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Objectives Nutritional support during the neonatal and postoperative period in congenital diaphragmatic hernia (CDH) is challenging and controversial. We aimed to report on early enteral nutritional support in symptomatic CDH patients during the pre- and postoperative period, including feasibility, associated factors with established full enteral nutrition, and weight at birth, discharge, and 18 months. Methods We retrospectively collected data on nutrition: type and volume of enteral nutrition and parental support. Enteral feeding was introduced preoperatively from day 1 after birth, increased step-wised (breastmilk preferred), and resumed after CDH repair on the first postoperative day. Baseline data were available from our CDH database. Results From 2011 to 2020, we identified 45 CDH infants. Twenty-two were girls (51.1%), 35 left sided (77.8%), and 40 underwent CDH repair (88.9%). Median (interquartile range) length of stay in the pediatric intensive care unit was 14.6 days (6.0–26.5), and 1-year mortality was 17.8%.Postoperatively, 120 and 160 mL/kg/d of enteral nutrition was achieved after a median of 6.5 (3.6–12.6) and 10.6 (7.6–21.7) days, respectively. In total, 31 (68.9%) needed supplemental parenteral nutrition in a median period of 8 days (5–18), and of those 11 had parenteral nutrition initiated before CDH repair. No complications to enteral feeding were reported. Conclusion Early enteral nutrition in CDH infants is feasible and may have the potential to reduce the need for parental nutrition and reduce time to full enteral nutrition in the postoperative period.

In 2014, in the United States, nearly 7% of newborns were twins. Congenital heart defects (CHDs) are more frequent in both monozygotic and dizygotic twins than in singletons. Still, the longer-term prognosis for CHD twins is unknown. Here we assess the mortality pattern for CHD twins up to age 36 years and compare it with that for non-CHD twins, non-CHD co-twins, and CHD singletons. We identified all twins and a 5% random sample of all singletons born in Denmark from 1977 to 2009 by linking Danish national population and health registers. CHD cases were defined as subjects having a primary inpatient diagnosis of CHD (excluding preterm ductus) within the first year of life, and mortality was assessed through 2013. Among 63,362 live-born twin individuals, a total of 373 twins (0.59%) had a CHD diagnosis, whereas the corresponding numbers for singletons were 383 of 98,647 (0.39%). During the follow-up, 82 (22.0%) CHD twins died compared with 91 (23.8%) CHD singletons (p = 0.56). Despite a 5 times higher proportion of prematurity, CHD twins had a tendency toward only a moderately increased neonatal mortality compared with CHD singletons (hazard ratio 1.5, 95% confidence interval 0.94 to 2.5), and after the neonatal period up to age 36 the tendency was reversed (hazard ratio 0.8, 95% confidence interval 0.5 to 1.2). A potential underlying mechanism for this mortality pattern is selective intrauterine and neonatal mortality of twins with the most severe CHD. In conclusion, the study indicates that the overall survival prognosis for CHD twins is similar to that of CHD singletons. In 2014, in the United States, nearly 7% of newborns were twins. Congenital heart defects (CHDs) are more frequent in both monozygotic and dizygotic twins than in singletons. Still, the longer-term prognosis for CHD twins is unknown. Here we assess the mortality pattern for CHD twins up to age 36 years and compare it with that for non-CHD twins, non-CHD co-twins, and CHD singletons. We identified all twins and a 5% random sample of all singletons born in Denmark from 1977 to 2009 by linking Danish national population and health registers. CHD cases were defined as subjects having a primary inpatient diagnosis of CHD (excluding preterm ductus) within the first year of life, and mortality was assessed through 2013. Among 63,362 live-born twin individuals, a total of 373 twins (0.59%) had a CHD diagnosis, whereas the corresponding numbers for singletons were 383 of 98,647 (0.39%). During the follow-up, 82 (22.0%) CHD twins died compared with 91 (23.8%) CHD singletons (p = 0.56). Despite a 5 times higher proportion of prematurity, CHD twins had a tendency toward only a moderately increased neonatal mortality compared with CHD singletons (hazard ratio 1.5, 95% confidence interval 0.94 to 2.5), and after the neonatal period up to age 36 the tendency was reversed (hazard ratio 0.8, 95% confidence interval 0.5 to 1.2). A potential underlying mechanism for this mortality pattern is selective intrauterine and neonatal mortality of twins with the most severe CHD. In conclusion, the study indicates that the overall survival prognosis for CHD twins is similar to that of CHD singletons.

