OBJECTIVE: To investigate: first, the association between endometriosis and preterm birth; second, the associations between endometriosis and preeclampsia, placenta previa, postpartum hemorrhage, stillbirth, and small-for-gestational-age infants (assessed by birthweight); and third, the risk of these adverse pregnancy outcomes with and without the use of medically assisted reproduction.
METHODS: Multicenter retrospective cohort study.
METHODS: 103 French maternity units.
METHODS: Deliveries by 368,935 women (377,338 infants) from 1999 through 2016.
METHODS: Endometriosis, defined as a single disease entity (endometriosis and/or ademyosis).
METHODS: The main outcome was the preterm birth rate (both < 37 and < 33 weeks). The secondary outcomes were rates of preeclampsia, placenta previa, postpartum hemorrhage, stillbirth, and small-for-gestational-age neonates.
RESULTS: Women in the endometriosis group had more frequent histories of infertility before the included pregnancy (34.7 vs 5.0%, P <10-4), more hospitalizations during the pregnancy (27.4 vs. 19.8%, P <10-4), and more planned cesarean sections (14.0 vs. 8.7, P <10-4); they were more often nulliparous (51.7 vs. 43.4%, P <10-4). The prevalence of preterm birth <37 weeks was 11.1% in the endometriosis group and 7.7% in the unexposed group, and <33 weeks 3.1% and 2.2% respectively. The adjusted relative risk for confounding factors was higher in the endometriosis than the unexposed group for preterm delivery <37 weeks (1.40, 95%CI 1.18-1.67) or <33 weeks (1.53, 95%CI 1.08-2.16). For the secondary outcomes, the adjusted risk ratios for preeclampsia, placenta previa, postpartum hemorrhage, and small-for-gestational-age status <10th and < 5th percentiles were higher in the endometriosis group. The adjusted risk ratios for stillbirth and small-for-gestational-age status <3rd percentile did not differ between the two groups, and those after stratification by medically assisted reproduction for preterm birth <37 and <33 weeks did not differ statistically significantly between them for the secondary outcomes, only the risk of placenta previa was higher in the medically assisted reproduction and no-medically assisted reproduction subgroups.
CONCLUSIONS: Pregnant women with endometriosis had higher risks of preterm birth and other poor pregnancy outcomes than women without endometriosis.

UNASSIGNED: Women with cardiometabolic pregnancy complications are at increased risk of future diabetes and heart disease which can be reduced through lifestyle management postpartum.
UNASSIGNED: This study aimed to explore preferred intervention characteristics and behaviour change needs of women with or without prior cardiometabolic pregnancy complications for engaging in postpartum lifestyle interventions.
UNASSIGNED: Quantitative cross-sectional study.
UNASSIGNED: Online survey.
UNASSIGNED: Overall, 473 women were included, 207 (gestational diabetes (n = 105), gestational hypertension (n = 39), preeclampsia (n = 35), preterm birth (n = 65) and small for gestational age (n = 23)) with and 266 without prior cardiometabolic pregnancy complications. Women with and without complications had similar intervention preferences, with delivery ideally by a healthcare professional with expertise in women\'s health, occurring during maternal child health nurse visits or online, commencing 7 weeks to 3 months post birth, with 15- to 30-min monthly sessions, lasting 1 year and including monitoring of progress and social support. Women with prior complications preferred intervention content on women\'s health, mental health, exercise, mother\'s diet and their children\'s health and needed to know more about how to change behaviour, have more time to do it and feel they want to do it enough to participate. There were significant differences between groups, with more women with prior cardiometabolic pregnancy complications wanting content on women\'s health (87.9% vs 80.8%, p = 0.037), mother\'s diet (72.5% vs 60.5%, p = 0.007), preventing diabetes or heart disease (43.5% vs 27.4%, p < 0.001) and exercise after birth (78.3% vs 68.0%, p = 0.014), having someone to monitor their progress (69.6% vs 58.6%, p = 0.014), needing the necessary materials (47.3% vs 37.6%, p = 0.033), triggers to prompt them (44.0% vs 31.6%, p = 0.006) and feeling they want to do it enough (73.4%, 63.2%, p = 0.018).
UNASSIGNED: These unique preferences should be considered in future postpartum lifestyle interventions to enhance engagement, improve health and reduce risk of future cardiometabolic disease in these high-risk women.

