Assessment of clinical pregnancies in up to eight ovarian stimulation with intrauterine insemination treatment cycles in those unable to proceed with in vitro fertilization.

OBJECTIVE: To study the primary objective of clinical pregnancy (CP) rate per ovarian stimulation with intrauterine insemination (OS-IUI) treatment cycle in patients with repetitive cycles up to a maximum of 8 cycles. DESIGN: Retrospective cohort. SETTING: Large fertility clinic. PATIENTS: A total of 37,565 consecutive OS-IUI cycles from 18,509 patients were included in this study. INTERVENTIONS: Those with anovulatory diagnoses, tubal factor infertility, male factor infertility, using donor sperm, canceled cycles, and those with missing data for either baseline characteristics or outcome were excluded. The CP rate was analyzed using generalized estimating equations and controlled for age, stimulation protocol, and body mass index. MAIN OUTCOMES MEASURES: Clinical pregnancy was defined as intrauterine gestation with fetal heartbeat visible on ultrasound. RESULTS: A total of 37,565 consecutive OS-IUI cycles from 2002 through 2019 at a private practice facility were evaluated. All cycles met inclusion criteria and were used in generalized estimating equation modeling. Patients aged <35 years comprised 47.6% of the cohort. After adjustment for confounders, the mean predicted probability of CP for cycles one to 8 was 15.7% per cycle. The mean predicted probability of CP in aggregated data from cycles 2 to 4 was only 1.7% lower compared with cycle 1 as the referent (16.7% vs. 15.0%, 95% confidence interval [CI] 2nd: 0.88 {0.82, 0.95}, 3rd: 0.86 {0.79, 0.93}, 4th: 0.88 {0.79, 0.98}). However, the 15.0% mean predicted probability of CP for the second through the fourth cycle was concordant with the mean for all included cycles (15.7%). The mean predicted probability of CP of cycles 5 to 8 was not significantly different compared with the referent (16.7% vs. 16.1%, 95% CI 5th: 0.97 [0.85, 1.11], 6th: 0.93 [0.79, 1.10], 7th: 1.01 [0.81, 1.26], 8th: 1.01 [0.76, 1.34]). The modeling of consecutive cycles suggested that the adjusted cumulative predicted probability of CP from OS-IUI continues to increase with each of the 8 successive cycles. CONCLUSION: Clinical pregnancy rates are satisfactory in up to 8 consecutive OS-IUI treatment cycles. These data are useful for counseling, especially in those patients for whom in vitro fertilization is not financially or ethically feasible.

Tobacco, Alcohol, Cannabis, and Other Drug Use in the US Before and During the Early Phase of the COVID-19 Pandemic.

Importance: Information about national substance use trends among youths and adults after mid-March 2020 is limited due to constraints on surveillance during the COVID-19 pandemic. Objective: To evaluate whether substance use prevalence in the early part of the pandemic (2020) differed from the prepandemic periods of 2018 to 2019 and 2016 to 2018. Design, Setting, and Participants: This cross-sectional study was a repeated analysis of 2016 to 2020 data from a nationally representative sample of youths and adults in the Population Assessment of Tobacco and Health (PATH) Study. Participants were representative of the US civilian noninstitutionalized population. Household residents age 13 years or older were interviewed in person from 2016 to 2019 and via telephone in 2020. Exposures: Age, calendar year. Main Outcomes and Measures: Past 30-day self-reported use of any tobacco, any alcohol, binge drinking, cannabis, and any other illegal or misused prescription drugs. Results: The overall nationally representative 2020 sample included 7129 youths (ages 13-17 years), 3628 young adults (ages 18-20 years), and 8874 adults (ages ≥21 years). Comparing 2018 to 2019 with 2020 among youths, prevalence of all substances used declined (eg, cannabis use declined in those aged 16-17 years from 14.9% to 7.6%; absolute difference, -7.3 percentage points [95% CI -8.8 to -5.8 percentage points]). Among young adults, prevalence of all substances other than any alcohol decreased significantly (eg, tobacco use declined from 37.8% to 22.8%; absolute difference, -15.1 percentage points [95% CI -16.8 to -13.3 percentage points]). In adults ages 21 to 24 years, any tobacco use declined from 39.0% to 30.9% (absolute difference, -8.2 percentage points [95% CI, -10.6 to -5.7 percentage points]), and alcohol use increased from 60.2% to 65.2% (absolute difference, 5.0 percentage points [95% CI, 2.3 to 7.7 percentage points]). Among adults aged 25 years or older, any tobacco use declined from 39.0% to 30.9% (absolute difference, -8.2 percentage points [95% CI, -10.6 to -5.7 percentage points]), cannabis use increased from 11.3% to 12.4% (absolute difference, 1.2 percentage points [95% CI, 0.3 to 2.0 percentage points]), and other substance use declined from 5.8% to 3.7% (absolute difference, -2.1 percentage points [95% CI, -2.9 to -1.4 percentage points]). Conclusions and Relevance: In this cross-sectional study, substance use decreased between 2019 and 2020 among those aged 13 to 20 years; consistent declines were not seen in older persons other than tobacco use reductions, and cannabis use increased among adults ages 25 years and older. While social changes during the COVID-19 pandemic could have affected substance use, findings should be interpreted with caution due to differences in data collection methods in 2016 to 2019 and 2020.

