Paracetamol overdose in Danish children and adolescents during the Covid-19 restrictions.

INTRODUCTION: To assess the effect of long-term isolation on the mental state of Danish youth. This study aimed to investigate trends in paracetamol overdoses among people under 18 years of age in Denmark during Covid-19 restrictions as an indicator of mental health. METHODS: All patients under the age of 18 years presenting with paracetamol overdose at one of the 18 paediatric departments in Denmark from 2016 to 2021 were included. They were identified in all Danish hospital databases using specific diagnostic codes. RESULTS: From 2016 to 2021, a total of 3,217 people under 18 years of age were admitted for paracetamol overdose. Among these, 86% (n = 2,755) were girls and 14% (n = 462) were boys. During 2020, a slight (7%) decrease in admissions was observed among both boys and girls compared with the preceding four-year mean value. In 2021, the number of overdoses among girls exceeded by 35% the former all-time high from 2016. Furthermore, the number of overdoses among girls exceeded the pre-four-year period mean value by 43%. Among boys, an 8% increase was seen from the highest ever previous value recorded in 2019 and a 23% increase compared with the previous four-year mean value. CONCLUSIONS: During the first year of restrictions, a slight decrease in paracetamol overdoses was observed, possibly associated with limited accessibility. The second year showed a considerable increase in paracetamol overdoses, which may imply an affected mental state among youth during the prolonged lockdown restrictions as seen in previous epidemics. Therefore, further studies are warranted to develop a pandemic preparedness plan to protect general mental health. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Gestational Age, Parent Education, and Education in Adulthood.

BACKGROUND: Adults born preterm (<37 weeks) have lower educational attainment than those born term. Whether this relationship is modified by family factors such as socioeconomic background is, however, less well known. We investigated whether the relationship between gestational age and educational attainment in adulthood differed according to parents' educational level in 4 Nordic countries. METHODS: This register-based cohort study included singletons born alive from 1987 up to 1992 in Denmark, Finland, Norway, and Sweden. In each study population, we investigated effect modification by parents' educational level (low, intermediate, high) on the association between gestational age at birth (25-44 completed weeks) and low educational attainment at 25 years (not having completed upper secondary education) using general estimation equations logistic regressions. RESULTS: A total of 4.3%, 4.0%, 4.8%, and 5.0% singletons were born preterm in the Danish (n = 331 448), Finnish (n = 220 095), Norwegian (n = 292 840), and Swedish (n = 513 975) populations, respectively. In all countries, both lower gestational age and lower parental educational level contributed additively to low educational attainment. For example, in Denmark, the relative risk of low educational attainment was 1.84 (95% confidence interval 1.44 to 2.26) in adults born at 28 to 31 weeks whose parents had high educational level and 5.25 (95% confidence interval 4.53 to 6.02) in adults born at 28 to 31 weeks whose parents had low educational level, compared with a reference group born at 39 to 41 weeks with high parental educational level. CONCLUSIONS: Although higher parental education level was associated with higher educational attainment for all gestational ages, parental education did not mitigate the educational disadvantages of shorter gestational age.

The role of parental education on the relationship between gestational age and school outcomes.

BACKGROUND: Individuals born preterm may experience difficulties beyond the neonatal period, such as poorer school outcomes. However, whether these outcomes are modified by family factors is less well-known. OBJECTIVES: To investigate whether parental educational level modify the relationship of gestational age with completion of final examinations and grade point average in compulsory education. METHODS: This nationwide register-based cohort study included singletons born in Denmark during 1995-2001. We investigated the differences in the associations between gestational age (24-44 weeks) and two school outcomes at 16 years according to parental educational level (lower (≤10 years), intermediate (11-13 years), and higher (>13 years)). Mixed-effect logistic regression and mixed-effect linear regression were used to model completion of final examination and grade point average, respectively. RESULTS: Of the 425 101 singletons, 4.7% were born before 37 weeks. The risk of not completing final examination increased with shorter gestational age and lower parental educational level. For instance, among adolescents whose parents had a lower educational level, the risk increased from 23.9% (95% CI, 23.1, 24.6) for those born in week 40 to 36.6% (95% CI, 31.5, 42.1) for those born in week 28. For adolescents whose parents had a higher educational level, the corresponding risk increase was 5.9% (95% CI, 5.7, 6.1) to 10.5% (95% CI, 8.6, 12.8), respectively. Grade point average decreased with shorter gestational age in adolescents born before 30 weeks and with lower parental educational level. The associations between gestational age and grade point average were similar across parental educational levels. For completions of final examination, the associations with gestational age were weaker with higher parental educational level. CONCLUSIONS: Shorter gestational age and lower parental educational level were associated with poorer school outcomes. Our findings suggest that parental educational level mitigates the adverse effects of shorter gestational age on some school outcomes.

