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Higher-Dose DHA Supplementation Modulates Immune Responses in Pregnancy and Is Associated with Decreased Preterm Birth.
Valentine, CJ, Khan, AQ, Brown, AR, Sands, SA, Defranco, EA, Gajewski, BJ, Carlson, SE, Reber, KM, Rogers, LK
Nutrients. 2021;(12)
Abstract
Pregnancy and parturition involve extensive changes in the maternal immune system. In our randomized, multi-site, double-blind superiority trial using a Bayesian adaptive design, we demonstrated that 1000 mg/day of docosahexaenoic acid (DHA) was superior to 200 mg/day in preventing both early preterm birth (less than 34 weeks' gestation) and preterm birth (less than 37 weeks' gestation). The goal of this secondary study is to compare the effects of 1000 mg/day versus 200 mg/day on maternal inflammation, a possible mechanism by which DHA may prevent preterm birth. Maternal blood samples were collected at enrollment (12-20 weeks' gestation) and at delivery. Red blood cell DHA levels were measured by gas chromatography, and plasma concentrations of sRAGE, IL-6, IL-1β, TNFα, and INFγ were measured by ELISA. Data were analyzed for associations with the DHA dose, gestational age at birth, and preterm birth (<37 weeks). Higher baseline and lower delivery levels of maternal sRAGE were associated with a greater probability of longer gestation and delivery at term gestation. Higher-dose DHA supplementation increased the probability of a smaller decrease in delivery sRAGE levels. Higher IL-6 concentrations at delivery were associated with the probability of delivering after 37 weeks, and higher-dose DHA supplementation increased the probability of greater increases in IL-6 concentrations between enrollment and delivery. These data provide a proposed mechanistic explanation of how a higher dose of DHA during pregnancy provides immunomodulatory regulation in the initiation of parturition by influencing sRAGE and IL-6 levels, which may explain its ability to reduce the risk of preterm birth.
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Nausea, vomiting and poor appetite during pregnancy and adverse birth outcomes in rural Nepal: an observational cohort study.
Regodón Wallin, A, Tielsch, JM, Khatry, SK, Mullany, LC, Englund, JA, Chu, H, LeClerq, SC, Katz, J
BMC pregnancy and childbirth. 2020;(1):545
Abstract
BACKGROUND Nausea and vomiting are experienced by a majority of pregnant women worldwide. Previous studies have yielded conflicting results regarding their impact on birth outcomes and few studies have examined this relationship in settings with limited resources. We aimed to determine the effect of nausea, vomiting and poor appetite during pregnancy on birth outcomes in rural Nepal. METHODS Observational cohort study using data collected in two randomized, community-based trials to assess the effect of influenza immunization during pregnancy on reproductive and respiratory outcomes among pregnant women and their offspring. Pregnant women in Sarlahi District, Nepal were recruited from 2011 to 2013. Exposure was defined as nausea, vomiting or poor appetite at any point during pregnancy and by trimester; symptoms were recorded monthly throughout pregnancy. Adverse outcomes were low birth weight (LBW), preterm birth and small for gestational age (SGA). Adjusted relative risks (aRR) with 95% CIs are reported from Poisson regressions with robust variance. RESULTS Among 3,623 pregnant women, the cumulative incidence of nausea, vomiting or poor appetite was 49.5% (n = 1793) throughout pregnancy and 60.6% (n = 731) in the first trimester. Significantly higher aRRs of LBW and SGA were observed among women experiencing symptoms during pregnancy as compared to symptom free women (LBW: aRR 1.20; 95% CI 1.05 1.28; SGA: aRR 1.16; 95% CI 1.05 1.28). Symptoms in the first trimester were not significantly associated with any of the outcomes. In the second trimester, we observed significantly higher aRRs for LBW and SGA (LBW: aRR 1.17; 95% CI 1.01 1.36; SGA: aRR 1.16; 95% CI 1.05 1.29) and a significantly lower aRR for preterm birth (aRR 0.75; 95% CI 0.59 0.96). In the third trimester, we observed significantly higher aRRs for LBW and SGA (LBW: aRR 1.20; 95% CI 1.01 1.43; SGA: aRR 1.14; 95% CI 1.01 1.29). CONCLUSIONS Symptoms of nausea, vomiting or poor appetite during pregnancy are associated with LBW, SGA and preterm birth in a setting with limited resources, especially beyond the first trimester. TRIAL REGISTRATION Prospectively registered at ClinicalTrials.gov on Dec 17, 2009 ( NCT01034254 ).
