Objective Although a higher maternal body mass index is associated with preterm birth, it is unclear whether excess gestational weight gain (GWG) or obesity drives increased risk. We and others have ...shown that the placenta harbors microbiota, which is significantly different among preterm births. Our aim in this study was to investigate whether the preterm placental microbiome varies by virtue of obesity or alternately by excess GWG. Study Design Placentas (n = 320) were collected from term and preterm pregnancies. Genomic DNA was extracted and subjected to metagenomic sequencing. Data were analyzed by clinical covariates that included the 2009 Institute of Medicine’s GWG guideline and obesity. Results Analysis of 16S recombinant RNA–based metagenomics revealed no clustering of the microbiome by virtue of obesity ( P = .161). Among women who spontaneously delivered preterm, there was again no clustering by obesity ( P = .480), but there was significant clustering by excess GWG ( P = .022). Moreover, among preterm births, detailed analysis identified microbial genera (family and genus level) and bacterial metabolic gene pathways that varied among pregnancies with excess GWG. Notably, excess GWG was associated with decreased microbial folate biosynthesis pathways and decreased butanoate metabolism (linear discriminate analysis, >3.0-fold). Conclusion Although there were no significant alterations in the microbiome by virtue of obesity per se, excess GWG was associated with an altered microbiome and its metabolic profile among those women who experienced a preterm birth.
Marijuana use and its effects in pregnancy Chabarria, Kristin C., MD; Racusin, Diana A., MD; Antony, Kathleen M., MD ...
American journal of obstetrics and gynecology,
10/2016, Letnik:
215, Številka:
4
Journal Article
Recenzirano
Background It is generally assumed that marijuana is one of the more widely used controlled substances during pregnancy. However, there remains a general paucity of population-based data regarding ...its use and subsequent perinatal morbidity. We hypothesized that direct patient query during pregnancy regarding marijuana, tobacco, and nicotine use would provide crucial initial population-based data on perinatal risk. Objective Our study sought to examine maternal and neonatal outcomes in pregnancies with reported marijuana exposure, in isolation or in combination with maternal cigarette smoking. Study Design We applied a retrospective cohort study design to subjects (n = 12,069) with available information on marijuana use and pregnancy outcomes. Since 2011, we have routinely and directly questioned all gravidae regarding use of marijuana, tobacco, and nicotine-containing products. We examined perinatal outcomes in marijuana smokers vs nonsmokers, as well as patients reporting both marijuana and cigarette smoking. Multivariate analysis enabled determination of adjusted odds ratios for maternal and fetal outcomes, adjusting for confounders. Significance was determined with Mann-Whitney U, χ2 , and Fischer exact tests (as appropriate). Results In all, 106/12,069 reported marijuana use (0.88%), with 48/12,069 (0.4%; or 48/106, 45%) concurrently using cigarettes and marijuana. After controlling for potential confounding variables, while marijuana use alone was not associated with significant adverse outcomes, use in combination with cigarette smoking was significantly associated with increased risk of multiple adverse perinatal outcomes (increased occurrence of maternal asthma adjusted odds ratio, 2.4; 95% confidence interval, 1.0–5.9; preterm birth adjusted odds ratio, 2.6; 95% confidence interval, 1.3–4.9; decreased <25th percentile head circumference adjusted odds ratio, 2.8; 95% confidence interval, 1.3–4.3; and decreased <25th percentile birthweight adjusted odds ratio, 2.8; 95% confidence interval, 1.6–5.0). Maternal pregnancy-related hypertension was not increased in marijuana smokers (adjusted odds ratio, 1.30; 95% confidence interval, 0.681–2.498), or in cigarette smokers (adjusted odds ratio, 1.4; 95%, confidence interval, 0.9–1.9). However, co-users had elevated rates of preeclampsia compared to nonusers (adjusted odds ratio, 2.5; 95% confidence interval, 1.4–5.0). Conclusion In our initial cohort analysis, after controlling for potential confounders, while marijuana exposure alone was not associated with significant perinatal adverse outcomes, co-use with cigarette smoking rendered increased risk over either alone. Due to observed prevalence of concurrent cigarette and marijuana use, it is of likely importance to counsel patients regarding use in pregnancy.
