Examining the relationship between autism spectrum disorder and neural tube defects.

Folate and vitamin B12 deficiencies have been strongly associated with neural tube defects, preliminary research suggests folate and B12 deficiency may also be associated with autism spectrum disorder (ASD). We examined the association between neural tube defects and ASD as a further avenue to examine the hypothesis that ASD is related to maternal folate and B12 deficiency during pregnancy. A retrospective case-control study was performed using the Military Health System Data Repository. Cases and matched controls were followed from birth until at least 6 months after their first autism diagnosis. International Classification of Diseases, 9th Revision, codes were used to identify neural tube defects in the health records. A total of 8760 cases between the ages of 2 and 18 years were identified. The prevalence of any neural tube defect was 0.11% in children without ASD and 0.64% in children with ASD. Children with autism were over 6 times as likely to have a neural tube defect. The increased odds of neural tube defect in children diagnosed with ASD, found through our methodology, supports prior studies. Although additional studies are needed to elucidate the relationship between ASD and maternal folate and vitamin B12 deficiency during pregnancy this study supports their use during pregnancy.

Cell-Free DNA to Detect Heart Allograft Acute Rejection.

BACKGROUND: After heart transplantation, endomyocardial biopsy (EMBx) is used to monitor for acute rejection (AR). Unfortunately, EMBx is invasive, and its conventional histological interpretation has limitations. This is a validation study to assess the performance of a sensitive blood biomarker-percent donor-derived cell-free DNA (%ddcfDNA)-for detection of AR in cardiac transplant recipients. METHODS: This multicenter, prospective cohort study recruited heart transplant subjects and collected plasma samples contemporaneously with EMBx for %ddcfDNA measurement by shotgun sequencing. Histopathology data were collected to define AR, its 2 phenotypes (acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), and controls without rejection. The primary analysis was to compare %ddcfDNA levels (median and interquartile range [IQR]) for AR, AMR, and ACR with controls and to determine %ddcfDNA test characteristics using receiver-operator characteristics analysis. RESULTS: The study included 171 subjects with median posttransplant follow-up of 17.7 months (IQR, 12.1-23.6), with 1392 EMBx, and 1834 %ddcfDNA measures available for analysis. Median %ddcfDNA levels decayed after surgery to 0.13% (IQR, 0.03%-0.21%) by 28 days. Also, %ddcfDNA increased again with AR compared with control values (0.38% [IQR, 0.31-0.83%], versus 0.03% [IQR, 0.01-0.14%]; P<0.001). The rise was detected 0.5 and 3.2 months before histopathologic diagnosis of ACR and AMR. The area under the receiver operator characteristic curve for AR was 0.92. A 0.25%ddcfDNA threshold had a negative predictive value for AR of 99% and would have safely eliminated 81% of EMBx. In addition, %ddcfDNA showed distinctive characteristics comparing AMR with ACR, including 5-fold higher levels (AMR ≥2, 1.68% [IQR, 0.49-2.79%] versus ACR grade ≥2R, 0.34% [IQR, 0.28-0.72%]), higher area under the receiver operator characteristic curve (0.95 versus 0.85), higher guanosine-cytosine content, and higher percentage of short ddcfDNA fragments. CONCLUSIONS: We found that %ddcfDNA detected AR with a high area under the receiver operator characteristic curve and negative predictive value. Monitoring with ddcfDNA demonstrated excellent performance characteristics for both ACR and AMR and led to earlier detection than the EMBx-based monitoring. This study supports the use of %ddcfDNA to monitor for AR in patients with heart transplant and paves the way for a clinical utility study. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070.

Prevalence of seroconversion symptoms and relationship to set-point viral load: findings from a subtype C epidemic, 1995-2009.

OBJECTIVE: To describe symptoms, physical examination findings, and set-point viral load associated with acute HIV seroconversion in a heterosexual cohort of HIV-discordant couples in Zambia. DESIGN: We followed HIV serodiscordant couples in Lusaka, Zambia from 1995 to 2009 with HIV testing of negative partners and symptom inventories 3 monthly, and physical examinations annually. METHODS: We compared prevalence of self-reported or treated symptoms (malaria syndrome, chronic diarrhea, asthenia, night sweats, and oral candidiasis) and annual physical examination findings (unilateral or bilateral neck, axillary, or inguinal adenopathy; and dermatosis) in seroconverting vs. HIV-negative or HIV-positive intervals, controlling for repeated observations, age, and sex. A composite score comprised of significant symptoms and physical examination findings predictive of seroconversion vs. HIV-negative intervals was constructed. We modeled the relationship between number of symptoms and physical examination findings at seroconversion and log set-point viral load using linear regression. RESULTS: Two thousand, three hundred and eighty-eight HIV-negative partners were followed for a median of 18 months; 429 seroconversions occurred. Neither symptoms nor physical examination findings were reported for most seroconverters. Seroconversion was significantly associated with malaria syndrome among nondiarrheic patients [adjusted odds ratio (aOR) = 4.0], night sweats (aOR = 1.4), and bilateral axillary (aOR = 1.6), inguinal (aOR = 2.2), and neck (aOR = 2.2) adenopathy relative to HIV-negative intervals. Median number of symptoms and findings was positively associated with set-point viral load (P < 0.001). CONCLUSION: Although most acute and early infections were asymptomatic, malaria syndrome was more common and more severe during seroconversion. When present, symptoms and physical examination findings were nonspecific and associated with higher set-point viremia.