A Randomized Trial of Maternal Docosahexaenoic Acid Supplementation to Reduce Inflammation in Extremely Preterm Infants.
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ABSTRACT:
SUBMITTER: Valentine CJ
PROVIDER: S-EPMC6706290 | biostudies-literature | 2019 Sep
REPOSITORIES: biostudies-literature
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Project description:Fetal and early postnatal inflammation have been associated with increased morbidity in extremely preterm infants. This study aimed to demonstrate if postpartum levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) were associated with early inflammation. In a cohort of 90 extremely preterm infants, DHA and AA in cord blood, on the first postnatal day and on postnatal day 7 were examined in relation to early systemic inflammation, defined as elevated C-reactive protein (CRP) and/or interleukin-6 (IL-6) within 72 h from birth, with or without positive blood culture. Median serum level of DHA was 0.5 mol% (95% CI (confidence interval) 0.2-0.9, P = 0.006) lower than the first postnatal day in infants with early systemic inflammation, compared to infants without signs of inflammation, whereas levels of AA were not statistically different between infants with and without signs of inflammation. In cord blood, lower serum levels of both DHA (correlation coefficient -0.40; P = 0.010) and AA (correlation coefficient -0.54; p < 0.001) correlated with higher levels of IL-6. Levels of DHA or AA did not differ between infants with and without histological signs of chorioamnionitis or fetal inflammation. In conclusion, serum levels of DHA at birth were associated with the inflammatory response during the early postnatal period in extremely preterm infants.
| S-EPMC7400618 | biostudies-literature
Project description:ImportanceMaternal docosahexaenoic acid (DHA) supplementation may prevent bronchopulmonary dysplasia, but evidence remains inconclusive.ObjectiveTo determine whether maternal DHA supplementation during the neonatal period improves bronchopulmonary dysplasia-free survival in breastfed infants born before 29 weeks of gestation.Design, setting, and participantsSuperiority, placebo-controlled randomized clinical trial at 16 Canadian neonatal intensive care units (June 2015-April 2018 with last infant follow-up in July 2018). Lactating women who delivered before 29 weeks of gestation were enrolled within 72 hours of delivery. The trial intended to enroll 800 mothers, but was stopped earlier.InterventionsThere were 232 mothers (273 infants) assigned to oral capsules providing 1.2 g/d of DHA from randomization to 36 weeks' postmenstrual age and 229 mothers (255 infants) assigned to placebo capsules.Main outcomes and measuresThe primary outcome was bronchopulmonary dysplasia-free survival in infants at 36 weeks' postmenstrual age. There were 22 secondary outcomes, including mortality and bronchopulmonary dysplasia.ResultsEnrollment was stopped early due to concern for harm based on interim data from this trial and from another trial that was published during the course of this study. Among 461 mothers and their 528 infants (mean gestational age, 26.6 weeks [SD, 1.6 weeks]; 253 [47.9%] females), 375 mothers (81.3%) and 523 infants (99.1%) completed the trial. Overall, 147 of 268 infants (54.9%) in the DHA group vs 157 of 255 infants (61.6%) in the placebo group survived without bronchopulmonary dysplasia (absolute difference, -5.0% [95% CI, -11.6% to 2.6%]; relative risk, 0.91 [95% CI, 0.80 to 1.04], P = .18). Mortality occurred in 6.0% of infants in the DHA group vs 10.2% of infants in the placebo group (absolute difference, -3.9% [95% CI, -6.8% to 1.4%]; relative risk, 0.61 [95% CI, 0.33 to 1.13], P = .12). Bronchopulmonary dysplasia occurred in 41.7% of surviving infants in the DHA group vs 31.4% in the placebo group (absolute difference, 11.5% [95% CI, 2.3% to 23.2%]; relative risk, 1.36 [95% CI, 1.07 to 1.73], P = .01). Of 22 prespecified secondary outcomes, 19 were not significantly different.Conclusions and relevanceAmong breastfed preterm infants born before 29 weeks of gestation, maternal docosahexaenoic acid supplementation during the neonatal period did not significantly improve bronchopulmonary dysplasia-free survival at 36 weeks' postmenstrual age compared with placebo. Study interpretation is limited by early trial termination.Trial registrationClinicalTrials.gov Identifier: NCT02371460.
