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Objective To evaluate the implementation of switch from intravenous-to-oral antibiotic therapy with amoxicillin in neonates with early-onset infection (EOI). Design, setting and patients A population-based multicentre cohort study. All term-born neonates with EOI were prospectively included between 1 December 2018 to 30 November 2020. Intervention Intravenous-to-oral switch antibiotic therapy in clinically stable neonates. Main outcome measures The primary outcome was readmission due to infection. Secondary outcomes were days of hospitalisation and antibiotic use in the pre-implementation versus post implementation period. Results During 2 years, 835 neonates commenced antibiotics for EOI (1.5% (95% CI 1.4% to 1.6%)) of all term live births). Of those, 554 (66%) underwent a full course of treatment. There were 23 episodes of culture-proven infection (0.42 per 1000 term live births (95% CI 0.27 to 0.63)). A total of 478 of 531 (90%) neonates with probable infection underwent switch therapy. None was readmitted due to infection. The median duration of hospitalisation was 3.0 days (IQR 2.5–3.5) and 7.4 days (IQR 7.0–7.5) in the switch and intravenous therapy groups, respectively. According to antibiotic surveillance data, 1.2% underwent a full course of treatment following implementation of oral switch therapy (2019–2020), compared with 1.2% before (2017–2018). Conclusion In clinical practice, switch therapy was safe and used in 9 of 10 neonates with probable EOI. Knowledge of the safety of antibiotic de-escalation is important as home-based oral therapy ameliorates the treatment burden for neonates, caregivers and healthcare systems. Despite the ease of oral administration, implementation of switch therapy did not increase the overall use of antibiotics., Objective: To evaluate the implementation of switch from intravenous-to-oral antibiotic therapy with amoxicillin in neonates with early-onset infection (EOI). Design, setting and patients: A population-based multicentre cohort study. All term-born neonates with EOI were prospectively included between 1 December 2018 to 30 November 2020. Intervention: Intravenous-to-oral switch antibiotic therapy in clinically stable neonates. Main outcome measures: The primary outcome was readmission due to infection. Secondary outcomes were days of hospitalisation and antibiotic use in the pre-implementation versus post implementation period. Results: During 2 years, 835 neonates commenced antibiotics for EOI (1.5% (95% CI 1.4% to 1.6%)) of all term live births). Of those, 554 (66%) underwent a full course of treatment. There were 23 episodes of culture-proven infection (0.42 per 1000 term live births (95% CI 0.27 to 0.63)). A total of 478 of 531 (90%) neonates with probable infection underwent switch therapy. None was readmitted due to infection. The median duration of hospitalisation was 3.0 days (IQR 2.5-3.5) and 7.4 days (IQR 7.0-7.5) in the switch and intravenous therapy groups, respectively. According to antibiotic surveillance data, 1.2% underwent a full course of treatment following implementation of oral switch therapy (2019-2020), compared with 1.2% before (2017-2018). Conclusion: In clinical practice, switch therapy was safe and used in 9 of 10 neonates with probable EOI. Knowledge of the safety of antibiotic de-escalation is important as home-based oral therapy ameliorates the treatment burden for neonates, caregivers and healthcare systems. Despite the ease of oral administration, implementation of switch therapy did not increase the overall use of antibiotics.

Background: In the SafeBoosC-III trial, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth did not reduce the incidence of death or severe brain injury in extremely preterm infants at 36 weeks’ postmenstrual age, as compared with usual care. Despite an association between severe brain injury diagnosed in the neonatal period and later neurodevelopmental disability, this relationship is not always strong. The objective of the SafeBoosC-III follow-up study is to assess mortality, neurodevelopmental disability, or any harm in trial participants at 2 years of corrected age. One important challenge is the lack of funding for local costs for a trial-specific assessment. Methods: Of the 1601 infants randomised in the SafeBoosC-III trial, 1276 infants were alive at 36 weeks’ postmenstrual age and will potentially be available for the 2-year follow-up. Inclusion criteria will be enrollment in a neonatal intensive care unit taking part in the follow-up study and parental consent if required by local regulations. We aim to collect data from routine follow-up programmes between the ages of 18 and 30 months of corrected age. If no routine follow-up has been conducted, we will collect informal assessments from other health care records from the age of at least 12 months. A local co-investigator blinded to group allocation will classify outcomes based on these records. We will supplement this with parental questionnaires including the Parent Report of Children’s Abilities—Revised. There will be two co-primary outcomes: the composite of death or moderate or severe neurodevelopmental disability and mean Bayley-III/IV cognitive score. We will use a 3-tier model for prioritisation, based on the quality of data. This approach has been chosen to minimise loss to follow-up assuming that little data is better than no data at all. Discussion: Follow-up at the age of 2 years is important for intervention trials in the newborn period as only time can show r

