Pharmacogenomics of maternal tobacco use: metabolic gene polymorphisms and risk of adverse pregnancy outcomes.
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ABSTRACT:
SUBMITTER: Aagaard-Tillery K
PROVIDER: S-EPMC3263385 | biostudies-literature | 2010 Mar
REPOSITORIES: biostudies-literature
Publications
Pharmacogenomics of maternal tobacco use: metabolic gene polymorphisms and risk of adverse pregnancy outcomes.
Aagaard-Tillery Kjersti K Spong Catherine Y CY Thom Elizabeth E Sibai Baha B Wendel George G Wenstrom Katharine K Samuels Philip P Simhan Hyagriv H Sorokin Yoram Y Miodovnik Menachem M Meis Paul P O'Sullivan Mary J MJ Conway Deborah D Wapner Ronald J RJ
Obstetrics and gynecology 20100301 3
<h4>Objective</h4>To assess whether functional maternal or fetal genotypes along well-characterized metabolic pathways (ie, CYP1A1, GSTT1, and CYP2A6) may account for varying associations with adverse outcomes among pregnant women who smoke.<h4>Methods</h4>DNA samples from 502 smokers and their conceptuses, alongside women in a control group, were genotyped for known functional allelic variants of CYP1A1 (Ile462Val AA>AG/GG), GSTT1(del), and CYP2A6 (Lys160His T>A). Modification of the associatio ...[more]
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Project description:BackgroundThe increased potential for negative pregnancy outcomes in both extremes of reproductive age is a well-debated argument. The aim of this study was to analyze the prevalence and the outcome of pregnancies conceived at extreme maternal ages.MethodsThis retrospective study considered all single consecutive pregnancies delivered in a tertiary referral center between 2001 and 2014. Patients were categorized into 4 groups according to maternal age at delivery (< 17 years; 18-28 years; 29-39 years; > 40 years). The following outcomes were considered (amongst others): pregnancy-related hypertensive disorders (PRHDs), neonatal resuscitation (NR), neonatal intensive care unit (NICU) admission, periventricular leucomalacia (PVL), and grade 3 and 4 intraventicular hemorrhage (IVH).ResultsDuring the considered period 22,933 single pregnancies gave birth in our unit. We observed 71 women aged < 17 years, and 1552 aged > 40 years. In each year throughout the study period, there was a significant increment in maternal age of 0.041 years (95% CI 0.024-0.058) every new year. Multivariate analysis concluded out that maternal age over 40 years was an independent risk factor for preterm delivery (OR 1.36 95% CI 1.16-1.61, p < 0.05, PRHDs (OR 2.36 95% CI 1.86-3.00, p < 0.05), GDM (OR 1.71 95% CI 1.37-2.12, p < 0.05) cesarean section (OR 1.99 95% CI 1.78-2.23, p < 0.05), abnormal fetal presentation (OR 1.29 95% CI 1.03-1.61, p < 0.05), and fetal PVL (OR 3.32 95% CI 1.17-9.44, p < 0.05). We also observed that maternal age under 17 years or over 40 years was an independent risk factor for grade 3 or 4 neonatal IVH (OR 2.97 95% CI 1.24-7.14, p < 0.05).ConclusionsThese findings confirm a negative impact of extreme maternal ages on pregnancy. These results should be carefully taken into account by maternal care providers in order to inform women adequately, supporting them in understanding potential risks associated with their procreation choices, and to improve clinical surveillance.
