echodense structure in the left ventricle. This structure was seen from different echocardiographic views adjacent to a hypokinetic area of the apex and lateral free wall. It was different in texture and motion from the underlying myocardium and thus met the diagnostic criteria of a left ventricular thrombus. This thrombus protruded into the cavum and was partly mobile. In view of a high embolic risk, thrombolytic therapy with recombinant tissue plasminogen activator was started. The thrombus resolved within 72 h without any embolic or bleeding complications. No recurrence of the thrombus was observed during a 3-month follow up period. [ABSTRACT FROM AUTHOR]

In an extremely low birth weight infant fed expressed own mother's milk exclusively during the first 6 months of life, introduction of a human milk fortifier resulted in improvement of biochemical alterations consistent with metabolic bone disease of prematurity. Attempts to discontinue fortification at 9 weeks (discharge) and 21 weeks of age induced deterioration of biochemical parameters, demonstrating a persistent need for mineral supplementation during the whole period of breast-feeding. The effects of long-term human milk fortification are discussed. [ABSTRACT FROM AUTHOR]

Although children and adolescents have a lower burden of SARS-CoV-2-associated disease compared to adults, assessing the risk for severe outcomes among SARS-CoV-2-infected children remains difficult due to a high rate of undetected cases. We combine data from three data sources - a national seroprevalence study (the SARS-CoV-2 KIDS study), the nationwide, state-based reporting system for PCR-confirmed SARS-CoV-2 infections in Germany, and a nationwide registry on children and adolescents hospitalized with either SARS-CoV-2 or pediatric inflammatory multisystem syndrome (PIMS-TS, also known as MIS-C) - in order to provide estimates on the risk of hospitalization for COVID-19-related treatment, intensive care admission, and death due to COVID-19 and PIMS-TS in children. The rate of hospitalization for COVID-19-related treatment among all SARS-CoV-2 seropositive children was 7.13 per 10,000, ICU admission 2.21 per 10,000, and case fatality was 0.09 per 10,000. In children without comorbidities, the corresponding rates for severe or fatal disease courses were substantially lower. The lowest risk for the need of COVID-19-specific treatment was observed in children aged 5-11 without comorbidities. In this group, the ICU admission rate was 0.37 per 10,000, and case fatality could not be calculated due to the absence of cases. The overall PIMS-TS rate was 2.47 per 10,000 SARS-CoV-2 infections, the majority being children without comorbidities., Conclusion: Overall, the SARS-CoV-2-associated burden of a severe disease course or death in children and adolescents is low. This seems particularly the case for 5-11-year-old children without comorbidities. By contrast, PIMS-TS plays a major role in the overall disease burden among all pediatric age groups., What Is Known: • SARS-CoV-2-associated burden of disease in children is considered to be low, but accurate risk estimates accounting for clinically undiagnosed infections are lacking. • Asymptomatic SARS-CoV-2 infections are common in children., What Is New: • We provide risk estimates for hospitalization for COVID-19-related treatment, ICU admission, death from COVID-19, and PIMS-TS for children with SARS-CoV-2 infections by pooling different data sources. • The risk for PIMS-TS exceeds the risk for severe COVID-19 in all age groups; the risk for severe COVID-19 is the lowest in 5-11 years old., (© 2022. The Author(s).)

Feeding disorders in ex-prematures do exist and may constitute a major challenge to their families' well being. A cases series of 86 ex-prematures with severe feeding disorders was analysed regarding co-morbidity, response to therapy and the long-term outcome after treatment. These children with a gestational age of <37 weeks had been referred for hospital rehabilitation because of severe feeding disorders, defined as tube feeding or average feeding times of more than 30 minutes. Behavioural therapy was the key element of the treatment. Ex-prematures accounted for 86/266 patients admitted for treatment of feeding disorders between 1995 and 2004. Whereas only 40.8% of these had cerebral palsy, 51.1% had a diagnosis of mental retardation and 87% had interaction problems. Response to treatment up to discharge was achieved in 61.6%. Univariat analyses showed that tube feeding at admission and swallowing difficulties were the best predictors of failure to respond to the intervention. Long-term follow-up data that were collected for 53 of the 86 children with similar initial response to therapy (64.2%) compared to children with no follow-up data (57.6%). Success of therapy after discharge was maintained in 94.1%; however, 25% of the children with normal BMI's at discharge and sustained success of therapy fell below the 3rd BMI percentile. Cerebral palsy, mental retardation and interaction problems appear to be important risk factors for severe feeding disorders in ex-prematures. A therapeutic intervention based on behavioural therapy achieved sustained success in almost two thirds of the children.

