Publications

Abstract

Background: The number of twin pregnancies continues to increase worldwide as both the number of pregnancies obtained by medically assisted reproduction and age at first pregnancy keep rising. Preterm delivery is the major complication associated with twin pregnancies. The effectiveness of preventive treatments such as progesterone or cervical cerclage for women with a short cervix is doubtful in twin pregnancies. The effectivity of cervical pessaries in preventing preterm birth and its associated morbidity and mortality is also controversial.

Objective: We sought to investigate if the Arabin pessary reduces adverse neonatal outcomes in twin pregnancies with a short cervix.

Study design: This open-label, multicenter, randomized controlled trial on twin pregnancies with a cervical length of <35 mm compared pessary placement at 16+0 to 24+0 weeks’ gestation with standard care alone. The primary endpoint was a composite of adverse neonatal outcomes, namely peripartum or neonatal death or significant neonatal morbidity before hospital discharge, defined as at least 1 of the following complications: bronchopulmonary dysplasia, intraventricular hemorrhage grade III to IV, periventricular leukomalacia, necrotizing enterocolitis grade II or higher, culture-proven sepsis, and retinopathy requiring treatment. A sample size of 308 pregnancies was planned to ensure 80% power to compare the proportions of women with at least 1 infant with an adverse neonatal outcome. The intention-to-treat analysis after multiple imputation of missing data, was supplemented with a secondary analysis that controlled for gestational age and cervical length, both at inclusion. The primary endpoint was also compared between randomization groups in the per-protocol population, which excluded patients with prespecified major protocol violations (mostly cervical cerclage and/or progesterone after inclusion). Secondary endpoints included preterm birth, spontaneous preterm birth, and pessary side effects.

Results: In total, 315 women were randomized to either receive a pessary (n=157) or standard management (n=158). Overall, 10.8% (34 women) of participants had a missing value for the primary endpoint, mostly (79%) because of the lack of paternal consent for neonatal data collection. In the intention-to-treat analysis, the adverse neonatal outcome occurred in 16.8% of the pessary group vs in 22.5% of the control group (risk ratio, 0.69; 95% confidence interval, 0.39-1.23; P=.210). The per-protocol analysis did not show any significant difference between groups (risk ratio, 0.78; 95% confidence interval, 0.47-1.28; P=.320). The occurrence of preterm birth or spontaneous preterm birth did not differ significantly between groups. No serious side effects were associated with pessary use.

Conclusion: Pessary use in our study did not significantly reduce adverse neonatal outcomes in twin pregnancies with a short cervix.

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Abstract

Objective: To assess survival to discharge without severe neonatal morbidity by planned mode of delivery for twins born before 32 weeks of gestation.

Methods: The JUMODA (JUmeaux MODe d’Accouchement) study was a French national prospective, population-based, cohort study of twin deliveries conducted from February 2014 to March 2015. This planned secondary analysis included diamniotic twin pregnancies from 26 0/7 through 31 6/7 weeks of gestation. Exclusion criteria included contraindications to vaginal delivery and situations for which planned cesarean delivery is favored, and neonatal prognosis depends largely on the underlying pathology rather than the planned mode of delivery. The primary outcome was survival to discharge without severe neonatal morbidity (bronchopulmonary dysplasia, grade 3 or grade 4 intraventricular hemorrhage, periventricular leukomalacia, stage 2 or stage 3 necrotizing enterocolitis). The association between planned mode of delivery and primary outcome was assessed by multivariate Poisson regression model. A propensity-score approach with inverse probability of treatment weighting also was performed to control for indication bias. Subgroup analyses according to birth order and sensitivity analyses limited to spontaneous preterm births only were performed.

Results: Among 424 very preterm twin pregnancies, 192 (45.3%) had a planned cesarean delivery and 232 (54.7%) had a planned vaginal delivery. Survival to discharge without severe morbidity did not differ in the two groups: 308 of 384 (80.2%) after planned cesarean and 375 of 464 (80.8%) after planned vaginal delivery (crude relative risk 0.99; 95% CI 0.91-1.15; adjusted relative risk 1.02; 95% CI 0.93-1.11). After applying inverse probability of treatment weighting, planned cesarean delivery still was not associated with higher survival to discharge without severe neonatal morbidity than planned vaginal birth (relative risk 1.11; 95% CI 0.84-1.46). Subgroup and sensitivity analyses showed similar results.

Conclusion: Planned cesarean delivery for very preterm twins is not associated with higher survival to discharge without severe neonatal morbidity than planned vaginal delivery. These results suggest that very preterm delivery should not be considered a per se indication for planned cesarean in twin pregnancies.