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Project description:ImportanceMaternal tobacco use during pregnancy (MTDP) persists across the globe. Longitudinal assessment of the association of MTDP with neurocognitive development of offspring at late childhood is limited.ObjectivesTo examine whether MTDP is associated with child neurocognitive development at ages 9 to 12 years.Design, setting, and participantsThis cohort study included children aged 9 and 10 years at wave 1 (October 2016 to October 2018) and aged 11 to 12 years at a 2-year follow-up (wave 2, August 2018 to January 2021) across 21 US sites in the Adolescent Brain Cognitive Development (ABCD) Study. Data were analyzed from June 2022 to December 2023.ExposureMTDP.Main outcomes and measuresOutcomes of interest were neurocognition, measured by the National Institutes of Health (NIH) Toolbox Cognition Battery, and morphometric brain measures through the region of interest (ROI) analysis from structural magnetic resonance imaging (sMRI).ResultsAmong 11 448 children at wave 1 (mean [SD] age, 9.9 [0.6] years; 5990 [52.3%] male), 1607 children were identified with MTDP. In the NIH Toolbox Cognition Battery, children with MTDP (vs no MTDP) exhibited lower scores on the oral reading recognition (mean [SE] B = -1.2 [0.2]; P < .001), picture sequence memory (mean [SE] B = -2.3 [0.6]; P < .001), and picture vocabulary (mean [SE] B = -1.2 [0.3]; P < .001) tests and the crystallized cognition composite score (mean [SE] B = -1.3 [0.3]; P < .001) at wave 1. These differential patterns persisted at wave 2. In sMRI, children with MTDP (vs no MTDP) had smaller cortical areas in precentral (mean [SE] B = -104.2 [30.4] mm2; P = .001), inferior parietal (mean [SE] B = -153.9 [43.4] mm2; P < .001), and entorhinal (mean [SE] B = -25.1 [5.8] mm2; P < .001) regions and lower cortical volumes in precentral (mean [SE] B = -474.4 [98.2] mm3; P < .001), inferior parietal (mean [SE] B = -523.7 [136.7] mm3; P < .001), entorhinal (mean [SE] B = -94.1 [24.5] mm3; P < .001), and parahippocampal (mean [SE] B = -82.6 [18.7] mm3; P < .001) regions at wave 1. Distinct cortical volume patterns continued to be significant at wave 2. Frontal, parietal, and temporal lobes exhibited differential ROI, while there were no notable distinctions in the occipital lobe and insula cortex.Conclusions and relevanceIn this cohort study, MTDP was associated with enduring deficits in childhood neurocognition. Continued research on the association of MTDP with cognitive performance and brain structure related to language processing skills and episodic memory is needed.
| S-EPMC10865146 | biostudies-literature
Project description:BACKGROUND:Obesity increases the risk for developing gestational diabetes mellitus (GDM) and preeclampsia (PE), which both associate with increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in women in later life. In the general population, metabolic syndrome (MetS) associates with T2DM and CVD. The impact of maternal MetS on pregnancy outcomes, in nulliparous pregnant women, has not been investigated. METHODS AND FINDINGS:Low-risk, nulliparous women were recruited to the multi-centre, international prospective Screening for Pregnancy Endpoints (SCOPE) cohort between 11 November 2004 and 28 February 2011. Women were assessed for a range of demographic, lifestyle, and metabolic health variables at 15 ± 1 weeks' gestation. MetS was defined according to International Diabetes Federation (IDF) criteria for adults: waist circumference ?80 cm, along with any 2 of the following: raised trigycerides (?1.70 mmol/l [?150 mg/dl]), reduced high-density lipoprotein cholesterol (<1.29 mmol/l [<50 mg/dl]), raised blood pressure (BP) (i.e., systolic BP ?130 mm Hg or diastolic BP ?85 mm Hg), or raised plasma glucose (?5.6 mmol/l). Log-binomial regression analyses were used to examine the risk for each pregnancy outcome (GDM, PE, large for gestational age [LGA], small for gestational age [SGA], and spontaneous preterm birth [sPTB]) with each of the 5 individual components for MetS and as a composite measure (i.e., MetS, as defined by the IDF). The relative risks, adjusted for maternal BMI, age, study centre, ethnicity, socioeconomic index, physical activity, smoking status, depression status, and fetal sex, are reported. A total of 5,530 women were included, and 12.3% (n = 684) had MetS. Women with MetS were at an increased risk for PE by a factor of 1.63 (95% CI 1.23 to 2.15) and for GDM by 3.71 (95% CI 2.42 to 5.67). In absolute terms, for PE, women with MetS had an adjusted excess risk of 2.52% (95% CI 1.51% to 4.11%) and, for GDM, had an adjusted excess risk of 8.66% (95% CI 5.38% to 13.94%). Diagnosis of MetS was not associated with increased risk for LGA, SGA, or sPTB. Increasing BMI in combination with MetS increased the estimated probability for GDM and decreased the probability of an uncomplicated pregnancy. Limitations of this study are that there are several different definitions for MetS in the adult population, and as there are none for pregnancy, we cannot be sure that the IDF criteria are the most appropriate definition for pregnancy. Furthermore, MetS was assessed in the first trimester and may not reflect pre-pregnancy metabolic health status. CONCLUSIONS:We did not compare the impact of individual metabolic components with that of MetS as a composite, and therefore cannot conclude that MetS is better at identifying women at risk. However, more than half of the women who had MetS in early pregnancy developed a pregnancy complication compared with just over a third of women who did not have MetS. Furthermore, while increasing BMI increases the probability of GDM, the addition of MetS exacerbates this probability. Further studies are required to determine if individual MetS components act synergistically or independently.