Unlabelled: The aim of this study was to evaluate the incidence of paediatric multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM) in Germany. In a prospective nationwide survey carried out between 1997 and 1999, all registered new cases of paediatric MS and ADEM with an onset before the age of 16 years were evaluated using a standardised questionnaire. A total of 132 patients with suspected or definite MS and 28 patients with an assumed diagnosis of ADEM were reported. Among these, 82% of the MS patients were 10 years of age or older, as opposed to 18% in the ADEM-cohort. The female-to-male ratio was 1.2:1 in the MS-cohort and 0.8:1 in the ADEM-cohort. Manifestation was polysymptomatic in 67% of the MS patients compared to 86% of the ADEM patients. The most frequent primary symptoms in the MS-cohort were cerebellar (44%), sensory (39%) or visual (36%), followed by brainstem (30%), pyramidal (29%) and cerebromental (22%) complaints., Conclusion: The incidence of paediatric MS in Germany is more than fourfold higher than that of paediatric ADEM; in addition, it shows a strikingly different age-distribution. With an estimated minimum of 50 new cases per year, the incidence of paediatric MS in Germany is much more frequent than previously believed.

Unlabelled: In Germany, a low coverage with hepatitis B and measles vaccines and a considerable delay in administration of all recommended vaccines were previously apparent. Whether there have been improvements and whether there are regional differences within Germany is not known. Using representative nationwide telephone interviews on 2,701 children born 1996-2003, we assessed vaccination coverage for the first dose or full primary series (2/3 doses, depending on vaccine used) at 24 months of age. The proportions vaccinated with the first dose, full priming and full immunisation (2/3 doses plus booster in the 2nd year of life) until the end of the recommended age (3, 5 and 15 months, respectively, for diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b (Hib) and hepatitis B vaccines (DTPPolioHibHep), and 15 for the first measles, mumps and rubella dose (MMR) were used as indicators of compliance with national guidelines. Coverage for polio, Hib and hepatitis B vaccines increased, while coverage for the first MMR dose remained constantly low at about 70%. Vaccination coverage differed substantially among the German states and was highest for the new states. Compliance with national guidelines increased from 2.5% to 15% for the full primary DTPPolioHibHep series, from 16.2% to 44.7% for the first MMR dose and from 1.0% to 19.3% for the full immunisation with all recommended vaccines (DTPPolioHibHepMMR)., Conclusion: Vaccination coverage at 24 months and compliance with national guidelines has improved for most vaccines in Germany. However, improving coverage for measles, mumps, rubella and eliminating the regional disparities remain a major challenge for the public health sector.

Unlabelled: Deaths in temporal association with vaccination of hexavalent vaccines have been recently reported. The objective of this paper is to assess whether these temporal associations can be attributed to chance. Standardised mortality ratios (SMR) for deaths within 1 to 28 days after administration of either of the two hexavalent vaccines in the 1st and 2nd year of life were determined using the respective annual rates for sudden unexpected deaths (SUDs) from the national vital statistics. The distribution of SUD cases and the vaccination uptake by month were estimated from surveys and sales figures for the individual vaccines. Sensitivity analyses were performed to account for limitations in the data sources. For one of the vaccines, Vaccine B, all SMRs were well below one. For the other, Vaccine A, SMRs exceeded one insignificantly on the 1st day after vaccination in the 1st year of life. In the 2nd year of life, however, the SMRs for SUD cases within 1 day of vaccination with vaccine A were 31.3 (95% CI 3.8-113.1; two cases observed; 0.06 cases expected) and 23.5 (95% CI 4.8-68,6) for within 2 days after vaccination (three cases observed; 0.13 cases expected). Extensive sensitivity analyses could not attribute these findings to limitations of the data sources., Conclusion: These findings based on spontaneous reporting do not prove a causal relationship between vaccination and sudden unexpected deaths. However, they constitute a signal for one of the two hexavalent vaccines which should prompt intensified surveillance for unexpected deaths after vaccination.