Objective Data from animal models show that in utero exposure to a maternal high-fat diet (HFD) renders susceptibility of these offspring to the adult onset of metabolic syndrome. We and others have ...previously shown that epigenetic modifications to histones may serve as a molecular memory of the in utero exposure, rendering the risk of adult disease. Because mice heterozygous for the Glut4 gene (insulin sensitive glucose transporter) born to wild-type (WT) mothers demonstrate exacterbated metabolic syndrome when exposed to an HFD in utero, we sought to analyze the genome-wide epigenetic changes that occur in the fetal liver in susceptible offspring. Study Design WT and Glut4+/− (G4+/− ) offspring of WT mothers that were exposed either to a control or an HFD in utero were studied. Immunoblotting was used to measure hepatic histone modifications of fetal and 5-week animals. Chromatin immunoprecipitation (ChIP) followed by hybridization to chip arrays (ChIP-on-chip) was used to detect genome-wide changes of histone modifications with HFD exposure. Results We found that levels of hepatic H3K14ac and H3K9me3 significantly increased with HFD exposure in WT and G4+/− fetal and 5-week offspring. Pathway analysis of our ChIP-on-chip data revealed differential H3K14ac and H3K9me3 enrichment along pathways that regulate lipid metabolism, specifically in the promoter regions of Pparg, Ppara, Rxra, and Rora. Conclusion We conclude that HFD exposure in utero is associated with functional alterations to fetal hepatic histone modifications in both WT and G4+/− offspring, some of which persist up to 5 weeks of age.
Background The US Preventive Services Task Force recommends low-dose aspirin for the prevention of preeclampsia among women at high risk for primary occurrence or recurrence of disease. ...Recommendations for the use of aspirin for preeclampsia prevention were issued by the US Preventive Services Task Force in September 2014. Objectives The objective of the study was to evaluate the incidence of recurrent preeclampsia in our cohort before and after the US Preventive Services Task Force recommendation for aspirin for preeclampsia prevention. Study Design This was a retrospective cohort study designed to evaluate the rates of recurrent preeclampsia among women with a history of preeclampsia. We utilized a 2-hospital, single academic institution database from August 2011 through June 2016. We excluded multiple gestations and included only the first delivery for women with multiple deliveries during the study period. The cohort of women with a history of preeclampsia were divided into 2 groups, before and after the release of the US Preventive Services Task Force 2014 recommendations. Potential confounders were accounted for in multivariate analyses, and relative risk and adjusted relative risk were calculated. Results A total of 17,256 deliveries occurred during the study period. A total of 417 women had a documented history of prior preeclampsia: 284 women before and 133 women after the US Preventive Services Task Force recommendation. Comparing the before and after groups, the proportion of Hispanic women in the after group was lower and the method of payment differed between the groups ( P <.0001). The prevalence of type 1 diabetes was increased in the after period, but overall rates of pregestational diabetes were similar (6.3% before vs 5.3% after P > .05). Risk factors for recurrent preeclampsia included maternal age >35 years (relative risk, 1.83; 95% confidence interval, 1.34–2.48), Medicaid insurance (relative risk, 2.08; 95% confidence interval, 1.15–3.78), type 2 diabetes (relative risk, 2.13; 95% confidence interval, 1.37–3.33), and chronic hypertension (relative risk, 1.96; 95% confidence interval, 1.44–2.66). The risk of recurrent preeclampsia was decreased by 30% in the after group (adjusted relative risk, 0.70; 95% confidence interval, 0.52–0.95). Conclusion Rates of recurrent preeclampsia among women with a history of preeclampsia decreased by 30% after release of the US Preventive Services Task Force recommendation for aspirin for preeclampsia prevention. Future prospective studies should include direct measures of aspirin compliance, gestational age at initiation, and explore the influence of race and ethnicity on the efficacy of this primary prevention.
The human microbiome acquires its vastness and diversity over a relatively short time period during development. Much is unknown, however, about the precise prenatal versus postnatal timing or its ...sources and determinants. Given early evidence of a role for influences during pregnancy and early neonatal and infant life on the microbiome and subsequent metabolic health, research investigating the development and shaping of the microbiome in the fetus and neonate is an important arena for study. This article reviews the relevant available literature and future questions on what shapes the microbiome during early development and mechanisms for doing so.