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Project description:ImportanceMany studies have evaluated whether in utero cannabis exposure is associated with fetal and neonatal outcomes, yet little is known about whether prenatal cannabis use is associated with maternal health outcomes during pregnancy.ObjectiveTo evaluate whether prenatal cannabis use is associated with maternal health outcomes during pregnancy.Design, setting, and participantsThis population-based retrospective cohort study included pregnancies in Northern California from January 2011 to December 2019 that lasted 20 weeks or longer and were screened for prenatal cannabis use.ExposuresPrenatal cannabis use was defined as any self-reported use during early pregnancy or a positive toxicology test result based on universal screening at entrance to prenatal care (approximately 8-10 weeks' gestation). Self-reported frequency of use (daily, weekly, monthly or less, never, unknown), use defined only by self-report, and use defined only by toxicology test results were examined.Main outcomes and measuresElectronic health record data were used to define the following outcomes: gestational hypertension, preeclampsia, eclampsia, gestational diabetes, gestational weight gain greater and less than guidelines, placenta previa, placental abruption, placenta accreta, and severe maternal morbidity. Adjusted risk ratios (aRRs) were calculated using a modified Poisson regression.ResultsThe sample (n = 316 722 pregnancies; 250 221 unique individuals) included 84 039 (26.5%) Asian/Pacific Islander, 20 053 (6.3%) Black, 83 145 (26.3%) Hispanic, and 118 333 (37.4%) White individuals; the mean (SD) age was 30.6 (5.4) years. Overall, 20 053 (6.3%) screened positive for prenatal cannabis use; 2.9% were positive by self-report, 5.3% by toxicology testing, and 1.8% by both. The frequency of cannabis use was 1930 (0.6%) daily, 2345 (0.7%) weekly, 4892 (1.5%) monthly or less, and 10 886 (3.4%) unknown. Prenatal cannabis use was associated with greater risk of gestational hypertension (aRR, 1.17; 95% CI, 1.13-1.21), preeclampsia (aRR, 1.08; 95% CI, 1.01-1.15), weight gain less than (aRR, 1.05; 95% CI, 1.01-1.08) and greater than (aRR, 1.09; 95% CI, 1.08-1.10) guidelines, and placental abruption (aRR, 1.19; 95% CI, 1.05-1.36). The pattern of results was similar when defining prenatal cannabis use only by self-report or only by toxicology testing, and associations between the frequency of prenatal cannabis use and outcomes varied with outcome.Conclusions and relevanceThe results of this cohort study suggest that prenatal cannabis use was associated with several adverse maternal health outcomes during pregnancy. Continued research is needed to understand whether characteristics of prenatal cannabis use (eg, dose, mode, and timing) moderate these associations.
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Project description:ObjectiveTo investigate the relationship between endometriosis and adverse pregnancy outcomes.MethodsWomen between ages 25 and 42 years in 1989 (n=116,429) reported detailed information on pregnancies and reproductive health at baseline and every 2 years thereafter in the Nurses' Health Study II, a cohort study. In 2009, they completed a detailed, pregnancy-focused questionnaire. A total of 196,722 pregnancies were reported. Adverse pregnancy outcomes included spontaneous abortion, ectopic pregnancy, stillbirth, gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (preeclampsia or gestational hypertension), preterm birth, and low birth weight. We estimated the relative risks (RRs) and 95% CIs of adverse pregnancy outcomes comparing pregnancies in women with and without a history of laparoscopically confirmed endometriosis using multivariable log-binomial regression, with generalized estimating equations to account for multiple pregnancies per woman.ResultsEndometriosis was associated with a greater risk of pregnancy loss (spontaneous abortion: RR 1.40, 95% CI 1.31-1.49; ectopic pregnancy: RR 1.46, 95% CI 1.19-1.80). Endometriosis was also associated with a greater risk of GDM (RR 1.35, 95% CI 1.11-1.63) and hypertensive disorders of pregnancy (RR 1.30, 95% CI 1.16-1.45).ConclusionsWe observed an association between laparoscopically confirmed endometriosis and several adverse pregnancy outcomes. Future research should focus on the potential biological pathways underlying these relationships to inform screening or preventive interventions.
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