Gestational Age and Socioeconomic Achievements in Young Adulthood: A Danish Population-Based Study.

Importance: The poor health outcomes associated with preterm birth are well established. However, it is less clear how small variations in gestational age, even within the term range, are associated with long-term opportunities and well-being, as measured by socioeconomic outcomes in adulthood. Objective: To examine the association of gestational age at birth with educational achievement, income, and primary source of income in adulthood. Design, Setting, and Participants: This Danish population-based, register-based cohort study examined all live-born singletons born in Denmark from 1982 to 1986 without congenital anomalies and who lived in Denmark at age 28 years. Data analysis was conducted from November 2, 2017, to June 15, 2018. Exposures: Gestational age at birth in completed weeks (22-45 weeks). Main Outcomes and Measures: Educational attainment, personal income, and primary source of income at age 28 years. Results: In a population of 228 030 singletons (4.0% preterm, 12.1% early term; 49.4% female), 36.3% had a tertiary education at age 28 years. Among adults born at 22 to 27 weeks of gestation, 21.6% had a tertiary education, and 23.2% had an income in the highest tertile. Using 40 weeks of gestation as the reference, the adjusted odds ratio for tertiary education for individuals born at 22 to 27 weeks of gestation was 0.21 (95% CI, 0.13-0.35) and the corresponding figures for 28 to 31, 33, 36, 38, and 43 to 45 weeks of gestation were 0.45 (95% CI, 0.37-0.55), 0.67 (95% CI, 0.54-0.83), 0.84 (95% CI, 0.77-0.93), 0.85 (95% CI, 0.81-0.89), and 0.93 (95% CI, 0.83-1.04), respectively. The adjusted odds ratio for highest income tertile for individuals born at 22 to 27 weeks of gestation was 0.66 (95% CI, 0.41-1.06) and the corresponding figures for 28 to 31, 33, 36, 38, and 43 to 45 weeks of gestation were 0.80 (95% CI, 0.68-0.94), 0.77 (95% CI, 0.63-0.93), 0.89 (95% CI, 0.82-0.96), 0.95 (95% CI, 0.91-0.99), and 1.00 (95% CI, 0.91-1.12), respectively. All estimates were adjusted for sex, birth year, parity, maternal age, maternal education, and maternal country of origin. Conclusions and Relevance: Shorter gestational duration even within the term range was associated with poorer socioeconomic outcomes in adulthood. While adults born at 35 to 38 weeks of gestation experienced only slightly increased risk of adverse socioeconomic outcomes, this may have a significant impact on public health, since a large proportion of all children are born in these weeks.

Association of Short Antenatal Corticosteroid Administration-to-Birth Intervals With Survival and Morbidity Among Very Preterm Infants: Results From the EPICE Cohort.

Importance: Administration-to-birth intervals of antenatal corticosteroids (ANS) vary. The significance of this variation is unclear. Specifically, to our knowledge, the shortest effective administration-to-birth interval is unknown. Objective: To explore the associations between ANS administration-to-birth interval and survival and morbidity among very preterm infants. Design, Setting, and Participants: The Effective Perinatal Intensive Care in Europe (EPICE) study, a population-based prospective cohort study, gathered data from 19 regions in 11 European countries in 2011 and 2012 on 4594 singleton infants with gestational ages between 24 and 31 weeks, without severe anomalies and unexposed to repeated courses of ANS. Data were analyzed November 2016. Exposure: Time from first injection of ANS to delivery in hours and days. Main Outcomes and Measures: Three outcomes were studied: in-hospital mortality; a composite of mortality or severe neonatal morbidity, defined as an intraventricular hemorrhage grade of 3 or greater, cystic periventricular leukomalacia, surgical necrotizing enterocolitis, or stage 3 or greater retinopathy of prematurity; and severe neonatal brain injury, defined as an intraventricular hemorrhage grade of 3 or greater or cystic periventricular leukomalacia. Results: Of the 4594 infants included in the cohort, 2496 infants (54.3%) were boys, and the mean (SD) gestational age was 28.5 (2.2) weeks and mean (SD) birth weight was 1213 (400) g. Mortality for the 662 infants (14.4%) unexposed to ANS was 20.6% (136 of 661). Administration of ANS was associated with an immediate and rapid decline in mortality, reaching a plateau with more than 50% risk reduction after an administration-to-birth interval of 18 to 36 hours. A similar pattern for timing was seen for the composite mortality or morbidity outcome, whereas a significant risk reduction of severe neonatal brain injury was associated with longer administration-to-birth intervals (greater than 48 hours). For all outcomes, the risk reduction associated with ANS was transient, with increasing mortality and risk for severe neonatal brain injury associated with administration-to-birth intervals exceeding 1 week. Under the assumption of a causal relationship between timing of ANS and mortality, a simulation of ANS administered 3 hours before delivery to infants who did not receive ANS showed that their estimated decline in mortality would be 26%. Conclusions and Relevance: Antenatal corticosteroids may be effective even if given only hours before delivery. Therefore, the infants of pregnant women at risk of imminent preterm delivery may benefit from its use.

