Prediction model for spontaneous preterm birth less than 32 weeks of gestation in low-risk women with mid-trimester short cervical length: a retrospective cohort study.

BACKGROUND: A short cervix in mid-trimester pregnancy is a risk factor for spontaneous preterm birth. However, there is currently a lack of predictive models and classification systems for predicting spontaneous preterm birth in these patients, especially those without additional risk factors for spontaneous preterm birth. METHODS: A retrospective observational cohort study of low-risk singleton pregnant women with a short cervix (≤ 25 mm) measured by transvaginal ultrasonography between 22 and 24 weeks was conducted. A multivariate logistic regression model for spontaneous preterm birth < 32 weeks in low-risk pregnant women with a short cervix was constructed. Moreover, we developed a nomogram to visualize the prediction model and stratified patients into three risk groups (low-, intermediate-, and high-risk groups) based on the total score obtained from the nomogram model. RESULTS: Between 2020 and 2022, 213 low-risk women with a short cervix in mid-trimester pregnancy were enrolled in the study. Univariate logistic analysis revealed that a high body mass index, a history of three or more miscarriages, multiparity, a short cervical length, leukocytosis, and an elevated C-reactive protein level were associated with spontaneous preterm birth < 32 weeks, but multivariate analysis revealed that multiparity (OR, 3.31; 95% CI, 1.13-9.68), leukocytosis (OR, 3.96; 95% CI, 1.24-12.61) and a short cervical length (OR, 0.88; 95% CI, 0.82-0.94) were independent predictors of sPTB < 32 weeks. The model incorporating these three predictors displayed good discrimination and calibration, and the area under the ROC curve of this model was as high as 0.815 (95% CI, 0.700-0.931). Patients were stratified into low- (195 patients), intermediate- (14 patients) and high-risk (4 patients) groups according to the model, corresponding to patients with scores ≤ 120, 121-146, and > 146, respectively. The predicted probabilities of spontaneous preterm birth < 32 weeks for these groups were 6.38, 40.62, and 71.88%, respectively. CONCLUSIONS: A noninvasive and efficient model to predict the occurrence of spontaneous preterm birth < 32 weeks in low-risk singleton pregnant women with a short cervix and a classification system were constructed in this study and can provide insight into the optimal management strategy for patients with different risk stratifications according to the score chart.

Identification of key metabolism-related genes and pathways in spontaneous preterm birth: combining bioinformatic analysis and machine learning.

Background: Spontaneous preterm birth (sPTB) is a global disease that is a leading cause of death in neonates and children younger than 5 years of age. However, the etiology of sPTB remains poorly understood. Recent evidence has shown a strong association between metabolic disorders and sPTB. To determine the metabolic alterations in sPTB patients, we used various bioinformatics methods to analyze the abnormal changes in metabolic pathways in the preterm placenta via existing datasets. Methods: In this study, we integrated two datasets (GSE203507 and GSE174415) from the NCBI GEO database for the following analysis. We utilized the "Deseq2" R package and WGCNA for differentially expressed genes (DEGs) analysis; the identified DEGs were subsequently compared with metabolism-related genes. To identify the altered metabolism-related pathways and hub genes in sPTB patients, we performed multiple functional enrichment analysis and applied three machine learning algorithms, LASSO, SVM-RFE, and RF, with the hub genes that were verified by immunohistochemistry. Additionally, we conducted single-sample gene set enrichment analysis to assess immune infiltration in the placenta. Results: We identified 228 sPTB-related DEGs that were enriched in pathways such as arachidonic acid and glutathione metabolism. A total of 3 metabolism-related hub genes, namely, ANPEP, CKMT1B, and PLA2G4A, were identified and validated in external datasets and experiments. A nomogram model was developed and evaluated with 3 hub genes; the model could reliably distinguish sPTB patients and term labor patients with an area under the curve (AUC) > 0.75 for both the training and validation sets. Immune infiltration analysis revealed immune dysregulation in sPTB patients. Conclusion: Three potential hub genes that influence the occurrence of sPTB through shadow participation in placental metabolism were identified; these results provide a new perspective for the development and targeting of treatments for sPTB.

Is the Transcription Factor NANOG Involved in Placental Aging?

