There are three primary methods of gestational age estimation: dating based on last menstrual period (LMP), ultrasound-based dating and neonatal estimates. We review the strengths and limitations of each method as well as their implications for research. Dating based on LMP is a simple, low-cost method of estimating gestational age. Limitations associated with the use of menstrual-based dating include reporting problems such as uncertainty regarding the LMP date, possibly due to bleeding not associated with menses, as well as concerns about the incidence of delayed ovulation, which can result in invalid estimates of gestation, even for women with certain LMP dates. Given that most women in the US have at least one ultrasound during pregnancy, it is becoming increasingly common for clinicians to verify menstrual dates using early ultrasound. To calculate gestational age with the use of ultrasound, fetal measurements are compared with a gestational age-specific reference. The primary limitation of this method is the fact that the gestational age estimates of symmetrically large or small fetuses will be biased. Further, given that ultrasound references were developed using pregnancies that were dated according to reliable LMP dates, they are potentially biased in the same direction as dates calculated according to LMP. Neonatal estimates of gestational age have been shown to be the least precise dating method. To highlight the research implications of the choice of a gestational dating method, we used data from the Routine Antenatal Diagnostic Imaging with Ultrasound Study to identify risk factors for post-term delivery. Risk factors for post-term delivery are shown to vary according to the choice of a gestational dating method, suggesting that some findings are an artefact of the choice of a method rather than evidence of causality.

Despite widespread use of volatile general anesthetics for well over a century, the mechanisms by which they alter specific CNS functions remain unclear. Here, we present evidence implicating the two-pore domain, pH-sensitive TASK-1 channel as a target for specific, clinically important anesthetic effects in mammalian neurons. In rat somatic motoneurons and locus coeruleus cells, two populations of neurons that express TASK-1 mRNA, inhalation anesthetics activated a neuronal K ϩ conductance, causing membrane hyperpolarization and suppressing action potential discharge. These membrane effects occurred at clinically relevant anesthetic levels, with precisely the steep concentration dependence expected for anesthetic effects of these compounds. The native neuronal K ϩ current displayed voltage-and time-dependent properties that were identical to those mediated by the open-rectifier TASK-1 channel. Moreover, the neuronal K ϩ channel and heterologously expressed TASK-1 were similarly modulated by extracellular pH. The decreased cellular excitability associated with TASK-1 activation in these cell groups probably accounts for specific CNS effects of anesthetics: in motoneurons, it likely contributes to anesthetic-induced immobilization, whereas in the locus coeruleus, it may support analgesic and hypnotic actions attributed to inhibition of those neurons.

Background: Evidence suggesting that persistent environmental pollutants may be reproductive toxicants underscores the need for prospective studies of couples for whom exposures are measured.Objectives: We examined the relationship between selected persistent pollutants and couple fecundity as measured by time to pregnancy.Methods: A cohort of 501 couples who discontinued contraception to become pregnant was prospectively followed for 12 months of trying to conceive or until a human chorionic gonadotrophin (hCG) test confirmed pregnancy. Couples completed daily journals on lifestyle and provided biospecimens for the quantification of 9 organochlorine pesticides, 1 polybrominated biphenyl, 10 polybrominated diphenyl ethers, 36 polychlorinated biphenyls (PCBs), and 7 perfluorochemicals (PFCs) in serum. Using Cox models for discrete time, we estimated fecundability odds ratios (FORs) and 95% CIs separately for each partner’s concentrations adjusting for age, body mass index, serum cotinine, serum lipids (except for PFCs), and study site (Michigan or Texas); sensitivity models were further adjusted for left truncation or time off of contraception (≤ 2 months) before enrollment.Results: The adjusted reduction in fecundability associated with standard deviation increases in log-transformed serum concentrations ranged between 18% and 21% for PCB congeners 118, 167, 209, and perfluorooctane sulfonamide in females; and between 17% and 29% for p,p´-DDE and PCB congeners 138, 156, 157, 167, 170, 172, and 209 in males. The strongest associations were observed for PCB 167 (FOR 0.79; 95% CI: 0.64, 0.97) in females and PCB 138 (FOR = 0.71; 95% CI: 0.52, 0.98) in males.Conclusions: In this couple-based prospective cohort study with preconception enrollment and quantification of exposures in both female and male partners, we observed that a subset of persistent environmental chemicals were associated with reduced fecundity.

Hyperthermia causes significant changes in myocardial cellular electrophysiological properties that include membrane depolarization, reversible and irreversible loss of excitability, and abnormal automaticity. There appear to be specific temperature ranges for reversible and irreversible electrophysiological changes. These observations may have important implications for tissue temperature monitoring during radiofrequency catheter ablation.

Summary Buck Louis GM, Schisterman EF, Sweeney AM, Wilcosky TC, Gore-Langton RE, Lynch CD, Boyd Barr D, Schrader SM, Kim S, Chen Z, Sundaram R, on behalf of the LIFE Study. Designing prospective cohort studies for assessing reproductive and developmental toxicity during sensitive windows of human reproduction and development – the LIFE Study. Paediatric and Perinatal Epidemiology 2011; 25: 413–424. The relationship between the environment and human fecundity and fertility remains virtually unstudied from a couple-based perspective in which longitudinal exposure data and biospecimens are captured across sensitive windows. In response, we completed the LIFE Study with methodology that intended to empirically evaluate a priori purported methodological challenges: implementation of population-based sampling frameworks suitable for recruiting couples planning pregnancy;obtaining environmental data across sensitive windows of reproduction and development;home-based biospecimen collection; anddevelopment of a data management system for hierarchical exposome data. We used two sampling frameworks (i.e. fish/wildlife licence registry and a direct marketing database) for 16 targeted counties with presumed environmental exposures to persistent organochlorine chemicals to recruit 501 couples planning pregnancies for prospective longitudinal follow-up while trying to conceive and throughout pregnancy. Enrolment rates varied from <1% of the targeted population (n = 424 423) to 42% of eligible couples who were successfully screened; 84% of the targeted population could not be reached, while 36% refused screening. Among enrolled couples, ~85% completed daily journals while trying; 82% of pregnant women completed daily early pregnancy journals, and 80% completed monthly pregnancy journals. All couples provided baseline blood/urine samples; 94% of men provided one or more semen samples and 98% of women provided one or more saliva samples. Women successfully used urinary fertility monitors for identifying ovulation and home pregnancy test kits. Couples can be recruited for preconception cohorts and will comply with intensive data collection across sensitive windows. However, appropriately sized sampling frameworks are critical, given the small percentage of couples contacted found eligible and reportedly planning pregnancy at any point in time.