This study examined the association between maternal serum vitamin B12 levels during early pregnancy and offspring autism spectrum disorders (ASD) and subtypes. Based on a Finnish national birth cohort, case offspring (n = 1558) born in 1987–2007 and diagnosed with ASD by 2015 were matched with one control on date of birth, sex and place of birth. Maternal vitamin B12 levels were measured during first and early second trimesters of pregnancy. High maternal vitamin B12 levels (≥81th percentile) was associated with increased risk for offspring childhood autism, adjusted odds ratio, 1.59, 95% confidence interval 1.06–2.41 (p = 0.026). No significant associations were observed between maternal vitamin B12 levels and offspring Asperger’s or pervasive developmental disorder/NOS.

Purpose: Epithelial ovarian cancer (EOC) is a lethal malignancy. CA125, the “best” available marker for detecting EOC, has insufficient sensitivity and specificity for earlier-stage disease and is not a meaningful screening tool, motivating the search for further biomarkers. Cancer biomarker discovery is enhanced by “omics” technologies. Discovery studies for EOC biomarkers should be conducted in pre-diagnosis blood samples from prospective cohorts to maximize likelihood of identifying markers that can detect disease before usual diagnosis and in earlier disease stage, while reducing methodologic biases. Experimental Design: Individual cohorts with pre-diagnosis blood samples have insufficient sample size for such studies. thus, we established “PREDICT” (“Prospective Early Detection Consortium for Ovarian Cancer")—a collaboration of nine prospective studies—to assemble a sufficient number of EOC cases with blood samples collected ≤18 months before diagnosis plus controls. The 457 cases and 1,687 controls have circulating CA125 measured using a clinical assay. Results: The discrimination capacity for single CA125 measurements in samples collected <6 months prior to diagnosis was high (area under the curve (AUC), PREDICT overall=0.92; range across cohorts of non-pregnant individuals=0.89–0.98), and declined with extended time between blood collection and diagnosis. Between-cohort variability in CA125 levels and predictive performance was observed. Conclusions: Ongoing investigations in PREDICT are evaluating the early detection potential of tumor-associated autoantibodies and microRNAs, using CA125 as a benchmark. PREDICT is a well-characterized resource for identifying and validating detection markers for EOC that may then be used in multi-modal screening, as a complement to CA125 and combined with imaging.

Human papillomavirus (HPV) vaccination may eventually eradicate oncogenic vaccine-targeted HPVs but only with a strategy that also protects unvaccinated individuals. We compared the impact of gender-neutral and girls-only vaccination strategies on the indirect and direct protection of unvaccinated and vaccinated young women against HPV16/18 infection using HPV16/18 seropositivity and PCR positivity 3–7 years post vaccination as the outcome measure. A total of 33 Finnish communities were randomized to one of three vaccination strategies: bivalent gender-neutral HPV vaccination (Arm A), girls-only HPV vaccination (Arm B), or control hepatitis B vaccination (Arm C). All individuals born between 1992 and 1995 and residing in these communities (n = 80,272) were invited to participate. Overall, 11,662 males and 20,513 females consented, corresponding to vaccination coverages of 25% and 45%, respectively, in 2007–2009. Between 2010 and 2014, 11,396 cervical samples were collected from 18-year-old participants and subjected to high-throughput PCR-based HPV genotyping. In addition, serum samples were obtained from 8022 unvaccinated women under 23 years of age residing in Arm A (n = 2657), Arm B (n = 2691), or Arm C (n = 2674) communities during the pre-vaccination (2005–2010) and post-vaccination (2011–2016) periods. To assess indirect vaccine effects using PCR and serological outcomes in unvaccinated women, we compared reductions in HPV16/18 prevalence from baseline within the gender-neutral and girls-only vaccination arms, using the control arm as a reference. A significant decrease in seroprevalence between the pre- and post-vaccination periods was detected in the gender-neutral communities for both HPV16 (seroprevalence ratio = 0.64) and HPV18 (0.72), whereas no comparable reductions were observed in the girls-only or control communities. In contrast, a significant reduction in HPV18 PCR-based prevalence from baseline to the post-vaccination period was observed in both the gender-neutral (0.32) and girls-only (0.61) communities. However, after accounting for ratios of seroprevalence rations for secular trends, the corresponding decrease in HPV18 seroprevalence was no longer statistically significant. Vaccine efficacy (VE) in Arm A or Arm B versus Arm C of vaccinated women measured the direct protection of vaccinated women by vaccination strategy. HPV16/18 VEs varied between 89% and 96% with some indication of herd effect against HPV18. Robust effectiveness of vaccination against PCR-confirmed cervical HPV16/18 infections, along with rapid indirect protection against HPV16/18 and HPV18 infections, was evident even with vaccination reaching only 25% and 45% coverage. Our results suggest that vaccine efficacy and herd effect induced by gender-neutral 2vHPV vaccination sets the stage for comprehensive HPV eradication, including the unvaccinated in the vaccinated communities.

Purpose:Epithelial ovarian cancer (EOC) is a lethal malignancy. Cancer antigen 125 (CA125), the “best” available marker for detecting EOC, has insufficient sensitivity and specificity for earlier-stage disease and is not a meaningful screening tool, motivating the search for further biomarkers. Cancer biomarker discovery is enhanced by “omics” technologies. Discovery studies for EOC biomarkers should be conducted in prediagnosis blood samples from prospective cohorts to maximize the likelihood of identifying markers that can detect disease before usual diagnosis and in earlier disease stage while reducing methodologic biases.Experimental Design:Individual cohorts with prediagnosis blood samples have insufficient sample size for such studies. Thus, we established “Prospective Early Detection Consortium for Ovarian Cancer” (“PREDICT”)—a collaboration of nine prospective studies—to assemble a sufficient number of EOC cases with blood samples collected ≤18 months before diagnosis plus controls. The 457 cases and 1,687 controls have circulating CA125 measured using a clinical assay.Results:The discrimination capacity for single CA125 measurements in samples collected <6 months prior to diagnosis was high (AUC; PREDICT overall = 0.92; range across cohorts of nonpregnant individuals = 0.89–0.98) and declined with extended time between blood collection and diagnosis. Between-cohort variability in CA125 levels and predictive performance was observed.Conclusions:Ongoing investigations in PREDICT are evaluating the early detection potential of tumor-associated autoantibodies and miRNAs using CA125 as a benchmark. PREDICT is a well-characterized resource for identifying and validating detection markers for EOC that may then be used in multimodal screening as a complement to CA125 and combined with imaging.

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