Infertility treatment and autism risk using the Modified Checklist for Autism in Toddlers (M-CHAT).

STUDY QUESTION: Are toddlers conceived by fertility treatment at higher risk of failing a screening tool for autism spectrum disorders (ASD) than toddlers not conceived by treatment? SUMMARY ANSWER: Compared with children not conceived by infertility treatment, children conceived by any infertility treatment, ovulation induction with or without intrauterine insemination (OI/IUI), or assisted reproductive technologies (ART) appeared to have had higher odds of failing an ASD screening; however, results were inconclusive and need replication. WHAT IS KNOWN ALREADY: Although most of the studies which have examined risk of ASD after ART show no association, the results are mixed. Thus, further studies are needed to clarify this association. STUDY DESIGN SIZE, DURATION: The Upstate KIDS Study is a population-based, prospective cohort study of children born in New York State between 2008 and 2010. Children were screened for ASD using the Modified Checklist for Autism in Toddlers (M-CHAT) at ages 18 and 24 months. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: The New York State live-birth registry was used to identify newborns conceived with and without fertility treatment with a 1:3 ratio, frequency matched on region of birth. At 18 and 24 months, 3183 and 3063 mothers, respectively, completed the M-CHAT questionnaire. The current analysis included 2586 singletons and 1296 twins with M-CHAT information at 18 and/or 24 months. Multivariable logistic regression with generalized estimating equations (GEE) was used to estimate odds ratios (aOR) and 95% confidence intervals (CI) after adjustment for covariates such as maternal age, education and plurality. MAIN RESULTS AND THE ROLE OF CHANCE: We found that 200 (5.2%) and 115 (3.0%) children failed the M-CHAT at 18 and 24 months, respectively. The associations between use of infertility treatment and failing the M-CHAT at 18 and/or 24 months were positive but inconclusive as they failed to exclude no association (18 months aOR 1.71, 95% CI: 0.81-3.61; 24 months aOR 1.78, 95% CI: 0.66-4.81; and both 18 and 24 months aOR 1.53, 95% CI: 0.78-2.99). The relationships between OI/IUI and ART with M-CHAT failure at 18 and/or 24 months were similar to those of using any fertility treatment. In vitro fertilization with intracytoplasmic sperm injection was not consistently positively or inversely associated with M-CHAT failure at each time point (18 months aOR 1.20, 95% CI: 0.51-2.83; 24 months aOR 0.93, 95% CI: 0.37-2.31; and both 18 and 24 months aOR 1.09, 95% CI: 0.50-2.60). LIMITATIONS REASONS FOR CAUTION: The M-CHAT is a screening tool used for ASD risk assessment, and therefore, M-CHAT failure does not indicate ASD diagnosis. In addition, we did not have power to detect associations of small magnitude. Finally, non-response to follow-up may bias the results. WIDER IMPLICATIONS OF THE FINDINGS: Despite lack of precision, the positive associations between ART and M-CHAT failure suggest that larger population-based studies with longer follow-up are needed. STUDY FUNDING/COMPETING INTEREST(S): Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; contracts HHSN275201200005C, HHSN267200700019C). The sponsor played no role in the study design, data collection, data analysis or interpretation, writing of the manuscript or decision to submit the article for publication. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Infertility treatment and children's longitudinal growth between birth and 3 years of age.

STUDY QUESTION: Does early childhood growth from birth through to 3 years of age differ by mode of conception? SUMMARY ANSWER: Findings suggest early childhood growth was comparable for children irrespective of infertility treatment, but twins conceived with ovulation induction with or without intrauterine insemination (OI/IUI) were slightly smaller than twins conceived without treatment. WHAT IS KNOWN ALREADY: Although studies have found that babies conceived with infertility treatment are born lighter and earlier than infants conceived without treatment, little research especially for non-assisted reproductive technology (ART) treatments has focused on their continued growth during early childhood. STUDY DESIGN, SIZE, DURATION: Upstate KIDS recruited infants born (2008-2010) to resident upstate New York mothers. Infants were sampled based on birth certificate indication of infertility treatment; specifically, for every singleton conceived by infertility treatment, three singletons without infertility treatment were recruited and matched on region of birth. All multiple births irrespective of treatment were also recruited. Children were prospectively followed, returning questionnaires every 4-6 months until 3 years of age. In total, 3905 singletons, 1129 sets of multiples (96% of whom were twins) enrolled into the study. Analyses included 3440 (88%) singletons (969 conceived with treatment; specifically, 433 with ART and 535 with OI/IUI) and 991 (88%) sets of multiples (439 conceived with treatment; specifically 233 with ART and 206 with OI/IUI) with growth data available. PARTICIPANTS/MATERIALS, SETTING, METHODS: Mothers reported infertility treatment use at baseline and children's height and weight from pediatric visits. Self-reported use of ART was previously verified by linkage with the US Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database. Mixed linear models with cubic splines accounting for age and age-gender interactions were used to estimate mean differences in growth from birth to 3 years by infertility treatment status and adjusting for maternal age, race, education, private insurance, smoking status during pregnancy, maternal pre-pregnancy and paternal body mass indices (BMI). MAIN RESULTS AND THE ROLE OF CHANCE: Compared with singletons conceived without treatment (n = 2471), singletons conceived by infertility treatment (433 by assisted reproductive technologies (ART), 535 by OI/IUI and 1 unknown specific type) did not differ in growth. Compared with twins not conceived with treatment (n = 1076), twins conceived with OI/IUI (n = 368) weighed slightly less over follow-up (122 g). They were also proportionally smaller for their length (-0.17 weight-for-length z-score units). No differences in mean size over the 3 years were observed for twins conceived by ART, though some evidence of rapid weight gain from birth to 4 months (adjusted OR 1.08; 95% CI: 1.00-1.16) suggestive of catch up growth was observed. LIMITATIONS, REASONS FOR CAUTION: Participants from upstate New York may not be representative of US infants. Although accounted for in statistical analysis, attrition during follow-up may have limited power to detect small differences. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first to prospectively track the growth of children conceived with and without infertility treatment in the USA, including a substantial number of twins. Our findings are similar to what was previously observed in the ART literature outside of the states. STUDY FUNDING/COMPETING INTERESTS: Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; contracts #HHSN275201200005C, #HHSN267200700019C). Authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

