Prediction Of Preterm Birth Research Articles

Prediction of preterm birth in women with fetal growth restriction - Is the weekly change in sFlt-1/PlGF ratio or PlGF levels useful?

To assess the rate of change in soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio and PlGF levels per week compared to a single sFlt-1/PlGF ratio or PlGF level to predict preterm birth for pregnancies complicated by fetal growth restriction. A prospective cohort study of pregnancies complicated by isolated fetal growth restriction. Maternal serum PlGF levels and the sFlt-1/PlGF ratio were measured at 4-weekly intervals from recruitment to delivery. We investigated the utility of PlGF levels, sFlt-1/PlGF ratio, change in PlGF levels per week or sFlt-1/PlGF ratio per week. Cox-proportional hazard models and Harrell's C concordance statistic were used to evaluate the effect of biomarkers on time to preterm birth. The total study cohort was 158 pregnancies comprising 91 (57.6%) with fetal growth restriction and 67 (42.4%) with appropriate for gestational age controls. In the fetal growth restriction cohort, sFlt-1/PlGF ratio and PlGF levels significantly affected time to preterm birth (Harrell's C: 0.85-0.76). The rate of increase per week of the sFlt-1/PlGF ratio (hazard ratio [HR] 3.91, 95% confidence interval [CI]: 1.39-10.99, p = 0.01, Harrell's C: 0.74) was positively associated with preterm birth but change in PlGF levels per week was not (HR 0.65, 95% CI: 0.25-1.67, p = 0.37, Harrell's C: 0.68). Both a high sFlt-1/PlGF ratio and low PlGF levels are predictive of preterm birth in women with fetal growth restriction. Although the rate of increase of the sFlt-1/PlGF ratio predicts preterm birth, it is not superior to either a single elevated sFlt-1/PlGF ratio or low PlGF level.

Outcomes of pregnancies complicated by cirrhosis: a retrospective cohort study

BackgroundAlthough pregnancy complicated by liver cirrhosis is rare, women with cirrhosis experience increased adverse pregnancy outcomes. This study aimed to evaluate pregnancy outcomes in women with liver cirrhosis and develop a predictive model using maternal factors for preterm birth in such pregnancies.MethodsA retrospective analysis was conducted on pregnancy outcomes of a cirrhosis group (n = 43) and a non-cirrhosis group (n = 172) in a university hospital between 2010 and 2022. Logistic regression evaluated pregnancy outcomes, and a forward stepwise logistic regression model was designed to predict preterm birth in pregnant women with cirrhosis. The model's predictive performance was evaluated using the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC).ResultsThe incidence of cirrhosis during pregnancy was 0.06% (50/81,554). Pregnant women with cirrhosis faced increased risks of cesarean section, preterm birth, intrahepatic cholestasis of pregnancy, thrombocytopenia, and postpartum hemorrhage. In pregnant women with cirrhosis, preterm birth risk significantly increased at an incidence rate of 46.51% (20/43). According to the prediction model, the key predictors of preterm birth in pregnant women with cirrhosis were intrahepatic cholestasis of pregnancy and total bilirubin. The model demonstrated accurate prediction, with an AUC of 0.847, yielding a model accuracy of 81.4%.ConclusionsPregnant women with cirrhosis face a heightened risk of adverse obstetric outcomes, particularly an increased incidence of preterm birth. The preliminary evidence shows that the regression model established in our study can use the identified key predictors to predict preterm birth in pregnant women with cirrhosis, with high accuracy.