A cohort of 1,749 newborns from the municipality of Odense, born during 1995 at the Odense University Hospital, were followed up prospectively for the development of cow's milk protein allergy/intolerance (CMPA/I) during the first year of life. Once a diagnosis of CMPA/I was confirmed, a milk-free diet was continued until a new milk challenge had shown development of tolerance. All infants with CMPA/I were rechallenged at 12 months of age and, in the event of continued clinical sensitivity to cow's milk protein, controlled rechallenges were performed every 6 months up to 3 years of age; and thereafter every 12 months until the age of 15 years. From the same birth cohort, 276 infants were randomly selected at birth for prospective non-interventional follow-up in order to investigate the natural course of sensitization and development of atopic disease during childhood. Standardized questionnaires on atopic heredity, environmental factors and presence of atopic symptoms were answered at 0, 6, 12 and 18 months and at 5, 10 and 15 years of age. Interviews on atopic history and environmental factors as well as physical examination were carried out at 18 months, 5, 10 and 15 years of age. Skin prick test and specific sIgE (Pharmacia CAP) testing were performed at 18 months, 5, 10 and 15 years of age against a panel of inhalant allergens (birch, grass, mugwort, dog, cat, horse, Dermatophagoidespteronyssinus, Dermatophagoides farinae, alternaria and cladosporium herbarum). Furthermore, lung function measurements were performed in children when 10 and 15 years of age. Based on controlled milk elimination and challenge procedures, the diagnosis of CMPA/I was confirmed in 39 out of 117 infants, with symptoms suggestive of CMPA/I, thus resulting in a 1-year incidence of CMPA/I of 2.2%. The overall prognosis of CMPA/I was good, with a total recovery of 56% at 1 year, 77% at 2 years, 87% at 3 years, 92% at 5 and 10 years and 97% at 15 years of age. In children younger than 10 years of age, 41% developed asthma and 31% rhinoconjunctivitis. Children with non-IgE-mediated CMPI had a good prognosis, whereas children with IgE-mediated CMPA in early childhood had a significantly increased risk for persistent CMPA, development of other food allergies, asthma and rhinoconjunctivitis. During early infancy, recurrent wheezing was the most prevalent disease (20%), followed by atopic dermatitis (14%) and food allergy (7%) at 18 months of age. Physician diagnosed asthma increased from 2% at 1.5 years of age to 9% at 10 years of age. Rhinoconjunctivitis increased from or = class 2; CAP RAST) showed a low rate of sensitization among asymptomatics (3%, 10% and 12%) compared with higher rates of sensitization of 8%, 39% and 30% among symptomatic atopics at 1.5, 5 and 10 years of age respectively. The highest rate of sensitization (53%) was found among children with current asthma at 10 years of age.

We hereby describe a case report of a 9-month-old girl, who was accidentally intoxicated with digoxin since her parents by mistake gave her digoxin instead of propranolol. At admission sinusbradycardia and a first-degree atrioventricular block was found and she was treated with antidigitalis Fab-fragment and atropine. After three days of hospitalization she was discharged well-being. We suspect that the explanation for this intoxication is due to confusion of bottles of magistral preparations of medicine, as they were very identical. Therefore we call for increased attention in children receiving this type of medicine.