| S-EPMC7361648 | biostudies-literature
Project description:ObjectiveTo evaluate changes in blood long-chain polyunsaturated fatty acid (LCPUFA) and oxylipin concentrations in very preterm infants from birth to 36 weeks' postmenstrual age (WPA) after providing an emulsified arachidonic acid (ARA):docosahexaenoic acid (DHA) supplement at two different concentrations.Study designThis prospective, randomized trial assigned infants to receive a supplement (1) 80:40 group (80 mg/kg/day ARA and 40 mg/kg/day DHA, n = 9) or (2) 120:60 group (120 mg/kg/day ARA and 60 mg/kg/day DHA, n = 9). Infants received supplement daily from birth until 36 WPA. At baseline, 21 days of life and 36 WPA, the LCPUFAs were measured in plasma by gas chromatography/mass spectrophotometry. Additionally, LCPUFAs and oxylipins were analyzed in whole blood by ultra-high-performance liquid chromatography-tandem mass spectrometry. Furthermore, a sample of oral mucosa was obtained to analyze single-nucleotide polymorphism located in the FADS1 gene by PCR.ResultsGestational age was similar between groups (80:40 = 28+6 [27+3; 30+3] completed weeks+days ; 120:60 = 29+6 [27+3; 30+5] completed weeks+days , p = 0.83). At 36 WPA, the change in plasma ARA was significantly different between groups (80:40 group = 0.15 [-0.67; 0.69] %nmol, 120:60 = 1.68 [1.38; 3.16] %nmol, p = 0.031). In whole blood, the levels of ARA-derived oxylipins (5-, 8-, 9-, 11-, 15-HETE and 8,9-EET) and EPA-derived oxylipins (18-HEPE) significantly increase from baseline to 36 WPA in the 120:60 group than the 80:40 group.ConclusionSupplementation at high doses (120:60 mg/kg/day) increased levels of ARA, and EPA- and ARA-derived oxylipins compared to low doses (80:40 mg/kg/day). Differences were detected in EPA metabolites without a significant increase in plasma DHA.
| S-EPMC9452757 | biostudies-literature
Project description:The DHA to Optimize Mother Infant Outcome (DOMInO) and Kansas DHA Outcomes Study (KUDOS) were randomized controlled trials that supplemented mothers with 800 and 600mg DHA/day, respectively, or a placebo during pregnancy. DOMInO was conducted in Australia and KUDOS in the United States. Both trials found an unanticipated and statistically significant reduction in early preterm birth (ePTB; i.e., birth before 34 weeks gestation). However, in each trial, the number of ePTBs were small. We used a novel Bayesian approach to estimate statistically derived low, moderate or high risk for ePTB, and to test for differences between the DHA and placebo groups. In both trials, the model predicted DHA would significantly reduce the expected proportion of deliveries in the high risk group under the trial conditions of the parent studies. Among the next 300,000 births in Australia we estimated that 1112 ePTB (95% credible interval 51-2189) could be avoided by providing DHA. And in the USA we estimated that 106,030 ePTB (95% credible interval 6400 to 175,700) could be avoided with DHA.
| S-EPMC5028118 | biostudies-literature
Project description:Little evidence is available to document that mechanical ventilation is an antecedent of systemic inflammation in preterm humans. We obtained blood on postnatal day 14 from 726 infants born before the 28th week of gestation and measured the concentrations of 25 inflammation-related proteins. We created multivariable models to assess the relationship between duration of ventilation and protein concentrations in the top quartile. Compared to newborns ventilated for fewer than 7 days (N=247), those ventilated for 14 days (N=330) were more likely to have elevated blood concentrations of pro-inflammatory cytokines (IL-1?, TNF-?), chemokines (IL-8, MCP-1), an adhesion molecule (ICAM-1), and a matrix metalloprotease (MMP-9), and less likely to have elevated blood concentrations of two chemokines (RANTES, MIP-1?), a matrix metalloproteinase (MMP-1), and a growth factor (VEGF). Newborns ventilated for 7-13 days (N=149) had systemic inflammation that approximated the pattern of newborns ventilated for 14 days. These relationships were not confounded by chorioamnionitis or antenatal corticosteroid exposure, and were not altered appreciably among infants with and without bacteremia. These findings suggest that 2 weeks of ventilation are more likely than shorter durations of ventilation to be accompanied by high blood concentrations of pro-inflammatory proteins indicative of systemic inflammation, and by low concentrations of proteins that might protect from inflammation-mediated organ injury.