PROBLEM: Accelerated placental aging is linked to abnormal fetal growth, preeclampsia (PE), and preterm birth (PTB). NANOG, a transcription factor, is known for its role in cellular reprogramming, self-renewal, and clonogenic growth. Its expression is regulated by Kruppel-like factor 4 (KLF4), which functions as both a transcriptional activator and repressor. This study evaluated the KLF4-NANOG pathway in placental samples from normal pregnancies (NP) as well as those with PE, fetal growth restriction (FGR), and PTB. METHOD OF STUDY: Placental samples from NP pregnancies and those with PE, FGR, and PTB were analyzed for NANOG and KLF4 expression using western blotting and immunohistochemistry. RESULTS: NANOG protein expression was significantly increased in placentas from PE, FGR, and PTB compared to NP (fold changes vs. NP: PE 2.48 ± 0.3, p = 0.002; FGR 1.64 ± 0.16, p = 0.03; PTB 6.03 ± 3.35, p = 0.01). Similarly, KLF4 protein expression was elevated in PE, FGR, and PTB placentas compared to NP (fold changes vs. NP: PE 5.78 ± 0.73, p = 0.001; FGR 2.61 ± 0.43, p = 0.02; PTB 11.42 ± 2.76, p = 0.0006). Immunohistochemistry revealed strong NANOG staining in the syncytiotrophoblast tissue of PE, FGR, and PTB samples, especially in extravillous trophoblasts, compared to NP placentas. CONCLUSIONS: The elevated expression of NANOG and KLF4 in abnormal placental tissues suggests their potential role as markers of enhanced placental aging and dysfunction. These findings underscore the importance of the KLF4-NANOG pathway in the pathology of PE, FGR, and PTB, providing a basis for future research into therapeutic targets for these conditions.

Association of maternal blood mercury concentration during the first trimester of pregnancy with birth outcomes.

Exposure to mercury has been associated with adverse effects on pregnancy outcomes. However, there is limited literature on mercury exposure and pregnancy outcomes in Chinese pregnant women. Our study was to investigate the possible association between maternal mercury exposure and spontaneous preterm birth and birth weight. This study was a nested case-control study. The association between blood mercury concentration and both spontaneous preterm birth and birth weight was analyzed using conditional logistic regression and linear regression adjusted for the potential confounding factors, respectively. The dose-response relationship between mercury concentration and birth outcomes was estimated using restricted cubic spline regression. The mean concentration of mercury was 2.8 ± 2.2 µg/L. A positive relationship was observed between maternal blood mercury concentration and SPB when analyzed as a continuous variable. However, it was not found to be statistically significant (adjusted OR = 1.10, 95% CI = 0.95-1.26, P = 0.202). Moderate mercury exposure was associated with a higher risk of SPB (Q3 vs. Q1: crude OR = 2.50, 95% CI = 1.16-5.41, P = 0.02; adjusted OR = 3.49, 95% CI = 1.33-9.11, P = 0.011). After considering the combined effects of chemicals other than mercury exposure (including lead, selenium, and cadmium), the results remained consistent. There was no statistically significant association between blood mercury levels and birth weight (adjusted coefficient = 18.64, P-value = 0.075). There were no statistically significant dose-response associations between mercury concentration and birth outcomes (SPB: P = 0.076; birth weight: P = 0.885). Public health policies should focus on reducing environmental releases of mercury, improving food safety standards, and providing education to pregnant women about the risks of mercury exposure and preventive measures.

Endometriosis and risk of adverse pregnancy outcomes: a retrospective multicenter cohort study.

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. DESIGN: Multicenter retrospective cohort study. SETTING: A total of 103 French maternity units. PATIENTS: Deliveries by 368,935 women (377,338 infants) from 1999 through 2016. EXPOSURE: Endometriosis, defined as a single disease entity (endometriosis and/or ademyosis) MAIN OUTCOMES MEASURES: 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%), more hospitalizations during the pregnancy (27.4 vs. 19.8%), and more planned cesarean sections (14.0 vs. 8.7); they more often were nulliparous (51.7 vs. 43.4%). The prevalence of preterm birth at <37 weeks was 11.1% in the endometriosis group and 7.7% in the unexposed group, and for <33 weeks, it was 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% confidence interval, 1.18-1.67) or <33 weeks (1.53, 95% confidence interval, 1.08-2.16). For the secondary outcomes, the adjusted risk ratios for preeclampsia, placenta previa, postpartum hemorrhage, and small-for-gestational-age status of <10th and <5th percentiles were higher in the endometriosis group. The adjusted risk ratios for stillbirth and small-for-gestational-age status of <3rd percentile did not differ between the two groups, and those after stratification by medically assisted reproduction for preterm birth at <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 non-medically assisted reproduction subgroups. CONCLUSION: Pregnant women with endometriosis had higher risks of preterm birth and other poor pregnancy outcomes than women without endometriosis.