Danes are unrivalled in satisfaction with life. The University of Leicester recently published the World Map of Happiness (http://news.bbc.co.uk/2/shared/bsp/hi/pdfs/28\_07\_06\_happiness\_map.pdf) with Denmark as number one. For more than 30 years this country with five million inhabitants has ranked first in Eurobarometer surveys (europa.eu.int/comm/public\_opinion/index\_en.htm). More than two thirds of Danes are “very satisfied” with their lives according to these surveys. In no other Eurobarometer country has this proportion exceeded a half, and for most of the countries the proportion is less than a third (figure)⇓. To explain Danish contentment we sifted through literature, statistics, and common knowledge. Proportion who report to be very satisfied in 15 EU countries according to Eurobarometers (europa.eu.int/comm/public\_opinion/index\_en.htm) We focused on accounting for why life satisfaction in Denmark substantially exceeds that in Sweden and Finland, the two Eurobarometer countries most similar to Denmark. We have ordered our hypotheses roughly from most to least implausible. Hair colour —It may indeed be the case that “blondes have more fun.” This hypothesis was launched in the 1950s by a commercial slogan for a hair dye and was cemented in popular culture in 1978 by rock musician Rod Stewart's album of the same title. Sweden, however, has a higher prevalence of blondes than Denmark.1 Genes —Genetic factors might influence differences in life satisfaction within a country,2 and Danes might have a special genetic constitution. Genotypes in Sweden, however, are similar to those in Denmark because most Swedes were Danes until the 17th century. Food— Meals in Denmark can be politely described as unmemorable. “Danish cuisine” is an oxymoron, except perhaps the open faced “butter breads” that accompany the beer and aquavit Danes consume for lunch. Older Danes satisfy their hunger with potatoes, gravy, and a bit of pork, and younger ones devour hotdogs, hamburgers, and Baltic-style pizzas. Danish …

Background— Smaller studies and many case series reports indicate that congenital heart defects may be more common in monochorionic twins than in dichorionic twins and singletons. Methods and Results— We investigated congenital heart defect occurrence in all twins and 5% of all singletons born in Denmark in 1977–2001 and followed through 2006 by linking the Danish Twin Registry and Statistics Denmark registers including the National Medical Birth Register and the Danish National Patient Register. Among 41 525 twin individuals, a total of 584 twins (1.4%) had a congenital heart defect registered in the Danish National Patient Register, whereas the corresponding numbers for singletons were 648 of 74 473 (0.87%; P 3 times as often in twins as in singletons, at 3.9 (95% confidence interval, 2.6–5.8) and 3.1 (95% confidence interval, 1.5–6.4), respectively. The increased occurrence in twins was also found in sensitivity analyses including only inpatients or only surgically treated cases regardless of whether preterm patent ductus arteriosus was included. We were not able to demonstrate a higher risk for congenital heart defect among monozygotic twins compared with dizygotic twins, and the congenital heart defect occurrence was also increased in dizygotic twins, who are all dichorionic. Conclusions— Congenital heart defect is more common in twins than in singletons, and the increased occurrence is not restricted to monochorionic twins. Intrauterine surveillance and a postnatal comprehensive cardiac assessment for both twins may be considered regardless of chorionicity and zygosity.

The aim of this study was to explore, in a large and non-censored twin cohort, the nature (i.e., additive versus non-additive) and magnitude (i.e., heritability) of genetic influences on inter-individual differences in hu- man longevity. The sample comprised all identified and traced non-emigrant like-sex twin pairs born in Denmark during the period 1870-1900 with a zygosity diagnosis and both members of the pairs surviving the age of 15 years. A total of 2872 pairs were included. Age at death was obtained from the Danish Central Person Register, the Danish Cause-of-Death Register and various other registers. The sample was almost non-censored on the date of the last follow-up (May 1, 1994), all but 0.6% had died, leaving a total of 2872 pairs for analysis. Proportions of variance attributable to genetic and environmental factors were assessed from variance-covariance matrices using the structural equation model approach. The most parsi- monious explanation of the data was provided by a model that included genetic dominance (non-additive genetic ef- fects caused by interaction within gene loci) and non-shared environmental factors (environmental factors that are in- dividual-specific and not shared in a family). The heri- tability of longevity was estimated to be 0.26 for males and 0.23 for females. The small sex-difference was caused by a greater impact of non-shared environmental factors in the females. Heritability was found to be constant over the three 10-year birth cohorts included. Thus, longevity seems to be only moderately heritable. The nature of ge- netic influences on longevity is probably non-additive and environmental influences non-shared. There is no evi- dence for an impact of shared (family) environment.

Tetralogy of Fallot is the most common cyanotic heart disease accounting for 5 to 8% of all cases of congenital heart disease. In a cohort of women with corrected Tetralogy of Fallot, followed concerning fertility and pregnancy outcome, we observed two cases of uncomplicated multiple pregnancies. Such pregnancies have not previously been described. Despite the overload on the operated heart resulting from a multiple pregnancy, both women experienced uncomplicated pregnancies and deliveries of healthy children. This reflects the good hemodynamic results of complete repair and meticulous pregnancy follow-up.

