Effects of FTO and PPAR? variants on intrauterine growth restriction in a Brazilian birth cohort
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ABSTRACT:
SUBMITTER: Barbieri M
PROVIDER: S-EPMC7945878 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundOur objectives were to examine the associations of neonatal and infant mortality with preterm birth and intrauterine growth restriction (IUGR), and to estimate the partial population attributable risk per cent (pPAR%) of neonatal and infant mortality due to preterm birth and IUGR.MethodsParticipants were HIV-negative pregnant women and their infants enrolled in Dar es Salaam, Tanzania. Gestational age calculated from date of last menstrual period was used to define preterm, and small for gestational age (SGA) was used as proxy for IUGR. Survival of infants was ascertained at monthly follow-up visits. Cox proportional hazard models were used to estimate the associations of preterm and SGA with neonatal and infant mortality.ResultsStudy included 7225 singletons, of whom 15% were preterm and 21% were SGA; majority of preterm or SGA babies had birthweight ?2500?g. Compared to term and appropriately sized babies (AGA), relative risks (RR) of neonatal mortality among preterm-AGA was 2.6 [95% CI 1.8, 3.9], RR among term-SGA was 2.3 [95% CI 1.6, 3.3], and the highest risk was among the preterm-SGA babies (RR 15.1 [95% CI 8.2, 27.7]). Risk associated with preterm was elevated throughout the infancy, and risk associated with SGA was elevated during the neonatal period only. The pPAR% of neonatal mortality for preterm was 22% [95% CI 17%, 26%] and for SGA it was 26% [95% CI 16%, 36%].ConclusionsPreterm and SGA birth substantially increased the risk of mortality. Interventions for prevention and management of these conditions are likely to reduce of infant mortality in Tanzania.
| S-EPMC7893612 | biostudies-literature
Project description:Objectives were to examine the growth patterns of preterm and growth-restricted infants and to evaluate the associations of prematurity and intrauterine growth restriction (IUGR) with risk of stunting, wasting and underweight. Data from a cohort of HIV-negative pregnant women-infant pairs were collected prospectively in Tanzania. Small for gestational age [SGA, birthweight (BW) <10th percentile] was used as proxy for IUGR. Anthropometry was measured monthly until 18 months. Length-for-age (LAZ), weight-for-length (WLZ), and weight-for-age (WAZ) z-scores were calculated using the 2006 World Health Organization (WHO) Child Growth Standards. Stunting, wasting and underweight were defined as binary outcomes using a cut-off of <-2 SD of the respective z-scores. Multivariate Cox proportional hazard models were used to assess the associations between preterm and SGA to time to stunting, wasting and underweight. The study included 6664 singletons. Preterm and appropriate for gestational age (AGA) infants had slightly better nutritional status than term-SGA infants and despite some catch-up growth, preterm-SGA infants had the poorest nutritional status. The gap in LAZ and WAZ z-scores among the groups remained similar throughout the follow-up. Compared with term-AGA babies, relative risk (RR) of stunting among preterm-AGA babies was 2.13 (95% confidence interval (CI) 1.93-2.36), RR among term-SGA was 2.21 (95% CI 2.02-2.41) and the highest risk was among the babies who were both preterm and SGA (RR = 7.58, 95% CI 5.41-10.64). Similar magnitude of RR of underweight was observed among the three groups. Preterm and SGA infants should be closely monitored for growth failure. Intervention to reduce preterm and SGA birth may lower risk of undernutrition in resource-limited settings.
| S-EPMC4300290 | biostudies-literature
Project description:BackgroundSevere iodine insufficiency in pregnancy has significant consequences, but there is inadequate evidence to indicate what constitutes mild or moderate insufficiency, in terms of observed detrimental effects on pregnancy or birth outcomes. A limited number of studies have examined iodine status and birth outcomes, finding inconsistent evidence for specific outcomes.MethodsMaternal iodine status was estimated from spot urine samples collected at 26-28 weeks' gestation from 6971 mothers in the Born in Bradford birth cohort. Associations with outcomes were examined for both urinary iodine concentration (UIC) and iodine-to-creatinine ratio (I:Cr). Outcomes assessed included customised birthweight (primary outcome), birthweight, small for gestational age (SGA), low birthweight, head circumference and APGAR score.ResultsThere was a small positive association between I:Cr and birthweight in adjusted analyses. For a typical participant, the predicted birthweight centile at the 25th percentile of I:Cr (59 μg/g) was 2.7 percentage points lower than that at the 75th percentile of I:Cr (121 μg/g) (99% confidence interval (CI) 0.8 to 4.6), birthweight was predicted to be 41 g lower (99% CI 13 to 69) and the predicted probability of SGA was 1.9 percentage points higher (99% CI 0.0 to 3.7). There was no evidence of associations using UIC or other birth outcomes, including stillbirth, preterm birth, ultrasound growth measures or congenital anomalies.ConclusionLower maternal iodine status was associated with lower birthweight and greater probability of SGA. Whilst small, the effect size for lower iodine on birthweight is comparable to environmental tobacco smoke exposure. Iodine insufficiency is avoidable, and strategies to avoid deficiency in women of reproductive age should be considered.Trial registrationClinicalTrials.gov NCT03552341. Registered on June 11, 2018.