A SART data cost-effectiveness analysis of planned oocyte cryopreservation versus in vitro fertilization with preimplantation genetic testing for aneuploidy considering ideal family size.

OBJECTIVE: To determine the cost-effectiveness of planned oocyte cryopreservation (OC) as a strategy for delayed childbearing to achieve 1 or 2 live births (LB) compared with in vitro fertilization (IVF) and preimplantation genetic testing for aneuploidy (PGT-A) at advanced reproductive age. DESIGN: Decision tree model with sensitivity analyses using data from the Society for Assisted Reproductive Technology Clinical Outcome Reporting System and other clinical sources. SETTING: Not applicable. PATIENT(S): A data-driven simulated cohort of patients desiring delayed childbearing with an ideal family size of 1 or 2 LB. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Probability of achieving ≥1 or 2 LB, average and maximum cost per patient, cost per percentage point increase in chance of LB, and population-level cost/LB. RESULT(S): For those desiring 1 LB, planned OC at age 33 with warming at age 43 decreased the average total cost per patient from $62,308 to $30,333 and increased the likelihood of LB from 50% to 73% when compared with no OC with up to 3 cycles of IVF/PGT-A at age 43. For those desiring 2 LB, 2 cycles of OC at age 33 and warming at age 40 yielded the lowest cost per patient and highest likelihood of achieving 2 LB ($51,250 and 77%, respectively) when compared withpursuing only 1 cycle of OC ($75,373 and 61%, respectively), no OC and IVF/PGT-A with embryo banking ($79,728 and 48%, respectively), or no OC and IVF/PGT-A without embryo banking ($79,057 and 19%, respectively). Sensitivity analyses showed that OC remained cost-effective across a wide range of ages at cryopreservation. For 1 LB, OC achieved the highest likelihood of success when pursued before age 32 and remained more effective than IVF/PGT-A when pursued before age 39, and for 2 LB, 2 cycles of OC achieved the highest likelihood of success when pursued before age 31 and remained more effective than IVF/PGT-A when pursued before age 39. CONCLUSION(S): Among patients planning to postpone childbearing, OC is cost-effective and increases the odds of achieving 1 or 2 LB when compared with IVF/PGT-A at a more advanced reproductive age.

Preconception hemoglobin A1c concentration in healthy women is not associated with fecundability or pregnancy loss.

