Prophylactic Intravenous Acetaminophen in Extremely Premature Infants: Minimum Effective Dose Research by Bayesian Approach.

BACKGROUND: Patent ductus arteriosus (PDA) in preterm infants is associated with increased morbidities and mortality. Prophylactic treatment with cyclooxygenase inhibitors, as indomethacin or ibuprofen, failed to demonstrate significant clinical benefits. Acetaminophen may represent an alternative treatment option. OBJECTIVE: This study evaluated the minimum effective dose of prophylactic acetaminophen to close the ductus and assessed the safety and tolerability profile in extremely preterm infants at 23-26 weeks of gestation. METHODS: A dose finding trial with Bayesian continual reassessment method was performed in a multicenter study with premature infants hospitalized in neonatal intensive care unit. Infants of 23-26 weeks of gestation and post-natal age ≤ 12 h were enrolled. Four intravenous acetaminophen dose levels were predefined. The primary outcome was the ductus arteriosus closing at two consecutive echocardiographies or at day 7. The main secondary objectives included the safety of acetaminophen on hemodynamics and biological hepatic function. RESULTS: A total of 29 patients were analyzed sequentially for the primary analysis with 20 infants assigned to the first dose level followed by 9 infants to the second dose level. No further dose level increase was necessary. The posterior probabilities of success, estimated from the Bayesian logistic model, were 46.1% [95% probability interval (PI), 24.9-63.9] and 67.6% (95% PI, 51.5-77.9) for dose level 1 and 2, respectively. A closing or closed pattern was observed among 19 patients at the end of treatment [65.5% (95% confidence interval (CI), 45.7-82.0)]. No change in alanine aminotransferase values was observed during treatment. A significant decrease in aspartate aminotransferase values was observed with postnatal age. No change in systolic and diastolic blood pressures was observed during treatment. CONCLUSIONS: Minimum effective dose to close the ductus was 25 mg/kg loading dose then 10 mg/kg/6 h for 5 days in extremely preterm infants. Acetaminophen was well tolerated in this study following these doses. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04459117.

Children With Intestinal Failure Undergoing Intestinal Rehabilitation Are at Risk for Essential Fatty Acid Deficiency.

BACKGROUND: Essential fatty acid (EFA) status may be compromised during the intestinal failure (IF) rehabilitation. Parenteral lipid restriction is used to treat intestinal failure associated liver disease (IFALD), while the enteral fatty acid (FA) absorption remains limited. We analyzed the FA status among pediatric IF and intestinal insufficiency patients. METHODS: We evaluated 49 patients aged 0-18 years attending our nationwide IF referral center. Their serum FA fractions were determined and examined against previous nutrition, parenteral lipid emulsion, and intestinal anatomy data. The patients were divided into 3 subgroups according to their dependence on parenteral nutrition (PN): full enteral (EN) (n = 33), supplemental PN (n = 14) or predominantly PN (n = 20). Trien:tetraen ratio (TTR) ≥0.2 was considered diagnostic for essential fatty acid deficiency (EFAD) and increased risk was suspected if TTR exceeded 0.1. RESULTS: We identified 8 (16%) patients with elevated TTR ≥0.1; in 3 of them the ratio exceeded 0.2. Five of these children belonged to supplemental PN group. This group carried the highest incidence of elevated TTR (P = 0.0016), with median TTR at 0.06 (interquartile range 0.03-0.09) and two-thirds of the analyzed TTR ≥0.5. Increased EFAD risk was associated with young age (P = 0.0291), current PN with low parenteral lipid content (P = 0.0003), and short remaining small bowel (P = 0.0013). CONCLUSIONS: IF children with supplemental PN carry the highest overall risk for EFAD. Young age, current PN, and short remaining small bowel also increase the risk for EFAD.

Food consumption and risk of childhood asthma.

BACKGROUND: The consumption of foods rich in n-3 polyunsaturated fatty acids has been proposed to protect against childhood asthma. This study explores the association of food consumption (including cow's milk (CM)-free diet) in early life and the risk of atopic and non-atopic asthma. METHODS: Food intake of 182 children with asthma and 728 matched controls was measured using 3-day food records, within the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study cohort. The diagnoses of food allergies came both from the written questionnaire and from the registers of the Social Insurance Institution. Conditional logistic regression with generalized estimating equations framework was used in the analyses. RESULTS: The diagnosis of cow's milk allergy (CMA) led to multiple dietary restrictions still evident at 4 yr of age. Even after adjusting for CMA, higher consumption of CM products was inversely associated with the risk of atopic asthma and higher consumption of breast milk and oats inversely with the risk of non-atopic asthma. Early consumption of fish was associated with a decreased risk of all asthma. CONCLUSIONS: Dietary intake in early life combined with atopy history has a clear impact on the risk of developing asthma. Our results indicate that CM restriction due to CMA significantly increases and mediates the association between food consumption and childhood asthma risk.

