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Birth outcomes across the spectrum of maternal age: dissecting aging effect versus confounding by social and medical determinants.
Olapeju, B, Hong, X, Wang, G, Summers, A, Burd, I, Cheng, TL, Wang, X
BMC pregnancy and childbirth. 2021;(1):594
Abstract
BACKGROUND Given the trend of increasing maternal age and associated adverse reproductive outcomes in the US, this study aimed to assess whether this association is due to an independent aging or confounded by sociodemographic, biomedical, or behavioral determinants in a predominantly Black US population. METHODS Data was from 8509 women enrolled in the Boston Birth Cohort. Adverse reproductive outcomes included spontaneous preterm delivery, cesarean delivery, and low birth weight. Covariates included sociodemographic (parity, race/ethnicity, education, marital status, income, receipt of public assistance, nativity); biomedical (obesity, hypertensive disorders, diabetes mellitus); and behavioral (consistent intake of multivitamin supplements, support from father of baby, support from family, major stress in pregnancy, cigarette smoking, alcohol intake). Analysis included Lowess and marginal probability plots, crude and adjusted sequential logistic regression models to examine age-outcome associations and to what degree the association can be explained by the above covariables. RESULT Overall, the study sample had high levels of spontaneous preterm birth (18%), cesarean delivery (33%) and low birth weight (26%). Unadjusted models showed no significant difference odds of spontaneous preterm birth by maternal age but higher odds of cesarean section (aOR: 1.77, 95% CI: 1.60, 1.95) and low birth weight (aOR: 1.15, 95% CI: 1.04, 1.28) among women 30 years or older. Adjustment for sociodemographic factors, biomedical conditions and behavioral factors revealed higher odds of spontaneous preterm birth: (aOR: 1.30, 95% CI: 1.14, 1.49), cesarean section deliveries (aOR: 1.68, 95% CI: 1.51, 1.87) and low birth weight (aOR: 1.36, 95% CI: 1.21, 1.53). Across all ages, optimal BMI status and consistent multivitamin supplement intake were protective of spontaneous preterm birth and low birth weight. CONCLUSION In this high-risk minority population, we demonstrated that the association between increasing maternal age and adverse pregnancy outcomes was due to an independent aging effect and the presence of confounding by sociodemographic, biomedical, and behavioral factors. Some modifiable risk factors to counteract aging effect, include optimizing BMI and consistent intake of multivitamin supplement. A fundamental change in how care is provided to women, particularly low income Black women, is needed with emphasis on the protective role of optimal nutritional status. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03228875.
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Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trials.
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Lancet (London, England). 2021;(10280):1183-1194
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BACKGROUND Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes. METHODS We did a systematic review of randomised trials comparing vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control, or with each other, in asymptomatic women at risk of preterm birth. We identified published and unpublished trials that completed primary data collection before July 30, 2016, (12 months before data collection began), by searching MEDLINE, Embase, CINAHL, the Maternity and Infant Care Database, and relevant trial registers between inception and July 30, 2019. Trials of progestogen to prevent early miscarriage or immediately-threatened preterm birth were excluded. Individual participant data were requested from investigators of eligible trials. Outcomes included preterm birth, early preterm birth, and mid-trimester birth. Adverse neonatal sequelae associated with early births were assessed using a composite of serious neonatal complications, and individually. Adverse maternal outcomes were investigated as a composite and individually. Individual participant data were checked and risk of bias assessed independently by two researchers. Primary meta-analyses used one-stage generalised linear mixed models that incorporated random effects to allow for heterogeneity across trials. This meta-analysis is registered with PROSPERO, CRD42017068299. FINDINGS Initial searches identified 47 eligible trials. Individual participant data were available for 30 of these trials. An additional trial was later included in a targeted update. Data were therefore available from a total of 31 trials (11 644 women and 16185 offspring). Trials in singleton pregnancies included mostly women with previous spontaneous preterm birth or short cervix. Preterm birth before 34 weeks was reduced in such women who received vaginal progesterone (nine trials, 3769 women; relative risk [RR] 0·78, 95% CI 0·68-0·90), 17-OHPC (five trials, 3053 women; 0·83, 0·68-1·01), and oral progesterone (two trials, 181 women; 0·60, 0·40-0·90). Results for other birth and neonatal outcomes were consistently favourable, but less certain. A possible increase in maternal complications was suggested, but this was uncertain. We identified no consistent evidence of treatment interaction with any participant characteristics examined, although analyses within subpopulations questioned efficacy in women who did not have a short cervix. Trials in multifetal pregnancies mostly included women without additional risk factors. For twins, vaginal progesterone did not reduce preterm birth before 34 weeks (eight trials, 2046 women: RR 1·01, 95% CI 0·84-1·20) nor did 17-OHPC for twins or triplets (eight trials, 2253 women: 1·04, 0·92-1·18). Preterm premature rupture of membranes was increased with 17-OHPC exposure in multifetal gestations (rupture <34 weeks RR 1·59, 95% CI 1·15-2·22), but we found no consistent evidence of benefit or harm for other outcomes with either vaginal progesterone or 17-OHPC. INTERPRETATION Vaginal progesterone and 17-OHPC both reduced birth before 34 weeks' gestation in high-risk singleton pregnancies. Given increased underlying risk, absolute risk reduction is greater for women with a short cervix, hence treatment might be most useful for these women. Evidence for oral progesterone is insufficient to support its use. Shared decision making with woman with high-risk singleton pregnancies should discuss an individual's risk, potential benefits, harms and practicalities of intervention. Treatment of unselected multifetal pregnancies with a progestogen is not supported by the evidence. FUNDING Patient-Centered Outcomes Research Institute.
