Whole-Genome Sequencing Analysis Reveals New Susceptibility Loci and Structural Variants Associated with Progressive Supranuclear Palsy.

Background: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of aggregated tau proteins in astrocytes, neurons, and oligodendrocytes. Previous genome-wide association studies for PSP were based on genotype array, therefore, were inadequate for the analysis of rare variants as well as larger mutations, such as small insertions/deletions (indels) and structural variants (SVs). Method: In this study, we performed whole genome sequencing (WGS) and conducted association analysis for single nucleotide variants (SNVs), indels, and SVs, in a cohort of 1,718 cases and 2,944 controls of European ancestry. Of the 1,718 PSP individuals, 1,441 were autopsy-confirmed and 277 were clinically diagnosed. Results: Our analysis of common SNVs and indels confirmed known genetic loci at MAPT, MOBP, STX6, SLCO1A2, DUSP10, and SP1, and further uncovered novel signals in APOE, FCHO1/MAP1S, KIF13A, TRIM24, TNXB, and ELOVL1. Notably, in contrast to Alzheimer's disease (AD), we observed the APOE ε2 allele to be the risk allele in PSP. Analysis of rare SNVs and indels identified significant association in ZNF592 and further gene network analysis identified a module of neuronal genes dysregulated in PSP. Moreover, seven common SVs associated with PSP were observed in the H1/H2 haplotype region (17q21.31) and other loci, including IGH, PCMT1, CYP2A13, and SMCP. In the H1/H2 haplotype region, there is a burden of rare deletions and duplications (P = 6.73×10-3) in PSP. Conclusions: Through WGS, we significantly enhanced our understanding of the genetic basis of PSP, providing new targets for exploring disease mechanisms and therapeutic interventions.

Cervantes y la enfermedad de Parkinson / No disponible

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Vaginal group B streptococcus status during intrapartum antibiotic prophylaxis.

OBJECTIVE: To assess maternal group B streptococcus (GBS) colonization status and the pharmacokinetic profile of penicillin G in the umbilical cord and amniotic fluid compartment during 4 hours of intrapartum antibiotic prophylaxis (IAP). METHODS: In a prospective study at a hospital in Montevideo, Uruguay, 60 GBS carriers in active labor after a singleton pregnancy of 37 weeks or more were enrolled between April 1, 2011, and April 30, 2012. Intravenous penicillin G was administered via a standard regimen. Rectovaginal samples were obtained before IAP initiation, and 2 and 4 hours after the initial dose. Penicillin G concentrations were measured by high-performance liquid chromatography. Samples were obtained from fetal cord blood in all cases and from amniotic fluid obtained from patients who delivered by cesarean. RESULTS: Among the 60 participants, 43 (72%) had a positive rectovaginal sample before IAP initiation. Of these women, 23 (53%) had negative cultures after 2 hours; after 4 hours, only 5 (12%) remained positive for GBS. The penicillin G concentration in amniotic fluid and cord blood was above the minimum inhibitory concentration (0.12 µg/mL) in all cases. CONCLUSION: Four hours of IAP was needed to reduce the number of women with positive GBS cultures to 12%. Therefore, 4 hours of IAP might be necessary to achieve overall effectiveness from this treatment.

Lawrence D. Longo: from chronic fetal hypoxia to proteomic predictors of fetal distress syndrome - a life devoted to research and mentoring based on virtue-ethics.

The present chapter presents the experience of the author during his fellowship granted by the Fogarty Foundation of the NIH in the Division of Perinatal Biology, Loma Linda University, from 1989 to 1991. Experiments on maternal and fetal responses to long-term hypoxemia (including high-altitude) were performed successfully in pregnant sheep and their fetuses.Cardiovascular, hormonal and blood flow distribution responses were studied under a strict experimental protocol. As result of this research, four papers were accepted for publication in major scientific journals, and have served as basis for further research.Most of all, the leadership, virtue-based ethics, perseverance and continuous stimulus of Lawrence D. Longo is presented as an example to follow for future generations.

Drug-induced parkinsonism.