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Objective: To study and compare the clinical effects of cervical pessary and progesterone for preventing preterm birth in singleton pregnant women with a short cervical length (CL). Methods: This study was a prospective cohort study. A total of 148 pregnant women with CL≤25 mm, as determined by ultrasound examination performed before 28 weeks of pregnancy, were included in the study. All subjects were admitted to West China Second Hospital, Sichuan University between August 2020 and December 2022. According to their treatment plans, the pregnant women were divided into a cervical pessary group (n=55) and a progesterone group (n=93). Spontaneous preterm birth before 37 weeks of pregnancy was defined as the main outcome index. Preterm birth (abortion) or spontaneous preterm birth (abortion) before 37, 34, 32, 30, and 28 weeks of pregnancy, mean extended gestational age, neonatal morbidity, and neonatal mortality were the secondary outcome indicators. The pregnancy outcomes and the neonatal outcomes of the two groups were compared and statistically analyzed. Results: There was no statistically significant difference in the incidence of preterm birth (including iatrogenic preterm birth, spontaneous preterm birth, and abortion) before 37, 34, 32, 30, and 28 weeks between the cervical pessary group and the progesterone group. When iatrogenic preterm birth was excluded, the incidence of spontaneous preterm birth before 37 weeks was lower in the cervical pessary group (23.6%) than that in the progesterone group (41.9%), with the difference between the two groups being statistically significant (P=0.024). There was no statistically significant difference in the incidence of spontaneous preterm birth (including miscarriage) before 34, 32, 30, and 28 weeks. There was no statistically significant difference in the incidence of neonatal morbidity, the rate of transfer to the neonatal care unit after birth, and the neonatal mortality rate between the two groups. Multivariate logistic analysis showed that treatment with cervical pessary was a protective factor for spontaneous preterm birth before 37 weeks compared to progesterone therapy. Conclusion: Using cervical pessary to prevent spontaneous preterm birth in singleton pregnant women with a short cervical length in the second trimester can significantly reduce the incidence of spontaneous preterm birth before 37 weeks.

Diabetes Mellitus as a Risk Factor for Spontaneous Preterm Birth in Women with a Short Cervix after Ultrasound-Indicated Cerclage.

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.

Preferred lifestyle intervention characteristics and behaviour change needs of postpartum women following cardiometabolic pregnancy complications.

BACKGROUND: Women with cardiometabolic pregnancy complications are at increased risk of future diabetes and heart disease which can be reduced through lifestyle management postpartum. OBJECTIVES: 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. DESIGN: Quantitative cross-sectional study. METHODS: Online survey. RESULTS: 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). CONCLUSION: 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.

Neonatal Outcomes after Maternal Biomarker-Guided Preterm Birth Intervention: The AVERT PRETERM Trial.

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.

Effects of Pregnancy-Onset Asthma on Perinatal Outcomes: A Retrospective Cohort Study.

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.

Evaluating the Efficacy of Cervical Tactile Ultrasound Technique as a Predictive Tool for Spontaneous Preterm Birth.

Background: Premature cervical softening and shortening may be considered an early mechanical failure that predispose to preterm birth. Purpose: This study aims to explore the applicability of an innovative cervical tactile ultrasound approach for predicting spontaneous preterm birth (sPTB). Materials and Methods: 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. Results: 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). Conclusion: 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.

Predicting Preterm Birth Using Cell-Free Ribonucleic Acid.

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.

The interrelation between microbial immunoglobulin coating, vaginal microbiota, ethnicity, and preterm birth.

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. CONCLUSION: 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.

A multisite study to develop and validate first trimester, circulating microparticle biomarkers for tiered risk stratification of spontaneous preterm birth in nulliparas.

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. STUDY DESIGN: 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. CONCLUSION: 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.

