Pregnancy outcomes following maternal macrolide use: A systematic review and meta-analysis.

To determine whether gestational use of all or specific macrolides (azithromycin, clarithromycin, roxithromycin or erythromycin) lead to an increase in rates of overall major congenital malformations, organ-specific malformations, and other adverse pregnancy outcomes in infants. PubMed/MEDLINE, Cochrane Central Register of Controlled Trials and Reprotox® databases were searched. Dichotomous outcomes or calculated log odds ratios and standard errors from observational studies are combined using the random-effects method in Review Manager 5.3. No significant increased risks for major congenital malformation (OR 1.06 [95% CI 0.99, 1.13]) and congenital heart defect (OR 1.05 [95% CI 0.92, 1.19]) following all macrolides use during the first trimester were detected. Prenatal azithromycin use was associated with a significantly increased risk of major congenital malformations in the analysis of cohort studies (OR 1.21 [95% CI 1.08-1.36]). This significance was also present in the sensitivity analysis. There were no statistically significant associations between the risk of organ specific malformations and all or specific macrolide exposures except for the decreased risk in hypospadias following erythromycin use in the meta-analysis of case-control studies (OR 0.38 [95% CI 0.18, 0.81]. Also, a significant 1.5-fold increased risk for spontaneous abortion following macrolide use was detected. A slight yet significantly increased rate of major congenital malformation with azithromycin exposure during pregnancy may be associated with maternal confounders. Nevertheless, level II ultrasound can be suggested following maternal azithromycin use during the first trimester. Future studies should take into account the inclusion of a disease-matched control group and accurate classification of the malformations.

Molecular mechanisms involved in pre-eclampsia through expressional regulation of endothelin-1.

INTRODUCTION: Preeclampsia (PE) is a condition affecting 2-8% of all pregnancies and is a leading cause of perinatal morbidity and mortality. In our study; we aim to investigate the differences in endothelin-1 (ET-1) at both tissue and blood level in the placenta, umbilical cord, and maternal blood obtained from different experimental groups and the changes in the contraction response of umbilical arteries in order to explain how PE affects mother and fetus. METHODS: Umbilical cord and placenta samples were obtained from normotensive controls (n = 10) and patients with preeclampsia (n = 10), aged 20-39 years, who delivered by cesarean section at term (between 37 and 39 weeks). All samples were investigated with isolated tissue bath, histopathological, immunohistochemical and real-time PCR methods. RESULTS: ET-1 messenger RNA expression levels and immunoreactivity were found significantly higher in the PE group while microRNA-1 and microRNA-125b (miR-125b) levels were significantly decreased in placenta compared to control. miR-125b levels were found significantly higher in maternal and umbilical cord blood samples of the PE group. The enlargement in intervillous space, decrease in villous branching, increase in syncytial knots and smaller lumen areas in umblicard cord vessels were also observed. In tissue bath experiments, there were no significant differences in ET-1 responses between groups. DISCUSSION: We tried to evaluate molecular mechanisms of PE pathogenesis through expressional regulation and contraction response of ET-1. Although quite abundant work in this field has previously highlighted the importance of ET-1 system, further work is needed to determine the molecular mechanisms underlying expressional regulation of ET-1 in PE.

The role of smoking in the development and progression of structural damage in axial SpA patients: A systematic review and meta-analysis.

OBJECTIVE: The objective of this study was to determine whether smoking was associated with the cumulative radiographic spinal damage and radiographic progression in patients with ankylosing spondylitis (AS). Thus, we conducted a systematic review and meta-analysis of the available studies to date. METHODS: An electronic search was conducted from inception to June 21, 2016, in EMBASE, the MEDLINE/PubMed Cochrane Central Register of Controlled Trials databases. Cross-sectional and longitudinal cohort studies investigating the association between smoking and cumulative spinal structural damage or radiographic progression were included. The outcome of interest was the presence of syndesmophytes in cross-sectional studies and radiographic progression in longitudinal studies. The quality assessment was done using the Agency for Healthcare Research and Quality checklist. The authors of potentially relevant studies were contacted regarding the unpublished data. Data from eligible cross-sectional studies were extracted and arranged in a 2x2 table. The odds ratios (ORs) and 95% confidence intervals (CIs) for the dichotomous outcome of interest were computed. RESULTS: The combined data of eight eligible cross-sectional studies for the assessment of association between smoking and cumulative spinal structural damage suggested a significant association (OR, 2.02; 95% CI, 1.51-2.70). No significant heterogeneity was detected between studies (I2=23.0%, p=0.25). The heterogeneity of the longitudinal study data did not permit us to undertake a meta-analysis. Hence, a qualitative review was performed. CONCLUSION: The results of our meta-analysis show that smoking is associated with increased cumulative spinal structural damage in patients with AS. Therefore, rheumatologists should encourage patients with AS to quit smoking.

Use of ondansetron during pregnancy and the risk of major congenital malformations: A systematic review and meta-analysis.