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Female genital tract microbiota affecting the risk of preterm birth: What do we know so far? A review.
Tsonis, O, Gkrozou, F, Harrison, E, Stefanidis, K, Vrachnis, N, Paschopoulos, M
European journal of obstetrics, gynecology, and reproductive biology. 2020;:168-173
Abstract
Spontaneous Preterm birth (SPTB) is a common obstetric complication affecting 12.9 million births worldwide and is the leading cause of neonatal morbidity and mortality. Disruption in the vaginal microbiota has an impact on the maternal immunological profile leading to SPTBs. Scientists have struggled to link maternal infectious agents with the dysregulation of the maternal immune response in cases of SPTBs. Throughout the last decade, important findings regarding the role of microbiota and its genome, the so-called microbiome, have linked alterations within the population of the microorganisms in our bodies with changes in nutrition, immunity, behaviour and diseases. In this review, evidence regarding the female genital tract microbiota and microbiome has been examined to help further our understanding of its role in disrupting the maternal immune system resulting in spontaneous preterm birth.
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Intrauterine infection, immune system and premature birth.
Helmo, FR, Alves, EAR, Moreira, RAA, Severino, VO, Rocha, LP, Monteiro, MLGDR, Reis, MAD, Etchebehere, RM, Machado, JR, Corrêa, RRM
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2018;(9):1227-1233
Abstract
Preterm birth accounts for nearly one million deaths among children under five years of age, and although its etiopathogenesis is not fully elucidated, ascending intrauterine infection and fetal inflammatory response seem to be the main triggers. The intense inflammatory response mediated by IL-1β, TNF-α, PAF, IFN-γ and IL-6, PGE2 and MMP-1 and MMP-9 causes fetal membrane damage and rupture, increased uterine contractions and biochemical and structural changes in the cervix. Furthermore, preterm neonates have deficient innate and adaptive immune responses characterized by reduced levels of IgG, opsonization and phagocytosis, as well as increased activation of Th1 cells in relation to Th2 cells. Therefore, this triad is favors the occurrence of neonatal complications, such as respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity and bronchopulmonary dysplasia. Due to serious maternal and child health complications of intrauterine infection, several studies have tried to identify biomarkers for the early diagnosis of this entity. This literature review aims to discuss the main scientific findings regarding the association between ascending intrauterine infection, immune system and preterm birth.
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Ureaplasma-associated prenatal, perinatal, and neonatal morbidities.
Silwedel, C, Speer, CP, Glaser, K
Expert review of clinical immunology. 2017;(11):1073-1087
Abstract
Ureaplasma species (spp.) have been acknowledged as major causative pathogens in chorioamnionitis and prematurity, but may also contribute to key morbidities in preterm infants. Several epidemiological and experimental data indicate an association of neonatal Ureaplasma colonization and/or infection with bronchopulmonary dysplasia. Furthermore, a potential causal relation with other inflammation-induced morbidities, such as intraventricular hemorrhage, white matter injury, necrotizing enterocolitis, and retinopathy of prematurity, has been debated. Areas covered: This review will summarize current knowledge on the role of Ureaplasma spp. in prenatal, perinatal, and neonatal morbidities, while furthermore examining mutual underlying mechanisms. We try to elaborate who is at particular risk of Ureaplasma-induced inflammation and subsequent secondary morbidities. Expert commentary: Most likely by complex interactions with immunological processes, Ureaplasma spp. can induce pro-inflammation, but may also downregulate the immune system. Tissue damage, possibly causing the above mentioned complications, is likely to result from both ways: either directly cytokine-associated, or due to a higher host vulnerability to secondary impact factors. These events are very likely to begin in prenatal stages, with the most immature preterm infants being most susceptible and at highest risk.
