Association of uterine fibroids with birthweight and gestational age.
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ABSTRACT: Purpose
To determine if fibroids or their characteristics are associated with birthweight and/or gestational age, and to assess the impact of race or ethnicity.Methods
Right from the Start (2000-2012) is a prospective cohort that enrolled women from the southern US in early pregnancy. Transvaginal ultrasounds were used to measure fibroid characteristics and confirm gestational age. Date of birth and birthweight were obtained from vital or medical records. We assessed whether fibroid presence, number, type, and volume were associated with birthweight and/or gestational age using multivariate analysis of covariance, accounting for a priori confounders.Results
Among 3926 women, 416 had one or more fibroids. Mean infant birthweight and gestational age were similar among women with and without fibroids. When adjusting for race or ethnicity, all associations were attenuated. Overall, women with and without fibroids had infants of similar birthweight (-20 grams, 95% confidence interval [CI] -77, 36) and gestational age (0.4 days, 95% CI -0.9, 1.8). Women with three or more fibroids were more likely to have lighter infants (-201 grams, 95% CI -345, -58).Conclusions
Race or ethnicity substantially confounds the associations. The clinical belief that uterine fibroids impair fetal growth is supported only by a significant decrease in birthweight for women with multiple fibroids.
SUBMITTER: Zhao SK
PROVIDER: S-EPMC8009686 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundWe examined the associations of maternal age with low birthweight (LBW) and preterm birth in four cohorts from a middle- and a high-income country, where the patterning of maternal age by socio-economic position (SEP) is likely to differ.MethodsPopulation-based birth cohort studies were carried out in the city of Pelotas, Brazil in 1982, 1993, and 2004, and in Avon, UK in 1991 [Avon Longitudinal Study of Parents and Children (ALSPAC)]. Adjustment for multiple indicators of SEP were applied.ResultsLow SEP was associated with younger age at childbearing in all cohorts, but the magnitudes of these associations were stronger in ALSPAC. Inverse associations of SEP with LBW and preterm birth were observed in all cohorts. U-shaped associations were observed between maternal age and odds of LBW in all cohorts. After adjustment for SEP, increased odds of LBW for young mothers (<20 years) attenuated to the null but remained or increased for older mothers (? 35 years). Very young (<16 years) maternal age was also associated with both outcomes even after full SEP adjustment. SEP adjusted odds ratio of having a LBW infant in women <16 years and ? 35 years, compared with 25-29 years, were 1.48 [95% confidence interval (CI) 1.00, 2.20] and 1.66 [95% CI 1.36, 2.02], respectively. The corresponding results for preterm birth were 1.80 [95% CI 1.23, 2.64)] and 1.38 [95% CI 1.15, 1.67], respectively.ConclusionConfounding by SEP explains much of the excess risk of LBW and preterm among babies born to teenage mothers as a whole, but not for mothers aged <16 or ? 35 years. Given that the proportion of women becoming pregnant at <16 years is smaller than for those ? 35 years, the population burden is greater for older age.
