Effect of arachidonic and docosahexaenoic acid supplementation on quality of growth in preterm infants: A secondary analysis of a randomized controlled trial.

BACKGROUND & AIMS: A balanced supply of arachidonic acid (ARA) and docosahexaenoic acid (DHA) may be crucial for quality of growth in preterm infants. This secondary analysis of a randomized controlled trial aimed to determine the effect of enhanced ARA and DHA supplementation on growth and body composition in infants born before 29 weeks of gestation. Furthermore, we aimed to study associations between human milk feeding, growth patterns and body composition. METHODS: The ImNuT-trial randomized 121 infants to receive a daily supplement with medium chain triglycerides (control) or 100 mg/kg ARA and 50 mg/kg DHA (ARA:DHA group) from the second day of life until 36 weeks postmenstrual age. Growth and body composition were evaluated up to 3 months corrected age. RESULTS: The ARA:DHA group showed better linear growth from birth to term equivalent age compared to the control group; mean difference in z score change from birth for length was 0.74 ([95% CI, 0.17-1.3]; p = 0.010). There were no differences in growth and body composition outcomes at 3 months corrected age between the groups. An increase in z score for weight after 36 weeks postmenstrual age and breastfeeding at 3 months corrected age were the strongest positive predictors of fat mass% at 3 months corrected age (both, p < 0.001). CONCLUSION: Early enhanced supplementation of ARA and DHA may be beneficial with respect to somatic growth in very preterm infants. CLINICAL TRIAL REGISTRATION: The trial has been registered on www. CLINICALTRIALS: gov, ID: NCT03555019.

Positive End-Expiratory Pressure in Newborn Resuscitation Around Term: A Randomized Controlled Trial.

BACKGROUND: International guidelines for resuscitation recommend using positive end-expiratory pressure (PEEP) during ventilation of preterm newborns. Reliable PEEP-valves for self-inflating bags have been lacking, and effects of PEEP during resuscitation of term newborns are insufficiently studied. The objective was to determine if adding a new PEEP valve to the bag-mask during resuscitation of term and near-term newborns could improve heart rate response. METHODS: This randomized controlled trial was performed at Haydom Lutheran Hospital in Tanzania (September 2016 to June 2018). Helping Babies Breathe-trained midwives performed newborn resuscitation using self-inflating bags with or without a new, integrated PEEP valve. All live-born newborns who received bag-mask ventilation at birth were eligible. Heart rate response measured by ECG was the primary outcome, and clinical outcome and ventilation data were recorded. RESULTS: Among 417 included newborns (median birth weight 3200 g), 206 were ventilated without and 211 with PEEP. We found no difference in heart rate response. Median (interquartile range) measured PEEP in the PEEP group was 4.7 (2.0-5.6) millibar. The PEEP group received lower tidal volumes (4.9 [1.9-8.2] vs 6.3 [3.9-10.5] mL/kg; P = .02) and had borderline lower expired CO2 (2.9 [1.5-4.3] vs 3.3 [1.9-5.0] %; P = .05). Twenty four-hour mortality was 9% in both groups. CONCLUSIONS: We found no evidence for improved heart rate response during bag-mask ventilation with PEEP compared with no PEEP. The PEEP valve delivered a median PEEP within the intended range. The findings do not support routine use of PEEP during resuscitation of newborns around term.

Use of nitrous oxide in children. / Bruk av lystgass hos barn.

BACKGROUND: In July 2013, the Department of Paediatric and Adolescent Medicine at Østfold Hospital Trust introduced nitrous oxide as an option for procedural sedation of children and adolescents. MATERIAL AND METHOD: During the period 13 July 2013-25 August 2017, 311 procedures were performed with nitrous oxide in 238 patients aged 4-17 years. Age, sex, type and duration of procedure, any supplementary medications, complications and whether the procedure would previously have required general anaesthesia, were recorded in a form. The child rated the effectiveness of nitrous oxide using a graded age-appropriate 10-point pain scale, and the nurse rated it as good, moderate or none. RESULTS: The children reported a median pain score of 2/10 (interquartile range 0-4), and nurses rated effectiveness as good in 247 of 304 (81 %) cases. For 43 % of procedures, the nurse felt that general anaesthesia would have been necessary had the department not had access to nitrous oxide. Adverse effects, most often dizziness, were reported in 110 of 311 procedures (35 %). In 7 of 311 procedures (2 %), the patient experienced adverse effects that resulted in stoppage of the procedure. The procedure was completed in 286 (92 %) children. INTERPRETATION: Nitrous oxide is a useful option for children who require procedural sedation, and means that more procedures can be performed without general anaesthesia.

Prenatal iron exposure and childhood type 1 diabetes.