Predicting Spontaneous Preterm Birth Using the Immunome.

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.

Vaginal microbiota and spontaneous preterm birth in pregnant women at high risk of recurrence.

We describe vaginal microbiota, including Gardnerella species and sexually transmitted infections (STIs), during pregnancy and their associations with recurrent spontaneous preterm birth (sPTB). We performed a prospective cohort study in a tertiary referral centre in the Netherlands, among pregnant women with previous sPTB <34 weeks' gestation. Participants collected three vaginal swabs in the first and second trimester. Vaginal microbiota was profiled with 16S rDNA sequencing. Gardnerella species and STI's were tested with qPCR. Standard care was provided according to local protocol, including screening and treatment for bacterial vaginosis (BV), routine progesterone administration and screening for cervical length shortening. Of 154 participants, 26 (16.9 %) experienced recurrent sPTB <37 weeks' gestation. Microbiota composition was not associated with sPTB. During pregnancy, the share of Lactobacillus iners-dominated microbiota increased at the expense of diverse microbiota between the first and second trimester. This change coincided with treatment for BV, demonstrating a similar change in microbiota composition after treatment. In this cohort of high-risk women, we did not find an association between vaginal microbiota composition and recurrent sPTB. This should be interpreted with care, as these women were offered additional preventive therapies to reduce sPTB according to national guidelines including progesterone and BV treatment. The increase observed in L. iners dominated microbiota and the decrease in diverse microbiota mid-gestation was most likely mediated by BV treatment. Our findings suggest that in recurrent sPTB occurring despite several preventive therapies, the microbe-related etiologic contribution might be limited.

Spontaneous Preterm Births in Malaysia: Are There Modifiable Antenatal Risk Factors?

Background Spontaneous preterm birth (SPB) is a global public health concern with devastating health effects on SPB survivors. This study aimed to determine modifiable antenatal risk factors associated with SPB among women attending government healthcare facilities in Malaysia. Methodology A retrospective record review of 49,416 national obstetrics registry data from 2015 was conducted and analyzed using binary logistic regression based on six antenatal factor divisions. Results Mothers with pre-existing diabetes had higher odds (adjusted odds ratio (aOR) = 3.09) of delivering prematurely than mothers without diabetes. Mothers with chronic hypertension with superimposed pre-eclampsia (aOR = 2.51) and gestational hypertension (aOR = 1.44) had higher odds of experiencing preterm birth than mothers with no hypertension. Underweight mothers had higher odds (aOR = 1.27) of delivering prematurely than mothers with an ideal body mass index (18.5 to <25.0 kg/m2). Mothers with moderate anemia (hemoglobin level: 7 to <9 g/dL) had higher odds (aOR = 1.18) of preterm birth than mothers with normal hemoglobin levels (≥11 g/dL). Conclusions Maternal biomarkers, such as glucose level, blood pressure, BMI, and hemoglobin level, play an important role in reducing the rate of SPB in Malaysia. This study recommends strengthening pre-pregnancy, antenatal, and postpartum care through multidisciplinary and multi-agency team collaboration, addressing both modifiable and non-modifiable risk factors and adopting a dual approach that combines preventive and curative care.

Molybdenum Concentration and the Risk of Spontaneous Preterm Birth: A Nested Case-Control Study - Beijing Municipality, China, 2018-2020.

What is already known about this topic?: The level of molybdenum (Mo) in a mother's urine has been linked to the growth rate of the fetus and the blood pressure levels in children. What is added by this report?: We evaluated the variations in maternal plasma Mo concentrations throughout pregnancy and their potential association with the risk of spontaneous preterm birth (SPB). What are the implications for public health practice?: Future research must determine the Mo levels in pregnant women across various regions in China. Moreover, particular attention needs to be given to the potential increase in Mo concentration throughout pregnancy and its possible adverse impacts on the health of both the mother and the fetus.

Changes of uterocervical angle and cervical length in early and mid-pregnancy and their value in predicting spontaneous preterm birth.