| S-EPMC4296235 | biostudies-literature
Project description:Uterine fibroids affect up to 77% of women by menopause and account for up to $34 billion in healthcare costs each year. Although fibroid risk is heritable, genetic risk for fibroids is not well understood. We conducted a two-stage case-control meta-analysis of genetic variants in European and African ancestry women with and without fibroids classified by a previously published algorithm requiring pelvic imaging or confirmed diagnosis. Women from seven electronic Medical Records and Genomics (eMERGE) network sites (3,704 imaging-confirmed cases and 5,591 imaging-confirmed controls) and women of African and European ancestry from UK Biobank (UKB, 5,772 cases and 61,457 controls) were included in the discovery genome-wide association study (GWAS) meta-analysis. Variants showing evidence of association in Stage I GWAS (P < 1 × 10-5) were targeted in an independent replication sample of African and European ancestry individuals from the UKB (Stage II) (12,358 cases and 138,477 controls). Logistic regression models were fit with genetic markers imputed to a 1000 Genomes reference and adjusted for principal components for each race- and site-specific dataset, followed by fixed-effects meta-analysis. Final analysis with 21,804 cases and 205,525 controls identified 326 genome-wide significant variants in 11 loci, with three novel loci at chromosome 1q24 (sentinel-SNP rs14361789; P = 4.7 × 10-8), chromosome 16q12.1 (sentinel-SNP rs4785384; P = 1.5 × 10-9) and chromosome 20q13.1 (sentinel-SNP rs6094982; P = 2.6 × 10-8). Our statistically significant findings further support previously reported loci including SNPs near WT1, TNRC6B, SYNE1, BET1L, and CDC42/WNT4. We report evidence of ancestry-specific findings for sentinel-SNP rs10917151 in the CDC42/WNT4 locus (P = 1.76 × 10-24). Ancestry-specific effect-estimates for rs10917151 were in opposite directions (P-Het-between-groups = 0.04) for predominantly African (OR = 0.84) and predominantly European women (OR = 1.16). Genetically-predicted gene expression of several genes including LUZP1 in vagina (P = 4.6 × 10-8), OBFC1 in esophageal mucosa (P = 8.7 × 10-8), NUDT13 in multiple tissues including subcutaneous adipose tissue (P = 3.3 × 10-6), and HEATR3 in skeletal muscle tissue (P = 5.8 × 10-6) were associated with fibroids. The finding for HEATR3 was supported by SNP-based summary Mendelian randomization analysis. Our study suggests that fibroid risk variants act through regulatory mechanisms affecting gene expression and are comprised of alleles that are both ancestry-specific and shared across continental ancestries.
| S-EPMC6582231 | biostudies-literature
Project description:ObjectiveWhether psychosocial adversity during pregnancy impacts fetal health outcomes at birth remains underexplored. This is a critical issue given significant social disadvantage and psychosocial stress faced by pregnant women worldwide.Study designMeasures of social disadvantage and psychological factors, and medical/reproductive and nutritional health status in pregnant women were obtained at each trimester. Using Structural Equation Modeling (SEM), we investigated the relationship of forms of adversity to each other and to infant gestational age, and birthweight.ResultsAmong 399 singletons, Social Disadvantage significantly predicted gestational age (p = 0.003), and residual birthweight (p = 0.006). There was a 0.4 week decrease in gestational age and a 3% decrease in birthweight for each standard deviation increase in Social Disadvantage.ConclusionSignificant negative effects of social adversity on the developing fetus were found. Notably, these effects emerged despite good prenatal care and after accounting for maternal age and medical reproductive risk factors.
| S-EPMC10079545 | biostudies-literature
Project description:Uterine fibroids are a major cause of morbidity in women of a reproductive age (and sometimes even after menopause). There are several factors that are attributed to underlie the development and incidence of these common tumors, but this further corroborates their relatively unknown etiology. The most likely presentation of fibroids is by their effect on the woman's menstrual cycle or pelvic pressure symptoms. Leiomyosarcoma is a very rare entity that should be suspected in postmenopausal women with fibroid growth (and no concurrent hormone replacement therapy). The gold standard diagnostic modality for uterine fibroids appears to be gray-scale ultrasonography, with magnetic resonance imaging being a close second option in complex clinical circumstances. The management of uterine fibroids can be approached medically, surgically, and even by minimal access techniques. The recent introduction of selective progesterone receptor modulators (SPRMs) and aromatase inhibitors has added more armamentarium to the medical options of treatment. Uterine artery embolization (UAE) has now been well-recognized as a uterine-sparing (fertility-preserving) method of treating fibroids. More recently, the introduction of ultrasound waves (MRgFUS) or radiofrequency (VizAblate™ and Acessa™) for uterine fibroid ablation has added to the options of minimal access treatment. More definite surgery in the form of myomectomy or hysterectomy can be performed via the minimal access or open route methods. Our article seeks to review the already established information on uterine fibroids with added emphasis on contemporary knowledge.