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Perinatal distress in women in low- and middle-income countries: allostatic load as a framework to examine the effect of perinatal distress on preterm birth and infant health.
Premji, S
Maternal and child health journal. 2014;(10):2393-407
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Abstract
In low- and middle-income countries (LMIC), determinants of women's and children's health are complex and differential vulnerability may exist to risk factors of perinatal distress and preterm birth. We examined the contribution of maternal perinatal distress on preterm birth and infant health in terms of infant survival and mother-infant interaction. A critical narrative and interpretive literature review was conducted. Peer-reviewed electronic databases (MEDLINE, Embase, Global Health, CINHAL), grey literature, and reference lists were searched, followed by a consultation exercise. The literature was predominantly from high-income countries. We identify determinants of perinatal distress and explicate changes in the hypothalamic-pituitary-adrenal axis, sympathetic, immune and cardiovascular systems, and behavioral responses resulting in pathophysiological effects. We suggest cultural-neutral composite measures of allostatic mediators (i.e., several biomarkers) of maternal perinatal distress as objective indicators of dysregulation in body systems in pregnant women in LMIC. Understanding causal links of maternal perinatal distress to preterm birth in women in LMIC should be a priority. The roles of allostasis and allostatic load are considered within the context of the health of pregnant women and fetuses/newborns in LMIC with emphasis on identifying objective indicators of the level of perinatal distress and protective factors or processes contributing to resilience while facing toxic stress. We propose a prospective study design with multiple measures across pregnancy and postpartum requiring complex statistical modeling. Building research capacity through partnering researchers in high-income countries and LMIC and reflecting on unique ethical challenges will be important to generating new knowledge in LMIC.
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Omega-3 fatty acid supplementation during pregnancy and respiratory symptoms in children.
Escamilla-Nuñez, MC, Barraza-Villarreal, A, Hernández-Cadena, L, Navarro-Olivos, E, Sly, PD, Romieu, I
Chest. 2014;(2):373-382
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BACKGROUND Prenatal consumption of omega-3 fatty acids can act as an adjuvant in the development of the immune system and affect the inflammatory response of neonates. METHODS We conducted a double-blind, randomized, placebo-controlled trial in Cuernavaca, Mexico. We randomly assigned 1,094 pregnant women (18-35 years of age) to receive 400 mg/d of algal docosahexaenoic acid (DHA) or placebo from 18 to 22 weeks of gestation through delivery. Birth outcomes and respiratory symptoms information until 18 months were available for 869 mother-child pairs. Questionnaires were administered, and maternal blood samples were obtained at baseline. Maternal atopy was based on specific IgE levels. During follow-up, information on infants' respiratory symptoms was collected through questionnaires administered at 1, 3, 6, 9, 12, and 18 months of age. Negative binomial regression models were used to evaluate the effect of supplementation on respiratory symptoms in infants. RESULTS Among infants of atopic mothers, a statistically significant protective effect of DHA treatment was observed on phlegm with nasal discharge or nasal congestion (0.78; 95% CI, 0.60-1.02) and fever with phlegm and nasal discharge or nasal congestion (0.53; 95% CI, 0.29-0.99), adjusting for potential confounders. CONCLUSIONS Our results support the hypothesis that DHA supplementation during pregnancy may decrease the incidence of respiratory symptoms in children with a history of maternal atopy. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT00646360; URL: www.clinicaltrials.gov.