Improvement in perinatal care for extremely premature infants in Denmark from 1994 to 2011.

INTRODUCTION: Major advances in perinatal care over the latest decades have increased the survival rate of extremely premature infants. Centralisation of perinatal care was implemented in Denmark from 1995. This study evaluates the effect of organisational changes of perinatal care on survival and morbidity of live-born infants with gestational ages (GA) of 22-28 weeks. METHODS: Three cohort studies were included from 1994-1995, 2003 and 2011. Data from live-born infants were extracted regarding risk factors, survival, bronchopulmonary dysplasia (BPD), cystic periventricular leukomalacia (cPVL) and intraventricular haemorrhage grade 3-4 (IVH 3-4). RESULTS: A total of 184, 83 and 127 infants were included from the cohorts. Delivery rates at level 3 Neonatal Intensive Care Unit (NICU) hospitals increased from 69% to 87%. Transfer rates to level 3 NICU almost doubled during the period. Survival rates were stationary, although a trend towards increased survival was observed for infants < 26 weeks. The frequency of infants receiving evidence-based treatment increased from 14% to 46%. IVH 3-4 rates were reduced from 21% to 12%, whereas BPD and cPVL rates did not change. Survival odds increased with higher gestational age and administration of surfactant. CONCLUSIONS: Centralisation of treatment of extremely premature infants has been implemented because more children are being born at highly specialised perinatal centres. Care improved as more infants received evidence-based treatment. IVH 3-4 rates declined. A trend towards increased survival was observed for infants with a GA < 26 weeks. FUNDING: none. TRIAL REGISTRATION: not relevant.

[Multiple mini interviews before the occupation of main training posts in paediatrics]. / Multiple miniinterview før besættelse af pædiatriske hoveduddannelsesstillinger er gennemførlige.

Interviews are mandatory in Denmark when selecting doctors for training positions. We used multiple mini interviews (MMI) at four recruitment rounds for the main training posts in paediatrics. In total, 125 candidates were evaluated and assessed by CV and MMI (4-5 stations). Reliability for individual stations in MMI assessed by Cronbach's alpha was adequate (0.63-0.92). The overall reliability assessed by G-theory was lower, suggesting that different skills were tested. The acceptability was high. Our experiences with MMI suggest good feasibility and reliability. An increasing number of stations may improve the overall reliability.

Cerebral white matter blood flow and arterial blood pressure in preterm infants.

UNLABELLED: It is generally assumed that one reason why white matter injury is common in preterm infants is the relatively poor vascular supply. AIM: To examine whether blood flow to the white matter is relatively more reduced at low blood pressure than is blood flow to the brain as a whole. METHODS: Thirteen normoxic preterm infants had blood flow imaging on 16 occasions with single-photon emission computed tomography (SPECT) using 99Tc labelled hexa-methylpropylenamide oxime (HMPAO) as the tracer. Gestational age was 26-32 weeks. Transcutaneous carbon dioxide was between 4.7 and 8.5 kPa and mean arterial blood pressure between 22 and 55 mmHg. RESULTS: There was no statistically significant direct relation between white matter blood flow percentage and any of the variables. Using non-linear regression, however, assuming a plateau over a certain blood pressure threshold and a positive slope below this threshold, the relation to white matter flow percentage was statistically significant (p = 0.02). The threshold was 29 mmHg (95% confidence limits 26-33). CONCLUSION: Our analysis supports the concept of periventricular white matter as selectively vulnerable to ischaemia during episodes of low blood pressure.

Neonatal cerebral oxygenation is not linked to foetal vasculitis and predicts intraventricular haemorrhage in preterm infants.