| S-EPMC3914832 | biostudies-other
Project description:BackgroundUterine fibroids are the most common benign uterine tumours present in women of reproductive age. Mifepristone (RU-486) competitively binds and inhibits progesterone receptors. Studies have suggested that fibroid growth depends on the sexual steroids. Mifepristone has been shown to decrease fibroid size. This review summarises the effects of mifepristone treatment on fibroids and the associated adverse effects as described in randomised controlled trials.ObjectivesTo determine the efficacy and safety of mifepristone for the management of uterine fibroids in pre-menopausal women.Search methodsWe searched the specialised register of the Cochrane Menstrual Disorders and Subfertility (Cochrane Menstrual Disorders and subfertility Review Group), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4), MEDLINE, EMBASE, PsycINFO, and CINAHL (to November 2011). We handsearched a number of journals, and searched reference lists, databases of ongoing trials and the Internet. There were no language restrictions.Selection criteriaOnly truly randomised controlled trials of mifepristone versus other forms of medical therapy or placebo in pre-menopausal women with confirmed uterine fibroids were included.Data collection and analysisFour authors independently extracted data and assessed trial quality. Data were analysed using the Peto odds ratios (OR) for dichotomous data and the weighted mean differences for continuous data, with 95% confidence intervals (CI). Meta-analyses were performed using the fixed-effect model.Main resultsThree studies involving 112 participants were included. Comparison interventions included different dosages of mifepristone, placebo and vitamin B tablets. There is evidence that treatment with mifepristone relieves heavy menstrual bleeding compared with placebo (Peto OR 17.84; 95% CI 6.72 to 47.38; 2 RCTs, 77 women, I(2) = 0%). Three studies (Bagaria 2009; Engman 2009; Fiscella 2006) were included in the meta-analysis of this comparison. There was no evidence of an effect of mifepristone on the fibroid volume (standardised mean difference (SMD) -0.02; 95% CI -0.38 to 0.41; 99 women). Two studies (Bagaria 2009; Fiscella 2006) were included in the meta-analysis of this comparison. There was no evidence of an effect of mifepristone on uterine volume (mean difference (MD) -77.24; 95% CI -240.62 to 86.14; 72 women). The pooled data suggest an increased adverse event (abnormal endometrial histology) in the mifepristone group compared to placebo (OR 31.65; 95% CI 4.83 to 207.35; 2 RCTs; 54 women; I(2) = 0%). Only one study (Bagaria 2009) reported endometrial hyperplasia at the end of the therapy (12/19 women in the mifepristone group versus 0/16 in the placebo group; OR 55.0; 95% CI 2.86 to 105.67). Engman 2009 found a significantly higher rate of cystic glandular dilatation in women in the mifepristone group (5/8 women biopsied) compared with the placebo group (1/11 women biopsied) (OR 16.67; 95% CI 1.36 to 204.03). One study (Fiscella 2006) suggested significant improvements (P < 0.001) for specific quality of life outcomes.Authors' conclusionsMifepristone reduced heavy menstrual bleeding and improved fibroid-specific quality of life. However, it was not found to reduce fibroid volume. Further well-designed, adequately powered RCTs are needed before a recommendation can be made on the use of mifepristone for the treatment of uterine fibroids.