Maternal dietary fatty acid intake during pregnancy and the risk of preclinical and clinical type 1 diabetes in the offspring.

The aim of the present study was to examine the associations between the maternal intake of fatty acids during pregnancy and the risk of preclinical and clinical type 1 diabetes in the offspring. The study included 4887 children with human leucocyte antigen (HLA)-conferred type 1 diabetes susceptibility born during the years 1997-2004 from the Finnish Type 1 Diabetes Prediction and Prevention Study. Maternal diet was assessed with a validated FFQ. The offspring were observed at 3- to 12-month intervals for the appearance of type 1 diabetes-associated autoantibodies and development of clinical type 1 diabetes (average follow-up period: 4·6 years (range 0·5-11·5 years)). Altogether, 240 children developed preclinical type 1 diabetes and 112 children developed clinical type 1 diabetes. Piecewise linear log-hazard survival model and Cox proportional-hazards regression were used for statistical analyses. The maternal intake of palmitic acid (hazard ratio (HR) 0·82, 95 % CI 0·67, 0·99) and high consumption of cheese during pregnancy (highest quarter v. intermediate half HR 0·52, 95 % CI 0·31, 0·87) were associated with a decreased risk of clinical type 1 diabetes. The consumption of sour milk products (HR 1·14, 95 % CI 1·02, 1·28), intake of protein from sour milk (HR 1·15, 95 % CI 1·02, 1·29) and intake of fat from fresh milk (HR 1·43, 95 % CI 1·04, 1·96) were associated with an increased risk of preclinical type 1 diabetes, and the intake of low-fat margarines (HR 0·67, 95 % CI 0·49, 0·92) was associated with a decreased risk. No conclusive associations between maternal fatty acid intake or food consumption during pregnancy and the development of type 1 diabetes in the offspring were detected.

Maternal intake of fatty acids during pregnancy and allergies in the offspring.

Fatty acids (FA) are known to have a number of immunological effects and, accordingly, may play a role in the development of allergic diseases. We investigated the effect of maternal intake of FA during pregnancy on the risk of allergic rhinitis, wheeze and atopic eczema in children aged 5 years. The present study analysed data from the Finnish Type 1 Diabetes Prediction and Prevention Nutrition Study, a population-based birth cohort study with a 5-year follow-up. Complete information on maternal diet (assessed by a validated FFQ) and International Study of Asthma and Allergies in Childhood-based allergic outcomes was available for 2441 children. Cox proportional regression and logistic regression were used for the analyses. After adjusting for potential confounding variables, high maternal consumption of butter and butter spreads (hazard ratio (HR) 1.33; 95 % CI 1.03, 1.71) and higher ratio of n-6:n-3 FA (HR 1.37; 95 % CI 1.07, 1.77) during pregnancy were associated with an increased risk of allergic rhinitis in the offspring by 5 years of age. High maternal intakes of total PUFA (HR 0.71; 95 % CI 0.52, 0.96) and α-linolenic FA (HR 0.73; 95 % CI 0.54, 0.98) were associated with a decreased risk of allergic rhinitis. However, these results lost their significance after adjustment for multiple comparisons. Overall, our data suggest that maternal consumption of butter, the ratio of n-6:n-3 FA and intake of PUFA and α-linolenic FA during pregnancy may be potential determinants of allergic rhinitis in the offspring.

Dietary fatty acid composition during pregnancy and the risk of asthma in the offspring.

BACKGROUND: Fatty acids (FA) modulate the immune system, and it has been proposed that they affect the incidence of IgE-mediated allergic diseases. We explored the association of maternal dietary FA composition during pregnancy with the risk of asthma in the offspring. METHODS: We analyzed data from the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study. Maternal dietary intake during pregnancy (8th month) was assessed by a validated 181-item food frequency questionnaire. The occurrence of asthma was assessed at the age of 5 yr with a questionnaire modified from the International Study of Asthma and Allergies in Childhood (ISAAC). Cox proportional hazards regression was used for the statistical analyses. RESULTS: Low maternal intakes of α-linolenic acid (18:3n-3) [lowest quarter vs. mid-half HR 1.67 (95% CI 1.12-2.48)] and total n-3-polyunsaturated fatty acids (PUFA) [HR 1.66 (95% CI 1.11-2.48)] during pregnancy were associated with an increased risk of asthma in the offspring, while a low intake of arachidonic acid (20:4n-6) [HR 0.52 (95% CI 0.32-0.84)] and high intake of total saturated fatty acids [highest quarter vs. mid-half HR 0.55 (95% CI 0.34-0.90)] and palmitic acid (16:0) [HR 0.51 (95% CI 0.31-0.83)] were associated with a decreased risk of asthma. The ratios of n-6 to n-3-PUFA and 18:2n-6 to 18:3n-3, and the maternal intake of oils, fish and fish products, showed no association with the risk of asthma. The associations found were independent of several perinatal and clinical confounders. CONCLUSION: Maternal intake of FA during pregnancy was associated with childhood asthma. Maternal α-linolenic acid, total n-3 PUFA and palmitic acid intake may decrease, while arachidonic acid intake may increase the risk of asthma in the offspring.