Removal Versus Retention of Cervical Cerclage With Preterm Prelabor Rupture of Membranes: Systematic Review and Meta-analysis

ABSTRACT One predictor of preterm birth (PTB) is a short cervical length before 24 weeks of gestation. For pregnant women with short cervical length and a history of PTB, cervical cerclage plus progesterone is offered. This procedure has been shown to reduce the risk of PTB, pregnancy loss, and perinatal morbidity and mortality. However, it also increases the risk of preterm, premature rupture of membrane (pPROM). When pPROM occurs, the decision must be made to either remove or retain the cerclage. This decision is a challenge due to a lack of evidence to support retaining cerclage, which could prolong the duration of pregnancy, or removing it, which may decrease the risk chorioamnionitis. In addition, guidelines from international societies are conflicting: a practice bulletin from the American College of Obstetricians and Gynecologists regards both removal and retention of cerclage in pregnancies complicated with pPROM as reasonable options, whereas a practice guideline from the Royal College of Obstetricians and Gynecologists supports the removal of cerclage. The aim of this study was to compare the removal of cervical cerclage with its retention on maternal and perinatal outcomes. This was a systematic review and meta-analysis using an electronic search of Medline, Embase, and Cochrane electronic databases in February 2023. Included were prospective and retrospective publications, reported in English, which evaluated perinatal outcomes of removing or retaining cervical cerclage complicated by pPROM. Excluded were case reports, case series, review articles, letters to the editors, or editorials. The primary outcomes were pregnancy latency from pPROM >48 hours and >7 days. Quality assessment of the included studies used the Newcastle-Ottawa Scale. A total of 6 studies, representing 377 women (169 in the removal group and 208 in the retention group), were included in this systematic review. The removal group had significantly lower rates of pregnancy latency than the retention group at >48 hours (47% vs 85%; odds ratio [OR], 0.15; 95% confidence interval [CI], 0.07–0.31; P < 0.0001) and >7 days (33% vs 57%; OR, 0.30; 95% CI, 0.11–0.83; P = 0.02). However, the removal group also had lower rates than the retention groups of chorioamnionitis (29% vs 41%; OR, 0.57; 95% CI, 0.34–0.96; P = 0.03) and Apgar score <7 at 5 minutes (16% vs 43%; OR, 0.22; 95% CI, 0.08–0.56; P = 0.002). No significant differences were observed in the rates of postpartum endometritis, cesarean delivery, respiratory distress syndrome, neonatal sepsis, intraventricular hemorrhage, necrotizing enterocolitis, birthweight, fetal death, and neonatal mortality. In conclusion, the group that had cervical cerclage removal had a lower risk of experiencing pregnancy latency at >48 hours and >7 days than the group with cerclage retention. However, the retention group had a higher risk of chorioamnionitis and Apgar <7 at 5 minutes.

Maternal Acylcarnitine Disruption as a Potential Predictor of Preterm Birth in Primigravida: A Preliminary Investigation.

Preterm birth, defined as any birth before 37 weeks of completed gestation, poses adverse health risks to both mothers and infants. Despite preterm birth being associated with several risk factors, its relationship to maternal metabolism remains unclear, especially in first-time mothers. Aims of the present study were to identify maternal metabolic disruptions associated with preterm birth and to evaluate their predictive potentials. Blood was collected, and the serum harvested from the mothers of 24 preterm and 42 term births at 28-32 weeks gestation (onset of the 3rd trimester). Serum samples were assayed by untargeted metabolomic analyses via liquid chromatography/mass spectrometry (QTOF-LC/MS). Metabolites were annotated by inputting the observed mass-to-charge ratio into the Human Metabolome Database (HMDB). Analysis of 181 identified metabolites by PLS-DA modeling using SIMCA (v17) showed reasonable separation between the two groups (CV-ANOVA, p = 0.02). Further statistical analysis revealed lower serum levels of various acyl carnitines and amino acid metabolites in preterm mothers. Butenylcarnitine (C4:1), a short-chain acylcarnitine, was found to be the most predictive of preterm birth (AUROC = 0.73, [CI] 0.60-0.86). These observations, in conjuncture with past literature, reveal disruptions in fatty acid oxidation and energy metabolism in preterm primigravida. While these findings require validation, they reflect altered metabolic pathways that may be predictive of preterm delivery in primigravida.