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Project description:BackgroundUterine fibroids are the most common non-malignant growths in women of childbearing age. They are associated with heavy menstrual bleeding and subfertility. Herbal preparations are commonly used as alternatives to surgical procedures.ObjectivesTo assess the benefits and risks of herbal preparations for uterine fibroids.Search strategyAuthors searched following electronic databases: the Trials Registers of the Cochrane Menstrual Disorders and Subfertility Group and the Cochrane Complementary Medicine Field, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE, EMBASE, the Chinese Biomedical Database, the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS), AMED, and LILACS. The searches ended on 31st December 2008.Selection criteriaRandomised controlled trials comparing herbal preparations with no intervention, placebo, medical treatment or surgical procedures in women with uterine fibroids. We also included trials of herbal preparations with or without conventional therapy.Data collection and analysisTwo review authors collected data independently. We assessed trial risk of bias according to our methodological criteria . We presented dichotomous data as risk ratios (RR) and continuous outcomes as mean difference (MD), both with 95% confidence intervals (CI).Main resultsWe included two randomised trials (involved 150 women) with clear description of randomisation methods. The methodological risk of bias of the trials varied. There were variations in the tested herbal preparations, and the treatment duration was six months. The outcomes available were not the primary outcomes selected for this review, such as symptom relief or the need for surgical treatment; trials mainly reported outcomes in terms of shrinkage of the fibroids.Compared with mifepristone, Huoxue Sanjie decoction showed no significant difference in the disappearance of uterine fibroids, number of patients with shrinking of uterine fibroids or average volume of uterine fibroids, but less effective than mifepristone on reducing average size of uterus (mean difference 23.23 cm(3),95% confidence interval 17.85 to 28.61). There was no significant difference between Nona Roguy herbal product and GnRH agonist in average volume of uterine fibroids or size of uterus. No serious adverse effects from herbal preparations was reported.Authors' conclusionsCurrent evidence does not support or refute the use of herbal preparations for treatment of uterine fibroids due to insufficient studies of large sample and high quality. Further high quality trials evaluating clinically relevant outcomes are warranted.
| S-EPMC3155698 | biostudies-literature
Project description:We review recent studies dealing with the molecular genetics and basic results of omics analysis of uterine leiomyoma (LM)-a common benign muscle tumor of the uterus. Whole genome studies of LM resulted in the discovery of many new gene nets and biological pathways, including its origin, transcriptomic, and epigenetic profiles, as well as the impact of the inter-cell matrix in LM growth and involvement of microRNA in its regulation. New data on somatic cell mutations ultimately involved in the origin, distribution and growth of LM are reviewed. Putative identification of LM progenitor SC (stem cells) giving rise to maternal fibroid nodes and junctional zones provide a new clue for hypotheses on the pathogenomics of LM. The reviewed data are consistent with at least two different but probably intimately interacted molecular mechanisms of LM. One of them (the genetic hypothesis) is focused primarily on the MED12 gene mutations and suggests its onset in the side population of embryonic myoblasts of the female reproductive system, which later gave rise to multiple small and medium fibroids. The single and usually large-size fibroids are induced by predominantly epigenetic disorders in LM SC, provoked by enhanced expression of the HMGA2 gene caused by its hypomethylation and epigenetic deregulation enhanced by hypoxia, muscle tension, or chromosome instability/aberrations. The pathogenomics of both genetic and epigenetic programs of LM with many peculiarities at the beginning later became rather similar and partly overlapped due to the proximity of their gene nets and epigenetic landscape. Pathogenomic studies of LM open ways for elaboration of novel strategies of prevention and treatment of this common disease.
| S-EPMC6940759 | biostudies-literature
Project description:Uterine leiomyomas (or fibroids) are the most common tumors in women of reproductive age. Early studies of two familial cancer syndromes, the multiple cutaneous and uterine leiomyomatosis (MCUL1), and the hereditary leiomyomatosis and renal cell cancer (HLRCC), implicated FH, a gene on chromosome 1q43 encoding the tricarboxylic acid cycle fumarate hydratase enzyme. The role of this metabolic housekeeping gene in tumorigenesis is still a matter of debate and pseudo-hypoxia has been suggested as a pathological mechanism. Inactivating FH mutations have rarely been observed in the nonsyndromic and common form of fibroids; however, loss of heterozygosity across FH appeared as a significant event in the pathogenesis of a subset of these tumors. To assess the role of FH and the linked genes in nonsyndromic uterine fibroids, we explored a two-megabase interval spanning FH in the NIEHS Uterine fibroid study, a cross-sectional study of fibroids in 1152 premenopausal women. Association mapping with a dense set of single nucleotide polymorphisms revealed several peaks of association (p = 10(-2)-8.10(-5)) with the risk and/or growth of fibroids. In particular, genes encoding factors suspected (cytosolic FH) or known (EXO1 - exonuclease 1) to be involved in DNA mismatch repair emerged as candidate susceptibility genes whereas those acting in the autophagy/apoptosis (MAP1LC3C - microtubule-associated protein) or signal transduction (RGS7 - Regulator of G-protein and PLD5- Phospoholipase D) appeared to affect tumor growth. Furthermore, body mass index, a suspected confounder altered significantly but unpredictably the association with the candidate genes in the African and European American populations, suggesting the presence of a major obesity gene in the studied region. With the high potential for occult tumors in common conditions such as fibroids, validation of our data in family-based studies is needed.