The AVERT PRETERM trial (NCT03151330) evaluated whether screening clinically low-risk pregnancies with a validated maternal blood biomarker test for spontaneous preterm birth (sPTB) risk, followed by preventive treatments for those screening positive, would improve neonatal outcomes compared to a clinically low-risk historical population that had received the usual care. Prospective arm participants with singleton non-anomalous pregnancies and no PTB history were tested for sPTB risk at 191/7-206/7 weeks\' gestation and followed up with after neonatal discharge. Screen-positive individuals (≥16% sPTB risk) were offered vaginal progesterone (200 mg) and aspirin (81 mg) daily, with twice-weekly nurse phone calls. Co-primary outcomes were neonatal morbidity and mortality, measured using a validated composite index (NMI), and neonatal hospital length of stay (NNLOS). Endpoints were assessed using survival analysis and logistic regression in a modified intent-to-treat population comprising screen-negative individuals and screen-positive individuals accepting treatment. Of 1460 eligible participants, 34.7% screened positive; of these, 56.4% accepted interventions and 43.6% declined. Compared to historical controls, prospective arm neonates comprising mothers accepting treatment had lower NMI scores (odds ratio 0.81, 95% CI, 0.67-0.98, p = 0.03) and an 18% reduction in severe morbidity. NNLOS was shorter (hazard ratio 0.73, 95% CI, 0.58-0.92, p = 0.01), with a 21% mean stay decrease among neonates having the longest stays. Sensitivity analyses in the entire intent-to-treat population supported these findings. These results suggest that biomarker sPTB risk stratification and preventive interventions can ameliorate PTB complications in singleton, often nulliparous, pregnancies historically deemed low risk.

Background: Preterm birth (PTB) is a significant challenge in contemporary obstetrics, affecting over one in ten infants worldwide and accounting for 75% of perinatal mortality. Short cervical length during mid-trimester is well known to be associated with an increased risk of spontaneous preterm birth (sPTB). Ultrasound-indicated cerclage (UIC) is recommended to prevent sPTB in women with a short cervix at mid-trimester and a history of sPTB. Objectives: This retrospective observational study aimed to examine the impact of diabetes and obesity on the occurrence of sPTB in women who underwent UIC due to mid-trimester cervical shortening. Methods/Results: The analysis revealed that cervical length at the time of operation, preoperative erythrocyte sedimentation rate levels, and diabetes were independent risk factors for sPTB. Additionally, the presence of diabetes, particularly when combined with obesity, significantly elevated the risk of sPTB. Women with pregestational diabetes or those requiring insulin treatment had a higher propensity for preterm delivery compared to those with gestational diabetes managed through diet control alone. Conclusions: These findings emphasize the importance of considering maternal metabolic factors, such as diabetes and obesity, in women with a short cervix when planning for UIC and highlight the crucial role of optimizing maternal glucose control and weight management in reducing the risk of sPTB.

BACKGROUND: It is unknown whether women with pregnancy-onset asthma are predisposed to worse pregnancy outcomes compared with women with pre-pregnancy asthma.
OBJECTIVE: To explore whether pregnancy-onset asthma leads to worse perinatal outcomes compared with pre-pregnancy asthma.
METHODS: Women who were discharged with a diagnosis of asthma and gave birth to a live singleton were included in this retrospective cohort analysis. Women were separated into groups based on whether the asthma was diagnosed during or before pregnancy. We compared clinical characteristics, perinatal outcomes, and asthma exacerbations (AEs) between groups.
RESULTS: A total of 335 women were included in this study, 39 of whom (11.6%) had pregnancy-onset asthma and 296 had pre-pregnancy asthma. All pregnant women in the pregnancy-onset group experienced AEs during pregnancy. The proportion of chronic hypertension, chronic hypertension with superimposed preeclampsia, and spontaneous preterm births in the pregnancy-onset group was significantly higher than that in the pre-pregnancy asthma group. After adjusting for age, body mass index, onset of asthma during pregnancy, and severity of AEs through multivariate analysis, pregnancy-onset asthma was an independent risk factor for spontaneous preterm birth (adjusted odds ratio = 7.71; 95% CI, 1.30-46.12) and severe AE was an independent risk factor for gestational hypertension and preeclampsia (adjusted odds ratio = 3.58; 95% CI, 1.30-9.87).
CONCLUSIONS: During pregnancy, pregnancy-onset asthma in women is associated with an exacerbation of the condition. Obstetricians should be vigilant for signs of asthma onset during pregnancy. Other health care providers should watch for symptoms of gestational hypertension and preeclampsia in pregnant women with preexisting or new-onset asthma.

UNASSIGNED: Premature cervical softening and shortening may be considered an early mechanical failure that predispose to preterm birth.
UNASSIGNED: This study aims to explore the applicability of an innovative cervical tactile ultrasound approach for predicting spontaneous preterm birth (sPTB).
UNASSIGNED: Eligible participants were women with low-risk singleton pregnancies in their second trimester, enrolled in this prospective observational study. A Cervix Monitor (CM) device was designed with a vaginal probe comprising four tactile sensors and a single ultrasound transducer operating at 5 MHz. The probe enabled the application of controllable pressure to the external cervical surface, facilitating the acquisition of stress-strain data from both anterior and posterior cervical sectors. Gestational age at delivery was recorded and compared against cervical elasticity.
UNASSIGNED: CM examination data were analyzed for 127 women at 240/7 - 286/7 gestational weeks. sPTB was observed in 6.3% of the cases. The preterm group exhibited a lower average cervical stress-to-strain ratio (elasticity) of 0.70 ± 0.26 kPa/mm compared to the term group\'s 1.63 ± 0.65 kPa/mm with a p-value of 1.1 × 10-4. Diagnostic accuracy for predicting spontaneous preterm birth based solely on cervical elasticity data was found to be 95.0% (95% CI, 88.5 - 100.0).
UNASSIGNED: These findings suggest that measuring cervical elasticity with the designed tactile ultrasound probe has the potential to predict spontaneous preterm birth in a cost-effective manner.