Validation of the Finnish ISAAC questionnaire on asthma against anti-asthmatic medication reimbursement database in 5-year-old children.

BACKGROUND: Valid identification of childhood asthma at the population level for epidemiological purposes remains a challenge. We aimed at validating the Finnish version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire based on parental-reported childhood asthma. MATERIALS AND METHODS: The ISAAC questionnaire has been validated against anti-asthmatic medication reimbursement data of the Finnish Social Insurance Institution, being the gold standard, among 2236 5-year-old consecutively born children (1996-2004) carrying human leukocyte antigen (HLA)-conferred susceptibility to type 1 diabetes. Two combined questionnaire questions (any wheezing symptom or use of asthma medication during the preceding 12 months plus ever asthma; any wheezing symptom or use of asthma medication during the preceding 12 months plus ever doctor-diagnosed asthma) were validated against valid reimbursement with purchase of at least one anti-asthmatic medication during a 12-month period. The validity of the questionnaire was estimated as the sensitivity, specificity, positive predictive value, negative predictive value, and Youden's index. RESULTS: The sensitivity 0.98 [95% confidence interval (CI) = 0.92-0.99]; specificity 0.98 (95% CI = 0.97-0.98); negative predictive value 1.00 (95% CI = 1.00-1.00); and Youden's index 0.96 (95% CI = 0.96-0.96) were the same for each of the two sets of combined questions. The positive predictive value for the first combined question was 0.63 (95% CI = 0.55-0.71), while it was 0.64 (95% CI = 0.57-0.72) for the second combined question. CONCLUSION: The Finnish ISAAC questionnaire was highly valid and is an acceptable instrument for the survey of the prevalence of parental-reported childhood asthma for epidemiological purposes.

Maternal diet during lactation and allergic sensitization in the offspring at age of 5.

The objective of this study was to examine the effect of maternal dietary intake during lactation on allergic sensitization at the age of 5 in children carrying HLA-DQB1-conferred susceptibility to type 1 diabetes. We analyzed data for 652 consecutively born children with complete information on maternal diet and allergen-specific immunoglobulin E (IgE) measurements who are participating in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition and allergy study. Analysis was performed using logistic regression. In models that included the significant uncorrelated dietary variables, maternal intake of butters and saturated fatty acids was associated with increased risk, while margarine was associated with a decreased risk, of sensitization to wheat allergen in the offspring. Maternal intake of potatoes, milks, and margarine and low-fat spreads were associated with decreased risk of sensitization to birch allergen. On the other hand, intake of potatoes decreased the risk, while vitamin C and eggs increased the risk, of cat allergic sensitization. Maternal intake of butters and saturated fatty acids during lactation may increase the risk, while margarines may decrease the risk, of sensitization to wheat allergen in the offspring. Maternal intake of potatoes, milks, and margarines may decrease the risk of sensitization to birch allergen. On the other hand, intake of potatoes may decrease the risk, while vitamin C and eggs may increase the risk, of cat allergic sensitization. These effects may persist regardless of maternal or parental allergic status.

Diet composition of pregnant Finnish women: changes over time and across seasons.

OBJECTIVE: To describe the diet of a population of pregnant Finnish women over a period of 7 years, with special attention paid to seasonal fluctuations in food consumption and nutrient intake. DESIGN: A validated 181-item FFQ was applied retrospectively, after delivery, to assess the maternal diet during the 8th month of pregnancy. SETTING: Type 1 Diabetes Prediction and Prevention Nutrition Study Cohort. SUBJECTS: The cohort comprised a total of 4880 women who had newly delivered during the years 1997-2004, with the offspring carrying increased genetic risk for type 1 diabetes mellitus. RESULTS: Over the study period, the proportion of energy derived from fat decreased while the intake from protein and carbohydrate increased. The intake of vitamin D increased from food sources. Seasonal variation was observed in the mean daily consumption of vegetables, fruits and berries and cereals. Intake of dietary fibre, total fat, MUFA, vitamins A, D, E and C, folate and iron also showed seasonal fluctuation. CONCLUSIONS: These results show an overall positive trend in the diet of pregnant Finnish women through the study years. However, there is still room for improvement, particularly in the types of dietary fats. Although food fortification with vitamin D since 2003 was reflected in the increased intake of vitamin D from foods, the mean intake levels still fell below the recommendations. Seasonal changes in food consumption were observed and related to corresponding fluctuations in nutrient intakes. The mean folate intake fell below the recommendation throughout the year.