| S-EPMC7288513 | biostudies-literature
Project description:BackgroundRapid weight gain in childhood may increase the risk of chronic adult diseases. Few studies have examined the effects of lifecourse weight gain on waist circumference (WC), hip circumference (HC), or waist-to-hip ratio (WHR).ObjectiveTo evaluate the effects of birthweight and weight gain from birth to age 23 years on WC, HC, and WHR in young adults.DesignPopulation-based birth cohort study started in 1982. A sample of 856 individuals was examined in 2006. Conditional growth analyses were carried out with adjustment for confounders. WC and HC were also mutually adjusted.ResultsWeight gains during all age ranges studied (birthweight, 0-2, 2-4, 4-15, 15-18/19, and 18/19-23 years) were positively associated with WC and HC in both sexes. These effects were strongest from 4 to 15 years range (beta = 5.0 cm for both circumferences). Proxies for visceral adipose tissue (WHR and WC adjusted for HC) were associated with weight gain after 2 years in females and after 4 years in males. Subcutaneous adipose and muscular tissues, assessed by HC adjusted for WC, were associated with birthweight and weight gain from 0 to 2 years in both sexes, and again with weight gains from 4 to 18 years in males and 4 to 15 years in females.ConclusionsWeight gains in utero and in the first 2 years had long-term effects on HC, but weight gain after age 4 years was strongly associated with WC. Weight gains up to age 2 years may reduce cardiovascular risk associated with adult fat patterns in a middle-income setting.
| S-EPMC3448044 | biostudies-literature
Project description:ImportanceBile acids play essential roles in metabolic modulation. Excessive serum total bile acid (sTBA) levels during pregnancy are associated with adverse perinatal outcomes; however, their association with the risk of intrauterine growth restriction (IUGR) remains unclear.ObjectiveTo investigate the association between maternal sTBA concentration during pregnancy and the risk of IUGR.Design, setting, and participantsThis retrospective cohort study included pregnant individuals who delivered live singleton neonates and had regular antenatal examination records available at a hospital-based center in Shanghai, China, from 2014 to 2018. Data were analyzed from July to November 2020.ExposuresMaternal sTBA concentration during pregnancy.Main outcomes and measuresFetal birth weight and probability of low birth weight (LBW) and IUGR.ResultsThis study included 68 245 singleton pregnancies with live births for analysis. The mean (SD) age of the pregnant individuals was 30.5 (3.8) years, 67 168 patients (98.4%) were Han, and 50 155 (73.5%) were nulliparous. Nonlinear regression models suggested that there was an inverted J-shaped association between maternal sTBA level during pregnancy and fetal birth weight, with a steep decrease in birth weight at high sTBA levels (estimated mean [SE] birth weight for sTBA of 40.8 ug/mL, 2879 [39.9] g) and greater birth weights at lower sTBA levels (estimated mean [SE] birth weight for sTBA 0.4 μg/mL, 3290 [3.9] g; and for 4.1 μg/mL, 3334 [1.6] g). Lower birth weight and a higher incidence of IUGR were observed in patients with gestational hypercholanemia (sTBA ≥4.08 μg/mL) compared with those without gestational hypercholanemia (birth weight: estimated adjusted mean [SE], 3309 [3.32] vs 3338 [0.80] g; P = .005; incidence of IUGR: 62 of 4467 [1.4%] vs 312 of 63 778 [0.5%]; P < .001). Moreover, compared with patients with sTBA concentrations of less than 4.08 μg/mL, those with gestational hypercholanemia had an increased risk of LBW (adjusted odds ratio [aOR], 1.29; 95% CI, 1.09-1.53) and IUGR (aOR, 2.18; 95% CI, 1.62-2.91). In addition, there was an additive interaction between hypertensive disorders in pregnancy (HDP) and hypercholanemia on LBW and IUGR risk. The highest risks of LBW and IUGR were found in pregnant individuals with both HDP and hypercholanemia compared with those with normotensive pregnancies with sTBA concentrations less than 4.08 μg/mL (LBW: aOR, 9.13; 95% CI, 6.88-12.12; IUGR: aOR, 19.14; 95% CI, 12.09-30.28).Conclusions and relevanceThis study found that gestational hypercholanemia was associated with an increased risk of LBW and IUGR, especially in pregnant individuals with HDP. Therefore, it would be meaningful to monitor sTBA concentration during the follow-up of pregnancies with potential IUGR.