INTRODUCTION: Drug-induced parkinsonism (DIP) is the second most common cause of parkinsonism after idiopathic Parkinson's disease (iPD). Initially reported as a complication of antipsychotics, it was later recognized as a common complication of antidepressants, calcium channel antagonists, gastrointestinal prokinetics, antiepileptic drugs and many other compounds. Despite being a major health problem in certain populations, it seems to be frequently overlooked by the medical community. AREAS COVERED: This paper approaches the concept of DIP, reviews its epidemiology, clinical features and ancillary tests recommended for a correct diagnosis. The authors discuss the different drugs and its pathogenic mechanisms. The relevance of an early recognition and recommendations for a correct management are commented. EXPERT OPINION: Prescribers need to remain vigilant for DIP, particularly in the elderly, patients taking multiple drugs and those with genetic risk factors involved in iPD. Cessation of the causing agent is the main treatment and there is no evidence of benefit for the use of anticholinergics or levodopa. If the medication cannot be withdrawn, it should be switched to agents with a lower risk of DIP.

Nanostructured polymer and lipid carriers for sunscreen. Biological effects and skin permeation.

The interest in developing new sunscreens is increasing due to the harmful effects of UV radiation on the skin, such as erythema, accelerated skin ageing (photoageing) and the induction of skin cancer. However, many molecular sunscreens penetrate into the skin causing photoallergies, phototoxic reactions and skin irritation. Thus, the aim of this work was the preparation and characterization of polymeric and solid lipid nanoparticles to act carriers of benzophenone-3 (BZ3), aiming to improve the safety of sunscreen products by increasing the sun protection factor (SPF), decreasing BZ3 skin penetration and decreasing BZ3 concentration in sunscreen formulation. BZ3 was encapsulated in poly(epsilon-caprolactone) (PCL) nanoparticles by the nanoprecipitation method and in solid lipid nanoparticles (SLN) by the hot high pressure homogenization method. The particles were stable for 40 days. The BZ3 encapsulated in PCL nanoparticles was released faster than BZ3 encapsulated in SLN. The sun protection factor increased when BZ3 was encapsulated in both nanostructures. However, BZ3 encapsulated in PCL nanoparticles decreased its skin permeation more than SLN-BZ3. Furthermore, BZ3 encapsulated in SLN did not exhibit cytotoxic or phototoxic effects in human keratinocytes (HaCaT cells) and BABL/c 3T3 fibroblasts, whereas PCL nanoparticles with BZ3 showed phototoxic potential in HaCaT cells. Nevertheless, BZ3 free and encapsulated in PCL nanoparticles or in SLN did not show allergic reactions in mice. Our results suggest that these nanostructures are interesting carriers for sunscreen.

What is the impact of education on Huntington's disease?

Huntington's disease (HD) is a neurodegenerative disease caused by a cytosine adenosine guanine (CAG) expansion in the huntingtin gene. The length of the triplet repeat is the most important factor in determining age of onset and the severity of the disease, but substantial variability of these parameters is attributed to other factors. To investigate the relationship between the years of education and the age at onset and the severity of the phenotype in patients with HD, we applied multiple linear regression analysis to examine the impact of education on the age at onset and the severity of the clinical scores assessed by the Unified Huntington's Disease Rating Scale (UHDRS) of 891 patients with HD from the multinational observational study "Registry" conducted by the European Huntintgton's Disease Network. The model was adjusted for CAG repeat length and age at the time of assessment. Patients with lengthier education exhibited earlier estimated age at onset but less severe clinical scores (motor = -3.6, P = 0.006; cognitive = 27.0, P < 0.001; behavioral = -3.0, P < 0.001; and functional capacity = 1.1 points, P < 0.001) than those with shorter education, after controlling for age and number of CAG repeats. These differences persisted throughout all quartiles of disease severity. An earlier recognition of symptoms and manifestations among the more educated patients could explain the earlier estimated age at onset in this group. The link between better clinical UHDRS scores and higher education might reflect a beneficial effect of education or its covariates on the course of HD.

Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington's disease.