AIM: The aim of the study was to compare the cerebral tissue oxygenation index (c-TOI) measured by near infrared spectroscopy (NIRS) in infants with and without foetal vasculitis. METHODS: Twenty-four infants with placental signs of a foetal inflammatory response (FIR), foetal vasculitis, were compared with 39 controls. NIRS examination was done within the first 24 h. RESULTS: Infants with FIR had a significant lower gestational age (26.8 +/- 2.4 vs. 29.8 +/- 2.4 weeks' gestation; p < 0.01), Hb (9.4 +/- 1.2 vs. 10.9 +/- 1.5 mM; p < 0.01) and blood P(CO2) (5.5 +/- 0.8 vs. 6.3 +/- 1.1 kPa, p < 0.01) compared to controls. There was no significant difference in arterial blood pressure, inspiratory oxygen content, needs of mechanical ventilation or c-TOI (73.6 +/- 8.1% vs. 73.9 +/- 8.1% (p = 0.9)). The effect of FIR on c-TOI was -0.3% (95% CI -3.9 to 4.5%). This result was not affected by inclusion of potential confounders in the analysis. Eight infants subsequently developed intra/periventricular haemorrhage: four with minor lesions and four with severe lesions. There was a significant negative correlation between the severity of the intraventricular haemorrhage and the cerebral oxygenation (p = 0.002). CONCLUSION: Cerebral oxygenation was not affected in the first day of life in preterm infants born with foetal vasculitis, while cerebral oxygenation in infants that later developed intraventricular haemorrhage was impaired.

Characteristics of neonatal units that care for very preterm infants in Europe: results from the MOSAIC study.

OBJECTIVES: We sought to compare guidelines for level III units in 10 European regions and analyze the characteristics of neonatal units that care for very preterm infants. METHODS: The MOSAIC (Models of Organising Access to Intensive Care for Very Preterm Births) project combined a prospective cohort study on all births between 22 and 31 completed weeks of gestation in 10 European regions and a survey of neonatal unit characteristics. Units that admitted > or = 5 infants at < 32 weeks of gestation were included in the analysis (N = 111). Place of hospitalization of infants who were admitted to neonatal care was analyzed by using the cohort data (N = 4947). National or regional guidelines for level III units were reviewed. RESULTS: Six of 9 guidelines for level III units included minimum size criteria, based on number of intensive care beds (6 guidelines), neonatal admissions (2), ventilated patients (1), obstetric intensive care beds (1), and deliveries (2). The characteristics of level III units varied, and many were small or unspecialized by recommended criteria: 36% had fewer than 50 very preterm annual admissions, 22% ventilated fewer than 50 infants annually, and 28% had fewer than 6 intensive care beds. Level II units were less specialized, but some provided mechanical ventilation (57%) or high-frequency ventilation (20%) or had neonatal surgery facilities (17%). Sixty-nine percent of level III and 36% of level I or II units had continuous medical coverage by a qualified pediatrician. Twenty-two percent of infants who were < 28 weeks of gestation were treated in units that admitted fewer than 50 very preterm infants annually (range: 2%-54% across the study regions). CONCLUSIONS: No consensus exists in Europe about size or other criteria for NICUs. A better understanding of the characteristics associated with high-quality neonatal care is needed, given the high proportion of very preterm infants who are cared for in units that are considered small or less specialized by many recommendations.

[Neonatal hypernatraemic dehydration--why increasing incidence?]. / Hypernatriaemisk dehydrering hos nyfødte--hvorfor stigende incidens?

INTRODUCTION: Neonatal dehydration with hypernatraemia is a serious condition with risk of cerebral damage and death. Recent studies have reported a rising incidence. MATERIALS AND METHODS: A retrospective study was conducted at Hvidovre Hospital over a 5-year period to identify term or near-term infants (>35 weeks of gestation) who were admitted with a weight-loss >10%. Infants admitted between the 3rd and the 14th day of life with a discharge diagnosis code indicating dehydration were also included. RESULTS: During the period a total of 89 infants were admitted and 24 had hypernatraemia. The incidence increased from 2.1 to 4.9 (RR 2,5-p >0.0008). All infants were breastfed and only 3 had had supplementation prior to admission. The weight-loss ranged between 270 and 1100 grams (equivalent to 10.1-29.7% reduction in birth weight) while lethargy and jaundice were frequent symptoms. Cerebral complications occurred for 8 infants and 2 developed permanent brain damage. CONCLUSIONS: Breastfeeding should be encouraged but supplementation may be necessary for some infants. Infants born to primiparous women, infants heavy for gestational age and infants who do not thrive on day 4-5 appear to have a high risk. These infants could be identified by regular weighing and, if necessary, supplementation and follow-up should be instituted.

[Prognostic value of PET and MRS in the assessment of cerebral status of children]. / Prognostisk vaerdi af PET og MRS ved evaluering af cerebral status hos børn.

We report a case of a 12-week-old previously normal infant with severe brain damage after an episode of asphyxia during an RS-virus infection. Sub-acute MRI was normal, but new functional techniques, PET (positron emission tomography) and MRS (magnetic resonance spectroscopy) were severely abnormal. At an outpatient clinic three months later, he had developed microencephaly and the MRI was now severely abnormal. The case shows the importance of using multimodality functional imaging techniques to assess the cerebral status of infants for prognosis and course of treatment.