| S-EPMC3518391 | biostudies-literature
Project description:Neonatal inflammation is associated with perinatal brain damage. We evaluated to what extent elevated blood levels of inflammation-related proteins supplement information about the risk of impaired early cognitive function provided by inflammation-related illnesses. From 800 infants born before the 28th week of gestation, we collected blood spots on days 1, 7 and 14, for analysis of 25 inflammation-related proteins, and data about culture-positive bacteremia, necrotizing enterocolitis (Bell stage IIIb), and isolated perforation of the intestine, during the first two weeks, and whether they were ventilated on postnatal day 14. We considered a protein to be persistently or recurrently elevated if its concentration was in the top quartile (for gestational age and day blood was collected) on two separate days one week apart. We assessed the children at 2 years of age with the Bayley Mental Development Index (MDI). The combinations of NEC and ventilation on day 14, and of bacteremia and ventilation on day 14 consistently provided information about elevated risk of MDI <55, regardless of whether or not a variable for an elevated protein concentration was included in the model. A variable for a persistently or recurrently elevated concentration of each of the following proteins provided additional information about an increased risk of MDI <55: CRP, SAA, IL-6, TNF-alpha, IL-8, MIP-1beta, ICAM-1, E-SEL, and IGFBP-1. We conclude that elevated blood concentrations of inflammation-related proteins provide information about the risk of impaired cognitive function at age 2 years that supplements information provided by inflammation-associated illnesses.
| S-EPMC3582030 | biostudies-literature
Project description:Study objectivesThis secondary analysis characterized sleep patterns for toddlers born preterm and tested effects of docosahexaenoic acid (DHA)+ arachidonic acid (AA) supplementation on children's caregiver-reported sleep. Exploratory analyses tested whether child sex, birth weight, and caregiver depressive symptomatology were moderators of the treatment effect.MethodsOmega Tots was a single-site 180-day randomized (1:1), double-blinded, placebo-controlled trial. Children (n = 377) were age 10 to 16 months at enrollment, born at less than 35 weeks' gestation, assigned to 180 days of daily 200 mg DHA + 200 mg AA supplementation or placebo (400 mg corn oil), and followed after the trial ended to age 26 to 32 months. Caregivers completed a sociodemographic profile and questionnaires about their depressive symptomatology (Center for Epidemiologic Studies Depression Scale) and the child's sleep (Brief Infant Sleep Questionnaire). Analyses compared changes in sleep between the DHA+AA and placebo groups, controlling for baseline scores. Exploratory post hoc subgroup analyses were conducted.ResultsEighty-one percent (ntx = 156; nplacebo = 150) of children had 180-day trial outcome data; 68% (ntx = 134; nplacebo = 122) had postintervention outcome data. Differences in change between the DHA+AA and placebo groups after 180 days of supplementation were not statistically significant for the entire cohort. Male children (difference in nocturnal sleep change = 0.44, effect size = 0.26, P = .04; sleep problems odds ratio = 0.36, 95% confidence interval = 0.15, 0.82) and children of depressed caregivers (difference in nocturnal sleep change = 1.07, effect size = 0.65, P = .006; difference in total sleep change = 1.10, effect size = 0.50, P = .04) assigned to the treatment group showed improvements in sleep, compared to placebo.ConclusionsAlthough there is no evidence of an overall effect of DHA+AA supplementation on child sleep, exploratory post hoc analyses identified important subgroups of children born preterm who may benefit. Future research including larger samples is warranted.Clinical trial registrationRegistry: ClinicalTrials.gov; Identifier: NCT01576783.CitationBoone KM, Rausch J, Pelak G, Li R, Turner AN, Klebanoff MA, Keim SA. Docosahexaenoic acid and arachidonic acid supplementation and sleep in toddlers born preterm: secondary analysis of a randomized clinical trial. J Clin Sleep Med. 2019;15(9):1197-1208.