Objective: To examine the relationship of preconception hemoglobin A1c, a marker of cumulative exposure to glucose over the preceding 2-3 months, with time to pregnancy, pregnancy loss, and live birth among fecund women without diagnosed diabetes or other medical diseases. Design: A secondary analysis of a prospective cohort of women participating in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial. Setting: Four US academic medical centers. Patients: A total of 1,194 healthy women aged 18-40 years with a history of one or two pregnancy losses attempting spontaneous conception were observed for up to six cycles while attempting pregnancy and throughout pregnancy if they conceived. Interventions: Not applicable. Main Outcome Measures: Time to pregnancy, human chorionic gonadotropin pregnancy, clinical pregnancy, pregnancy loss, and live birth. Results: Although increasing preconception A1c level was associated with reduced fecundability (fecundability odds ratio [FOR] per unit increase in A1c 0.74; 95% confidence interval [CI] 0.57, 0.96) in unadjusted models and models adjusted for age, race, smoking and treatment arm (FOR 0.79; 95% CI 0.60, 1.04), results were attenuated after further adjustment for body mass index (FOR 0.91; 95% CI 0.68, 1.21). Preconception A1c levels among women without diagnosed diabetes were not associated with live birth or pregnancy loss. Conclusionss: Among healthy women without diagnosed diabetes, we observed no association of A1c with live birth or pregnancy loss. The association between A1c and fecundability was influenced by body mass index, a strong risk factor for both diabetes and infertility. These data support current recommendations that preconception A1c screening should be reserved for patients with risk factors for diabetes. Clinical Trial Registration Number: ClinicalTrials.gov: NCT00467363.

Leukocyte telomere length is inversely associated with a metabolic risk score in Mesoamerican children.

OBJECTIVE: Leukocyte telomere length (LTL) may be involved in the etiology of the metabolic syndrome (MetS). We examined the associations of LTL with MetS and its components among Mesoamerican children and their adult parents, in a region where MetS prevalence is high. METHODS: We conducted a cross-sectional study of 151 children aged 7-12 years and 346 parents from the capitals of Belize, Honduras, Nicaragua, Costa Rica, Panama, and Chiapas State, Mexico. We quantified LTL by qPCR on DNA extracted from whole blood. In children, we created an age- and sex-standardized metabolic risk score using waist circumference (WC), the homeostasis model of insulin resistance (HOMA-IR), blood pressure, serum high-density lipoprotein (HDL) cholesterol, and serum triglycerides. In adults, MetS was defined according to the National Cholesterol Education Program's Adult Treatment Panel III definition. We estimated mean differences in metabolic risk score and prevalence ratios of MetS across quartiles of LTL using multivariable-adjusted linear and Poisson regression models, respectively. RESULTS: In children, every 1 LTL z-score was related to an adjusted 0.05 units lower (95% CI: -0.09, -0.02, P = 0.005) MetS risk score, through WC, HOMA-IR, and HDL. Among adults, LTL was not associated with MetS prevalence; however, every 1 LTL z-score was associated with an adjusted 34% lower prevalence of high fasting glucose (95% CI: 3%, 55%, p = .03). CONCLUSIONS: Among Mesoamerican children, LTL is associated with an improved metabolic profile; among adults, LTL is inversely associated with the prevalence of high fasting glucose.

Prospective associations between leukocyte telomere length and adiposity in childhood.

Leukocyte telomere length (LTL) is associated with obesity and may be involved in its aetiology, but few studies have focused on children and most have been cross-sectional. We assessed the relation of LTL with adiposity development in a prospective study of Colombian children. We quantified LTL at enrollment in 722 children aged 5-12 years and measured anthropometry annually for a median 6 years. Using mixed effects models, we estimated changes in adiposity measures including BMI and waist circumference (WC)-for-age z-scores in relation to baseline LTL z-score. In girls, longer LTL was linearly related to a lower increase in WC z-score from age 6 to 16 years. Every 1 SD LTL was associated with an adjusted 0.13 units lower increase in WC (95% CI: -0.23, -0.03; p = 0.01). In conclusion, longer LTL among girls in middle childhood is associated with smaller increases in WC, an indicator of abdominal adiposity.

Circulating Vascular Endothelial Growth Factor and Soluble fms-Like Tyrosine Kinase-1 as Biomarkers for Endometrial Remodeling Across the Menstrual Cycle.