Endocannabinoids act as neuromodulatory and neuroprotective cues by engaging type 1 cannabinoid receptors. These receptors are highly abundant in the basal ganglia and play a pivotal role in the control of motor behaviour. An early downregulation of type 1 cannabinoid receptors has been documented in the basal ganglia of patients with Huntington's disease and animal models. However, the pathophysiological impact of this loss of receptors in Huntington's disease is as yet unknown. Here, we generated a double-mutant mouse model that expresses human mutant huntingtin exon 1 in a type 1 cannabinoid receptor-null background, and found that receptor deletion aggravates the symptoms, neuropathology and molecular pathology of the disease. Moreover, pharmacological administration of the cannabinoid Δ(9)-tetrahydrocannabinol to mice expressing human mutant huntingtin exon 1 exerted a therapeutic effect and ameliorated those parameters. Experiments conducted in striatal cells show that the mutant huntingtin-dependent downregulation of the receptors involves the control of the type 1 cannabinoid receptor gene promoter by repressor element 1 silencing transcription factor and sensitizes cells to excitotoxic damage. We also provide in vitro and in vivo evidence that supports type 1 cannabinoid receptor control of striatal brain-derived neurotrophic factor expression and the decrease in brain-derived neurotrophic factor levels concomitant with type 1 cannabinoid receptor loss, which may contribute significantly to striatal damage in Huntington's disease. Altogether, these results support the notion that downregulation of type 1 cannabinoid receptors is a key pathogenic event in Huntington's disease, and suggest that activation of these receptors in patients with Huntington's disease may attenuate disease progression.

Transcranial approach to pituitary adenomas invading the cavernous sinus: A modification of the classical technique to be used in a low-technology environment.

OBJECTIVE: Pituitary adenomas invading the cavernous sinus represent a therapeutic challenge. Those tumors have been traditionally treated with incomplete surgical removal, observation and/ or adjunctive medical therapy, and radiotherapy. In relatively recent years, some authors have suggested a main direct surgical approach to cavernous sinus (CS) with the aim of complete removal of the adenoma, either by a modified trans-sphenoidal route, using or not an endoscopy-assisted approach, or by a transcranial direct approach. The latter has the advantage of allowing direct exposure of the lesion with a view of the surgical field unhindered by important neurovascular structures. MATERIALS AND METHODS: We report a technical modification of the classical epidural approach for CS adenoma removal. This was used in 14 patients. Surgical technique included a fronto-orbito-zygomatic craniotomy with extradural anterior clinoidectomy, and intradural approach to the Hakuba's triangle for intracavernous dissection. The tumors were removed under direct vision. RESULTS: Total macroscopical removal was achieved in all but one case. This patient required postoperative radiation therapy as well as adjuvant dopaminergic regime for achieving control of preoperatively increased hormonal values. No other case required radiotherapy. Hormonal and/ or clinical control was also achieved in all the remaining cases. Out of the remaining 13 cases, all appeared to be tumor free at an average postoperative observation at 78 months (34 to 90 months). Significant surgical sequels were detected in only 1 case (persistent 3(rd) nerve palsy and moderate hemiparesis). CONCLUSIONS: This experience, though limited, would suggest that the transcranial limited CS exposure through the Hakuba's triangle may allow adequate removal of intracavernous pituitary adenomas with very good long-term results and acceptable complication rate.

Prevention of senescence progression in reversibly immortalized human ensheathing glia permits their survival after deimmortalization.

Reversible immortalization holds great potential for primary tissue expansion to develop cell-based therapies as well as for basic research. Human olfactory ensheathing glia (hOEG) are promising candidates for treating spinal cord injury and for studying extrinsic neuroregenerative mechanisms. We used lentivectors with Cre/loxP technology to achieve reversible gene transfer of BMI1, SV40 large T antigen (TAg), a short hairpin RNA against p53 (shp53), and the catalytic subunit of telomerase (TERT) in primary cultures of hOEG from human donor cadaver olfactory bulbs. Several combinations of these genes were able to immortalize hOEG, conserving their antigenic markers and neuroregenerative properties but only those transduced by BMI1/TERT did not accumulate karyotypic alterations or increase senescence marker levels. Strikingly, these were also the only cells which continued to proliferate after transgene removal by Cre recombinase delivery, whereas hOEG immortalized by shp53 or TAg in combination with TERT entered into growth arrest and died. These data support the idea that immortalization and halting senescent changes are separate processes; hOEG immortalized by BMI1/TERT can revert back to their former primary cell replicative state when deimmortalized, whereas those transduced by the other combinations depend on the presence of these transgenes to maintain their aberrant proliferative state.

Park2-null/tau transgenic mice reveal a functional relationship between parkin and tau.