| S-EPMC6760416 | biostudies-literature
Project description:BackgroundInflammation is strongly associated with premature birth and neonatal morbidities. Increases in infant haptoglobin, haptoglobin-related protein (Hp&HpRP), and interleukin-6 (IL-6) levels are indicators of intra-amniotic inflammation (IAI) and have been linked to poor neonatal outcomes. Inflammation causes epigenetic changes, specifically suppression of miR-29 expression. The current study sought to determine whether miR-29b levels in cord blood or neonatal venous blood are associated with IAI, identified by elevated IL-6 and Hp, and subsequent clinical morbidities in the infant.MethodsWe tested 92 cord blood samples from premature newborns and 18 venous blood samples at 36 weeks corrected gestational age. MiR-29b, Hp&HpRP, and IL-6 were measured by polymerase chain reaction and enzyme-linked immunosorbent assay, respectively.ResultsDecreased levels of miR-29b were observed in infants exposed to IAI with elevated Hp&HpRP and IL-6 levels and in infants delivered by spontaneous preterm birth. Lower miR-29 levels were also observed in women diagnosed with histological chorioamnionitis or funisitis and in infants with cerebral palsy. Higher levels of miR-29 were measured in infants small for gestational age and in venous samples from older infants.ConclusionsMiR-29 may be an additional biomarker of IAI and a potential therapeutic target for treating poor newborn outcomes resulting from antenatal exposure to IAI.ImpactDecreases in miR-29b are associated with intrauterine inflammation. Hp&HpRP increases are associated with decreased miR-29b. MiR-29b may be an additional biomarker for neonatal outcomes and a potential therapeutic target for intrauterine inflammation.
| S-EPMC7649129 | biostudies-literature
Project description:Necrotizing enterocolitis (NEC) is an inflammatory bowel disease and a leading cause of morbidity and mortality in preterm infants. In this study, a randomized double-blind parallel-group (1:1) trial was carried out in two neonatal intensive care units of two tertiary hospitals. Two hundred and twenty-five preterm newborns with an expected functional gastrointestinal tract were recruited and received an enteral dose of 75 mg of docosahexaenoic acid (DHA)/kg body weight or high-oleic sunflower oil daily for 14 days from the first enteral feed after birth. Confirmed NEC was evaluated with Bell's scale from stage ≥ IIa. Two hundred and fourteen randomized infants were analyzed in terms of the intent-to-treat (DHA-group: n = 105; control-group: n = 109); data for two hundred infants were analysed per protocol. Confirmed NEC was lower in infants from the DHA-group compared with the control-group (0/100 vs. 7/100; p = 0.007), with RR = 0.93 (95% CI 0.881 to 0.981), risk difference = -7%, (95% CI -12.00 to -1.99), and number needed-to-treat = 15 (95% CI 8.3 to 50). Intent-to-treat analysis showed a lower level of treatment failure in the DHA-group compared with the control-group (6/105 (6%) vs. 16/109 (15%); p = 0.03, RR = 0.905, (95% CI 0.826 to 0.991)). The results after multivariate-regression analysis remained significant. Adverse events (apart from the incidence of NEC) were not different between groups. A daily dose of DHA for 14 days starting with the first enteral feed may prevent NEC in preterm infants.
| S-EPMC7922869 | biostudies-literature
Project description:BackgroundDue to insufficient evidence, extremely preterm infants (≤28 wk of gestation) rarely receive early progressive feeding (small increments of feeding volumes between 1 and 4 d after birth). We hypothesized that early progressive feeding increases the number of full enteral feeding days in the first month after birth.ObjectiveThe aim of this study was to determine the feasibility and efficacy of early progressive feeding in extremely preterm infants.DesignIn this single-center randomized trial, extremely preterm infants born between September 2016 and June 2017 were randomly assigned to receive either early progressive feeding without trophic feeding (early feeding group) or delayed progressive feeding after a 4-d course of trophic feeding (delayed feeding group). Treatment allocation occurred before or on feeding day 1. The primary outcome was the number of full enteral feeding days in the first month after birth. Secondary outcomes were death, necrotizing enterocolitis (NEC), culture-proven sepsis, growth percentiles at 36 wk postmenstrual age, use of parenteral nutrition, and need for central venous access.ResultsSixty infants were included (median gestational age: 26 wk; mean ± SD birth weight: 832 ± 253 g). The primary outcome differed between groups (median difference favoring the early feeding group: +2 d; 95% CI: 0, 3 d; P = 0.02). Early progressive feeding reduced the use of parenteral nutrition (4 compared with 8 d; P ≤ 0.01) and the need for central venous access (9 compared with 13 d; P ≤ 0.01). The outcome of culture-proven sepsis (10% compared with 27%; P = 0.18), restricted growth (weight, length, and head circumference <10th percentile) at 36 wk postmenstrual age (25% compared with 50%; P = 0.07), and the composite outcome of NEC or death (27% compared with 20%; P = 0.74) did not differ between groups.ConclusionEarly progressive feeding increases the number of full enteral feeding days in extremely preterm infants. This trial was registered at www.clinicaltrials.gov as NCT02915549.
| S-EPMC6692650 | biostudies-literature