Time intervals between pumping did not affect breastmilk protein produced by mothers of preterm infants.

AIM: Few studies investigate factors that might influence the content of expressed breastmilk. This study aims to investigate the influence of the intervals between breastmilk pumping and the time of the day on protein and fat concentration in breastmilk. METHODS: Mothers of very preterm infants in a neonatal ward who expressed more than 400 mL per day were included. Expressed breastmilk was obtained from each mother over 30 h who were pumping at strictly planned and varying intervals: 2, 3, 4 and 6 h. All samples were analysed using infrared transmission spectroscopy. RESULTS: Ten mothers participated at a median of 22 days postpartum. A total of 176 milk samples were analysed, and the average protein and fat concentrations in g/100 mL were 1.1 ± 0.23 and 4.2 ± 1.3, respectively. The time intervals between breast pumping sessions did not impact protein content, but fat content decreased by longer intervals (p < 0.01). The time of the day for milk pumping did not influence the protein or fat content. CONCLUSION: A single milk sample collected after any 2-6 h interval, at any time during the day, represents the protein content in the breastmilk, but not the fat content which decreased with longer intervals.

Long-Term Neurodevelopmental Outcome of Monochorionic Twins after Laser Therapy or Umbilical Cord Occlusion for Twin-Twin Transfusion Syndrome.

INTRODUCTION: We sought to assess the incidence of severe neurodevelopmental impairment (NDI) in monochorionic twins treated for twin-twin transfusion syndrome (TTTS) and compare it to the incidence in uncomplicated monochorionic twins. MATERIAL AND METHODS: We included TTTS pregnancies treated by fetoscopic selective laser coagulation (FSLC) or umbilical cord occlusion (UCO) in 2004-2015. Primary outcome was severe NDI defined as cerebral palsy, bilateral blindness or bilateral deafness (ICD-10 diagnoses), and severe cognitive and/or motor delay (assessed by the Ages and Stages Questionnaires [ASQ]). RESULTS: A total of 124 children after TTTS and 98 controls were followed up at 25 months of age (SD 11.4). Severe NDI was found in 8.9% of the TTTS children (10.5% [9/86] after FSLC; 5.3% [2/38] after UCO) compared to 3.1% in the control group (p = 0.10). The odds ratio for severe NDI was 1.8 in cases versus controls (p = 0.37). The total ASQ score was significantly lower in the TTTS group than in controls (p = 0.03) after FSLC (p = 0.03) and after UCO (p = 0.14). DISCUSSION: Children after TTTS appear to have a higher risk of severe NDI and score significantly lower on the ASQ compared to monochorionic twins from uncomplicated pregnancies.

Administering different levels of parenteral phosphate and amino acids did not influence growth in extremely preterm infants.

AIM: When a new high amino acid parenteral nutrition (PN) solution was introduced to our hospital, a design error led to decreased phosphate levels. This prompted us to examine the effect of three different PN solutions on plasma phosphate, plasma calcium and weight increases on extremely preterm infants. METHOD: This was a retrospective study of 186 infants with a gestational age of <28 weeks during their first month of life. They were divided into three groups based on the PN they received during hospitalisation. Group one received high levels of phosphate and low levels of amino acids. Group two received low levels of phosphate and high levels of amino acids. Group three received high levels of both phosphate and amino acids. RESULTS: The lowest plasma phosphate values varied significantly between groups one (1.80 ± 0.46 mmol/L), two (1.05 ± 0.48 mmol/L) and three (1.40 ± 0.37 mmol/L) (p < 0.001), but no significant difference in weight increase was seen (p = 0.497). CONCLUSION: The phosphate content of the PN influenced plasma phosphate and plasma calcium levels, but increasing the levels of both phosphate and amino acids did not improve weight gain during the first month of life.

COpenhagen Neuroplastic TRaining Against Contractures in Toddlers (CONTRACT): protocol of an open-label randomised clinical trial with blinded assessment for prevention of contractures in infants with high risk of cerebral palsy.

