BACKGROUND: Acid suppression therapy (AST), including proton pump inhibitors (PPIs) and histamine H 2 -receptor antagonists (H 2 RAs), is frequently prescribed to treat symptomatic gastroesophageal reflux in otherwise healthy infants. PPI use has been associated with increased fracture risk in older adults; 2 preliminary studies in children have conflicting results.
METHODS:A retrospective cohort of children born 2001 to 2013 who were followed for $2 years was formed. Those with osteogenesis imperfecta, cholestasis, or child maltreatment were excluded. Prescription data were used to identify AST prescription before age 1 year. International Classification of Diseases, Ninth Revision, Clinical Modification codes identified fractures after age 1 year. A Cox proportional hazard analysis assessed fracture hazard and was adjusted for sex, prematurity, low birth weight, previous fracture, anti-epileptics, and overweight or obesity.RESULTS: Of 851 631 included children, 97 286 (11%) were prescribed AST in the first year of life; 7998 (0.9%) children were prescribed PPI, 71 578 (8%) were prescribed H 2 RA, and 17 710 (2%) were prescribed both a PPI and H 2 RA. Infants prescribed AST had an earlier median first fracture age (3.9 vs 4.5 years). After adjustment, increased fracture hazard was associated with PPI use (21%) and PPI and H 2 RA use (30%), but not H 2 RA use alone. Longer duration of AST treatment and earlier age of first AST use was associated with increased fracture hazard.CONCLUSIONS: Infant PPI use alone and together with H 2 RAs is associated with an increased childhood fracture hazard, which appears amplified by days of use and earlier initiation of ASTs. Use of AST in infants should be weighed carefully against possible fracture.WHAT'S KNOWN ON THIS SUBJECT: Proton pump inhibitors (PPIs) are used frequently in the treatment of symptomatic gastroesophageal reflux. Studies in adults have revealed an association between PPIs and increased fracture risk, but this has not been well studied in infants and children.
WHAT THIS STUDY ADDS:This study included young children without known serious medical conditions prescribed acid suppression therapy during the first year of life, likely for symptomatic treatment of reflux. A positive association was found between PPI use and childhood fracture incidence.
Few studies have investigated the impact of lifestyle interventions during pregnancy on post-partum weight retention and infant growth. Thirty seven previously non-exercising, overweight or obese pregnant women were randomly assigned to a walking intervention or non-intervention control. For the follow-up study, weight of the mother and weight, length and body composition of the infant were collected at 1 month post-partum (n=37) and 6 months post-partum (n=33). Analysis of variance and linear regression were conducted to determine the differences and association in maternal post-partum weight retention and child outcomes. At 6 months post-partum, weight retention of obese women in the intervention group (Int-OB) was -0.10±8.11 kg; while, obese women in the control group (Con-OB) was 6.35±7.47 kg. A significantly higher percentage of Con-OB women retained more than 5 kg at 6 months post-partum (P=0.046). Even though statistically non-significant between the groups, the growth trend observed among offspring of obese women in the control group was consistently higher than the offspring of obese women in the intervention group from birth to 6-months. Third trimester gestational weight gain rate significantly predicted 6-m weight-for-length z-score after controlling for birth weight, treatment group and pre-pregnancy body mass index (r 2=0.31, β=1.75, P=0.03). The reduced post-partum weight retention observed among the obese women in the intervention group may be explained in part by the lifestyle modification during pregnancy.
PurposeInspiring high partial pressure of oxygen (FiO2 > 0.6) for a prolonged duration can lead to lung damage termed pulmonary oxygen toxicity (PO2T). While current practice is to limit oxygen exposure, there are clinical and military scenarios where higher FiO2 levels and partial pressures of oxygen are required. The purpose of this study is to develop a non-invasive breath-based biomarker to detect PO2T prior to the onset of clinical symptoms.MethodsMale Yorkshire swine (20–30 kg) were placed into custom airtight runs and randomized to air (0.209 FiO2, n = 12) or oxygen (>0.95 FiO2, n = 10) for 72 h. Breath samples, arterial blood gases, and vital signs were assessed every 12 h. After 72 h of exposure, animals were euthanized and the lungs processed for histology and wet-dry ratios.ResultsSwine exposed to hyperoxia developed pulmonary injury consistent with PO2T. Histology of oxygen-exposed swine showed pulmonary lymphatic congestion, epithelial sloughing, and neutrophil transmigration. Pulmonary injury was also evidenced by increased interstitial edema and a decreased PaO2/FiO2 ratio in the oxygen group when compared to the air control group. Breath volatile organic compound (VOC) sample analysis identified six VOCs that were combined into an algorithm which generated a breath score predicting PO2T with a ROC/AUC curve of 0.72 defined as a of PaO2/FiO2 ratio less than 350 mmHg.ConclusionExposing swine to 72 h of hyperoxia induced a pulmonary injury consistent with human clinical endpoints of PO2T. VOC analysis identified six VOCs in exhaled breath that preceded PO2T. Results show promise that a simple, non-invasive breath test could potentially predict the risk of pulmonary injury in humans exposed to high partial pressures of oxygen.
Background: Optimal dosage for growth hormone (GH) therapy in short, prepubertal children born small for gestational age (SGA) is controversial. Methods: SGA OPTIMIS (NCT00249821) is a multicenter, open-label, parallel-group, pilot study of short children born SGA who had received recombinant human GH (r-hGH) (57 µg/kg/day) for 3 years. Children were randomized 1:1 to receive either 57 or 35 µg/kg/day r-hGH during year 4. The primary endpoint was height gain during year 4. Results: 22 children were randomized (57 µg/kg/day, n = 10; 35 µg/kg/day, n = 12) and 21 completed the fourth year of therapy; 22 were included in efficacy analyses. During year 4, mean [standard deviation (SD)] height velocity was 6.4 (1.4) and 4.4 (1.2) cm/year (p = 0.001) and height velocity SD score (SDS) was 0.3 (0.3) and –0.1 (0.2) (p = 0.002) in the 57 and 35 µg/kg/day groups, respectively. The 57 µg/kg/day group continued with catch-up growth, had a significantly higher mean weight gain (p = 0.015) and significantly higher insulin-like growth factor-I levels at 12 months (p = 0.038). Five treatment-emergent adverse events were reported; none was serious or caused study withdrawal. Conclusions: Children who continued receiving 57 µg/kg/day r-hGH in year 4 had significantly greater height gain than those receiving 35 µg/kg/day r-hGH.
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