Iron overload due to environmental or genetic causes have been associated diabetes. We hypothesized that prenatal iron exposure is associated with higher risk of childhood type 1 diabetes. In the Norwegian Mother and Child cohort study (n = 94,209 pregnancies, n = 373 developed type 1 diabetes) the incidence of type 1 diabetes was higher in children exposed to maternal iron supplementation than unexposed (36.8/100,000/year compared to 28.6/100,000/year, adjusted hazard ratio 1.33, 95%CI: 1.06-1.67). Cord plasma biomarkers of high iron status were non-significantly associated with higher risk of type 1 diabetes (ferritin OR = 1.05 [95%CI: 0.99-1.13] per 50 mg/L increase; soluble transferrin receptor: OR = 0.91 [95%CI: 0.81-1.01] per 0.5 mg/L increase). Maternal but not fetal HFE genotypes causing high/intermediate iron stores were associated with offspring diabetes (odds ratio: 1.45, 95%CI: 1.04, 2.02). Maternal anaemia or non-iron dietary supplements did not significantly predict type 1 diabetes. Perinatal iron exposures were not associated with cord blood DNA genome-wide methylation, but fetal HFE genotype was associated with differential fetal methylation near HFE. Maternal cytokines in mid-pregnancy of the pro-inflammatory M1 pathway differed by maternal iron supplements and HFE genotype. Our results suggest that exposure to iron during pregnancy may be a risk factor for type 1 diabetes in the offspring.

Fetal and Maternal Genetic Variants Influencing Neonatal Vitamin D Status.

Objective: Several genetic polymorphisms determine vitamin D status. We aimed to estimate the strength of association of established 25-hydroyxvitamin D (25OHD)-associated variants in the mother and in the fetus, with 25OHD concentration in newborn umbilical cord plasma. Methods: We randomly selected 578 mother and child dyads from the prospective Norwegian Mother and Child Cohort study. 25OHD was assayed in maternal samples taken shortly after delivery and in cord samples. We genotyped the mother and child for single nucleotide polymorphisms in or near GC, DHCR7, CYP2R1, and CYP24A1, previously confirmed to be associated with 25OHD, and computed genetic risk score (GRS). The genetic associations were replicated in an independent sample of 594 subjects. Results: Although both fetal and maternal GRS were associated with cord 25OHD, only fetal GRS remained significantly associated with cord 25OHD in a regression model with maternal and fetal GRS simultaneously (1.6 nmol/L per fetal 25OHD-increasing allele; 95% confidence interval, 0.6 to 2.5, P = 0.0001). Two fetal single nucleotide polymorphisms in the GC gene (rs2282679 and rs222040) were the strongest genetic predictors of cord 25OHD [4.0 (2.1 to 5.9) and 3.0 (1.3 to 4.8) nmol/L per fetal allele, P < 0.001], followed by rs12785878 in DHCR7 [2.0 (0.1 to 3.8) nmol/L, P = 0.037]. The independent replication sample gave similar results. With fetal genotype included in a regression model with environmental factors, R2 for cord 25OHD was 0.28. Conclusions: We show that fetal 25OHD-modifying genotype was a stronger predictor of cord 25OHD than corresponding maternal genotype. This raises interesting questions about fetal acquisition and placental transfer of 25OHD.

Association between maternal iron supplementation during pregnancy and risk of celiac disease in children.

BACKGROUND & AIMS: The aim of our study was to determine whether the use of iron supplements during pregnancy affects the risk for celiac disease in children. METHODS: We assessed data from the prospective Norwegian Mother and Child cohort study, in which individuals with celiac disease were identified by answers on questionnaires and linkage to the Norwegian Patient Register. Complete data were available for 78,846 children (mean age 5.9 years, range 2-12 years); 314 children were identified with celiac disease. Questionnaires were given to pregnant women to collect information on use of iron-containing supplements, diet, anemia, and levels of hemoglobin. RESULTS: Celiac disease was diagnosed in 4.65 of 1000 children whose mothers took iron supplements while they were pregnant, compared with 3.15 of 1000 children whose mothers did not. After adjusting for children's age, sex, and age of gluten introduction, and the presence of celiac disease in mothers, iron supplementation during pregnancy remained significantly associated with celiac disease in children (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.05-1.68; P = .019). However, celiac disease was not associated with the mothers' intake of iron from foods (adjusted OR, 1.00; 95% CI, 0.97-1.03). Anemia before or during the early stages of pregnancy was not significantly associated with the risk of celiac disease in children (adjusted OR, 1.24; 95% CI, 0.84-2.00; P = .24). The use of iron supplements during pregnancy remained significantly associated with celiac disease in children after adjusting for children who were given iron supplements before 18 months of age, which itself was associated with celiac disease. CONCLUSIONS: In a prospective Norwegian Mother and Child cohort study, we found an increased risk of celiac disease in children whose mothers used iron supplements during pregnancy; this association does not appear to arise from maternal anemia.