First-trimester urinary extracellular vesicles as predictors of preterm birth: an insight into immune programming.

Background: The programming of innate and adaptive immunity plays a pivotal role in determining the course of pregnancy, leading to either normal term birth (TB) or preterm birth (PB) through the modulation of macrophage (M1/M2) differentiation. Extracellular vesicles (EVs) in maternal blood, harboring a repertoire of physiological and pathological messengers, are integral players in pregnancy outcomes. It is unknown whether urinary EVs (UEVs) could serve as a non-invasive mechanistic biomarker for predicting PB. Methods: This study investigated first-trimester UEVs carrying M1 messengers with altered immune programming, aiming to discern their correlation to subsequent PB. A birth cohort comprising 501 pregnant women, with 40 women experiencing PB matched to 40 women experiencing TB on the same day, was examined. First-trimester UEVs were isolated for the quantification of immune mediators. Additionally, we evaluated the UEV modulation of "trained immunity" on macrophage and lymphocyte differentiations, including mRNA expression profiles, and chromatin activation modification at histone 3 lysine 4 trimethylation (H3K4me3). Results: We found a significant elevation (p < 0.05) in the particles of UEVs bearing characteristic exosome markers (CD9/CD63/CD81/syntenin) during the first trimester of pregnancy compared to non-pregnant samples. Furthermore, UEVs from PB demonstrated significantly heightened levels of MCP-1 (p = 0.003), IL-6 (p = 0.041), IL-17A (p = 0.007), IP-10 (p = 0.036), TNFα (p = 0.004), IL-12 (p = 0.045), and IFNγ (p = 0.030) relative to those from TB, indicative of altered M1 and Th17 differentiation. Notably, MCP-1 (>174pg/mL) exhibited a sensitivity of 71.9% and specificity of 64.6%, and MCP-1 (>174pg/mL) and IFNγ (>8.7pg/mL) provided a higher sensitivity (84.6%) of predicting PB and moderate specificity of 66.7%. Subsequent investigations showed that UEVs from TB exerted a significant suppression of M1 differentiation (iNOS expression) and Th17 differentiation (RORrT expression) compared to those of PB. Conversely, UEVs derived from PB induced a significantly higher expression of chromatin modification at H3K4me3 with higher production of IL-8 and TNFα cytokines (p < 0.001). Implications: This pioneering study provides critical evidence for the early detection of altered M1 and Th17 responses within UEVs as a predictor of PB and early modulation of altered M1 and Th17 polarization associated with better T-cell regulatory differentiation as a potential prevention of subsequent PB.

Neutrophil-Lymphocyte Ratio, Platelet-Lymphocyte Ratio, and Length of Cervix as Predictors of Premature Delivery during the Covid-19 Pandemic at Cipto Mangunkusumo General Hospital

Abstract &#x0D; Objective: The percentage of neonatal death continues to increase on a yearly basis, in which prematurity is the main cause of mortality. This study determines the descriptive outcomes between neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLT), and cervical length as predictors of preterm birth.&#x0D; Methods: A retrospective analytical study is conducted using medical records from Dr. Cipto Mangunkusumo National General Hospital. The subjects of this study includes pregnant women diagnosed with preterm delivery in Dr. Cipto Mangunkusumo National General Hospital from April 2020 to June 2021. Data on neutrophil-lymphocyte and platelet-lymphocyte ratios were obtained from a complete blood test during admission. Cervical length is measured using transvaginal ultrasound. The three variables are compared to the control group, which consists of pregnant women with full term delivery.&#x0D; Results: This study conducted a study with a total of 81 subjects with preterm delivery and 92 subjects with full term delivery. There were no significant difference in neutrophil-lymphocyte and platelet-lymphocyte ratios between preterm and a-term delivery (p=0.795 and p=0.475). Cervical length was significantly longer in preterm compared to full term delivery (24,50 vs 3,15 mm; p = 0,031). The neck cervical length of several participants was not assessed. Cervical length in preterm delivery obtained only 21 patients and data from 10 subjects from the full term group.&#x0D; Conclusion: The ratio of neutrophil-lymphocyte and platelet-lymphocyte cannot be used as predictors of preterm birth in all pregnant women. To reduce bias in this research, studies with prospective study design with a specified subject criteria are needed.&#x0D; Keywords: cervical length, neutrophil-lymphocyte ratio, platelet lymphocyte ratio, premature delivery