Objective: To explore the feasibility of transvaginal ultrasound measurement of uterocervical angle (UCA) and cervical length (CL) in early and mid-pregnancy and evaluate their combined prediction of spontaneous preterm birth (sPTB) in singleton pregnancies. Patients and Methods: This retrospective study comprised 274 pregnant women who underwent transvaginal ultrasound measurement of CL in mid-pregnancy (15-23+6 weeks); in 75 among them, CL also had been measured in early-pregnancy (<14 weeks). These 274 pregnant women were further divided into a preterm group (n = 149, <37 weeks gestation) and a control group (n = 125, >37 weeks gestation) according to delivery before or after 37 weeks, respectively. In the preterm group, 35 patients delivered before 34 weeks and the remaining 114 delivered between 34 and 37 weeks. Results: The optimal threshold of CL to predict preterm birth risk in women with <37 weeks gestation was 3.38 cm, and the optimal threshold of the UCA to predict preterm birth risk in the same group of women was 96°. The optimal threshold of CL to predict preterm birth risk in women with <34 weeks gestation was 2.54 cm, while that of the UCA in the same group of patients was 106°. The area under the curve for predicting preterm birth by combining the UCA and CL measurements was greater than that by using the UCA or CL alone (p < 0.01). The sensitivity and specificity for predicting preterm birth at <34 weeks gestation was 71.7% and 86.4%, respectively; and the sensitivity and specificity for predicting preterm birth at <37 weeks gestation was 87.6% and 80.6%, respectively. The difference between the two groups in CL and UCA were not significant in early pregnancy (p > 0.01), but only in mid-pregnancy (p < 0.01). There was a negative correlation between UCA and gestational week at delivery (r = -0.361, p < 0.001) and a positive correlation between CL and gestational week at delivery (r = 0.346, p < 0.001) in mid-pregnancy. The proportion of deliveries at <34 weeks was highest when the UCA was >105°, and the proportion of deliveries between 35 and 37 weeks was highest when the UCA was between 95° and 105°. The proportion of deliveries at <34 weeks was highest when the CL was <2.5 cm. Conclusion: The combination of UCA and CL has a better ability to predict preterm birth than either measurement alone. A more obtuse UCA or a shorter CL is associated with an earlier spontaneous preterm birth. The UCA increases from early to mid-pregnancy, while the CL decreases from early to mid-pregnancy.

Risk factors of early spontaneous preterm birth despite carrying a cervical pessary in singleton pregnancies with a short cervix: Development of a risk prediction model.

Introduction: We aimed to identify the incidence and risk factors of spontaneous preterm birth in pessary carriers with singleton pregnancies and a short cervix in the mid-trimester of pregnancy. Material and Methods: Patient data were obtained from the PECEP Trial. We analyzed singleton pregnancies in pessary carriers with a short cervix (≤25 mm) between 18 and 22 gestational weeks. Demographics and obstetric history were compared to identify risk factors for spontaneous preterm birth < 34 gestational weeks. Each demographic and obstetric variable was compared between spontaneous preterm birth < 34 and ≥ 34 weeks of gestation.Regression analysis was used to identify risk factors. A risk score model was generated using the odds ratio for significant factors. The risk score model and spontaneous preterm birth risk were assessed using the receiver operating characteristic curve. Perinatal outcomes were compared by risk score. Results: Among 190 pregnant individuals, 12 (6.3%) had spontaneous preterm birth < 34 gestational weeks. In the bivariate analysis, statistically significant differences between those with and without spontaneous preterm birth were only observed for mean cervical length at diagnosis and mean cervical length after pessary placement. By multiple logistic regression analysis, maternal age (OR 0.818; 95% CI 0.69-0.97; P 0.020), cervical length at diagnosis (OR 0.560; 95% CI 0.43-0.73; P < 0.001) and smoking status (OR 7.276; 95% CI 1.02-51.80; P 0.048) remained significantly associated with spontaneous preterm birth.The ROC curve from the multiple logistic regression analysis, including cervical length, maternal age and smoking status, had an area under the curve (AUC) of 0.952 (P < 0.001). The ROC curve for the risk score model incorporating all three variables had an AUC of 0.864 (95% CI 0.77-0.96; P < 0.001). A high-risk score was predictive of spontaneous preterm birth with a sensitivity of 75%, specificity of 84%, positive predictive value of 24%, and negative predictive value of 98%.Women with a high-risk score had a significantly reduced latency to delivery and poorer neonatal outcomes than those with a low-risk score. Conclusions: Patients at a high risk for spontaneous preterm birth despite pessary therapy may be identified using cervical length at diagnosis added to maternal age and smoking status.