OBJECTIVE: To characterize variation in circulating vascular endothelial growth factor (VEGF) and its receptor, soluble fms-like tyrosine kinase-1 (sFLT-1), across the menstrual cycle in normal ovulating women in relation to reproductive hormones to identify the utility of VEGF and sFLT-1 as peripheral biomarkers of endometrial remodeling. METHODS: Ninety-six healthy, regularly menstruating ovulatory women, aged 18-44 years, enrolled in the BioCycle Study, a prospective cohort study at a U.S. academic research center. Vascular endothelial growth factor and sFLT-1 were measured in concurrently collected plasma, serum, and urine up to eight times across a single cycle. Reproductive hormones were measured in serum. Mean concentrations of VEGF and sFLT-1 were compared across phases of the cycle, and correlations between specimen types were calculated. Harmonic models estimated associations between VEGF and sFLT-1 and characteristics of hormonal patterns. RESULTS: No variation in VEGF or sFLT-1 levels were detected over the menstrual cycle. Median (25th percentile, 75th percentile) concentrations of VEGF during the menstrual cycle were 31.2 pg/mL (24.1, 56.9) in plasma, 194.1 pg/mL (125.4, 350.2) in serum, and 101.7 pg/mL (64.2, 165.8) in urine. Plasma and serum measures were consistently correlated, whereas urinary measures were not. Vascular endothelial growth factor was not consistently associated with reproductive hormone concentrations, although sFLT-1 was associated with higher mean and amplitude of estradiol. CONCLUSION: Circulating VEGF and sFLT-1 did not vary across the menstrual cycle and therefore are unlikely to be useful peripheral biomarkers of endometrial changes across the menstrual cycle. For studies measuring circulating VEGF for other reasons, plasma may be the preferred medium and timing to menstrual cycle phase need not be considered for reproductive-age women.

Vitamin D status in infancy and cardiometabolic health in adolescence.

BACKGROUND: Vitamin D deficiency is associated with obesity-related conditions, but the role of early life vitamin D status on the development of obesity is poorly understood. OBJECTIVES: We assessed whether serum 25-hydroxyvitamin D [25(OH)D] at age 1 y was related to metabolic health through adolescence. METHODS: We quantified serum 25(OH)D in samples obtained at age 1 y from 306 participants in a cohort study in Santiago, Chile. Anthropometry was performed at ages 5, 10, and 16/17 y. At 16/17 y, we determined body composition using DXA and quantified metabolic parameters in a blood sample. We examined the associations of infancy 25(OH)D with BMI-for-age z-score (BMIZ) at ages 5, 10, and 16/17 y; with percentage fat and percentage lean body mass at age 16/17 y; and with a metabolic syndrome (MetS) score and its components at age 16/17 y. RESULTS: Infancy 25(OH)D was inversely associated with BMIZ in childhood. Every 25-nmol/L difference in 25(OH)D was related to an adjusted 0.11 units lower BMIZ at age 5 y (95% CI: -0.20, -0.03; P = 0.01) and a 0.09 unit lower BMIZ change from ages 1 to 5 y (95% CI: -0.17, -0.01; P = 0.02). Also, every 25-nmol/L 25(OH)D in infancy was associated with an adjusted 1.3 points lower percentage body fat mass (95% CI: -2.2, -0.4; P = 0.005) and an adjusted 0.03 units lower MetS score (95% CI: -0.05, -0.01; P = 0.01) at age 16/17 y, through inverse associations with waist circumference and the HOMA-IR. CONCLUSIONS: Serum 25(OH)D at age 1 y is inversely associated with childhood BMIZ, percentage body fat at age 16/17 y, and a MetS score at age 16/17 y. Intervention studies are warranted to examine the effects of vitamin D supplementation in early life on long-term cardiometabolic outcomes.

Is opioid use safe in women trying to conceive?