Mutations, haplotypes, and polymorphisms of tau and Park-2 genes constitute risk factors for developing tauopathies. In order to analyze the possible relationship between parkin and tau we generated a double-mutant mouse deficient for Park-2 expression and overexpressing a mutant tau protein (hTauVLW). Mice develop normally, although the median survival rate is considerably reduced with respect to wild type (45%). Aggregates of phosphorylated tau in neurons and reactive gliosis are quite abundant in cortex and hippocampus of these mice. Moreover, while in young transgenic mice the hTauVLW immunostained transgene product is observed in both cell bodies and dendrites, the hTauVLW mutant protein is only detected in the neuronal cell bodies when Park-2 gene is additionally deleted. Moreover, DNA fragmentation was detected by the TUNEL method, and cerebral atrophy is also present in these regions. The levels of phosphorylated tau and Hsp70 are increased in the double-mutant mice, while CHIP expression in hippocampus is lower when the Park-2 gene is deleted. Thus, the combination of Park-2 gene deletion with hTauVLW transgene overexpression in mice produces serious neuropathological effects, which reflect the existence of some relationship between both proteins.

Megalin mediates the transport of leptin across the blood-CSF barrier.

Leptin, a peptide hormone secreted by adipose tissue, exhibits a large range of central and peripheral actions. It has been proposed that the participation of leptin in diseases such as obesity is due to, at least in part, its impaired transport across the blood-brain barrier (BBB). Since, the mechanisms by which brain takes up leptin remain unclear, we set out to study how leptin may cross the BBB. We have used different immunoassays and lentiviral vectors to analyze the role of megalin in the transport of leptin in rodents and humans. We demonstrate that circulating leptin is transported into the brain by binding to megalin at the choroid plexus epithelium. Indeed, the downregulation of megalin expression in physiological and pathological situations such as aging and Alzheimer's disease was correlated with poor entry of leptin into the brain. Moreover, amyloid beta (Abeta) deposits of choroid plexus could be disturbing megalin function. The present data indicate that leptin represents a novel megalin ligand of importance in the levels and therapeutic actions of leptin into the brain.

Drug-induced parkinsonism.

Drug-induced parkinsonism (DIP) is the second cause of akinetic rigid syndrome in the Western world and its prevalence is increasing and approaching that of idiopathic Parkinson's disease due to the ageing of the population and to the rising of polypharmacotherapy. DIP was initially reported as a complication of neuroleptics in psychiatric patients, but it has also been described with a great diversity of compounds such as antiemetics, drugs used for the treatment of vertigo, antidepressants, calcium channel antagonists, antiarrythmics, antiepileptics, cholinomimetics and other drugs. Although traditionally considered reversible, DIP may persist after drug withdrawal. At least 10% of patients with DIP develop persistent and progressive parkinsonism in spite of the discontinuation of the causative drug. Irreversible or progressive DIP has been considered as an indication of presymptomatic parkinsonian deficit, unmasked but not caused by the offending drug, but it could be explained by persistent toxicity of the responsible pharmacological agents on the nigrostriatal dopamine pathway. The best treatment of DIP is prevention, including the avoidance of prescription of causative drugs whenever it is not strictly necessary. In patients who require potentially risky medication, it is necessary to perform adequate monitoring for early parkinsonian deficits and early discontinuation if these deficits appear. Atypical neuroleptics are associated with lower risk than first generation antipsychotic drugs. Special precautions are needed in elderly subjects, in patients treated with multiple drugs for prolonged periods of time and in those with familial risk factors including familial parkinsonism or tremor, or in those with genetic variants of genes involved in idiopathic Parkinson's disease.

Cytotoxicity of materials used in perforation repair tested using the V79 fibroblast cell line and the granulocyte-macrophage progenitor cells.