Prediction of spontaneous preterm birth in women with previous full dilatation cesarean delivery

A previous term (≥37 weeks' gestation), full-dilatation cesarean delivery is associated with an increased risk for a subsequent spontaneous preterm birth. The mechanism is unknown. We hypothesized that the cesarean delivery scar characteristics and scar position relative to the internal cervical os may compromise cervical function, thereby leading to shortening of the cervical length and spontaneous preterm birth. This study aimed to determine the relationship of cesarean delivery scar characteristics and position, assessed by transvaginal ultrasound, in pregnant women with previous full-dilatation cesarean delivery with the risk of shortening cervical length and spontaneous preterm birth. This was a single-center, prospective cohort study of singleton pregnant women (14 to 24 weeks' gestation) with a previous term full-dilatation cesarean delivery who attended a high-risk preterm birth surveillance clinic (2017-2021). Women underwent transvaginal ultrasound assessment of cervical length, cesarean delivery scar distance relative to the internal cervical os, and scar niche parameters using a reproducible transvaginal ultrasound technique. Spontaneous preterm birth prophylactic interventions (vaginal cervical cerclage or vaginal progesterone) were offered for short cervical length (≤25 mm) and to women with a history of spontaneous preterm birth or late miscarriage after full-dilatation cesarean delivery. The primary outcome was spontaneous preterm birth; secondary outcomes included short cervical length and a need for prophylactic interventions. A multivariable logistic regression analysis was used to develop multiparameter models that combined cesarean delivery scar parameters, cervical length, history of full-dilatation cesarean delivery, and maternal characteristics. The predictive performance of models was examined using the area under the receiver operating characteristics curve and the detection rate at various fixed false positive rates. The optimal cutoff for cesarean delivery scar distance to best predict a short cervical length and spontaneous preterm birth was analyzed. Cesarean delivery scars were visualized in 90.5% (220/243) of the included women. The spontaneous preterm birth rate was 4.1% (10/243), and 12.8% (31/243) of women developed a short cervical length. A history- (n=4) or ultrasound-indicated (n=19) cervical cerclage was performed in 23 of 243 (9.5%) women; among those, 2 (8.7%) spontaneously delivered prematurely. A multiparameter model based on absolute scar distance from the internal os best predicted spontaneous preterm birth (area under the receiver operating characteristics curve, 0.73; 95% confidence interval, 0.57-0.89; detection rate of 60% for a fixed 25% false positive rate). Models based on the relative anatomic position of the cesarean delivery scar to the internal os and the cesarean delivery scar position with niche parameters (length, depth, and width) best predicted the development of a short cervical length (area under the receiver operating characteristics curve, 0.79 [95% confidence interval, 0.71-0.87]; and 0.81 [95% confidence interval, 0.73-0.89], respectively; detection rate of 73% at a fixed 25% false positive rate). Spontaneous preterm birth was significantly more likely when the cesarean delivery scar was <5.0 mm above or below the internal os (adjusted odds ratio, 6.87; 95% confidence interval, 1.34-58; P =.035). In pregnancies following a full-dilatation cesarean delivery, cesarean delivery scar characteristics and distance from the internal os identified women who were at risk for spontaneous preterm birth and developing short cervical length. Overall, the spontaneous preterm birth rate was low, but it was significantly increased among women with a scar located <5.0 mm above or below the internal cervical os. Shortening of cervical length was strongly associated with a low scar position. Our novel findings indicate that a low cesarean delivery scar can compromise the functional integrity of the internal cervical os, leading to cervical shortening and/or spontaneous preterm birth. Assessment of the cesarean delivery scar characteristics and position seem to have use in preterm birth clinical surveillance among women with a previous, full-dilatation cesarean delivery and could better identify women who would benefit from prophylactic interventions.