| S-EPMC8290304 | biostudies-literature
Project description:Intrauterine growth restriction (IUGR) is a serious pathological complication associated with compromised fetal development during pregnancy. The aim of the study was to broaden knowledge about the transcriptomic complexity of the human placenta by identifying genes potentially involved in IUGR pathophysiology. RNA-Seq data were used to profile protein-coding genes, detect alternative splicing events (AS), single nucleotide variant (SNV) calling, and RNA editing sites prediction in IUGR-affected placental transcriptome. The applied methodology enabled detection of 37,501 transcriptionally active regions and the selection of 28 differentially-expressed genes (DEGs), among them 10 were upregulated and 18 downregulated in IUGR-affected placentas. Functional enrichment annotation indicated that most of the DEGs were implicated in the processes of inflammation and immune disorders related to IUGR and preeclampsia. Additionally, we revealed that some genes (S100A13, GPR126, CTRP1, and TFPI) involved in the alternation of splicing events were mainly implicated in angiogenic-related processes. Significant SNVs were overlapped with 6533 transcripts and assigned to 2386 coding sequence (CDS), 1528 introns, 345 5' untranslated region (UTR), 1260 3'UTR, 918 non-coding RNA (ncRNA), and 10 intergenic regions. Within CDS regions, 543 missense substitutions with functional effects were recognized. Two known mutations (rs4575, synonymous; rs3817, on the downstream region) were detected within the range of AS and DEG candidates: PA28? and PINLYP, respectively. Novel genes that are dysregulated in IUGR were detected in the current research. Investigating genes underlying the IUGR is crucial for identification of mechanisms regulating placental development during a complicated pregnancy.
| S-EPMC6471577 | biostudies-literature
Project description:Fetal intrauterine growth is influenced by complex interactions between the maternal genes, environment and fetal genes. The aim of this study was to assess the effect of GWAS-identified genetic variants associated with birth weight on intrauterine fetal growth in 665 children. Fetal growth was estimated by two-dimensional ultrasound scans at 20, 25 and 32 weeks of gestation and growth trajectories were modeled using mixed linear regression. A genetic risk score (GRS) of birth weight-raising variants was associated with intrauterine growth showing an attenuating effect on the unconditional daily reduction in proportional weight gain of 8.92 × 10-6 percentage points/allele/day (p = 2.0 × 10-4), corresponding to a mean difference of 410 g at 40 weeks of gestation between a child with lowest and highest GRS. Eight variants were independently associated with intrauterine growth throughout the pregnancy, while four variants were associated with fetal growth in the periods 20-25 or 25-32 weeks of gestation, indicating that some variants may act in specific time windows during pregnancy. Four of the intrauterine growth variants were associated with type 2 diabetes, hypertension or BMI in the UK Biobank, which may provide basis for further understanding of the link between intrauterine growth and later risk of metabolic disease.
| S-EPMC5976727 | biostudies-literature
Project description:Preeclampsia (PE), a maternal hypertensive disorder, and intrauterine growth restriction (IUGR), pathologically poor fetal growth, often co-occur and are associated with placental insufficiency (PI). PI is more common in early-onset PE (EOPE) than late-onset PE (LOPE). However, the relationship between these disorders remains unclear. While DNA methylation (DNAm) alterations have been previously identified in PE and IUGR, few studies validated the findings in an independent cohort. This study aims to identify altered DNAm in EOPE, LOPE, and normotensive IUGR, validate these alterations, and use the findings to better understand the relationships between these related disorders. Placental samples from a discovery cohort (43 controls, 22 EOPE, 18 LOPE, 11 IUGR) and validation cohort (15 controls, 22 EOPE, 11 LOPE) were evaluated using the Illumina HumanMethylation450 array. To minimize gestational age (GA) effects, EOPE samples were compared to pre-term controls (GA <37 weeks), while LOPE and IUGR were compared to term controls (GA >37 weeks). Linear regression identified 1703 differentially methylated (DM) sites (FDR<0.05, ∆β>0.1) in EOPE, 5 in LOPE, and 0 in IUGR. Of the 1703 sites associated with EOPE in the discovery cohort, 599 were validated in the second cohort. These sites cluster samples from both cohorts into 3 distinct methylation clusters. Interestingly, LOPE samples diagnosed between 34-36 weeks and had co-occurring IUGR clustered with the EOPE methylation cluster. DNAm profiling may provide an independent tool to refine clinical diagnoses into subgroups with more uniform pathology. The challenges in reproducing genome-wide DNAm studies are also discussed. DNA methylation data of the validation cohort can be found at GSE98224.
