An exploratory study of associations with spontaneous preterm birth in primigravid pregnant women with a normal cervical length.

BACKGROUND: Predictors of spontaneous preterm birth in primigravid women remain undetermined. AIM: We evaluated whether biomarkers in vaginal secretions and/or differences in the dominant bacterium in the vaginal microbiome predicted the risk for spontaneous preterm birth in primigravid women with a cervical length >25mm. STUDY DESIGN: In a prospective study, 146 second trimester pregnant women with their first conception and a cervix >25mm were enrolled. The vaginal microbiome composition was characterized by analysis of 16S ribosomal RNA gene sequences. The concentrations of d- and l-lactic acid, matrix metalloproteinase (MMP) 2, 8 and 9 and tissue inhibitor of metalloproteinase (TIMP) 1 and 2 in vaginal secretions were measured by ELISA. Cervical length was determined by vaginal ultrasonography. Pregnancy outcome data were subsequently collected. There was a spontaneous preterm birth (SPTB) in 13 women (8.9%) while in an additional 8 women (5.5%) preterm delivery was medically indicated. Lactobacillus iners was the dominant vaginal bacterium in 61.5% of women with a SPTB but only in 31.2% of those who delivered at term (p = .0354). The vaginal concentration of TIMP-1 (p = .0419) and L-lactic acid (p = .0495) was higher in women with a SPTB as compared to those who delivered at term. Lactobacillus iners dominance was associated with elevated levels of TIMP-1 (p = .0434) and TIMP-2 (p = .0161) and lower levels of D-lactic acid (p < .0001) compared to when L. crispatus was dominant. CONCLUSION: In this exploratory study of primigravid women, elevations in vaginal TIMP-1 and L- lactic acid and L. iners dominance in the vaginal microbiome are associated with an increased occurrence of SPTB.

The influence of race on cervical length in pregnant women in Brazil.

OBJECTIVES: Short cervical length is a predictor of preterm birth. We evaluated if there were racial differences in variables associated with cervical length in pregnant Brazilian women. METHODS: Cervical length was determined by vaginal ultrasound in 414 women at 21 weeks gestation. All women were seen at the same clinic and analyzed by the same investigators. Women found to have a short cervix (≤25 mm) received vaginal progesterone throughout gestation. Composition of the vaginal microbiome was determined by analysis of the V1-V3 region of the gene coding for bacterial 16S ribosomal RNA. Demographic, clinical and outcome variables were determined by chart review. Subjects were 53.4% White, 37.2% mixed race and 9.4% Black. RESULTS: Pregnancy, medical history and education level were similar in all groups. Mean cervical length was shorter in Black women (28.4 mm) than in White (32.4 mm) or mixed race (32.8 mm) women (p≤0.016) as was the percentage of women with a short cervix (23.1, 12.2, 7.8% in Black, White, mixed race respectively) (p≤0.026). Mean cervical length increased with maternal age in White (p=0.001) and mixed race (p=0.045) women but not Black women. There were no differences in bacterial dominance in the vaginal microbiota between groups. Most women with a short cervix delivered at term. CONCLUSIONS: We conclude that Black women in Brazil have a shorter cervical length than White or mixed race women independent of maternal age, pregnancy and demographic history or composition of the vaginal microbiome.

Vaginal Biomarkers That Predict Cervical Length and Dominant Bacteria in the Vaginal Microbiomes of Pregnant Women.