INTRODUCTION: Contractures are frequent causes of reduced mobility in children with cerebral palsy (CP) already at the age of 2-3 years. Reduced muscle use and muscle growth have been suggested as key factors in the development of contractures, suggesting that effective early prevention may have to involve stimuli that can facilitate muscle growth before the age of 1 year. The present study protocol was developed to assess the effectiveness of an early multicomponent intervention, CONTRACT, involving family-oriented and supervised home-based training, diet and electrical muscle stimulation directed at facilitating muscle growth and thus reduce the risk of contractures in children at high risk of CP compared with standard care. METHODS AND ANALYSIS: A two-group, parallel, open-label randomised clinical trial with blinded assessment (n=50) will be conducted. Infants diagnosed with CP or designated at high risk of CP based on abnormal neuroimaging or absent fidgety movement determined as part of General Movement Assessment, age 9-17 weeks corrected age (CA) will be recruited. A balanced 1:1 randomisation will be made by a computer. The intervention will last for 6 months aiming to support parents in providing daily individualised, goal-directed activities and primarily in lower legs that may stimulate their child to move more and increase muscle growth. Guidance and education of the parents regarding the nutritional benefits of docosahexaenic acid (DHA) and vitamin D for the developing brain and muscle growth will be provided. Infants will receive DHA drops as nutritional supplements and neuromuscular stimulation to facilitate muscle growth. The control group will receive standard care as offered by their local hospital or community. Outcome measures will be taken at 9, 12, 18, 24, 36 and 48 months CA. Primary and secondary outcome measure will be lower leg muscle volume and stiffness of the triceps surae musculotendinous unit together with infant motor profile, respectively. ETHICS AND DISSEMINATION: Full approval from the local ethics committee, Danish Committee System on Health Research Ethics, Region H (H-19041562). Experimental procedures conform with the Declaration of Helsinki. TRIAL REGISTRATION NUMBER: NCT04250454. EXPECTED RECRUITMENT PERIOD: 1 January 2021-1 January 2025.

Increased risk of ALL among premature infants is not explained by increased prevalence of pre-leukemic cell clones.

The multi-hit hypothesis for paediatric leukemogenesis states that an initial genetic hit (often occurring prenataly) must be followed by one or more hit(s) before a cell become leukeamic. Studies have demonstrated the presence of pre-leukaemic t(12;21)-positive cells at levels 10(-3) to 10(-4) in 1% of newborns (i.e. 100-fold their risk of t(12;21)-positive ALL), but only at levels of 10(-5) to 10(-6) in 0.5% adults. As the risk of developing ALL is inversely associated to the gestational age at birth, we investigated if this increased risk could be explained by an increase in prevalence and quantity of pre-leukaemic t(12;21)-positive children born prematurely. Using a sensitive qRT-PCR assay, we screened messenger RNA from fresh umbilical cord-blood samples from 256 premature children. In none of the neonates, t(12;21)-positive cells could be demonstrated. Therefore, no increase in the prevalence and magnitude of preleukaemic t(12;21)-positive cells compared to previously published data from mature children could be demonstrated. This indirectly supports the theory that prevalence and quantity of preleukaemic t(12;21)-positive cells peaks at term or early childhood and that exogenous factors are necessary to initiate their clearance.

[Perinatal care of the extremely preterm infants].

In 2018, The Danish Society of Obstetrics and Gynecology and the Danish Paediatric Society agreed on a national consensus guideline on the treatment of imminent preterm delivery prior to 25 weeks. This review summarises the recommendations: at 22 weeks transfer to a tertiary hospital, at 23 weeks tocolysis, antenatal steroid and newborn resuscitation with parental consent, if the infant is viable, and at 24 weeks caesarean section due to foetal distress. Newborn resuscitation is standard of care, unless not indicated for other reasons at 24 weeks.

[Acute, severe liver insufficiency caused by extrahepatic biliary atresia in a newborn]. / Akut, svær leverinsufficiens forårsaget af binyretumor hos nyfødt.

A newborn female was hospitalized due to metabolic acidosis and conjugated hyperbilirubinaemia. Extrahepatic biliary atresia (EHBA) was suspected why a (99m)Tc-mebrofenin cholescintigraphy was performed. It showed poor hepatocyte tracer uptake and no drainage to the gut. The hepatocyte dysfunction was caused by an obstructing adrenal gland neuroblastoma later visualised by ultrasound and MRI. The cholescintigraphy is a non-invasive modality to exclude or confirm the suspicion of EHBA. Furthermore neonatal conjugated hyperbilirubinaemia demands the use of a multimodality imaging strategy for differential diagnosis to EHBA.

A Danish reference chart for assessment of psychomotor development based on the Ages & Stages Questionnaire.

INTRODUCTION: 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. MATERIAL AND METHODS: A total of 298 children were randomly chosen among the Danish population in three different groups: 9-, 18- and 21 month-old children. The parents received the 10-month ASQ when their child had reached a corrected age of nine months and the 24-month ASQ questionnaire when their child had reached the corrected age of 18 or 21 months. RESULTS: The total scores were normally distributed in both groups. There was a highly significant (p < 0.001) linear regression between ASQ total score and adjusted age for both the 10- and the 24-month ASQ. CONCLUSION: The results of the study show that the overall development can be assessed when the child is scored with an ASQ intended for older children. Screening for developmental delay in children in the age range of 8-10 months or 18-22 can be quickly assessed by reference to a chart. The chart can also be used as a reference when monitoring the quality in neonatal services by the developmental outcome and this ensures that children are classified according to Danish standards.