Background: Heavy alcohol use during pregnancy can harm the fetus, but the relation to most obstetric outcomes remains unclear. We therefore aimed to describe maternal characteristics and estimate the association between heavy prenatal alcohol exposure and 22 adverse obstetric and birth outcomes. Methods: We carried out a Danish nationwide register-based historical cohort study, including all singleton births from Jan 1, 1996, to Dec 31, 2018. Births of women who had emigrated to Denmark were excluded from the study due to missing data and women who migrated within 1 year before or during pregnancy were also excluded due to loss to follow-up. Data were extracted from the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Prescription Registry, the Danish Civil Registration System, and the Population Education Register. Logistic regression models were used to estimate crude and adjusted odds ratios (ORs) of obstetric and birth outcomes. Heavy alcohol use was defined by hospital contacts for alcohol-attributable diagnoses given to the mother, her infant, or both, or maternal redeemed prescriptions for drugs to treat alcohol dependence within 1 year before or during pregnancy. Findings: Of 1 191 295 included births, 4823 (0·40%) were defined as heavily alcohol-exposed and 1 186 472 were categorised as a reference group with no identified heavy prenatal alcohol exposure. Heavy-alcohol-exposed births more often had mothers with psychiatric diagnoses (49·8% vs 9·6%), substance use (22·0% vs 0·4%), tobacco use (64·3% vs 15·8%), and low educational level (64·1% vs 17·6%) than did the reference group. For heavy-alcohol-exposed births, significantly increased adjusted ORs were found for small for gestational age (OR 2·20 [95% CI 1·97–2·45]), preterm birth (OR 1·32 [1·19–1·46]), haemorrhage in late pregnancy (OR 1·25 [1·05–1·49]), and preterm prelabour rupture of membranes (OR 1·18 [1·00–1·39]). Decreased adjusted ORs were found for pos

Objectives Prematurity, being small for gestational age and early neonatal ward admission are the major neonatal conditions that may interfere with breastfeeding supportive practices in infants born at gestational age ≥35+0 weeks. We aimed to investigate the associations between gestational age, small for gestational age, early neonatal ward admission and exclusive breastfeeding at one and four months. Methods A register-based cohort-study of all Danish singletons with gestational age ≥35+0 weeks born in 2014–2015. In Denmark, health visitors routinely conduct free home visits throughout infants’ first year and thereby report breastfeeding data to The Danish National Child Health Register. These data were linked with data from other national registers. Logistic regression models estimated the odds ratio for exclusive breastfeeding at one and four months, adjusted for confounding variables. Results The study population comprised 106,670 infants. Compared to gestational age 40 weeks, the adjusted odds ratio for exclusive breastfeeding at one month showed a decreasing tendency from gestational age ≥42 (n = 2,282) (1.07; 95% confidence interval (CI) 0.97–1.17) to 36 weeks (n = 2,062) (0.80; 95% CI 0.73–0.88). Small for gestational age (n = 2,342) was associated with decreased adjusted odds ratio for exclusive breastfeeding at one month (0.84; 95% CI 0.77–0.92). Neonatal ward admission was associated with increased adjusted odds ratio for exclusive breastfeeding at one month among late preterm infants (gestational age 35–36 weeks; n = 3,139) (1.31; 95% CI 1.12–1.54), as opposed to among early term (gestational age 37–38 weeks; n = 19,171) (0.84; 95% CI 0.77–0.92) and term infants (gestational age >38 weeks; n = 84,360) (0.89; 95% CI 0.83–0.94). The associations seemed to persist at four months. Conclusions Decreasing gestational age and small for gestational age were associated with decreased exclusive breastfeeding rates. Ne, Objectives Prematurity, being small for gestational age and early neonatal ward admission are the major neonatal conditions that may interfere with breastfeeding supportive practices in infants born at gestational age ≥35+0 weeks. We aimed to investigate the associations between gestational age, small for gestational age, early neonatal ward admission and exclusive breastfeeding at one and four months. Methods A register-based cohort-study of all Danish singletons with gestational age ≥35+0 weeks born in 2014–2015. In Denmark, health visitors routinely conduct free home visits throughout infants’ first year and thereby report breastfeeding data to The Danish National Child Health Register. These data were linked with data from other national registers. Logistic regression models estimated the odds ratio for exclusive breastfeeding at one and four months, adjusted for confounding variables. Results The study population comprised 106,670 infants. Compared to gestational age 40 weeks, the adjusted odds ratio for exclusive breastfeeding at one month showed a decreasing tendency from gestational age ≥42 (n = 2,282) (1.07; 95% confidence interval (CI) 0.97–1.17) to 36 weeks (n = 2,062) (0.80; 95% CI 0.73–0.88). Small for gestational age (n = 2,342) was associated with decreased adjusted odds ratio for exclusive breastfeeding at one month (0.84; 95% CI 0.77–0.92). Neonatal ward admission was associated with increased adjusted odds ratio for exclusive breastfeeding at one month among late preterm infants (gestational age 35–36 weeks; n = 3,139) (1.31; 95% CI 1.12–1.54), as opposed to among early term (gestational age 37–38 weeks; n = 19,171) (0.84; 95% CI 0.77–0.92) and term infants (gestational age >38 weeks; n = 84,360) (0.89; 95% CI 0.83–0.94). The associations seemed to persist at four months. Conclusions Decreasing gestational age and small for gestational age were associated with decreased exclusive breastfeeding rates. Neonatal ward admission was associated wit

