Epidemiology Branch, National Institute of Child Health and Human Development, National Institutes of Health/DHHS, 6100 Executive Boulevard, Rm. 7B03, Rockville, MD 20852, USA. gb156i@nih.gov
The determinants of successful human reproduction and development may act as early as periconceptionally, underscoring the need to capture exposures during these critical windows when assessing potential toxicants. To identify such toxicants, couples must be studied longitudinally prior to conception without regard to a couple's ability to ascertain a clinically recognized pregnancy. We examined the utility and feasibility of prospective pregnancy study designs by conducting a systematic review of the literature to summarize relevant information regarding the planning, implementation, and success of previously published prospective pregnancy studies. Information concerning design elements and participation was abstracted from 15 eligible studies (from a total of 20 identified studies) using a standardized form. The primary author of each study was contacted to review our summary of their work and obtain missing information. Our findings confirm the ability to recruit women/couples from diverse populations using a variety of recruitment strategies. Among the studies we reviewed, 4-97% of eligible individuals were successfully contacted, with enrollment rates ranging from 42 to 100%. Length of follow-up varied from 3 to 12 months. A high percentage of women provided urine (57-98%) and blood (86-91%) specimens and most male partners (94-100%) provided semen samples. These data support the feasibility of this design.
prospective pregnancy study design, reproductive toxicant assessment, periconceptional exposure measurement, developmental toxicology, preconception cohort methodology, early pregnancy loss detection, environmental reproductive hazards, systematic review pregnancy design, conception to birth monitoring, critical window exposure
PMID 14698935 14698935 DOI 10.1289/ehp.6262 10.1289/ehp.6262
Cite this article
Buck, G. M., Lynch, C. D., Stanford, J. B., Sweeney, A. M., Schieve, L. A., Rockett, J. C., Selevan, S. G., & Schrader, S. M. (2004). Prospective pregnancy study designs for assessing reproductive and developmental toxicants. Environmental health perspectives, 112(1), 79-86. https://doi.org/10.1289/ehp.6262
Buck GM, Lynch CD, Stanford JB, Sweeney AM, Schieve LA, Rockett JC, et al. Prospective pregnancy study designs for assessing reproductive and developmental toxicants. Environ Health Perspect. 2004;112(1):79-86. doi:10.1289/ehp.6262
Buck, G. M., et al. "Prospective pregnancy study designs for assessing reproductive and developmental toxicants." Environmental health perspectives, vol. 112, no. 1, 2004, pp. 79-86.
Schisterman EF et al., 2013·Paediatr Perinat Epidemiol
Low-dose aspirin (LDA) has been proposed to improve pregnancy outcomes in couples experiencing recurrent pregnancy loss. However, results from studies of LDA on pregnancy outcomes have been inconsistent, perhaps because most studies evaluated LDA-initiated post-conception. The purpose of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial was to determine whether preconception-initiated LDA improves livebirth rates in women with one to two prior losses. We performed a multicentre, block randomised, double-blind, placebo-controlled trial. Study participants were recruited using community-based advertisements and physician referral to four university medical centres in the US (2006-12). Eligible women were aged 18-40 years actively trying to conceive, with one to two prior losses. Participants were randomised to receive daily LDA (81 mg/day) or a matching placebo, and all were provided with daily 400-mcg folic acid. Follow-up continued for ≤6 menstrual cycles while attempting to conceive. For those who conceived, treatment was continued until 36 weeks gestation. The primary outcome was the cumulative livebirth rate over the trial period. There were 1228 women randomised (615 LDA, 613 placebo). Participants had a mean age of 28.7, were mostly white (95%), well educated (86% more than high school education), and employed (75%) with a household income >$100 000 annually (40%). The characteristics of those in the treatment and placebo arms were well balanced. We describe the study design, recruitment, data collection, and baseline characteristics of participants enrolled in EAGeR, which aimed to determine the effect of LDA on livebirth and other pregnancy outcomes in these women.
Examples of a combined approach using in vivo as well as in vitro methods for the assessment of prenatal toxicity are presented. The topics discussed include the analysis of the possible embryotoxic potential of valproic acid (VPA), female sex hormones, bis(tri-n-butyltin) oxide (TBTO), and acyclovir and the problem of supplementing in vitro systems with drug-metabolizing activity.
Objective Complicated grief reactions follow some pregnancy outcomes, like miscarriage, stillbirth, neonatal death, infant death, selective reduction, or termination of pregnancy. Stigma can delay treatment and worsen outcomes. Screening tools such as the Edinburgh Postnatal Depression Scale detect complicated grief poorly, and specific tools for prolonged or complicated grief after a reproductive loss are cumbersome. In this study, a five-item questionnaire to detect complicated grief after reproductive loss of any type was designed and preliminary validated. Methods A questionnaire patterned after the extensively validated Brief Grief Questionnaire (BGQ) was created by a group of physicians and lay advocates to employ non-traumatic but specific language related to grief after miscarriage, stillbirth, neonatal death, infant death, selective reduction, or termination of pregnancy. One hundred and forty women at a large academic center were recruited in person and via social media to validate the questionnaire with well-studied instruments for anxiety (7-item Panic Disorder Severity Scale, PDSS), trauma (22-item Impact of Events Scale), and reproductive grief and depressive symptoms (33-item Perinatal Grief Scale [PGS]). Results The response rate was 74.9%. Of the 140 participants, 18 (12.8%) experienced their loss during high-risk pregnancies, and 65 (46.4%) were recruited via social media. Seventy-one (51%) respondents had a score > 4, a positive screen for the BGQ. On average, women experienced their loss 2 years prior to participation (IQR 1-5 years). Cronbach's alpha was 0.77 (95% CI: 0.69-0.83). The goodness of fit indices of the model met Fornell and Larker criteria (RMSEA = 0.167, CFI = 0.89, SRMR = 0.06). The AVE was 0.42 and the CR 0.78. Conclusions This investigator-created screening tool is internally consistent and meets preliminary criteria for discriminant validity. This tool can be refined prior to testing for sensitivity and specificity in screening for complicated grief after a reproductive loss.
The number of sperm that reaches the oocytes in mammalian species is limited. In mice, 8-10 oocytes are ovulated, a similar number of sperm reaches the oocytes, and nearly all oocytes are fertilized via natural mating. Meanwhile, our improved superovulation technique (ultrasuperovulation: administration of inhibin antiserum and equine chorionic gonadotropin [IASe]) produced 100 oocytes from a single female C57BL/6 mouse but resulted in only approximately 20 fertilized oocytes via mating. We hypothesized that sperm shortage in the ampulla might cause this low fertilization rate. Mice were mated in the proestrus stage or after hormone injection, but ovulation timing was not considered. In clinical application, the rhythm method supports fertilization by testing the ovulation period and synchronizing the ovulation and copulation timings. Therefore, this study examined the effects of ovulation and copulation timings on in vivo fertilization in female mice with IASe. Synchronization of the ovulation and copulation timings increased fertilization efficiency in female mice with ultrasuperovulation. The number of embryos obtained post ovulation was three times higher than that obtained pre ovulation. This study suggests that synchronized ovulation and copulation timings improve the efficiency of in vivo fertilization in IASe-treated female mice. This technique can be used to produce genetically modified mice and develop technologies for infertility treatment.