AIMS: To investigate whether ondansetron use during pregnancy is associated with increased rates of major or subgroups of malformations. METHODS: PubMed/MEDLINE, Cochrane and Reprotox® databases were searched. Observational studies comprising an exposed and control group (healthy and/or disease-matched) were included. RESULTS: No significant increased risk for major malformations, heart defects, orofacial clefts, genitourinary malformations or hypospadias were identified in our primary analysis. A significant heterogeneity existed for isolated cleft palate. Elevated point estimates and altered statistical significances were present for some of the outcomes among secondary analyses. CONCLUSIONS: Ondansetron use during pregnancy was not associated with a significant increase in rate of major or selected subgroups of malformations in our primary analysis. However, results of the secondary analyses warrant the need for continued surveillance. These results may be reassuring for pregnant women in whom ondansetron use is clinically indicated since the absolute risks of possible concerns appear to be low.

Pregnancy outcomes following quinolone and fluoroquinolone exposure during pregnancy: A systematic review and meta-analysis.

OBJECTIVE: To investigate whether maternal exposure to quinolones, fluoroquinolones and specifically ciprofloxacin is associated with major malformations and other adverse pregnancy outcomes. METHODS: MEDLINE/PubMed, Embase and Reprotox® databases were searched. Observational studies with an exposed and control group were included. RESULTS: Analysis of 8 cohort and 2 case-control studies showed no significant increases in rates of major malformations for quinolone (OR, 1.04; 95% CI 0.89-1.21), fluoroquinolone (RR, 0.89; 95% CI 0.70-1.14) and ciprofloxacin exposure (RR, 0.72; 95% CI 0.43-1.19). For fluoroquinolones, live birth rate was significantly decreased (RD, -0.04; 95% CI -0.08 to -0.01) whereas elective termination rate (RD, 0.04; 95% CI 0.02-0.05) was significantly increased. CONCLUSIONS: Quinolone, fluoroquinolone and ciprofloxacin exposure were not associated with a significant increase in major malformations and adverse pregnancy outcomes, other than significantly decreased live birth rate and increased elective termination rate which may be the indicators of misperceived teratogenic risk.

Pregnancy outcomes after maternal use of thiocolchicoside: A case series.

OBJECTIVE: The 2014 report by European Medicines Agency (EMA) restricted the use of thiocolchicoside for all reproductive-age women. In this study, we aim to expand the systematically-collected human data and discuss it within the frame provided by this report. METHODS: We identified and evaluated the outcomes of 48 prospectively recorded pregnancies referred to Terafar (Teratology Information Service, Izmir, Turkey). RESULTS: Of 42 pregnancies with first-trimester exposure and known outcomes, 31 resulted in live births, four in miscarriage and seven ended with elective terminations. There were 26 normal outcomes, two major and three minor congenital malformations among the live births. CONCLUSIONS: Despite a number of limitations, our results and previous case series collectively strengthen the view that thiocolchicoside is unlikely to be a major teratogen. EMA's 2014 report should be revised to reflect this finding, while current restrictions on use should continue until more detailed safety information is available.

Maternal SSRI discontinuation, use, psychiatric disorder and the risk of autism in children: a meta-analysis of cohort studies.

We undertook an exclusive meta-analysis of cohort studies investigating the possible link between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and autism spectrum disorders (ASD) in children to further investigate our previous suggestion of confounding by indication. The point estimates regarding the following cohorts were extracted and pooled: (1) pregnant women who discontinued SSRI until 3 months before pregnancy; (2) pregnant women who were exposed to SSRI during pregnancy; and (3) pregnant women with maternal psychiatric disorder but no exposure to SSRI during pregnancy. Although the pooled point estimate of the first cohort showed a trend for increase, it did not reach significance. The pooled point estimates of the latter cohorts showed a significant association with ASD which strengthens our previous suggestion of confounding by indication. Future studies should be adequately designed to differentiate whether the previously suggested association is a result of maternal psychiatric disorder or SSRI exposure or both.

Prenatal selective serotonin reuptake inhibitor use and the risk of autism spectrum disorder in children: A systematic review and meta-analysis.

OBJECTIVE: To determine whether an up-to-date systematic review and meta-analysis of observational studies would support the previously suggested associations regarding prenatal selective serotonin reuptake inhibitor (SSRI) use and the risk for autism spectrum disorders (ASD) in children. METHODS: PubMed/MEDLINE, Cochrane Central Register of Controlled Trials and Reprotox databases were searched; observational studies with an exposed and unexposed group were included. RESULTS: The meta-analysis of case-control studies demonstrated a significantly increased risk of ASD in the children whose mothers were prenatally exposed to SSRIs during different exposure time windows (except third trimester). The qualitative review of the cohort studies suggested inconsistent findings. CONCLUSIONS: The significant association between preconception-only SSRI exposure and ASD in the children and negative/inconsistent findings among cohort studies weaken the significant associations detected in this meta-analysis. We suggest that confounding by indication still cannot be ruled out regarding prenatal SSRI exposure and ASD in children.