Background Heavy prenatal alcohol exposure is harmful and can lead to fetal alcohol spectrum disorders. A systematic review and meta-analysis identified 428 comorbidities in individuals with fetal alcohol spectrum disorders, and reported pooled prevalence estimates. We aimed to investigate overall risk of morbidities in heavy prenatal alcoholexposed children by estimating risk of the identified comorbidities, and previously unidentified diseases and healthrelated problems. Methods Our Danish nationwide register-based cohort study included all singleton births. Individuals were followed up to age 18 years, between 1996 and 2018. Stillbirths and children of immigrants were not included in the study, and births of women who migrated within 1 year before or during pregnancy were also excluded due to loss to follow-up. Data on health and education were extracted from the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Prescription Registry, the Danish Civil Registration System, and the Population Education Register. We estimated crude and standardised risk differences of hospital diagnoses. Heavy prenatal alcohol exposure was defined by hospital contacts with alcohol-attributable diagnoses given to the mother or her child, or by maternal redeemed prescriptions for drugs to treat alcohol dependence 1 year before or during pregnancy. Findings Of 1407 689 identified singleton births, 219 186 were excluded for reasons including they were born to immigrants, lost to follow-up, or were stillbirths. Of the remaining 1 188 503 children, 4799 (0·4%) had heavy prenatal alcohol exposure and 1 183704 (99·6%) were classified as non-alcohol-exposed births. 578179 (48·6%) babies were female and 610 324 (51·4%) were male. We found 234 of 428 previously identified comorbidities in individuals with fetal alcohol spectrum disorder, of which 29 conditions had a standardised risk difference o, Background: Heavy prenatal alcohol exposure is harmful and can lead to fetal alcohol spectrum disorders. A systematic review and meta-analysis identified 428 comorbidities in individuals with fetal alcohol spectrum disorders, and reported pooled prevalence estimates. We aimed to investigate overall risk of morbidities in heavy prenatal alcohol-exposed children by estimating risk of the identified comorbidities, and previously unidentified diseases and health-related problems. Methods: Our Danish nationwide register-based cohort study included all singleton births. Individuals were followed up to age 18 years, between 1996 and 2018. Stillbirths and children of immigrants were not included in the study, and births of women who migrated within 1 year before or during pregnancy were also excluded due to loss to follow-up. Data on health and education were extracted from the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Prescription Registry, the Danish Civil Registration System, and the Population Education Register. We estimated crude and standardised risk differences of hospital diagnoses. Heavy prenatal alcohol exposure was defined by hospital contacts with alcohol-attributable diagnoses given to the mother or her child, or by maternal redeemed prescriptions for drugs to treat alcohol dependence 1 year before or during pregnancy. Findings: Of 1 407 689 identified singleton births, 219 186 were excluded for reasons including they were born to immigrants, lost to follow-up, or were stillbirths. Of the remaining 1 188 503 children, 4799 (0·4%) had heavy prenatal alcohol exposure and 1 183 704 (99·6%) were classified as non-alcohol-exposed births. 578 179 (48·6%) babies were female and 610 324 (51·4%) were male. We found 234 of 428 previously identified comorbidities in individuals with fetal alcohol spectrum disorder, of which 29 conditions had a standardised risk difference of at least 0·5%, predominantly related to brain f