Objectives To determine whether twins in recent\ud cohorts show similar academic performance in\ud adolescence to singletons and to test the effect of\ud birth weight on academic performance in twins and\ud singletons.\ud Design Follow-up study.\ud Setting Denmark.\ud Participants All twins (n = 3411) and a 5% random\ud sample of singletons (n = 7796) born in Denmark\ud during 1986-8.\ud Main outcome measures Test scores in ninth grade\ud (age 15 or 16), birth weight, gestational age at birth,\ud parents’ age, and parents’ education.\ud Results Ninth grade test scores were normally\ud distributed, with almost identical mean and standard\ud deviations for twins and singletons (8.02 v 8.02 and\ud 1.05 v 1.06) despite the twins weighing on average\ud 908 g (95% confidence interval 886 to 930 g) less\ud than the singletons at birth. Controlling for birth\ud weight, gestational age at birth, age at test, and\ud parents’ age and education confirmed the similarity of\ud test scores for twins and singletons (difference 0.04,\ud 95% confidence interval − 0.03 to 0.10). A significant,\ud positive association between test score and birth\ud weight was observed in both twins and singletons, but\ud the size of the effect was small: 0.06-0.12 standard\ud deviations for every kilogram increase in birth weight.\ud Conclusions Although older cohorts of twins have\ud been found to have lower mean IQ scores than\ud singletons, twins in recent Danish cohorts show\ud similar academic performance in adolescence to that\ud of singletons. Birth weight has a minimal effect on\ud academic performance in recent cohorts; for twins\ud this effect is best judged relative to what is a normal\ud birth weight for twins and not for singletons.

An inverse association between height and risk of coronary heart disease (CHD) is well demonstrated, but it is not known whether this association is because of genetic factors, socioeconomic background, or other environmental factors. Four population-based twin cohorts with register-based follow-up data on CHD mortality from Denmark (1966-1996), Finland (1975-2001), and Sweden (1963-2001 and 1972-2001) were used to investigate this question; response rates varied between 65% and 86%. Together, the cohorts included 74,704 twin individuals (35,042 complete twin pairs) with 5,943 CHD deaths during 1.99 million person-years of follow-up. Cox and conditional logistic regression models were used. Per 1-standard deviation decrease in height, height was inversely associated with CHD mortality in men (hazard ratio = 1.08, 95% confidence interval (CI): 1.04, 1.12) and in women (hazard ratio = 1.06, 95% CI: 1.01, 1.10). A twin who had died from CHD was on average shorter than the co-twin within monozygotic pairs (odds ratio = 1.27, 95% CI: 1.12, 1.44, with no sex difference), whereas a weaker association was found within dizygotic pairs in men (odds ratio = 1.01, 95% CI: 0.91, 1.13) and in women (odds ratio = 1.14, 95% CI: 1.01, 1.28). The inverse association between height and CHD mortality found within monozygotic discordant twin pairs suggests that this association is because of environmental factors that directly affect height and CHD risk.

OBJECTIVE: To assess the overall and cause specific mortality of people from birth to 55 years with cleft lip and palate.DESIGN: Long term follow up study.SETTING: Danish register of deaths.PARTICIPANTS: People born with cleft lip and palate between 1943 and 1987, followed to 1998.MAIN OUTCOME MEASURES: Observed and expected numbers of deaths, summarised as overall and cause specific standardised mortality ratios.RESULTS: 5331 people with cleft lip and palate were followed for 170 421 person years. The expected number of deaths was 259, but 402 occurred, corresponding to a standardised mortality ratio of 1.4 (95% confidence interval 1.3 to 1.6) for males and 1.8 (1.5 to 2.1) for females. The increased risk of mortality was nearly constant for the three intervals at follow up: first year of life, 1-17 years, and 18-55 years. The participants had an increased risk of all major causes of death.CONCLUSIONS: People with cleft lip and palate have increased mortality up to age 55. Children born with cleft lip and palate and possibly other congenital malformations may benefit from specific preventive health measures into and throughout adulthood.