The uterocervical angle-cervical length ratio: A promising predictor of preterm birth?

To predict spontaneous preterm birth (sPTB) (labor before 37 weeks of pregnancy) in low-risk singleton pregnancies during the second trimester, using ultrasound markers: uterocervical angle (UCA) and cervical length (CL). In a prospective observational cohort study, we followed primigravid women with singleton pregnancies without known risk factors for sPTB from 16+0-23+6 weeks of pregnancy until birth. Transvaginal ultrasonography on admission revealed the UCA and CL, and maternal history was obtained from submitted patient profiles. Logistic regression models disclosed significant predictive variables, and receiver operating curves (ROCs) demonstrated optimal cut-offs and test accuracy indices. Predictive functions of variables were compared using positive and negative likelihood ratios. In a sample of 357 participants, 41 (11.5%) experienced sPTB. UCA and CL were significantly associated with sPTB when adjusting for other variables (adjusted odds ratio: UCA 1.05, 95% confidence interval [CI] 1.02-1.07 and CL 0.82, 95% CI 0.75-0.90). Optimal cut-offs were estimated to be 106° and 33 mm for UCA and CL, respectively. We devised the novel index UCA/CL with an area under the ROC of 0.781 (95% CI 0.734-0.823), cut-off = 3.09°/mm, and improved likelihood ratios (positive: 3.18, 2.47, and 4.22; negative: 0.63, 0.52, and 0.51 for UCA, CL, and UCA/CL, respectively). The second-trimester UCA/CL was found to be a promising index to predict sPTB in low-risk singleton pregnancies. Further multicenter studies may generalize this conclusion to other gestational ages or risk groups and make it more comprehensive by considering other risk factors.

Predicting preterm birth within 2 weeks in asymptomatic women with a short cervix: Combined effects of cervicovaginal fluid cytokine levels and fetal fibronectin test.

To predict preterm birth (PTB) accurately, we conducted a comprehensive cytokine assay using cervicovaginal fluid (CVF) and evaluated the additive effects of cytokine levels on the fetal fibronectin (fFN) test. A total of 645 CVF samples were collected from 256 asymptomatic pregnant women between 24 and 35 weeks gestation, exhibiting short cervix. After selection based on specific criteria, 17 cytokines in 105 CVF samples were simultaneously measured using multiplex assay. Multivariate logistic regression analysis was performed to evaluate the association between cytokine levels and impending PTB, which is defined as PTB within 2 weeks after CVF collection. Moreover, receiver operating characteristic (ROC) analysis was performed in women with positive fFN results, which was validated using another set of 65 CVF samples. In positive fFN women, the CCL2 level was significantly higher in the impending PTB group than the other group (p < 0.01) and a predictor of impending PTB (adjusted odds ratio 1.020, 95% confidence interval [95% CI] 1.003-1.038, p = 0.020). The cutoff value of CCL2 was 64.8 pg/mL (are under the curve 0.726, p = 0.004, 95% CI 0.593-0.859, sensitivity 45.2%, specificity 91.7%). Additionally, the reliable classification performance of proposed ROC model could be validated. However, measuring cytokine levels could not help in predicting impending PTB in women with negative fFN or normal labor onset in healthy-term women. Comprehensive analysis of CVF cytokines revealed that the CCL2 level significantly improves the prediction of impending PTB in asymptomatic fFN-positive women with a short cervix, which may contribute to better clinical management.