Background Gestational diabetes mellitus (GDM) is one of most common complications of pregnancy, with incidence rates varying by maternal age, race/ethnicity, obesity, parity, and family history. ...Given its increasing prevalence in recent decades, covariant environmental and sociodemographic factors may be additional determinants of GDM occurrence. Objective We hypothesized that environmental risk factors, in particular measures of the food environment, may be a diabetes contributor. We employed geospatial modeling in a populous US county to characterize the association of the relative availability of fast food restaurants and supermarkets to GDM. Study Design Utilizing a perinatal database with >4900 encoded antenatal and outcome variables inclusive of ZIP code data, 8912 consecutive pregnancies were analyzed for correlations between GDM and food environment based on countywide food permit registration data. Linkage between pregnancies and food environment was achieved on the basis of validated 5-digit ZIP code data. The prevalence of supermarkets and fast food restaurants per 100,000 inhabitants for each ZIP code were gathered from publicly available food permit sources. To independently authenticate our findings with objective data, we measured hemoglobin A1c levels as a function of geospatial distribution of food environment in a matched subset (n = 80). Results Residence in neighborhoods with a high prevalence of fast food restaurants (fourth quartile) was significantly associated with an increased risk of developing GDM (relative to first quartile: adjusted odds ratio, 1.63; 95% confidence interval, 1.21–2.19). In multivariate analysis, this association held true after controlling for potential confounders ( P = .002). Measurement of hemoglobin A1c levels in a matched subset were significantly increased in association with residence in a ZIP code with a higher fast food/supermarket ratio (n = 80, r = 0.251 P < .05). Conclusion As demonstrated by geospatial analysis, a relationship of food environment and risk for gestational diabetes was identified.
The incidence of obesity in pregnancy has increased over the past 2 decades, with nearly 50% of U.S. women aged 15-49 years classified as overweight or obese. Obesity (independent of diabetes) among ...gravidae poses unique risks that extend toward the fetus, with several large population-based analyses demonstrating independent increased risks for fetal malformations including neural tube defects, cardiac anomalies, and orofacial clefts, as well as stillbirth and macrosomia. Unfortunately, several lines of evidence also suggest that the quality of the prenatal fetal anatomic survey and certain aspects of prenatal diagnostic screening programs are significantly limited. The net effect is that among obese gravidae, the increased risk of fetal anomalies is further offset by a concomitant diminished ability to sonographically detect such malformations in the prenatal interval. The purpose of this summary review is to systematically examine the evidence suggesting an increased risk of fetal malformations in obese gravidae, the contributing role of diabetes, and the limitations of prenatal diagnostic and sonographic screening among this at-risk population.
Background Preterm birth (PTB) is a multifactorial disorder, and air pollution has been suggested to increase the risk of occurrence. However, large population studies controlling for multiple ...exposure measures in high-density settings with established commuter patterns are lacking. Objective We performed a geospatial analysis with the use of a publicly available database to identify whether residence during pregnancy, specifically with regard to exposure to traffic density and mobility in urban and suburban neighborhoods, may be a contributing risk factor for premature delivery. Study Design In our cohort study, we analyzed 9004 pregnancies with as many as 4900 distinct clinical and demographic variables from Harris County, Texas. On the basis of primary residency and occupational zip code information, geospatial analysis was conducted. Data on vehicle miles traveled (VMT) and percentages of inhabitants traveling to work were collected at the zip code level and additionally grouped by the three recognized regional commuter loop high-density thoroughfares resulting from two interstate/highway belts (inner, middle, and outer loops). PTB was categorized as late (34 1/7 to 36 6/7 weeks) and early PTB (22 1/7 to 33 6/7 weeks), and unadjusted odds ratios (OR) and adjusted ORs were ascribed. Results PTB prevalence in our study population was 10.1% (6.8% late and 3.3% early preterm), which is in accordance with our study and other previous studies. Prevalence of early PTB varied significantly between the regional commuter loop thoroughfares OR for inner vs outer loop: 0.58 (95% confidence interval, 0.39–0.87), OR for middle vs outer loop, 0.74 (0.57–0.96). The ORs for PTB and early PTB were shown to be lower in gravidae from neighborhoods with the highest VMT/acre OR for PTB, 0.82 (0.68–0.98), OR for early PTB, 0.78 (0.62–0.98). Conversely, risk of PTB and early PTB among subjects living in neighborhoods with a high percentage of inhabitants traveling to work over a greater distance demonstrated a contrary tendency OR for PTB, 1.18 (1.03–1.35), OR for early PTB, 1.48 (1.17–1.86). In logistic regression models, the described association between PTB and residence withstood and could not be explained by differences in maternal age, gravidity or ethnicity, tobacco use, or history of PTB. Conclusion While PTB is of multifactorial origin, the present study shows that community-based risk factors (namely urban/suburban location, differences in traffic density exposure, and need for traveling to work along high–vehicle density thoroughfares) may influence risk for PTB. Further research focusing on previously unrecognized community-based risk factors may lead to innovative future prevention measures.