Tandem mass spectrometry offers the chance to improve newborn screening (NBS) for phenylketonuria and to expand screening programmes at minimal additional costs. So far, however, there are only limited data available on the incidence of a broader range of disorders presently being considered, their natural course, the benefits achievable and potential harm associated with screening. Based on a literature search and experience from the Bavarian extended screening trial, these questions are addressed using medium-chain acyl-CoA dehydrogenase deficiency (MCADD) as an example. The data retrieved are sufficient for estimation of the incidence of MCADD cases identifiable by NBS and for diagnosis following clinical symptoms. Clinically detected cases ascertained by active surveillance in populations with highly developed and freely accessible health care systems consistently amount to only 33% of those identified by NBS. This difference cannot be explained by the difference in the proportion of the homozygous 985A-->G mutation, which accounts for about 50% of cases identified in NBS. Further research is needed to assess the contribution of MCADD to unexplained deaths in infancy. Retrospective cohort studies enrolling at least 500,000 children would allow for a more precise estimate of the natural course of disease in particular with regard to less severe adverse outcomes. The most relevant gap in knowledge concerns the long-term outcome of children identified following symptoms and by newborn screening. Since randomised controlled trials are unlikely to be feasible on this issue, a standardised documentation protocol should be implemented in follow-up studies for cases identified either by high risk screening or newborn screening. A proposal for the content of such observational studies is made.

Unlabelled: A 7-valent pneumococcal conjugate (7-vPc) vaccine was shown to be highly effective in California preventing 89.1% of all invasive pneumococcal infections (IPI) regardless of serotype. There is concern whether a similar effectiveness will be attained in Germany where 52% of all IPI in children <16 years were caused by the serotypes in the vaccine. The study was based on prospective, active surveillance of IPI in German children aged <16 years during 1997 to 2000. Coverage by the 7-vPc vaccine (with and without 6A) in unvaccinated children in the Kaiser Permanente Trial (KPT) was compared to the coverage in German children in the same age period as in the KPT. The proportion of potentially preventable cases was estimated both for unvaccinated children in the KPT and for Germany by multiplication of the coverage rates with the vaccine efficacy estimate from the KPT (intention to treat analysis). Successful serotyping could be attained for 38.3% of the 1,743 German IPI cases. In the age period from 7 to 43 months concerned in the KPT, the proportion of cases with serotypes covered by the 7-vPc vaccine (+6A) was 91% (95% CI 80%-97%) in the unvaccinated children in the KPT compared to 76% (95% CI 71%-80%) in Germany. The respective estimates for the number of potentially preventable IPI cases were 85% (95% CI 75%-91%) in the KPT compared to 71% (95% CI 67%-75%) in Germany., Conclusion: Age specific serotype coverage rates have to be considered for extrapolation of the Kaiser Permanente Trial to the German situation. Although 14% lower than in the Kaiser Permanente Trial, 71% of potentially preventable cases of invasive pneumococcal infection still predict an excellent effectiveness for the 7-valent pneumococcal conjugate vaccine in Germany.

Unlabelled: Overweight and obesity are major public health issues. Childhood obesity often persists throughout adulthood. Recently a higher prevalence of obesity in adults whose mothers smoked during pregnancy was reported. The aim of this study was to assess whether this association is also detectable in pre-school children in a different setting and to identify the critical period for intrauterine exposure to inhaled smoke products in pregnancy. We analysed questionnaire data on early feeding and lifestyle factors of 8,765 German children aged 5.00 to 6.99 years. Obesity was defined as a body mass index >97th percentile. The prevalence estimates for obesity were: mother never smoked 2.8% (95% CI 2.4%-3.2%), smoked after pregnancy only 1.6% (95%CI 0.4%-4.1%), smoked throughout pregnancy 6.2% (95% CI 4.5%-8.3%), smoked before pregnancy, but not throughout 4.5% (95%CI 3.6%-5.7%). These associations could not be explained by confounding due to a number of constitutional, sociodemographic and lifestyle factors. The unadjusted/adjusted odds ratios were: smoked during pregnancy: 2.32 (95% CI 1.63%-3.30%)/1.92 (95% CI 1.29%-2.86%); smoked before, but not throughout pregnancy: 1.67 (95%CI 1.26%-2.22%)/1.74 (95%CI 1.29%-2.34%)., Conclusion: the association of maternal smoking in pregnancy and obesity was also detectable in children at school entry. Since smoking after pregnancy was not associated with childhood obesity, intrauterine exposure rather than family lifestyle factors associated with smoking appears to be instrumental. There appears to be a role for early intrauterine exposure.