AIM: To compare the cytotoxicity of materials used to repair perforations using permanent V79 fibroblasts and murine granulocyte-macrophage progenitor cells (CFU-GM). METHODOLOGY: Set specimens from amalgam, glass-ionomer, SuperEBA, N-Rickert, MTA and gutta-percha were eluted with culture medium for 72 h and their cytotoxicities were assessed by incubating the extracts with V79 and bone marrow-derived progenitors for 24 h and 7 days, respectively. Cytotoxicity on V79 cells was judged using the total nucleic acid content (NAC), neutral red uptake (NRU) and reduction of the tetrazolium salt (MTT). The number of bone marrow CFU-GM colonies determined in clonal cultures stimulated with recombinant murine granulocyte-macrophage colony-stimulating factor was used to assess cytotoxicity to progenitor cells. Statistical analyses were conducted using the one-way analysis of variance and Tukey's test where appropriate. RESULTS: All materials were cytotoxic in both cell systems; however, CFU-GM was more sensitive to the extracts than V79 cells. A similar rank order of toxicity was observed in V79 cells using the NAC and the MTT assays: glass-ionomer > N-Rickert congruent with SuperEBA > gutta-percha > amalgam congruent with MTA (P < 0.05). In contrast, the NRU test exhibited a lower sensitivity to MTA, gutta-percha and amalgam extracts. In the clonal culture assay, the toxicity was less pronounced in the presence of gutta-percha, SuperEBA and MTA. Similar cellular responses were found by placing the set specimens directly in the clonal culture dishes. CONCLUSIONS: The sensitivity of toxicity depended on the choice of the endpoint and the cell-culture system. Nevertheless, MTA was ranked as the least cytotoxic cement in both cell systems.

Effect of pethidine administered during the first stage of labor on the acid-base status at birth.

OBJECTIVE: To evaluate the association between the use of pethidine during the first stage of labor and the presence, type and timing of acidosis in the newborn at birth. STUDY DESIGN: Secondary data analysis of a randomized controlled trial, which included term singleton pregnancies diagnosed with dystocia and requiring active management of labor. Women were randomized to receive either 100 mg of pethidine or placebo. Statistical analyses were performed using chi(2) or Fisher's exact tests for proportions and multiple linear regression for continuous outcomes. RESULTS: Three hundred and eighty-three pregnant women with a valid arterial blood cord sample were included in the final analysis. Lower pH and bicarbonate levels, as well as higher pCO(2) levels were found in the pethidide group. A higher incidence of acidosis was found in the pethidine group (pH<7.12 OR: 8.59 95% C.I. 3.29, 22.46). The highest frequency of acidosis was encountered when pethidine-delivery interval was 5 h. CONCLUSION: Pethidine use during the first stage of labor was associated with an increased risk of acidosis at birth.

Violacein cytotoxicity on human blood lymphocytes and effect on phosphatases.

Given the importance of protein phosphorylation in the context of cellular functions, abnormal protein phosphatase activity has been implicated in several diseases, including cancer. These critical roles of protein phosphatases qualify them as potential targets for the development of medicinal compounds that possess distinct modes of action such as violacein. In this work, studies with this natural indolic pigment at a concentration of 10.0 micromol L(-1) demonstrated a 20% activation of total protein phosphatase extracted from human lymphocytes. Although no alteration was observed on protein tyrosine phosphatase (CD45), 30% of inhibition was achieved in cytoplasmatic protein phosphatase activity after incubation with 10.0 micromol L(-1) violacein. Additionally, 5.0 micromol L(-1) of violacein inhibited by 50% the serum tartrate-resistant acid phosphatase activity. Violacein presented toxic effect on lymphocytes with IC50 values of 3 and 10 micromol L(-1) for protein content and protein phosphatase activity, respectively. These findings suggest an important role for protein phosphatases in the mechanisms controlling proliferation and cell death.

A new mutation of the tau gene, G303V, in early-onset familial progressive supranuclear palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is a clinicopathological syndrome related to tau deposits and in linkage disequilibrium with tau polymorphisms. Some rare familial PSP cases have been related to tau gene mutations. OBJECTIVE: To present the clinical, pathological, and molecular data of one family with early-onset autosomal dominant PSP. DESIGN: We performed clinical examinations, quantitative neurological tests, positron emission tomographic scans with fluorodopa F 18 and raclopride C 11, analysis of tau mutations, neuropathological examinations, and protein analyses on brain specimens. RESULTS: Three family members had PSP confirmed by pathological features in the proband. A novel mutation of tau, G303V, was found in the proband and other family members. tau Isoforms with 4 microtubule-binding repeats were overexpressed in the proband brain. CONCLUSIONS: The G303V mutation of tau is associated with autosomal dominant PSP. Expression of 4 microtubule-binding repeat tau isoforms is increased in the proband.

Cannabinoid CB(1) receptors in the basal ganglia and motor response to activation or blockade of these receptors in parkin-null mice.