Background: Opioids are commonly prescribed to women of reproductive age, including after delivery and miscarriage. However, to our knowledge, opioid use has not been frequently studied in relation to the common reproductive complications of impaired fecundability and pregnancy. We examined the association of opioid use during the critical window of pregnancy establishment with fecundability and pregnancy loss. Methods: We measured opioid use by urine screening and self-report at multiple time points during preconception and early pregnancy in a prospective cohort of women attempting conception (n=1228). The main outcomes included time to hCG-detected pregnancy and incidence of live birth and pregnancy loss. We estimated fecundability odds ratios (FOR) and risk ratios (RR) with 95% confidence intervals (CI) adjusting for sociodemographic characteristics, reproductive characteristics, and use of antidepressants, tobacco, alcohol, and marijuana. Results: Prevalence of preconception opioid use was 18% (n=226 of 1228), and in early pregnancy was 5% (n=33 of 685). Opioid use while attempting pregnancy was associated with reduced fecundability (FOR: 0.71; 95% CI: 0.50, 1.0). Risk of pregnancy loss increased as opioid exposure was detected later in gestation, from the beginning of the cycle of conception (RR: 1.5; 95% CI 0.85, 2.6), to week 4 of pregnancy (RR: 2.1; 95% CI: 1.1, 4.1), and to week 4 and 8 of pregnancy (RR: 2.5; 95% CI: 1.3, 5.0). Conclusions: Our results are consistent with the hypothesis that opioid exposure while trying to conceive may be harmful, even among healthy, non-opioid-dependent women. Possible risks to fecundability and pregnancy viability are relevant to patients and providers when evaluating pain management approaches.ClinicalTrials.gov registration number: #NCT00467363.

Urinary selective serotonin reuptake inhibitors across critical windows of pregnancy establishment: a prospective cohort study of fecundability and pregnancy loss.

OBJECTIVE: To prospectively investigate the association of selective serotonin reuptake inhibitor (SSRI) exposure through critical windows of pregnancy establishment with fecundability and pregnancy loss. DESIGN: Prospective cohort study using longitudinal urine measurements of common SSRIs while women are actively trying to conceive. SETTING: Four clinical sites. PATIENT(S): A total of 1,228 women without uncontrolled depression/anxiety, attempting natural conception while participating in a randomized trial of preconception-initiated low-dose aspirin. INTERVENTIONS(S): Not applicable. MAIN OUTCOME MEASURE(S): Urinary SSRIs (fluoxetine, sertraline, escitalopram/citalopram) were measured while trying to conceive and, for women who became pregnant, at weeks 0, 4, and 8 of pregnancy. Fecundability odds ratios and incidence of pregnancy loss and live birth were estimated. RESULT(S): A total of 172 women (14%) were exposed to SSRIs while trying to conceive. SSRI exposure was associated with 24% reduced fecundability, and accordingly, a nonsignificant 9% lower live birth incidence, with significantly lower live birth in fluoxetine-exposed women. SSRI exposure was not associated with subsequent pregnancy loss, whether exposure was before conception or at 0, 4, or 8 weeks of gestation, although estimates varied by specific SSRI drug. CONCLUSION(S): Women using SSRIs may have more difficulty becoming pregnant, and although SSRI exposure overall was not associated with pregnancy loss, fluoxetine deserves caution and future study. CLINICAL TRIAL REGISTRATION NUMBER: NCT00467363.

Prescription Opioid Use Among Populations of Reproductive Age: Effects on Fertility, Pregnancy Loss, and Pregnancy Complications.

Prescription opioid use is common among men and women of reproductive age, including during assisted-reproduction procedures. Opioid use disorder and chronic use are associated with harms to fertility and pregnancy outcomes, but it is unclear whether these associations extend to common short-term patterns of prescription opioid use. We conducted a literature review using PubMed, Embase, Web of Science, and Scopus to identify studies of nonchronic, nondependent opioid use and reproductive endpoints including fertility, pregnancy loss, and pregnancy complications (i.e., preterm birth, birth weight, gestational diabetes, and hypertensive disorders of pregnancy). Seventeen studies were included. Although results of the studies suggest possible harms of short-term opioid use on fertility and pregnancy loss, methodologic limitations and the small number of studies make the literature inconclusive. This review highlights important data gaps that must be addressed to make conclusions about potential reproductive effects of short-term opioid use. These include the need for additional data on opioid use before clinically recognized pregnancy; accurate measurement of opioid exposure by multiple means with detailed information on the types and quantity of opioids used; assessment of important confounders, including opioid use indication, comorbidities, and use of other medications and substances; and studies of paternal opioid use, fertility, and pregnancy outcomes. A primary limitation of this review targeting studies of nonchronic opioid exposure is the possibility that selected studies included populations with unspecified chronic or dependent opioid use. Efforts to understand the impact of the prescription opioid epidemic should address potential reproductive harms of these medications among people of reproductive age.

Serum polyunsaturated fatty acids in infancy are associated with body composition in adolescence.