2018-05-11 | GSE100197 | GEO
Project description:BACKGROUND:Preeclampsia and intrauterine growth restriction are placental dysfunction-related disorders (PDDs) that require a referral decision be made within a certain time period. An appropriate prediction model should be developed for these diseases. However, previous models did not demonstrate robust performances and/or they were developed from datasets with highly imbalanced classes. OBJECTIVE:In this study, we developed a predictive model of PDDs by machine learning that uses features at 24-37 weeks' gestation, including maternal characteristics, uterine artery (UtA) Doppler measures, soluble fms-like tyrosine kinase receptor-1 (sFlt-1), and placental growth factor (PlGF). METHODS:A public dataset was taken from a prospective cohort study that included pregnant women with PDDs (66/95, 69%) and a control group (29/95, 31%). Preliminary selection of features was based on a statistical analysis using SAS 9.4 (SAS Institute). We used Weka (Waikato Environment for Knowledge Analysis) 3.8.3 (The University of Waikato, Hamilton, NZ) to automatically select the best model using its optimization algorithm. We also manually selected the best of 23 white-box models. Models, including those from recent studies, were also compared by interval estimation of evaluation metrics. We used the Matthew correlation coefficient (MCC) as the main metric. It is not overoptimistic to evaluate the performance of a prediction model developed from a dataset with a class imbalance. Repeated 10-fold cross-validation was applied. RESULTS:The classification via regression model was chosen as the best model. Our model had a robust MCC (.93, 95% CI .87-1.00, vs .64, 95% CI .57-.71) and specificity (100%, 95% CI 100-100, vs 90%, 95% CI 90-90) compared to each metric of the best models from recent studies. The sensitivity of this model was not inferior (95%, 95% CI 91-100, vs 100%, 95% CI 92-100). The area under the receiver operating characteristic curve was also competitive (0.970, 95% CI 0.966-0.974, vs 0.987, 95% CI 0.980-0.994). Features in the best model were maternal weight, BMI, pulsatility index of the UtA, sFlt-1, and PlGF. The most important feature was the sFlt-1/PlGF ratio. This model used an M5P algorithm consisting of a decision tree and four linear models with different thresholds. Our study was also better than the best ones among recent studies in terms of the class balance and the size of the case class (66/95, 69%, vs 27/239, 11.3%). CONCLUSIONS:Our model had a robust predictive performance. It was also developed to deal with the problem of a class imbalance. In the context of clinical management, this model may improve maternal mortality and neonatal morbidity and reduce health care costs.
| S-EPMC7265111 | biostudies-literature
Project description:BackgroundAn increase in vascular resistance of uterine vessels is associated with intrauterine growth restriction (IUGR). Sildenafil citrate, a phosphodiesterase-5 inhibitor that stabilizes cyclic guanosine monophosphate (cGMP) and increases nitric oxide levels, improves placental perfusion by dilation of spiral arteries and is beneficial in managing IUGR. This study aims to determine the effectiveness of sildenafil citrate in improving perinatal outcomes in IUGR pregnancies.MethodsMeta-analysis was performed on data extracted from all studies specific to sildenafil citrate in IUGR management, searching relevant articles on PubMed, Medline, Google Scholar, Embase, and Cochrane databases. Publications identified by the manual search, based on references in reviews, were also included. Dichotomous results were presented as risk ratio (95% confidence interval), while continuous results were expressed as mean difference (MD); samples represented by the random effects model.ResultsNine trials were included where the sildenafil citrate effect was compared with a placebo or no intervention. A significant increase in birth weight [SMD (95% CI), 0.69 (0.31, 1.07)] was seen in IUGR pregnancies managed with sildenafil. However, gestational age (SMD (95% CI), 0.44 (-0.05, 0.94], fetal death rate [RR (95% CI), 0.56 (0.17, 1.79)] in IUGR pregnancies was not changed by sildenafil. Neonatal death [RR (95% CI), 0.93 (0.47, 1.86)] and neonatal intensive care unit (NICU) admissions [RR (95% CI), 0.76 (0.50, 1.17)] were not significantly different between sildenafil and control groups.ConclusionSildenafil citrate increases birth weight and prolonged pregnancies but did not affect stillbirth rate, neonatal death, and NICU admission.Trial registrationThe study was registered in PROSPERO on September 18, 2021 (CRD42021271992).
| S-EPMC10236759 | biostudies-literature