AIM: To determine the risk of rehospitalization for respiratory syncytial virus (RSV) infection during the first 2 y of life in extremely preterm infants.METHODS: Records on all rehospitalizations during the first 2 living years of all infants born with gestational age RESULTS: Among 240 eligible infants, 43 (18%) had been rehospitalized 48 times owing to RSV. In infants (n = 210) without CLD the risk of rehospitalization for RSV was 16%, whereas in infants with CLD (n = 30) it was 30% (p = 0.065). Eighteen infants (38%) required respiratory support (supplemental oxygen only 3, continuous positive airway pressure 14, mechanical ventilation 1). Apart from CLD the only factor that could be associated with increased risk of hospitalization for RSV was discharge during autumn (p = 0.05). No infant died from RSV infection.CONCLUSION: The high rate of rehospitalization for RSV in extremely preterm infants in Denmark, especially in infants with CLD, should lead to considerations concerning more widespread use of prophylaxis against RSV in these infants.

Cause-specific mortality data on Danish monozygotic (MZ) and dizygotic (DZ) twins are used to analyze the influence of smoking and body mass index (BMI) on heritability estimates of susceptibility to coronary heart disease (CHD). The sample includes 1209 like-sexed twin pairs born between 1890 and 1920, where both individuals were still alive and answered a questionnaire, including information about smoking, height and weight, in 1966. The analysis was conducted with both sexes pooled due to the relatively small number of twin pairs. Follow-up was conducted from 1 January 1966 to 31 December 1993. We use the correlated gamma-frailty model with observed covariates for the genetic analysis of frailty to account for censoring and truncation in the lifetime data. During the follow-up, 1437 deaths occurred, including 435 deaths due to CHD. Proportions of variance of frailty attributable to genetic and environmental factors were analyzed using the structural equation model approach. Different standard biometric models are fitted to the data to evaluate the magnitude and nature of genetic and environmental factors on mortality. Using the best fitting model without covariates, heritability of frailty to CHD was found to be 0.45 (0.11). This result changes only slightly to 0.54 (0.16) after controlling for smoking and BMI. This analysis underlines the existence of a substantial genetic influence on individual frailty associated with mortality caused by CHD. No evidence for common genetic factors acting on smoking, BMI, and susceptibility to CHD are found which indicates that the association between smoking and susceptibility to CHD and BMI and susceptibility to CHD is not confounded by common genetic factors.

The collectins mannan-binding lectin (MBL) and lung surfactant protein D (SP-D) play a significant role in innate immunity. Structural as wells as promoter variants are known for MBL and different alleles correlate with low MBL concentrations in serum and predispose to infectious diseases. Structural variants are also known for SP-D but these have not been linked to disease states. The aim of the present study was to provide heritability estimates for the constitutional levels of MBL and SP-D in children. A population of 26 monozygotic (MZ) and 36 dizygotic (DZ) like-sexed twin pairs aged 6-9 years was studied. Intraclass correlations were significantly higher in MZ than in DZ twins, indicating substantial genetic influence on both MBL and SP-D levels. Biometric model fitting showed that the estimated heritability was 0.96 (95% CI 0.92-0.97) for MBL with the presence of non-additive genetic factors and non-shared environmental factors and 0.91 (95% CI 0.83-0.95) for SP-D with additive genetic and non-shared environmental factors. The data indicate quantitatively very strong genetic dependence for the serum levels of both MBL and SP-D.

Background: IgE is a major determinant of allergic disease. Twin analysis of serum levels of IgE has been carried out previously in children and adults with heritability estimates of 30% to 70% on the basis of ANOVA. Objective: This study included the analysis of serum IgE in a population of 126 twins, 27 monozygotic pairs and 36 dizygotic pairs, studied at birth (cord blood [CB] IgE) and consecutively at the age of 6 to 9 years of age (serum IgE). Methods: IgE was determined by means of RIA. ANOVA, correlation analysis, and structural equation modeling by maximal likelihood analysis was used for genetic analysis. Results: Structural equation modeling by maximal likelihood analysis showed the best-fitting model to be the AE model (A for additive genetic variance and E for environmental variance) both at birth and later in childhood. The estimated heritability was 0.92 (95% CI, 0.84-0.95) for CB IgE and 0.78 (95% CI, 0.60-0.87) for serum IgE. The correlation between CB IgE and serum IgE was 0.04. Conclusions: The study demonstrated a higher genetic dependency of serum IgE than previously recognized. The low correlation between the IgE levels at birth and later in childhood suggested that different effector mechanisms may be operating at different ages. (J Allergy Clin Immunol 2001;107:659-63.)