The effects of interferon-beta on interleukin-10 in multiple sclerosis patients.

The incidence of the neuropathological lesions and the severity of the clinical symptoms in multiple sclerosis (MS) are correlated with the amount of the transferred autoreactive T cells. The balance between the T helper 1 (Th1) and T helper 2 (Th2) cytokine phenotypes may affect the activity of the disease in MS patients. Interleukin-10 (IL-10) is a cytokine secreted by Th2 cells. Thus, it has been thought that inducing IL-10 may have therapeutic effects in the treatment of MS patients. In this study, in order determine whether different types of prophylaxis change the secretion of IL-10, we measured the levels of IL-10 in relapsing-remitting type multiple sclerosis (RRMS) patients receiving interferon-beta 1b (IFN-beta 1b) or azathioprine (AZA). Our study consisted of RRMS patients (n=45) and healthy subjects (n=15) as control group. Patients were categorized into three groups as those receiving either IFN-beta 1b or AZA and those not receiving prophylaxis. Each group was compared with the control group. Serum IL-10 levels were determined using ELISA method. IL-10 levels of those receiving IFN-beta 1b were found to be significantly higher than that of other groups. These results support that the ability of inducing anti-inflammatory cytokine IL-10 plays a role in the clinical advantage of IFN-beta 1b in MS treatment.

Synthesis and antimicrobial activity of some new 2-phenyl-N-substituted carboxamido-1H-benzimidazole derivatives.

Some 1H-benzimidazole-carboxamide derivatives were prepared and their antimicrobial activities against Staphyloccus aureus, Escherichia coli and Candida albicans evaluated. Compounds 18, 22, and 25 exhibited the best activity against Candida albicans.

Synthesis and antimicrobial activities of 5-fluoro-1,2,6-trisubstituted benzimidazole carboxamide and acetamide derivatives.

Some 5-fluoro-6-substitute-1 H-benzimidazole-2-carbamates (12a-e), 5-fluoro-6-substituted 1H-benzimidazole-2-acetate (13a-e) and 2-acetamide (14a-f) derivatives, 2-acetamido-5-fluoro-6-(morpholin-4-yl)-1-propyl-1H-benzimidazole (15), and 1-cyclopropyl-2-ethyl-5-fluoro-6-(4-methylpiperazin-1-yl)- 1H-benzimidazole (16) were synthesized, and their antimicrobial and antifungal activities evaluated. Compound 12c exhibited the best activity against Candida albicans.

Synthesis and antimicrobial activity of some new piperidinyl benzimidazoles.

A series of 2-(4-methylpiperidin-1-yl)-1,5(6)-disubstituted-1H-benzimidazoles (1-18) were prepared through the reaction of 2-chloro (or 2-chloromethyl)-1H-benzimidazole derivatives with 4-methylpiperidine. For the preparation of the individual isomers, compounds 7, 9 and 18 were synthesized by a multistep procedure. The prepared compounds were screened for their in vitro antibacterial and antifungal activities. Compound 3 and 4 exhibited the best antifungal activity.

Synthesis of 1,2,5(6)-trisubstituted benzimidazoles and evaluation of their antimicrobial activities.

A series of 22 benzimidazoles, having several substituents on the azole and benzene nuclei, were prepared and evaluated in vitro for antimicrobial activity. At first 2-chloro or 2-chloromethyl-5(6)-substituted-1H-benzimidazoles were synthesized, which were then substituted at C-2 with several piperazine or piperidine derivatives. The antibacterial activity of these compounds against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa, and the antifungal activity against Candida albicans, Candida stellatoidea, Candida parapsilosis, and Candida pseudotropicalis were determined as the MIC values. Since compound 12 exhibits good activity, in order to clarify the effect of substituents at C-1 on the activity, benzimidazole derivatives having ethyl, allyl, benzyl, and p-fluorobenzyl substituents at C-1 were prepared, and slightly increased activity was seen.