Prediction of preterm birth in growth-restricted and appropriate-for-gestational-age infants using maternal PlGF and the sFlt-1/PlGF ratio-A prospective study.

To assess the utility of placental growth factor (PlGF) levels and the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio to predict preterm birth (PTB) for infants with fetal growth restriction (FGR) and those appropriate for gestational age (AGA). Prospective, observational cohort study. Tertiary maternity hospital in Australia. There were 320 singleton pregnancies: 141 (44.1%) AGA, 83 (25.9%) early FGR (<32+0 weeks) and 109 (30.0%) late FGR (≥32+0 weeks). Maternal serum PlGF and sFlt-1/PlGF ratio were measured at 4-weekly intervals from recruitment to delivery. Low maternal PlGF levels and elevated sFlt-1/PlGF ratio were defined as <100 ng/L and >5.78 if <28 weeks and >38 if ≥28 weeks respectively. Cox proportional hazards models were used. The analysis period was defined as the time from the first measurement of PlGF and sFlt-1/PlGF ratio to the time of birth or censoring. The primary study outcome was overall PTB. The relative risks (RR) of birth within 1, 2 and 3 weeks and for medically indicated and spontaneous PTB were also ascertained. The early FGR cohort had lower median PlGF levels (54 versus 229 ng/L, p < 0.001) and higher median sFlt-1 levels (2774 ng/L versus 2096 ng/L, p < 0.001) and sFlt-1/PlGF ratio higher (35 versus 10, p < 0.001). Both PlGF <100 ng/L and elevated sFlt-1/PlGF ratio were strongly predictive for PTB as well as PTB within 1, 2 and 3 weeks of diagnosis. For both FGR and AGA groups, PlGF <100 ng/L or raised sFlt-1/PlGF ratio were strongly associated with increased risk for medically indicated PTB. The highest RR was seen in the FGR cohort when PlGF was <100 ng/L (RR 35.20, 95% CI 11.48-175.46). Low maternal PlGF levels and elevated sFlt-1/PlGF ratio are potentially useful to predict PTB in both FGR and AGA pregnancies.

No additional risk of congenital anomalies after first-trimester dydrogesterone use: a systematic review and meta-analysis.

No additional risk of congenital anomalies after first-trimester dydrogesterone use: a systematic review and meta-analysis.

Validating the ratio of insulin like growth factor binding protein 4 to sex hormone binding globulin as a prognostic predictor of preterm birth in Viet Nam: a case-cohort study

Objective To validate a serum biomarker developed in the USA for preterm birth (PTB) risk stratification in Viet Nam. Methods Women with singleton pregnancies (n = 5000) were recruited between 19+0-23+6 weeks’ gestation at Tu Du Hospital, Ho Chi Minh City. Maternal serum was collected from 19+0-22+6 weeks’ gestation and participants followed to neonatal discharge. Relative insulin-like growth factor binding protein 4 (IGFBP4) and sex hormone binding globulin (SHBG) abundances were measured by mass spectrometry and their ratio compared between PTB cases and term controls. Discrimination (area under the receiver operating characteristic curve, AUC) and calibration for PTB <37 and <34 weeks’ gestation were tested, with model tuning using clinical factors. Measured outcomes included all PTBs (any birth ≤37 weeks’ gestation) and spontaneous PTBs (birth ≤37 weeks’ gestation with clinical signs of initiation of parturition). Results Complete data were available for 4984 (99.7%) individuals. The cohort PTB rate was 6.7% (n = 335). We observed an inverse association between the IGFBP4/SHBG ratio and gestational age at birth (p = 0.017; AUC 0.60 [95% CI, 0.53-0.68]). Including previous PTB (for multiparous women) or prior miscarriage (for primiparous women) improved performance (AUC 0.65 and 0.70, respectively, for PTB <37 and <34 weeks’ gestation). Optimal performance (AUC 0.74) was seen within 19-20 weeks’ gestation, for BMI >21 kg/m2 and age 20-35 years. Conclusion We have validated a novel serum biomarker for PTB risk stratification in a very different setting to the original study. Further research is required to determine appropriate ratio thresholds based on the prevalence of risk factors and the availability of resources and preventative therapies.