BACKGROUND: Polyunsaturated fatty acids (PUFA) have been related to the development of adiposity. N-3 PUFA appears to be protective against obesity risk, while n-6 PUFA may be associated with greater adiposity. However, most studies have been conducted among adults. The role of PUFA in infancy is unknown. OBJECTIVE: To examine associations of serum PUFA at age 1 year with age- and sex-adjusted body mass index Z score (BMIZ) change through age 16 years and body composition at 16 years. METHODS: We quantified serum PUFA in 636 Chilean infants aged 1 year. We measured BMIZ at ages 1, 5, 10 and 16 years, and body composition by dual energy X-ray absorptiometry at 16 years. We estimated differences in 1- to 16-years BMIZ change between PUFA quartiles from multivariable linear mixed models with restricted cubic splines. At 16 years, we estimated differences in total fat mass (ToFM), truncal fat mass (TrFM), total lean mass (TLM), percent total fat mass (%ToFM) and percent truncal fat mass (%TrFM) between PUFA quartiles using linear regression. RESULTS: PUFA were not associated with BMIZ change. Alpha-linolenic acid (ALA) was positively associated with TrFM (P = .03) and %TrFM (P < .0001) at 16 years while eicosapentaenoic acid (EPA) was inversely associated with %TrFM (P = .001). Docosapentaenoic acid (DPA) was positively associated with ToFM (P = .01), TrFM (P = .009), %ToFM (P = .02) and %TrFM (P = .02). Gamma-linolenic acid (GLA) and the Δ6-desaturase (D6D) activity index were each positively, linearly associated with ToFM, TrFM and %ToFM. The Δ5-desaturase (D5D) activity index was inversely associated with %TrFM (P = .04). CONCLUSIONS: ALA, DPA, GLA and the D6D index at 1 year of age were positively associated with adiposity at age 16 years, while EPA and the D5D index were inversely associated with central adiposity. Our results related to EPA and desaturase indices are in agreement with limited prior studies.

Micronutrient status and leukocyte telomere length in school-age Colombian children.

PURPOSE: Leukocyte telomere length (LTL) is a biomarker of inflammation and oxidative stress that predicts chronic disease risk. Nutritional factors are related to LTL in adulthood, but these associations are not well characterized in children. We examined whether micronutrient status biomarkers were associated with LTL in school-age children. METHODS: We conducted a cross-sectional study of 330 boys and 393 girls aged 5-12 years from Bogotá, Colombia. We quantified blood concentrations of hemoglobin, ferritin, zinc, vitamin A, folate, and vitamin B-12; and measured LTL using qPCR in DNA extracted from buffy coat. We estimated mean differences in LTL by quartiles of micronutrient status biomarkers and categories of relevant sociodemographic and anthropometric covariates with the use of linear regression. RESULTS: In girls, plasma vitamin B-12 was positively associated with LTL (adjusted LTL difference between extreme vitamin B-12 quartiles = 0.11; P, trend = 0.02). LTL was also positively associated with birth order in girls (P, trend = 0.02). In boys, LTL was not related to the micronutrient status biomarkers but, unexpectedly, it was positively associated with birth weight (P = 0.02), height-for-age Z score (P, trend = 0.01), and serum C-reactive protein (P, trend = 0.01). CONCLUSIONS: LTL is associated with vitamin B-12 status among girls. LTL is also associated with birth weight, height, and C-reactive protein in boys.

Maternal fatty acid concentrations and newborn DNA methylation.