Objective We sought to extend our prior observations and histopathologically characterize key metabolic enzymes ( CYP1A1 ) with markers of oxidative damage in the placental sections from smokers. ...Study Design Placental specimens were collected from term singleton deliveries from smokers (n = 10) and nonsmokers (n = 10) and subjected to a detailed histopathological examination. To quantify the extent of oxidative damage, masked score-graded (0-6) histopathology against 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxydeoxyguanisine (8-OHdG) was performed. Minimal significance ( P < .05) was determined with a Fisher's exact and a 2-tailed Student t test as appropriate. Results We observed a significant increase in the presence of syncytial knots in placentas from smokers (70% vs 10%, P = .02). These gross observations were accompanied by a significant aberrant placental aromatic hydrocarbon metabolism (increased CYP1A1, 4.4 vs 2.1, P = .002) in addition to evidence of oxidative damage (4-HNE 3.4 vs 1.1, P = .00005; 8-OHdG 4.9 vs 3.1, P = .0038). Conclusion We observed a strong association between maternal tobacco use and aberrant placental metabolism, syncytial knot formation, and multiple markers of oxidative damage.
Background We have recently shown in both non-human primates and in rodents that fetal and neonatal hepatic expression of the circadian transcription factor, Npas2 , is modulated by a high fat ...maternal diet and plays a critical role in establishing life-long metabolic homeostasis. Similarly, we and others have also established the importance of the maternal and early postnatal diet on establishment of the early gut microbiome. Objective We hypothesized that altered circadian gene expression solely in the neonatal liver would result in gut microbiome dysbiosis, especially with diet-induced metabolic stress (ie, restricted feeding). Using a murine model in which we conditionally knock out Npas2 in the neonatal liver, we aimed to determine the role of the circadian machinery in gut dysbiosis with restricted feeding. Study Design We collected fecal samples from liver Npas2 conditional knockout (n = 11) and wild-type (n = 13) reproductive-aged mice before (study day 0) and after the restricted feeding study (study day 17). Extracted DNA was sequenced using the MiSeq Illumina platform using primers specific for the V4 region of the 16S ribosomal DNA gene. The resulting sequences were quality filtered, aligned, and assigned taxonomy. Principal coordinate analysis was performed on unweighted and weighted UniFrac distances between samples with a permutation analysis of variance to assess clustering significance between groups. Microbial taxa that significantly differ between groups of interest was determined using linear discriminate analysis effect size and randomForrest. Results Principal coordinate analysis performed on weighted UniFrac distances between male conditional knockout and wild-type cohorts revealed that the gut microbiome of the mice did not differ by genotype at the start of the restricted feeding study but did differ by virtue of genotype at the end of the study ( P = .001). Moreover, these differences could be at least partially attributed to restricted feeding–associated alterations in relative abundance of the Bacteroides genus, which has been implicated as crucial to establishing a healthy gut microbiome early in development. Conclusion Here we have provided an initial key insight into the interplay between neonatal establishment of the peripheral circadian clock in the liver and the ability of the gut microbiome to respond to dietary and metabolic stress. Because Npas2 expression in the liver is a target of maternal high-fat diet–induced metabolic perturbations during fetal development, we speculate that these findings have potential implications in the long-term metabolic health of their offspring.
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