Cervicovaginal microbiome in twin vs singleton gestations.

BACKGROUND: The vaginal microbiome diversity profile varies by race and ethnicity and changes considerably from the nonpregnant state to the pregnant state, specifically with a shift to Lactobacillus predominance in singleton gestations. There is a paucity of data that evaluate the cervicovaginal microbiome in women with twin gestations as a distinct population from those with singleton gestations. OBJECTIVE: We sought to characterize the cervicovaginal microbiome diversity profiles among twin gestations in the second trimester of pregnancy. STUDY DESIGN: In this prospective cross-sectional cohort study, women with twin gestations were matched to singleton controls without a history of a short cervix or preterm birth by gestational age ±2 weeks and race. Cervicovaginal lavage samples were collected from 14 to 24 weeks of gestation during prenatal visits followed by a cervical length measurement. Cervicovaginal microbiota were analyzed with 16S RNA gene sequencing and classified into community state types based on Lactobacillus species predominance. Microbiome alpha and beta diversities were compared between twin and singleton gestations. RESULTS: A total of 19 twin gestations and 19 singleton gestations underwent second-trimester cervicovaginal microbiome analysis. The groups were similar in gestational age at sample collection, maternal age, parity, body mass index, preterm birth history, and comorbidity. The cohort was predominantly of Black race (79%). Of twin gestations, 79% were dichorionic and diamniotic and 21% monochorionic and diamniotic. Of note, 3 twin gestations and 1 singleton gestation were complicated by a short cervix (P=.6). The vaginal microbiome of twin gestations had decreased alpha and beta diversities compared with singleton gestations. Twin gestations had lower taxon abundance and decreased variability in taxon abundance than singleton gestations. Overall, there was decreased diversity of community state type groups among twin gestations compared with singleton gestations. Community state types I and III were more prevalent among twin gestations, whereas community state types II and IV were similar among these 2 groups. Community state type IV, which is defined by a lack of Lactobacillus species and the presence of diverse strict anaerobes, was the predominant type among microbiota profiles of twin gestations (55%) and singleton gestations (64%). Community state type V was more prevalent in singleton gestations. When stratified by race, we found similar alpha diversity in Black and non-Black patients with twin gestations. CONCLUSION: In our predominantly Black population of pregnant women, the second-trimester vaginal microbiome in twin gestations showed decreased alpha and beta diversities compared with singleton controls. Our findings increased the understanding of the content of microbial communities in the second trimester of pregnancy in twin gestations and suggested a potential mechanism for preterm birth in twin gestations.

Pregnancy duration with use of 17-α-hydroxyprogesterone caproate in a retrospective cohort at high risk of recurrent preterm birth.

BACKGROUND: The use of 17-α-hydroxyprogesterone caproate for the prevention of recurrent spontaneous preterm birth has become widespread, yet there are conflicting data regarding its efficacy. OBJECTIVE: We sought to determine whether administration of 17-α-hydroxyprogesterone caproate was associated with pregnancy prolongation in women at a high risk of recurrent spontaneous preterm birth. STUDY DESIGN: This is a retrospective cohort study of women with singleton pregnancies and a history of spontaneous preterm birth at <37 weeks' gestation who received care at our academic tertiary care center between 2009 and 2019. We included women with gestations that progressed beyond 16 weeks. We excluded those who underwent history-indicated cerclage placement. We first examined the characteristics of women who received 17-α-hydroxyprogesterone caproate and those who did not. Covariates with a P value of ≤.2 on this univariate analysis were considered for incorporation into a Cox proportional hazards model to assess the association between 17-α-hydroxyprogesterone caproate use and pregnancy prolongation up to 35 weeks. RESULTS: Of 861 women included in the study, 570 (66.2%) reported non-Hispanic black racial identity, 237 (27.5%) lived in zip codes with a high infant mortality rate (≥12.1/1000 infants), 287 (33.3%) had more than 1 previous spontaneous preterm birth, 372 (43.2%) had previous spontaneous preterm birth at ≤32 weeks' gestation, and 242 (28.1%) were smokers. Here, 152 pregnancies (17.6%) were complicated by spontaneous preterm birth at <35 weeks' gestation. Factors independently associated with pregnancy duration up to 35 weeks included weight gain of <0.2 kg (0.5 lb) per week, first recorded weight of <98 kg (215 lb), obstetrical history, non-Hispanic white racial identity, lack of prenatal care, and vaginal bleeding. Gestational age at delivery was also independently associated with interventions typically employed for midtrimester cervical shortening and/or dilation, including ultrasound- and examination-indicated cerclage, pessary placement, and vaginal progesterone administration. The use of 17-α-hydroxyprogesterone caproate was not associated with pregnancy prolongation (adjusted hazard ratio, 0.83; 95% confidence interval, 0.60-1.15). CONCLUSION: The risk profile of our cohort is similar to that of women enrolled in the landmark trial that led to the Food and Drug Administration's approval of 17-α-hydroxyprogesterone caproate. Despite the high-risk nature of the pregnancies examined, we found no association between use of the medication in daily clinical practice and pregnancy prolongation up to 35 weeks. This finding adds to the mounting evidence that calls into question the drug's efficacy in reducing the risk of recurrent spontaneous preterm birth.