In many impoverished regions of the world, it may not be possible to assess two major risk factors for preterm birth: a short cervical length and the depletion of vaginal lactobacilli. We determined whether measuring specific compounds in vaginal fluid might be a simple, noninvasive, and cost-effective way to predict the bacteria that dominate the vaginal microbiome and indicate the presence of a shortened cervix (<25 mm). Vaginal fluid samples were prospectively collected from mid-trimester pregnant women, and the concentrations of d- and l-lactic acid, tissue inhibitor of matrix metalloproteinases TIMP-1 and TIMP-2, matrix metalloproteinases MMP-2 and MMP-8, the 70-kDa heat shock protein, a2 isoform of vacuolar ATPase, and sequestrome-1 were quantified by an enzyme-linked immunosorbent assay (ELISA). The compositions of vaginal microbiomes were assessed by analysis of the V1-V3 regions of 16S rRNA genes, while cervical length was determined by transvaginal ultrasonography. The vaginal microbiomes could be clustered into five community state types (CSTs), four of which were dominated by a single Lactobacillus species. The dominance of Lactobacillus crispatus or Lactobacillus jensenii in the vaginal microbiome predicted the level of d-lactic acid present. Several of the biomarkers, especially TIMP-1, in combination with the subject's age and race, were significantly associated with cervical length. Using piecewise structural equation modeling, we established a causal network that links CST to cervical length via biomarkers. We concluded that measuring levels of TIMP-1 and d-lactic acid in vaginal secretions might be a straightforward way to assess the risk for preterm birth due to a short cervix and microbiome composition.IMPORTANCE Premature birth and its complications are the largest contributors to infant death in the United States and globally. A short cervical length and the depletion of Lactobacillus species are known risk factors for preterm birth. However, in many resource-poor areas of the world, the technology to test for their occurrence is unavailable, and pregnant women with these risk factors are neither identified nor treated. In this study, we used path analysis to gain an unprecedented understanding of interactions between vaginal microbiome composition, the concentrations of various compounds in vaginal secretions, and cervical length. We identified low-cost point-of-care measures that might be used to identify pregnant women at risk for preterm birth. The use of these measures coupled with appropriate preventative or treatment strategies could reduce the incidence of preterm births in poor areas of the world that lack access to more sophisticated diagnostic methods.

Prenatal imaging findings in fetal Zika virus infection.

PURPOSE OF REVIEW: The aim of this review is to report the most recent observations concerning intrauterine Zika virus (ZIKV) infection and associated neuroimaging. RECENT FINDINGS: ZIKV outbreak in Brazil in 2015 was associated with an impressive registration of cases of congenital microcephaly in women with symptoms suggestive of ZIKV infection. Clinical and laboratory testing for ZIKV and hypothetic etiopathogenetic mechanisms are described. Diagnostic tests on blood, urine and amniotic fluid should be performed in all mothers with symptoms suggestive of intrauterine ZIKV infection. ZIKV causes multiple teratogenic malformations, mainly affecting the developing brain. SUMMARY: Neuroimaging investigation contributes to the prenatal detection of microcephaly and other brain abnormalities in cases of intrauterine ZIKV infection. Neuroimaging is based antenatally on two-dimensional and three-dimensional ultrasound and fetal MRI, whereas computed tomography scan is performed postnatally. Although neuropathology associated with intrauterine ZIKV infection is characterized by nonspecific findings of brain disorder, reduced cortical gyration and white-matter hypomyelination or dysmyelination and cerebellar hypoplasia have been consistently observed in the majority of fetuses and newborns. Prenatal or postnatal genetic workup should be carried out to exclude cases of primary microcephaly. Follow-up should rely upon MRI and computed tomography scan as well as neuropediatrician to better define developmental outcome in survivors.

Endothelial dysfunction after pregnancy-induced hypertension.

OBJECTIVE: To carry out long-term analysis of the presence of endothelial dysfunction after the development of pregnancy-induced hypertension (PIH). METHODS: In a retrospective cohort study, data were analyzed from 60 women who delivered at a tertiary maternity hospital in Fortaleza, Ceara, Brazil, between 1992 and 2002. Thirty women had a history of PIH and 30 had no history of complications. Anthropometric and laboratory data were collected, and endothelial function was evaluated by flow-mediated dilatation of the brachial artery. Continuous variables were analyzed via Student t test, and Mann-Whitney test was used to compare means. Clinical and metabolic measures were categorized according to cardiovascular risk by cutoff points determined by national consensus; χ2 and Fisher exact tests were used to compare the groups. Relative risk was calculated for variables that were statistically significant (P<0.05). RESULTS: Women with a history of PIH had higher body mass index (P=0.03), systolic blood pressure (P=0.03), low-density lipoprotein cholesterol (P=0.02), and fasting glucose (P=0.02) compared with women with no pregnancy complications. The frequency of endothelial dysfunction was 60% among all women, with a significant difference between the 2 groups (P=0.01). CONCLUSION: Women with a history of PIH were found to have a higher frequency of long-term endothelial dysfunction.