Key Points

Question: Is endometriosis associated with preterm birth?

Findings: In this cohort study of 1351 women with or without endometriosis, endometriosis was not significantly associated with preterm birth after adjusting for the risk factors for preterm delivery. Disease phenotype did not appear to alter the result.

Meaning: The findings suggest that modification of pregnancy monitoring or management strategies to prevent preterm birth for women with endometriosis may not be needed.

Abstract

Importance: Endometriosis is an inflammatory disease with a heterogeneous presentation that affects women of childbearing age. Given the limitations of previous retrospective studies, it is still unclear whether endometriosis has adverse implications for pregnancy outcomes.

Objective: To evaluate the association between the presence of endometriosis and preterm birth and whether the risk varied according to the disease phenotype.

Design, Setting, and Participants: This cohort study with exposed and unexposed groups was conducted in 7 maternity units in France from February 4, 2016, to June 28, 2018. Participants included women with singleton pregnancies who were followed up before 22 weeks’ gestation along with their newborns delivered at or after 22 weeks’ gestation. The final follow-up occurred in July 2019. Data were analyzed from October 7, 2020, to February 7, 2021.

Exposures: Women in the endometriosis group had a documented history of endometriosis and were classified according to 3 endometriosis phenotypes: isolated superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA; potentially associated with SUP), and deep endometriosis (DE; potentially associated with SUP and OMA). Women in the control group did not have a history of clinical symptoms of endometriosis before their current pregnancy.

Main Outcomes and Measures: The primary outcome was preterm birth between 22 weeks and 36 weeks 6 days of gestation. Association between endometriosis and the primary outcome was assessed through univariate and multivariate logistic regression analyses and was adjusted for the following risk factors associated with preterm birth: maternal age, body mass index (calculated as weight in kilograms divided by height in meters squared) before pregnancy, country of birth, parity, previous cesarean delivery, history of myomectomy and hysteroscopy, and preterm birth. The same analysis was performed according to the 3 endometriosis phenotypes (SUP, OMA, and DE).

Results: Of the 1351 study participants (mean [SD] age, 32.9 [5.0] years) who had a singleton delivery after 22 weeks of gestation, 470 were assigned to the endometriosis group (48 had SUP [10.2%], 83 had OMA [17.7%], and 339 had DE [72.1%]) and 881 were assigned to the control group. No difference was observed in the rate of preterm deliveries before 37 weeks 0 days of gestation between the endometriosis and control groups (34 of 470 [7.2%] vs 53 of 881 [6.0%]; P = .38). After adjusting for confounding factors, endometriosis was not associated with preterm birth before 37 weeks’ gestation (adjusted odds ratio, 1.07; 95% CI, 0.64-1.77). The results were comparable for the different disease phenotypes (SUP: 6.2% [3 of 48]; OMA: 7.2% [6 of 83]; and DE: 7.4% [25 of 339]; P = .84).

Conclusions and Relevance: This cohort study found no association between endometriosis and preterm birth, and the disease phenotype did not appear to alter the result. Monitoring the pregnancy beyond the normal protocols or changing management strategies for women with endometriosis may not be warranted to prevent preterm birth.

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Abstract

The plasmid-mediated quinolone resistance (PMQR) genes have been shown to promote high-level bacterial resistance to fluoroquinolone antibiotics, potentially leading to clinical treatment failures. In Escherichia coli, sub-minimum inhibitory concentrations (sub-MICs) of the widely used fluoroquinolones are known to induce the SOS response. Interestingly, the expression of several PMQR qnr genes is controlled by the SOS master regulator, LexA. During the characterization of a small qnrD-plasmid carried in E. coli, we observed that the aminoglycosides become able to induce the SOS response in this species, thus leading to the elevated transcription of qnrD. Our findings show that the induction of the SOS response is due to nitric oxide (NO) accumulation in the presence of sub-MIC of aminoglycosides. We demonstrated that the NO accumulation is driven by two plasmid genes, ORF3 and ORF4, whose products act at two levels. ORF3 encodes a putative flavin adenine dinucleotide (FAD)-binding oxidoreductase which helps NO synthesis, while ORF4 codes for a putative fumarate and nitrate reductase (FNR)-type transcription factor, related to an O₂-responsive regulator of hmp expression, able to repress the Hmp-mediated NO detoxification pathway of E. coli. Thus, this discovery, that other major classes of antibiotics may induce the SOS response could have worthwhile implications for antibiotic stewardship efforts in preventing the emergence of resistance.