BACKGROUND: Vaginal microbiota composition is associated with spontaneous preterm birth (sPTB), depending on ethnicity. Host-microbiota interactions are thought to play an important underlying role in this association between ethnicity, vaginal microbiota and sPTB.
METHODS: In a prospective cohort of nulliparous pregnant women, we assessed vaginal microbiota composition, vaginal immunoglobulins (Igs), and local inflammatory markers. We performed a nested case-control study with 19 sPTB cases, matched based on ethnicity and midwifery practice to 19 term controls.
RESULTS: Of the 294 included participants, 23 pregnancies ended in sPTB. We demonstrated that Lactobacillus iners-dominated microbiota, diverse microbiota, and ethnicity were all independently associated with sPTB. Microbial Ig coating was associated with both microbiota composition and ethnicity, but a direct association with sPTB was lacking. Microbial IgA and IgG coating were lowest in diverse microbiota, especially in women of any ethnic minority. When correcting for microbiota composition, increased microbial Ig coating correlated with increased inflammation.
CONCLUSIONS: In these nulliparous pregnant women, vaginal microbiota composition is strongly associated with sPTB. Our results support that vaginal mucosal Igs might play a pivotal role in microbiota composition, microbiota-related inflammation, and vaginal community disparity within and between ethnicities. This study provides insight in host-microbe interaction, suggesting that vaginal mucosal Igs play an immunomodulatory role similar to that in the intestinal tract. Video Abstract.

BACKGROUND: Despite much research, advances in early prediction of spontaneous preterm birth (sPTB) has been slow. The evolving field of circulating microparticle (CMP) biology may identify novel blood-based, and clinically useful, biomarkers.
OBJECTIVE: To test the ability of a previously identified, 7-marker set of CMP-derived proteins from the first trimester of pregnancy, in the form of an in vitro diagnostic multivariate index assay (IVDMIA), to stratify pregnant patients according to their risk for sPTB.
METHODS: We employed a previously validated set of CMP protein biomarkers, utilizing mass spectrometry assays and a nested case-control design in a subset of participants from the Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be (nuMoM2b). We evaluated these biomarkers in the form of an IVDMIA to predict risk for sPTB at different gestational ages. Plasma samples collected at 9- to 13-weeks\' gestation were analyzed. The IVDMIA assigned subjects to 1 of 3 sPTB risk categories: low risk (LR), moderate risk (MR), or high risk (HR). Independent validation on a set-aside set confirmed the IVDMIA\'s performance in risk stratification.
RESULTS: Samples from 400 participants from the nuMoM2b cohort were used for the study; of these, 160 delivered<37 weeks and 240 delivered at term. Through Monte Carlo simulation in which the validation results were adjusted based on actual weekly sPTB incidence rates in the nuMoM2b cohort, the IVDMIA stratifications demonstrated statistically significant differences among the risk groups in time-to-event (birth) analysis (P<.0001). The incidence-rate adjusted cumulative risks of sPTB at ≤32 weeks\' gestation were 0.4%, 1.6%, and 7.5%, respectively for the LR, MR, and HR groups, respectively. Compared to the LR group, the corresponding risk ratios of the IVDMIA assigned MR and HR group were 4.25 (95% confidence interval [CI] 2.2-7.9) and 19.92 (95% CI 10.4-37.4), respectively.
CONCLUSIONS: A first trimester CMP protein biomarker panel can be used to stratify risk for sPTB at different gestational ages. Such a multitiered stratification tool could be used to assess risk early in pregnancy to enable timely clinical management and interventions, and, ultimately, to enable the development of tailored care pathways for sPTB prevention.

Throughout pregnancy, the maternal peripheral circulation contains valuable information reflecting pregnancy progression, detectable as tightly regulated immune dynamics. Local immune processes at the maternal-fetal interface and other reproductive and non-reproductive tissues are likely to be the pacemakers for this peripheral immune \"clock.\" This cellular immune status of pregnancy can be leveraged for the early risk assessment and prediction of spontaneous preterm birth (sPTB). Systems immunology approaches to sPTB subtypes and cross-tissue (local and peripheral) interactions, as well as integration of multiple biological data modalities promise to improve our understanding of preterm birth pathobiology and identify potential clinically actionable biomarkers.

Spontaneous preterm birth (sPTB) is a complex and clinically heterogeneous condition that remains incompletely understood, leading to insufficient interventions to effectively prevent it from occurring. Cell-free ribonucleic acid signatures in the maternal circulation have the potential to identify biologically relevant subtypes of sPTB. These could one day be used to predict and prevent sPTB in asymptomatic individuals, and to aid in prognosis and management for individuals presenting with threatened preterm labor and preterm prelabor rupture of membranes.