| S-EPMC3604173 | biostudies-literature
Project description:ObjectiveTo evaluate the extent to which uterine fibroids are associated with antimüllerian hormone (AMH) concentrations.DesignCross-sectional study.SettingBaseline data from the Study of the Environment, Lifestyle, and Fibroids, which is a 5-year longitudinal study of African American women.Patient(s)A total of 1,643 women aged 23-35 years without a known history of fibroids.ExposureFibroid presence.Intervention(s)None.Main outcome measure(s)The primary outcome was percent difference in the mean AMH concentration between participants with fibroids and those without fibroids. The secondary outcomes were percent differences in the mean AMH concentrations in participants with different numbers, sizes, types, and positions of fibroids and the percent difference in the mean AMH concentration in participants with different uterine volumes.Result(s)At least 1 fibroid was identified on ultrasound in 362 (22%) participants. There was a small difference in the mean AMH concentrations in participants with fibroids (age-adjusted model: -4.6%, 95% confidence interval (CI): -14.5% to 6.5%; multivariable model: -4.6%, 95% CI: -14.4% to 6.3%). The mean AMH concentrations were found to decrease with increasing fibroid number. Although differences in AMH concentrations were not statistically significant, compared with no fibroids, the mean percent differences in AMH concentrations for 1, 2-3, and ≥4 fibroids were -1.2% (95% CI: -13.2% to 12.5%), -7.1% (95% CI: -23.3% to 12.5%), and -17.5% (95% CI: -38.2% to 10.0%), respectively. There were no consistent associations between AMH concentrations and fibroid location, size, or uterine volume.Conclusion(s)The presence of fibroids was not materially associated with AMH concentrations. Other than a monotonic inverse relationship between fibroid number and AMH concentrations, no other fibroid characteristics were consistently or appreciably associated, although associations were imprecise.
| S-EPMC8983564 | biostudies-literature
Project description:Uterine fibroids (UFs) are benign tumors that arise from a single genetically altered mesenchymal stem cell under the influence of gonadal hormones. UFs are the most common benign gynecologic tumors in premenopausal women worldwide. It is estimated that nearly 70% to 80% of women will develop UFs at some point during their lifetime. UFs often present with abnormal uterine bleeding (AUB), pelvic fullness, and may have deleterious effects on fertility. The natural regression of UFs begins in menopause. This is, however, a generality as this pathology may still be present in this age group. Many clinicians are concerned about hormone therapy (HT) because of UFs regrowth; nevertheless, research of this subject remains inconclusive. If UFs are present in perimenopause or menopause, they typically manifest as AUB, which represents up to 70% of all gynecological consultations in perimenopausal and postmenopausal women. As AUB is a broad symptom and may not be specific to UFs, a thorough evaluation is required for correct diagnosis and proper treatment accordingly. Understanding the unique characteristics of the available treatment modalities is crucial in deciding the appropriate treatment approach. Decision on treatment modality should be made based on selection of the least morbidity and lowest risk for each patient. Multiple modalities are available; however, surgery remains the method of choice, with the best cure rates. Various attempts to create an inexpensive, safe, and effective drug for the treatments of UFs are still in the early stages of the clinical trials with some showing great promise. Treatment options include tibolone, aromatase inhibitors, selective estrogen receptor modulators, uterine artery embolization, and selective progesterone receptor modulators.
| S-EPMC6994343 | biostudies-literature