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Magnesium levels in relation to rates of preterm birth: a systematic review and meta-analysis of ecological, observational, and interventional studies.
Zhang, Y, Xun, P, Chen, C, Lu, L, Shechter, M, Rosanoff, A, He, K
Nutrition reviews. 2021;(2):188-199
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CONTEXT Experimental studies suggest that magnesium levels in pregnant women may affect the length of gestation, as magnesium affects the activity of smooth muscle in the uterus. Little is known about the association between magnesium levels or supplementation and the rate of preterm birth. OBJECTIVE The aim of this systematic review was to summarize the data on magnesium soil levels and preterm birth rates from ecological, observational, and interventional studies. DATA SOURCES Soil magnesium levels were obtained from US Geological Survey data, and preterm birth rates were acquired from the March of Dimes Foundation. Relevant epidemiological and clinical studies published until April 2019 in peer-reviewed journals were retrieved from PubMed, Google Scholar, and related reference lists. STUDY SELECTION Original studies published in English, conducted in humans, and in which magnesium (dietary/supplemental intake or biomarkers) was an exposure and preterm birth was an outcome were included. DATA EXTRACTION Eleven studies were included in the systematic review. Meta-analysis was performed on 6 studies. Overall relative risk (RR) and corresponding 95%CIs for risk of preterm birth in relation to magnesium supplementation were estimated by a random-effects model. RESULTS The ecological study revealed an inverse correlation between magnesium content in soil and rates of preterm birth across the United States (r = -0.68; P < 0.001). Findings from 11 observational studies generally support an inverse association between serum magnesium levels and rates of preterm birth. Of the 6 eligible randomized controlled trials, which included 3068 pregnant women aged 20 to 35 years and 352 preterm infants, the pooled RR was 0.58 (95%CI, 0.35-0.96) for women in the magnesium supplementation group compared with women in the control group. CONCLUSIONS Accumulated evidence from ecological, observational, and interventional studies consistently indicates that adequate magnesium intake during pregnancy may help reduce the incidence of preterm birth.
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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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Maternal Vitamin D Levels During Pregnancy and Their Effects on Maternal-Fetal Outcomes: A Systematic Review.
Gilani, S, Janssen, P
Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC. 2020;(9):1129-1137
Abstract
To synthesize and critically review the current evidence available on maternal vitamin D deficiency and its effects on maternal-fetal outcomes, this study reviewed the maternal-fetal outcomes, including prolonged labour or cesarean delivery, preeclampsia, gestational diabetes, low birth weight and small for gestational age, and preterm birth. An extensive systematic searched was performed in Medline and EMBASE, where a medical subject heading (MeSH) was used with terms "Vitamin D/25(OH)D" and "pregnancy/fetal outcomes"; these terms were combined with "and." In Web of Science and Google Scholar, a key word search was used. Nineteen articles were included for full review. This review found that the current state of the evidence is equivocal for maternal-fetal outcomes such as the risk of prolonged labour and cesarean delivery, gestational diabetes, low birth weight and small for gestational age, and preterm birth. Although some previous studies have found improvement in pregnancy outcomes with sufficient vitamin D levels, others have not shown any association with the aforementioned outcomes. This systematic review also highlights an association between the risk of preeclampsia and maternal vitamin D levels that is found to be consistent among studies.
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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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Influence of clinical characteristics on maternal DHA and other polyunsaturated fatty acid status in pregnancy: A systematic review.
Wilson, NA, Mantzioris, E, Middleton, PF, Muhlhausler, BS
Prostaglandins, leukotrienes, and essential fatty acids. 2020;:102063
Abstract
INTRODUCTION Omega-3 DHA is important for the prevention of preterm birth, however there is limited knowledge of the determinants of omega-3 status during pregnancy. The primary objective of this systematic review was to synthesise data from existing studies assessing relationships between clinical factors and maternal DHA status. MATERIALS AND METHODS The Medline, Embase, Amed, and CINAHL databases were searched for studies reporting measures of maternal omega-3 status and one or more clinical characteristics. RESULTS Eighteen studies were included in the final analyses. Factors associated with a higher BMI (overweight, higher gestational weight gain, gestational diabetes), or lower parity were each associated with higher omega-3 status in the majority of studies, with mixed findings for other comparisons. DISCUSSION Inconsistent findings between studies make it difficult to draw clear conclusions about the relationship between clinical factors and maternal omega-3 DHA status. However, maternal overweight and associated metabolic conditions may increase lipid metabolism.