Background: In the SafeBoosC-III trial, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth did not reduce the incidence of death or severe brain injury in extremely preterm infants at 36 weeks' postmenstrual age, as compared with usual care. Despite an association between severe brain injury diagnosed in the neonatal period and later neurodevelopmental disability, this relationship is not always strong. The objective of the SafeBoosC-III follow-up study is to assess mortality, neurodevelopmental disability, or any harm in trial participants at 2 years of corrected age. One important challenge is the lack of funding for local costs for a trial-specific assessment. Methods: Of the 1601 infants randomised in the SafeBoosC-III trial, 1276 infants were alive at 36 weeks' postmenstrual age and will potentially be available for the 2-year follow-up. Inclusion criteria will be enrollment in a neonatal intensive care unit taking part in the follow-up study and parental consent if required by local regulations. We aim to collect data from routine follow-up programmes between the ages of 18 and 30 months of corrected age. If no routine follow-up has been conducted, we will collect informal assessments from other health care records from the age of at least 12 months. A local co-investigator blinded to group allocation will classify outcomes based on these records. We will supplement this with parental questionnaires including the Parent Report of Children's Abilities-Revised. There will be two co-primary outcomes: the composite of death or moderate or severe neurodevelopmental disability and mean Bayley-III/IV cognitive score. We will use a 3-tier model for prioritisation, based on the quality of data. This approach has been chosen to minimise loss to follow-up assuming that little data is better than no data at all. Discussion: Follow-up at the age of 2 years is important for intervention trials in the newborn period as only time can show real

Congenital hydrops fetalis describes an abnormal accumulation of fluid in two or more compartments in a fetus. The disease is categorized based on the aetiology: immune- and non-immune hydrops fetalis. Today, the nonimmune form is the most common. Once born, the child is initially handled symptomatically and will often needintensive care and treatment. Even though approximately one in five cases is still idiopathic, genetic diagnostictools have become increasingly important in the diagnostic process. The prognosis depends on the aetiology andthe gestational age when diagnosed and at birth, as argued in this review.

Neonatal herpes simplex disease (HSV) is a rare but life-threatening infection associated with high rates of morbidity and mortality. Recent studies indicate that the incidence rate has continued to rise over the past decades, while the mortality remains unchanged. Early clinical suspicion of HSV and parenteral antiviral treatment of acute disease is essential for the prognosis. The subsequent use of suppressive therapy with oral acyclovir has further enhanced the long-term prognosis. This review presents evidence of risk factors, clinical presentation, prevention, and management of HSV in newborns.

Approximately 60% of term newborn infants are jaundiced during the first week of life, which is caused by unconjugated bilirubin. Bilirubin encephalopathy is seen with severe hyperbilirubinaemia, when unbound bilirubin crosses the blood-brain barrier. The chronic form is called kernicterus spectrum disorder. To avoid this devastating condition, the treatment of choice for neonatal hyperbilirubinaemia is phototherapy, which is most efficient with LED light of 478-nm wavelength. In this review, we argue, that a systematic approach to hyperbilirubinaemic infants as well as surveillance of extreme neonatal hyperbilirubinaemia is highly important.

Seizures in the neonatal period are practically always a symptom of an underlying illness. Quick diagnosis and treatment can be crucial to the outcome. A few aetiological factors account for most of the seizures. However, a significant number is caused by rare conditions such as metabolic or genetic disorders, and arriving at the right diagnosis can be challenging. Previous studies indicate, that a standardized algorithm clearly improves the diagnostic success. This article presents an overview of aetiological factors and an algorithm for a standardized work-up.

OBJECTIVES: Several studies suggest a relationship between gestational age at birth and risk of school difficulties. Our study aimed to investigate the association between the entire range of gestational ages and significant school difficulties measured as 1) More than nine hours per week special educational support and 2) Failing to complete compulsory school.METHODS: A population-based register study including all children attending the Danish compulsory school in 2015/2016 and all live-born infants born in Denmark from 1992 to 1997. Data were collected and linked using multiple registers held by Statistic Denmark. Multiple logistic regression analyses were used to estimate the association between gestational age and significant school difficulties, adjusted for explanatory variables.RESULTS: For measurement 1) "Special educational support" 615,789 children entered the analyses after exclusion of those with missing neonatal data. The risk of special educational support increased gradually across the entire range of gestation from 40 to ≤24 weeks: The adjusted odds ratio was 1.07 (95% confidence interval 1.03-1.12) at 39 weeks of gestational and 6.18 (95% confidence interval 5.17-7.39) at gestational ages < 28 weeks. For measurement 2) "Failing to complete compulsory school" the cohort consisted of 374,798 children after exclusion of those who died, had emigrated and/or had missing neonatal data. The risk of failing to complete compulsory school increased across the entire range of gestational ages: The adjusted odds ratio was 1.07 (95% confidence interval 1.04-1.10) at 39 weeks of gestation and 2.99 (95% confidence interval 2.41-3.71) at gestational ages < 28 weeks. In both sets of analyses GA = 40 weeks was used as reference.CONCLUSIONS: We confirm a clear association between the degree of prematurity and significant school difficulties across the entire range of gestational ages from ≤ 24 to 40 weeks.