[Neonatal consequences of vacuum-assisted delivery]. / Neonatale konsekvenser efter vakuumekstraktion.

About 5000 babies annually, or 1/12 of all births, are the result of vacuum-assisted delivery in Denmark. Towards the end of the 1990'ies, the US FDA published a national warning concerning increasing complications and mortality after vacuum-assisted delivery, and other countries followed. One explanation is that training is no longer given the needed focus. Recent introduction of new requirements on Danish specialist training and the fact that vacuum-assisted delivery is an important procedure in obstetrics provides the basis for this article which systematically reviews the neonate consequences for the termed baby following vacuum-assisted delivery.

[Induced hypothermia in infants born with hypoxic-ischaemic encephalopathy]. / Hypotermibehandling af nyfødte med hypoksisk iskaemisk encefalopati.

INTRODUCTION: 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. MATERIAL AND METHODS: This retrospective study comprises data from medical records of newborn children born with HIE during a period of 32 months. Relevant data for cooling were recorded. Structured neurological examinations were carried out on survivors when they were ten and or 18 months old. RESULTS: A total of 32 infants fulfilled the criteria for cooling, the incidence being 0.4/1000 births. Twenty infants were cooled for 72 hours. Eleven infants had cooling discontinued before 72 hours because of their grave prognosis. One infant had cooling discontinued because of pulmonary hypertension. Most infants were cooled before six hours of age (median four hours). The mortality rate was 41%. A total of 45% were cooled without being placed in a ventilator. The side effects were of no major concern. Eight children had a neurological follow-up. One child had developed cerebral palsy and two children suffered delayed development. CONCLUSION: Total body cooling was carried out before six hours of age in the vast majority of infants born with HIE. Side effects were of less concern. Respiratory support with a ventilator could be avoided in 45% of the infants cooled for 72 hours. The mortality rate was 41%.

Ages and Stages Questionnaire used to measure cognitive deficit in children born extremely preterm.

AIM: To validate the Ages and Stages Questionnaire (ASQ) and to measure average cognitive deficit in children born extremely preterm. METHODS: Parents of 30 term children aged 36-42 mo completed the ASQ and the children underwent the Wechsler Preschool and Primary Scales of Intelligence--Revised. In a second study, the ASQ was obtained in 22 children born extremely preterm and 19 term children at the age of 35-44 mo. RESULTS: The overall ASQ score correlated significantly with IQ (p=0.007). The children born extremely preterm had an ASQ score of -1.06 SD below the score of the term children (p=0.048). CONCLUSION: The ASQ identified a developmental deficit of the expected magnitude.

Developmental delay at 12 months in children born extremely preterm.

AIM: To evaluate the feasibility and validity of a structured telephone interview to assess the development of children born extremely preterm. METHODS: The parents of 88 children born with a gestational age below 28 wk admitted to the neonatal intensive care unit (NICU) at Rigshospitalet, Copenhagen, were interviewed by telephone when their child was 1 y of age, corrected for preterm birth. A fully structured questionnaire on psychomotor function was used (Revised Prescreening Developmental Questionnaire (R-PDQ)). The parents of 30 children born at term without complications were interviewed for comparison. The interview was conducted by NICU staff. To validate the R-PDQ, parents of 22 children in the preterm group and parents of 19 children in the reference group conducted an Ages and Stages Questionnaire (ASQ) when their children had reached the age of 3-3(1/2) y. RESULTS: The R-PDQ was easy to use by staff and well accepted by parents. The mean score in the preterm group was 14.9+/-3.9 vs 17.7+/-2.7 in the term group (p<0.001). Three children had developmental scores below-2 SD. The R-PDQ score was associated with the ASQ score 2 y later. CONCLUSION: A structured questionnaire administrated by telephone is an alternative and usable tool for assessing neurodevelopmental deficit in children born extremely preterm. The mean developmental delay in the preterm group compared to the term group (about-1 SD) was close to expectations.

Doxapram and developmental delay at 12 months in children born extremely preterm.

AIM: To examine the relation of doxapram to a developmental score achieved by a structured telephone interview in a group of extremely-preterm-born children. METHODS: Parents of 88 children born extremely preterm were contacted by telephone and interviewed by a structured questionnaire (R-PDQ) when the corrected age of their child was 9-15 mo. RESULTS: We found that doxapram treatment was associated with a deficit in age-adjusted R-PDQ score. CONCLUSION: Doxapram may have a negative effect on neurodevelopmental outcome.