Prevention and cure: preterm labour and the menopause

Abstract

The ability to predict the risk of preterm labour at a clinically important gestation (e.g. early preterm labour at <34 weeks) at an early stage in pregnancy when preventive measures can be initiated is likely to be more valuable than predicting late preterm birth (34–36 weeks) at a late stage in pregnancy. This is the philosophy that underpins use of mid-trimester ultrasound screening to detect women with short cervical length and subsequent progesterone treatment, which has been shown to reduce the rate of preterm birth at <33 weeks by 45% and decrease the rate of neonatal complications, including neonatal respiratory distress syndrome (Romero et al. Am J Obstet Gynecol 2012;206,124.e1–19). The human body harbours assorted, multifaceted and copious microbiota, the composition of which is influenced by body site, host genetics, environmental exposures and host age (Goodrich et al. Cell 2014;159:789–99; Ursell et al. J Allergy Clin Immunol 2012;129:1204–8). It has been estimated that one-quarter of preterm births are associated with microbial invasion of the amniotic cavity (Romero et al. Science 2014;345:760–5). Is screening of the vaginal microbiome early in gestation and implementation of strategies to alter its composition a viable strategy for prevention of infection-related preterm birth? Previous reports suggested that microbiota membership remained relatively stable in the vagina, gut andmouth during pregnancy, and pregnancy outcomes might be predicted by features of the microbiota early in gestation (DiGiulio et al. Proc Natl Acad Sci USA 2015;112:11060–5), which could allow instigation of interventions to reduce the risk of pretermbirth. Assessment of the vaginal microbiota can be performed using various nextgeneration-sequencing and PCR-based platforms, including the sequencing of 16S ribosomal RNA (rRNA). Gene sequencing enables the precise identification of bacteria species that are present. In this issue on pages 349–58, Tabatabaei and colleagues report the results of a study of the vaginal microbiome composition as assessed by sequencing the V4 region of the 16S rRNA gene. Samples were self-collected during early pregnancy by 94 women who went on to have a spontaneous preterm birth (17 early [<34 weeks] and 77 late [34–36 weeks] preterm births) and by 356 controls who had a term delivery (≥37 weeks). Their results demonstrate that the vaginal microbial community oligotypes with Lactobacillus dominance (Lactobacillus gasseri/Lactobacillus johnsonii, Lactobacillus crispatus/Lactobacillus acidophilus or Bifidobacterium longum/Bifidobacterium breve) were associated with a decreased risk of early but not late preterm birth. Furthermore, using a classification scheme that separates the dominant bacteria into five community state types (CSTs) (Ravel et al. Proc Natl Acad Sci USA 2011;108 (Suppl 1):4680–7), they report that the CST composed of bacteria predominant in women with bacterial vaginosis (Gardnerella vaginalis, Atopobium vaginae and Veillonellaceae bacterium) was associated with an increased risk of early but not late preterm birth as compared with CSTs with low diversity and nondominance of Lactobacillus. The choice of examining the V4 region of 16SrRNA may not be ideal (as discussed in an accompanying mini commentary by Witkin on page 359), as it limited the investigators’ ability to precisely identify bacteria on a species level. Nevertheless, the study from Tabatabaei is the largest analysis based on next-generation sequencing to date with a nested case– control design that explores the differences in vaginal microbiome composition between women who spontaneously deliver preterm or at term, and indicates that detection of vaginal microbial composition in the first trimester may be used to identify those women who are destined to have early preterm delivery. As studies exploring the association between specific vaginal microbiome composition across pregnancy and risk of spontaneous preterm birth reach a consensus, the next step is to determine whether alterations in microbial composition are possible (with prebiotics, probiotics or antibiotics) and whether this will lead to a decrease in the rate of preterm birth. The management of menopausal symptoms in women who have had breast cancer is often difficult. The majority are reluctant to use hormonereplacement therapy (HRT) because of a likely increased risk of breast cancer. Most breast cancers are estrogen-receptor positive, and as a result anti-estrogenic endocrine therapy will be recommended for most affected women. Both tamoxifen and aromatase inhibitors are associated with vasomotor symptoms (Cella and Fallowfield Breast Cancer Res Treat 2008;107:167–80) and these will usually persist for the duration of exposure, which can be between 5 and 10 years (Fallowfield et al. Br J Cancer 2012;106:1062–7; Love and Feyzi J Natl Cancer Inst 1993;85:673–4). Another group of women who may be reluctant to use HRT is made up of those who have undergone risk-reducing salpingo-oophorectomy (RRSO) because of BCRA carriage. Menopausal symptoms are likely to be troublesome in these women as menopausal symptoms are more severe after acute surgical menopause than after natural menopause (Benshushan et al. Climacteric 2009;12:404–9). The safety of HRT use in women who have undergone RRSO is