The endocannabinoid transmission becomes overactive in the basal ganglia in Parkinson's disease (PD), as reported in patients and animal models of this disease. In the present study, we examined the status of cannabinoid CB(1) receptors in the basal ganglia of female and male Park-2 knockout mice, a genetic model of PD that progresses with no neuronal death and that may be considered representative of early and presymptomatic parkinsonian deficits. We found an increase in the density of CB(1) receptors in the substantia nigra compared to wild-type animals with no changes in other basal ganglia, although this occurred only in females. Despite this increase, the motor inhibition caused by the acute administration of the cannabinoid agonist Delta(9)-tetrahydrocannabinol to Park-2 knockout female mice was markedly of lesser magnitude compared with the response found in wild-type animals. By contrast, the administration of the CB(1) receptor antagonist SR141716 resulted in a hyperkinetic response in parkin-null mice, response that was almost absent in wild-type animals and that was accompanied by a decrease in tyrosine hydroxylase activity in the caudate-putamen. However, parkin-null male mice exhibited normal levels of CB(1) receptors in the substantia nigra and the remaining basal ganglia, with the only exception of a small decrease in the lateral part of the caudate-putamen. This was associated with an increase in mRNA levels for superoxide dismutase in this structure. In addition, the administration of Delta(9)-tetrahydrocannabinol to parkin-null male mice caused a motor inhibition that was significantly greater than in the case of their wild-type counterparts, and that was accompanied by an increase in tyrosine hydroxylase activity in the caudate-putamen. In summary, extending the data obtained in humans and animal models of basal ganglia neurodegeneration, changes in CB(1) receptors were also observed in parkin-null mice, a model of PD that may be considered representative of early stages of this disease. These changes are associated with differences in behavioral responses to cannabinoid agonists or antagonists between Park-2 knockout and wild-type mice, although parkin-null mice exhibited evident gender-dependent differences for both levels of CB(1) receptors and motor responses to agonists or antagonists.

Genetic linkage of autosomal dominant progressive supranuclear palsy to 1q31.1.

Progressive supranuclear palsy (PSP) is a disorder of unknown pathogenesis. Familial clusters of PSP have been reported related to mutations of protein tau. We report the linkage of a large Spanish family with typical autosomal dominant PSP to a new locus in chromosome 1. Four members of this family had typical PSP, confirmed by neuropathology in one case. At least five ancestors had similar disease. Other members of the family have incomplete phenotypes. The power of the linkage analysis was increased by detecting presymptomatic individuals with 18F-fluoro-dopa and 18F-deoxyglucose positron emission tomography. We screened the human genome with 340 polymorphic markers and we enriched the areas of interest with additional markers. The disease status was defined according to the clinical and positron emission tomography data. We excluded linkage to the tau gene in chromosome 17. PSP was linked, in this family, to one area of 3.4 cM in chromosome 1q31.1, with a maximal multipoint < OD score of +3.53. This area contains at least three genes, whose relevance in PSP is unknown. We expect to further define the gene responsible for PSP, which could help to understand the pathogenesis of this disease and to design effective treatment.

Effect of amoxicillin sulbactam in threatened preterm labour with intact membranes: a randomised controlled trial.

OBJECTIVE: To determine whether treatment with amoxicillin-sulbactam in women with threatened idiopathic preterm labour will prolong the gestation and reduce preterm birth rates in a Latin-American population. METHODS: A double-blind, placebo-controlled, randomized trial was conducted in 96 women who were hospitalized for preterm labour between 24 and 34 weeks of gestation at the Pereira Rossell Hospital, in Montevideo, Uruguay. The primary outcome measure was prematurity. The sample size was calculated a priori based on the hospital database. Statistical analyses were performed using the t-test, chi square, weighted mean difference (WMD) and relative risk (RR) with their confidence intervals (95% CI). Analysis by intention-to-treat. RESULTS: Out of 47 patients assigned for antibiotics, 43 completed the treatment. There were no significant statistical differences between antibiotics and placebo group in prematurity (RR:1.04, 95% CI: 0.59, 1.84), prolongation of pregnancy (WMD:0.23, 95% CI: -0.96, 1.42) and other perinatal outcomes. CONCLUSION: Antibiotics did not prove to have benefits in improving perinatal outcomes in this Latin American population.