BACKGROUND: Preconception nutrition sets the stage for a healthy pregnancy. Maternal fatty acids (FAs) are related to beneficial neonatal outcomes with DNA methylation proposed as a mechanism; however, few studies have investigated this association and none with preconception FAs. OBJECTIVES: We examined the relations of maternal plasma FA concentrations at preconception (n = 346) and 8 weeks of gestation (n = 374) with newborn DNA methylation. METHODS: The Effects of Aspirin in Gestation and Reproduction Trial (2006-2012) randomly assigned women with previous pregnancy loss to low dose aspirin or placebo prior to conception. We measured maternal plasma phospholipid FA concentration at preconception (on average 4 mo before pregnancy) and 8 weeks of gestation. Cord blood DNA from singletons was measured using the MethylationEPIC BeadChip. We used robust linear regression to test the associations of FA concentration with methylation ß-values of each CpG site, adjusting for estimated cell count using a cord blood reference, sample plate, maternal sociodemographic characteristics, cholesterol, infant sex, and epigenetic-derived ancestry. False discovery rate correction was used for multiple testing. RESULTS: Mean ± SD concentrations of preconception marine (20:5n-3+22:6n-3+22:5n-3) and ω-6 PUFAs, SFAs, MUFAs, and trans FAs were 4.7 ± 1.2, 38.0 ± 2.0, 39.4 ± 1.8, 11.6 ± 1.1, and 1.0 ± 0.4 % of total FA, respectively; concentrations at 8 weeks of gestation were similar. Preconception marine PUFA concentration was associated with higher methylation at GRAMD2 (P = 1.1 × 10-8), LOXL1 (P = 5.5 × 10-8), SIK3 (P = 1.6 × 10-7), HTR1B (P = 1.9 × 10-7), and MCC (P = 2.1 × 10-7) genes. Preconception SFA concentration was associated with higher methylation at KIF25-AS1 and lower methylation at SLC39A14; other associations exhibited sensitivity to outliers. The trans FA concentration was related to lower methylation at 3 sites and higher methylation at 1 site. FAs at 8 weeks of gestation were largely unrelated to DNA methylation. CONCLUSIONS: Maternal preconception FAs are related to newborn DNA methylation of specific CpG sites, highlighting the importance of examining nutritional exposures preconceptionally. This trial was registered at clinicaltrials.gov as NCT00467363.

Pilot randomized trial of short-term changes in inflammation and lipid levels during and after aspirin and pravastatin therapy.

BACKGROUND: Inflammation and elevated blood lipids are associated with infertility. Aspirin and statin therapy may improve infertility treatment outcomes among overweight and obese women with systemic inflammation, but little is known about the short-term effects of statins in this population. We conducted a pilot study of aspirin, pravastatin, or combined treatment among a group of overweight and obese, reproductive-aged women. Our goal was to characterize short-term changes in inflammatory and lipid biomarkers during and after treatment. METHODS: In this open-label trial, women aged 18-40 years with a body mass index ≥25 kg/m2 were randomized to receive either 162 mg aspirin, 40 mg pravastatin, or both. The study medication was taken daily for 2 weeks, and participants were then followed for a two-week washout period. Participants provided blood samples at baseline, after the intervention period, and after the washout period. The outcomes were changes in biomarkers of inflammation and lipids measured in blood components at each timepoint. RESULTS: Nine, 8, and 8 women were randomized to the aspirin, pravastatin, and combined arms, respectively. Analyses were conducted among 8, 7, and 7 women in the aspirin, pravastatin, and combined arms for whom biomarker data was available at baseline. High-sensitivity C-reactive protein (hsCRP) levels were lower after treatment in all arms and continued to decrease after washout in the pravastatin and combined arms. Results were consistent between the whole sample and women with baseline hsCRP between 2 and 10 mg/L. Low-density lipoprotein (LDL) cholesterol was lower after treatment in the pravastatin and combined arms and rose slightly after washout. CONCLUSIONS: Our results provide preliminary evidence that short-term aspirin and pravastatin therapy reduces hsCRP and LDL cholesterol among overweight and obese women of reproductive age, including those with low-grade inflammation. Because of these short-term effects, these drugs may improve infertility treatment outcomes in this population, which we will assess in a future randomized trial.

Serum Polyunsaturated Fatty Acids in Middle Childhood and Body Mass Index Change Through Adolescence.

