Differences in pre-pregnancy diet quality by occupation among employed women

Objective: Maternal risk factors for pregnancy outcomes are known to vary by employment status. We evaluated whether pre-pregnancy diet quality varies by occupation in a population-based sample.Design: We analysed interview data from 7341 mothers in a national case-control study of pregnancy outcomes. Self-reported job(s) held during the 3 months before pregnancy were classified using Standard Occupational Classification (SOC) codes. Usual diet in the year before conception was assessed with a semi-quantitative FFQ and evaluated using the Diet Quality Index for Pregnancy (DQI-P). Using logistic regression, we calculated adjusted OR and 95 % CI to estimate associations between low diet quality (defined as the lowest quartile of DQI-P scores) and occupation types.Setting: The National Birth Defects Prevention Study: Arkansas, California, Georgia, Iowa, Massachusetts, North Carolina, New Jersey, New York, Texas, Utah.Participants: Employed mothers of infants born between 1997 and 2011.Results: No occupation was strongly associated with low diet quality. Moderate but relatively imprecise associations were observed for women employed in management (OR: 1·3; 95 % CI: 1·1, 1·7); arts, design, entertainment, sports and media (OR: 1·4; 95 % CI: 0·9, 2·1); protective service (OR 1·3; 95 % CI: 0·7, 2·5) and farming, fishing, and forestry occupations (OR: 0·5; 95 % CI: 0·2, 1·1).Conclusions: Our analyses suggest that women in certain occupations may have lower diet quality in the months before pregnancy. Further research is needed to determine whether certain occupations could benefit from interventions to improve diet quality in the workplace for women of reproductive age

Is maternal employment site a source of exposure misclassification in studies of environmental exposures and birth outcomes? A simulation-based bias analysis of haloacetic acids in tap water and hypospadias

Background: In population research, exposure to environmental contaminants is often indirectly assessed by linking residence to geocoded databases of environmental exposures. We explored the potential for misclassification of residence-based environmental exposure as a result of not accounting for the workplace environments of employed pregnant women using data from a National Birth Defects Prevention Study (NBDPS) analysis of drinking water haloacetic acids and hypospadias. Methods: The original analysis used NBDPS data from women with haloacetic acid exposure information in eight states who delivered an infant with second- or third-degree hypospadias (cases) or a male infant without a birth defect (controls) between 2000 and 2005. In this bias analysis, we used a uniform distribution to randomly select 11%-14% of employed women that were assumed to change municipal water systems between home and work and imputed new contaminant exposures for tap water beverages consumed at work among the selected women using resampled values from the control population. Multivariable logistic regression was used to estimate the association between hypospadias and haloacetic acid ingestion with the same covariates and exposure cut-points as the original study. We repeated this process across 10,000 iterations and then completed a sensitivity analysis of an additional 10,000 iterations where we expanded the uniform distribution (i.e., 0%, 28%). Results: In both simulations, the average results of the 10,000 iterations were nearly identical to those of the initial study. Conclusions: Our results suggest that household estimates may be sufficient proxies for worksite exposures to haloacetic acids in tap water

Maternal exposure to disinfection by-products and risk of hypospadias in the national birth defects prevention study (2000–2005)

The purpose of this study was to estimate the association between 2nd and 3rd degree hypospadias and maternal exposure to disinfection by-products (DBPs) using data from a large case-control study in the United States. Concentration estimates for total trihalomethanes (TTHMs), the sum of the five most prevalent haloacetic acids (HAA5), and individual species of each were integrated with data on maternal behaviors related to water use from the National Birth Defects Prevention Study (NBDPS) to create three different exposure metrics: (1) household DBP concentrations; (2) estimates of DBP ingestion; (3) predicted uptake (i.e., internal dose) of trihalomethanes (THMs) via ingestion, showering, and bathing. The distribution of DBP exposure was categorized as follows: (Q1/referent) < 50%; (Q2) ≥ 50% to < 75%; and (Q3) ≥ 75%. Logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Generally, null associations were observed with increasing TTHM or HAA5 exposure. An increased risk was observed among women with household bromodichloromethane levels in the second quantile (aOR: 1.8; 95% CI: 1.2, 2.7); however, this association did not persist after the inclusion of individual-level water-use data. Findings from the present study do not support the hypothesis that maternal DBP exposures are related to the occurrence of hypospadias