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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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Human milk fatty acid profile across lactational stages after term and preterm delivery: A pooled data analysis.
Floris, LM, Stahl, B, Abrahamse-Berkeveld, M, Teller, IC
Prostaglandins, leukotrienes, and essential fatty acids. 2020;:102023
Abstract
BACKGROUND Lipids in human milk (HM) provide the majority of energy for developing infants, as well as crucial essential fatty acids (FA). The FA composition of HM is highly variable and influenced by multiple factors. We sought to increase understanding of the variation in HMFA profiles and their development over the course of lactation, and after term and preterm delivery, using a pooled data analysis. OBJECTIVE To review the literature and perform a pooled data analysis to qualitatively describe an extensive FA profile (36 FAs) in term and preterm colostrum, transitional - and mature milk up to 60 days postpartum. DESIGN A Medline search was conducted for HMFA profile data following term or preterm delivery. The search was confined to English language papers published between January 1980 and August 2018. Studies reporting original data, extensive FA profiles in HM from healthy mothers were included. Weighted least squares (WLS) means were calculated from the pooled data using random or fixed effect models. RESULTS Our pooled data analysis included data from 55 studies worldwide, for a total of 4374 term milk samples and 1017 preterm milk samples, providing WLS means for 36 FAs. Patterns in both term and preterm milk were apparent throughout lactation for some FAs: The most abundant FAs (palmitic, linoleic and oleic acid) remained stable over time, whereas several long-chain polyunsaturated FAs (including ARA and DHA) seemed to decrease and short- and medium-chain FAs increased over time. CONCLUSIONS High heterogeneity between individual studies was observed for the reported levels of some FAs, whereas other FAs were remarkably consistent between studies. Our pooled data suggests that specific FA categories fluctuate according to distinct patterns over the course of lactation; many of these patterns are comparable between term and preterm milk.
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Prostaglandin and prostamide concentrations in amniotic fluid of women with spontaneous labor at term with and without clinical chorioamnionitis.
Peiris, HN, Romero, R, Vaswani, K, Gomez-Lopez, N, Tarca, AL, Gudicha, DW, Erez, O, Maymon, E, Reed, S, Mitchell, MD
Prostaglandins, leukotrienes, and essential fatty acids. 2020;:102195
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OBJECTIVE Prostaglandins (PGs) are considered universal mediators for the process of physiological parturition. This is based on observations that amniotic fluid concentrations of PGs are elevated prior to and during the onset of labor (mostly utilizing immunoassays). Distinguishing PGs from similarly structured molecules (i.e. prostamides; PG-EA) is difficult given the cross-reactivity of available antibodies and the chemical similarity between these compounds. Herein, this limitation was overcome by utilizing mass spectrometry to determine PG and PG-EA concentrations in amniotic fluid of women with spontaneous labor at term and in those with clinical chorioamnionitis (CHAM), the most common infection-related diagnosis made in labor and delivery units worldwide. STUDY DESIGN Liquid chromatography-tandem mass spectrometry (LC MS/MS) was used to determine the PG and PG-EA content in amniotic fluid samples of women with spontaneous labor at term with (n = 14) or without (n = 28) CHAM. Controls included women who delivered at term without labor (n = 10). RESULTS PGE2, PGF2α, and 13,14-dihydro-15-keto-PGF2α (PGFM) were higher in amniotic fluid of women with spontaneous labor at term than in those without labor. PGE2, PGF2α, and PGFM were also higher in amniotic fluid of women with CHAM than in those without labor. However, PGE2-EA and PGF2α-EA were lower in amniotic fluid of women with CHAM than in those without CHAM. The ratios of PGE2 to PGE2-EA and PGF2α to PGF2α-EA were higher in amniotic fluid of women with spontaneous labor at term with or without CHAM than in those without labor; yet, the ratio of PGF2α to PGF2α-EA was greater in women with CHAM than in those without this clinical condition. CONCLUSIONS Spontaneous labor at term with or without CHAM is characterized by elevated amniotic fluid concentrations of prostaglandins (PGE2, PGF2α, and PGFM) but not prostamides. Quantification of these products by LC MS/MSlc==may potentially be of utility in identifying their physiological functions relevant to parturition. SUMMARY Prostaglandins (PGs) are critical for the onset and progression of labor. Structural similarities of PGs and prostamides (PG-EA) prevents their specific identification by immunoassay. We utilized LC MS/MS to determine PG and PG-EA content in amniotic fluid (AF) of women with spontaneous labor at term with or without CHAM and women who delivered at term without labor. Higher aamniotic ffluid PG levels were observed in women with spontaneous labor with and without CHAM compared to women delivering without labor. PG-EA levels in amniotic fluid of women with spontaneous labor and CHAM were lower than in women with spontaneous labor without CHAM but not those without labor. Ratios of PGs to PG-EAs were higher in AF of women with labor and CHAM compared to those without labor. Delineation of these products by LC MS/MS may potentially be of utility in identifying their physiological functions relevant to parturition.