OBJECTIVE: To describe the incidence, age at diagnosis, and associations between perinatal risk factors of feeding and eating disorders (FED) diagnosed at hospital in children aged 0 to 3 years.METHODS: A nationwide cohort of 901 227 children was followed until 48 months of age in the national registers from 1997 to 2010. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) for FED diagnosis according to the International Classification of Diseases and associations with perinatal risk factors.RESULTS: A total of 1365 children (53% girls) were diagnosed with FED at hospital, corresponding to a cumulative incidence of 1.6 per 1000 live births. High risk of FED was seen in children born before gestational week 28 (HR, 3.52; 95% confidence interval [CI], 2.15-5.78). HRs were 3.74 for children small for gestational age ≤3 SD (95% CI, 2.71-5.17) and 4.71 in those with congenital malformations (95% CI, 3.86-5.74). Increased risk of FED was associated with female gender (HR, 1.2; 95% CI, 1.08-1.34), maternal smoking in pregnancy (HR, 1.24; 95% CI, 1.08-1.42), immigrant status (HR, 2.24; 95% CI, 1.92-2.61), and being the firstborn (HR, 1.33; 95% CI, 1.19-1.50).CONCLUSIONS: FED in referred children aged 0 to 3 years are associated with perinatal adversities, female gender, maternal smoking in pregnancy, being firstborn, and having immigrant parents. The results suggest complex causal mechanisms of FED and underscore the need for a multidisciplinary approach in the clinical management of young children with persistent problems of feeding, eating, and weight faltering.

The passage of foetal blood into maternal circulation is termed a foetomaternal haemorrhage (FMH). Most cases are clinically insignificant. However, in some cases a large FMH causes serious anaemia in the newborn child. Flow cytometry is a precise and fast method to analyse maternal blood for FMH and can be used both antenatally and postnatally. The clinician should consider using the analysis in cases of unexplained anaemia. We describe a case with severe FMH.

The aim of this study was to obtain Ages and Stages Questionnaire (ASQ) scores from the background population so that these may be used as a reference group to extremely preterm children at nine and 18 months of corrected age.

Aim To determine if adolescents who are born very preterm (<32wks; of gestation) and/or with very low birthweight (VLBW; <1500g) have a higher risk of experiencing clinically significant anxiety problems. Method We used a systematic review and meta-analysis. We searched the databases ISI Web of Knowledge, PubMed, PsycNET, Educational Resources Information Center (ERIC), Latin American and Caribbean Literature on the Health Sciences (LILACS), and Virtual Health Library (VHL) with equivalent search expressions (from the databases inception to June 2011). Also, we screened reference lists of identified articles. We selected casecontrol studies of adolescents 11 to 20 years old who were very preterm/VLBW and had a matched reference group born at term with normal birthweight that reported a validated anxiety outcome measure. For data extraction, two authors independently reviewed titles, abstracts, and full articles identified through the searches. Subsequently two authors independently extracted data. Results We included six studies with 1519 adolescents (787 very preterm/VLBW, 732 comparisons). The general risk of developing clinically significant anxiety problems was nearly doubled (p<0.05) in the very preterm/VLBW population (OR 2.27, 95% confidence interval 1.154.47). The overall prevalences were 9.9% in the very preterm/VLBW group and 5.5% in the comparison group. Interpretation Those born very preterm/VLBW have an increased risk of developing clinically significant anxiety problems in adolescence.

Studies on high-risk singleton gestations have shown a preventive effect of progesterone treatment on preterm delivery. This study was conducted to investigate the preventive effect of vaginal micronized progesterone in a large population of twin gestations.

Progesterone treatment reduces the risk of preterm delivery in high-risk singleton pregnancies. Our aim was to evaluate the preventive effect of vaginal progesterone in high-risk twins.

To investigate the risk of developing psychiatric disorders in individuals born prematurely (born before 37 weeks of gestation).

Randomised studies have demonstrated the efficacy of hypothermia for the treatment of perinatal hypoxic-ischaemic encephalopathy (HIE) in term or late preterm infants. In August 2006, the Neonatology Department at Rigshospitalet, Copenhagen, introduced total body cooling for infants born at term with HIE.

Udgivelsesdato: 13. oktober