Entwicklungsstörungen des zentralen Nervensystems

Entwicklungsstörungen des Zentralnervensystems stellen mit einer Häufigkeit von 1 pro 100 Lebendgeborene die häufigsten Entwicklungsstörungen des Menschen dar und werden meist bereits im Rahmen der Feindiagnostik im Verlauf einer Schwangerschaft diagnostiziert. Sie können isoliert oder im Rahmen von Syndromen auftreten. Prä- und postnatale Mortalität und Morbidität hängen entscheidend ab von Art der Entwicklungsstörung und Beteiligung weiterer Organsysteme. Ursächlich spielen sowohl genetische Veränderungen als auch umweltbedingte Faktoren eine Rolle. Zu Letzteren zählen teratogene Substanzen, Virusinfektionen, Toxoplasmose-Infektion, Strahlenexposition, Stoffwechselkrankheiten, schwere Mangel- und Fehlernährung, Hyperthermie, Adipositas und Diabetes mellitus der Schwangeren. Die Kenntnis des zeitlichen Ablaufs der ZNS-Entwicklung ermöglicht eine zeitliche Einordnung der Entstehung unterschiedlicher Entwicklungsstörungen. Für eine ätiologische und prognostische Einordnung einer Malformation des ZNS ist neben einer detaillierten Anamnese und klinischen Untersuchung die prä- und postnatale Bildgebung entscheidend. Während pränatal die Ultraschalldiagnostik, oft ergänzt durch fetale MRT, von großer Bedeutung ist, ist postnatal die MRT die Methode der Wahl. Häufig fallen als klinische Zeichen einer Entwicklungsstörung des Gehirns eine Mikro- oder Makrozephalie auf. Für einen Teil der ZNS-Entwicklungsstörungen besteht die Möglichkeit, die zugrunde liegende genetische Ursache mittels Chromosomenanalyse, Array-CGH oder Kandidatengen-Sequenzierung anhand fetalen Gewebes, welches durch Chorionzottenbiopsie oder Amniozentese gewonnen werden kann, zu identifizieren. Postnatal kommt auch der Next-Generation-Sequenzierung in der Routinediagnostik eine zunehmend große Rolle zu

Cycling cancer persister cells arise from lineages with distinct programs

Non-genetic mechanisms have recently emerged as important drivers of cancer therapy failure1, where some cancer cells can enter a reversible drug-tolerant persister state in response to treatment2. Although most cancer persisters remain arrested in the presence of the drug, a rare subset can re-enter the cell cycle under constitutive drug treatment. Little is known about the non-genetic mechanisms that enable cancer persisters to maintain proliferative capacity in the presence of drugs. To study this rare, transiently resistant, proliferative persister population, we developed Watermelon, a high-complexity expressed barcode lentiviral library for simultaneous tracing of each cell's clonal origin and proliferative and transcriptional states. Here we show that cycling and non-cycling persisters arise from different cell lineages with distinct transcriptional and metabolic programs. Upregulation of antioxidant gene programs and a metabolic shift to fatty acid oxidation are associated with persister proliferative capacity across multiple cancer types. Impeding oxidative stress or metabolic reprogramming alters the fraction of cycling persisters. In human tumours, programs associated with cycling persisters are induced in minimal residual disease in response to multiple targeted therapies. The Watermelon system enabled the identification of rare persister lineages that are preferentially poised to proliferate under drug pressure, thus exposing new vulnerabilities that can be targeted to delay or even prevent disease recurrence

Cycling cancer persister cells arise from lineages with distinct programs

Non-genetic mechanisms have recently emerged as important drivers of cancer therapy failure1, where some cancer cells can enter a reversible drug-tolerant persister state in response to treatment2. Although most cancer persisters remain arrested in the presence of the drug, a rare subset can re-enter the cell cycle under constitutive drug treatment. Little is known about the non-genetic mechanisms that enable cancer persisters to maintain proliferative capacity in the presence of drugs. To study this rare, transiently resistant, proliferative persister population, we developed Watermelon, a high-complexity expressed barcode lentiviral library for simultaneous tracing of each cell's clonal origin and proliferative and transcriptional states. Here we show that cycling and non-cycling persisters arise from different cell lineages with distinct transcriptional and metabolic programs. Upregulation of antioxidant gene programs and a metabolic shift to fatty acid oxidation are associated with persister proliferative capacity across multiple cancer types. Impeding oxidative stress or metabolic reprogramming alters the fraction of cycling persisters. In human tumours, programs associated with cycling persisters are induced in minimal residual disease in response to multiple targeted therapies. The Watermelon system enabled the identification of rare persister lineages that are preferentially poised to proliferate under drug pressure, thus exposing new vulnerabilities that can be targeted to delay or even prevent disease recurrence