Predicting preterm birth using explainable machine learning in a prospective cohort of nulliparous and multiparous pregnant women.

Preterm birth (PTB) presents a complex challenge in pregnancy, often leading to significant perinatal and long-term morbidities. "While machine learning (ML) algorithms have shown promise in PTB prediction, the lack of interpretability in existing models hinders their clinical utility. This study aimed to predict PTB in a pregnant population using ML models, identify the key risk factors associated with PTB through the SHapley Additive exPlanations (SHAP) algorithm, and provide comprehensive explanations for these predictions to assist clinicians in providing appropriate care. This study analyzed a dataset of 3509 pregnant women in the United Arab Emirates and selected 35 risk factors associated with PTB based on the existing medical and artificial intelligence literature. Six ML algorithms were tested, wherein the XGBoost model exhibited the best performance, with an area under the operator receiving curves of 0.735 and 0.723 for parous and nulliparous women, respectively. The SHAP feature attribution framework was employed to identify the most significant risk factors linked to PTB. Additionally, individual patient analysis was performed using the SHAP and the local interpretable model-agnostic explanation algorithms (LIME). The overall incidence of PTB was 11.23% (11 and 12.1% in parous and nulliparous women, respectively). The main risk factors associated with PTB in parous women are previous PTB, previous cesarean section, preeclampsia during pregnancy, and maternal age. In nulliparous women, body mass index at delivery, maternal age, and the presence of amniotic infection were the most relevant risk factors. The trained ML prediction model developed in this study holds promise as a valuable screening tool for predicting PTB within this specific population. Furthermore, SHAP and LIME analyses can assist clinicians in understanding the individualized impact of each risk factor on their patients and provide appropriate care to reduce morbidity and mortality related to PTB.

Functional MRI assessment of the lungs in fetuses that deliver very Preterm: An MRI pilot study

ObjectivesTo compare mean pulmonary T2* values and pulmonary volumes in fetuses that subsequently spontaneously delivered before 32 weeks with a control cohort with comparable gestational ages and to assess the value of mean pulmonary T2* as a predictor of preterm birth < 32 weeks’ gestation. MethodsMRI datasets scanned at similar gestational ages were selected from fetuses who spontaneously delivered < 32 weeks of gestation and a control group who subsequently delivered at term with no complications. All women underwent a fetal MRI on a 3 T MRI imaging system. Sequences included T2-weighted single shot fast spin echo and T2* sequences, using gradient echo single shot echo planar sequencing of the fetal thorax. Motion correction was performed using slice-to-volume reconstruction and T2* maps generated using in-house pipelines. Lungs were manually segmented and volumes and mean T2* values calculated for both lungs combined and left and right lung separately. Linear regression was used to compare values between the preterm and control cohorts accounting for the effects of gestation. Receiver operating curves were generated for mean T2* values and pulmonary volume as predictors of preterm birth < 32 weeks’ gestation. ResultsDatasets from twenty-eight preterm and 74 control fetuses were suitable for analysis. MRI images were taken at similar fetal gestational ages (preterm cohort (mean ± SD) 24.9 ± 3.3 and control cohort (mean ± SD) 26.5 ± 3.0). Mean gestational age at delivery was 26.4 ± 3.3 for the preterm group and 39.9 ± 1.3 for the control group. Mean pulmonary T2* values remained constant with increasing gestational age while pulmonary volumes increased. Both T2* and pulmonary volumes were lower in the preterm group than in the control group for all parameters (both combined, left, and right lung (p < 0.001 in all cases). Adjusted for gestational age, pulmonary volumes and mean T2* values were good predictors of premature delivery in fetuses < 32 weeks (area under the curve of 0.828 and 0.754 respectively). ConclusionThese findings indicate that mean pulmonary T2* values and volumes were lower in fetuses that subsequently delivered very preterm. This may suggest potentially altered oxygenation and indicate that pulmonary morbidity associated with prematurity has an antenatal antecedent. Future work should explore these results correlating antenatal findings with long term pulmonary outcomes.