BACKGROUND: Polyunsaturated fatty acids (PUFA) status in childhood may be associated with adiposity development. OBJECTIVE: To assess associations of serum PUFA biomarkers in childhood with change in body mass index (BMI)-for-age Z scores (BMIZ) through adolescence. METHODS: We quantified serum PUFA at ages 5 and 10 years among 418 children from Santiago, Chile. BMI was measured at 5, 10, and 16 years. We compared BMIZ change through age 16 years between quartiles of PUFA at 5 and 10 years and PUFA change 5-10 years by fitting growth curves from mixed effects models. RESULTS: At age 5 years, serum docosahexaenoic acid was inversely associated with BMIZ change from ages 5 to 16 years. At age 10 years, arachidonic acid (AA) was nonlinearly positively related to BMIZ change from ages 10 to 16 years. Change in AA and the Δ5-desaturase (D5D) activity index between 5 and 10 years were each positively associated with BMIZ change from ages 10 to 16 years. Change in eicosapentaenoic acid was inversely associated with change in BMIZ. CONCLUSIONS: Serum long-chain n-3 PUFA in middle childhood were associated with less BMI gain through adolescence, whereas AA and D5D activity was related to greater BMI gain.

Sociodemographic, Anthropometric, and Dietary Predictors of Polyunsaturated Fatty Acids in Adipose Tissue Among Mesoamerican Children and Their Parents.

BACKGROUND: Polyunsaturated fatty acid (PUFA) intake is low throughout Latin America. Improving PUFA status could be an effective intervention against chronic disease, but information on sociodemographic and dietary patterning of PUFA status in the region is limited. OBJECTIVE: To characterize sociodemographic, anthropometric, and dietary predictors of PUFA status biomarkers in adipose tissue among children and their parents from Mesoamerica. METHODS: This was a cross-sectional study of 220 children aged 7 to 12 years and 471 parents from capital cities of Guatemala, El Salvador, the Dominican Republic, Honduras, Nicaragua, Panama, Costa Rica, and Belize, as well as Tuxtla Gutiérrez in Mexico. The PUFA from gluteal adipose tissue was quantified using gas chromatography. Participants reported sociodemographic information and the type of vegetable oil used for cooking. We estimated percent mean differences in linoleic acid (LA), total long-chain n-6 PUFA (n-6 LCPUFA), α-linolenic acid (ALA), and total long-chain n-3 PUFA (n-3 LCPUFA) between levels of predictors using multivariable-adjusted linear regression models. RESULTS: Country was the strongest predictor of any PUFA, whereas body mass index was positively associated with n-6 LCPUFA in children and adults. Cooking primarily with soybean oil was positively associated with LA in children and adults and ALA in adults. Cooking with canola oil was positively related to n-6 LCPUFA in adults and n-3 LCPUFA in children and adults. Cooking with palm oil was associated with low adipose tissue levels of all n-6 and n-3 PUFA. CONCLUSIONS: Adipose tissue PUFA status in Mesoamerica is associated with country of origin and the type of oil used for cooking.

Sociodemographic correlates and family aggregation of leukocyte telomere length in adults and children from Mesoamerica.

OBJECTIVE: Telomere length is a biomarker of cumulative stress and inflammation related to chronic disease risk. We examined the associations of leukocyte telomere length (LTL) with sociodemographic and anthropometric variables and estimated LTL family aggregation in Central America, a region with a high burden of chronic disease where LTL has not been studied. METHODS: We conducted a cross-sectional study of 174 school age children and their parents in the capital cities of Belize, Honduras, Nicaragua, Costa Rica, Panama, and the city of Tuxtla-Gutierrez in Mexico. We measured LTL by quantitative PCR in DNA extracted from whole blood. We compared the distribution of LTL by categories of sociodemographic and anthropometric characteristics using linear regression. Family aggregation was estimated with correlation coefficients and intraclass correlations. RESULTS: In mothers, LTL was inversely associated with age (P, trend < .0001) and positively associated with height (P = .0002). Among fathers, LTL was inversely associated with food insecurity (P, trend = .0004). In children, boys had 0.10 log units shorter LTL than girls (95% CI: -0.17, -0.03; P = .004). LTL was inversely associated with parental education (P, trend = .01) and positively associated with paternal age at birth (P, trend < .0001), maternal LTL (P, trend = .007), and paternal LTL (P, trend = .02). LTL varied significantly by country of origin among all family members. Aggregation was greatest between children and their mothers, and mostly occurred at the country, rather than family, level. CONCLUSION: LTL is associated with age and height in women; food insecurity in men; and sex, parental education, parental LTL, and paternal age at birth among children.