The Endocannabinoid System - The Prediction of Spontaneous Preterm Birth in High-Risk Women: Protocol of a Study.

Spontaneous preterm birth (sPTB) is a major cause of perinatal morbidity and mortality, even in developed countries. Prediction of sPTB is therefore a valuable tool to reduce the associated risks. The current standard for the prediction of sPTB consists, in addition to anamnestic data, of previous sPTB and previous second trimester miscarriage, measurement of cervical length by transvaginal ultrasound (TVU CL) together with assessment of fetal fibronectin levels in cervicovaginal fluid. Other evaluation parameters, such as the level of endocannabinoids in the pregnant woman's blood, could increase the sensitivity of this management. Endocannabinoids (eCBs) are a part of the endocannabinoid system (ECS); out of them anandamide (arachidonoyl-ethanolamide, AEA), in particular, plays an important role in the regulation of pregnancy and childbirth. We present the protocol for an open, non-randomized study to evaluate concentrations of AEA and other endocannabinoids: 2 linoleoylglycerol (2-AG), 2 linoleoylglycerol (2-LG), 2 oleoylglycerol (2-OG), and 2 arachidonoyldopamine (2-ADOPA or also NADA) in the blood of pregnant women as potential predictors of sPTB. In a total of 230 women with a history of sPTB or miscarriage, eCBs levels between 22 and 28 weeks of gestation will be assessed from maternal blood, in addition to the standard procedure. The aim of the study is to determine the relationship between blood concentrations of the endocannabinoids tested and the risk of sPTB. The results of this study will describe the prognostic significance of maternal blood eCBs levels for sPTB, and could subsequently enable improved screening programs for early identification of sPTB.

Prediction of Preterm Birth with the Uterocervical Angle in Singleton Pregnancies Treated with a Cervical Pessary.

Cervical pessaries are an established therapy option for patients at risk for spontaneous preterm birth (sPTB). The uterocervical angle (UCA) remains a promising sPTB predictor. However, its clinical significance has yet to be described in patients treated with a pessary. This study analyzed data of patients treated with a pessary because of cervical shortening in singleton pregnancies. The patients were divided into 2 groups according to transvaginal ultrasound findings: the funneling group (n = 68) and the no-funneling group (n = 42). Moreover, we analyzed patients within these prespecified groups according to the UCA < 95° and ≥ 95°. Delivery occurred significantly earlier in patients treated with a pessary and with a high UCA ≥ 95°(p = 0.006). The median gestational age at delivery in patients treated with a pessary and with no funneling and a UCA < 95° vs. ≥ 95° were 39.00 and 36.14 weeks, respectively (p = 0.005). In cases with funneling and a UCA < 95° vs. ≥ 95° the mean gestational age at delivery was 38.14 and 38.07 weeks respectively (p=1,00). There was a significant negative linear correlation between UCA and the gestational age at delivery in all patients (p = 0.04), which was even profound in the group without funneling (p = 0.0002). However, we found no significant correlation between cervical length and gestational age at delivery in all patients (p = 0.42) as well as in the group without funneling (p = 0.28). In spite of pessary treatment, patients with UCA ≥ 95° presented with a higher risk of sPTB compared to patients with UCA < 95°. This suggests that the UCA seems to be a better predictor of sPTB than the cervical length in patients receiving pessary treatment.

A Machine Learning Algorithm using Clinical and Demographic Data for All-Cause Preterm Birth Prediction.

Preterm birth remains the predominant cause of perinatal mortality throughout the United States and the world, with well-documented racial and socioeconomic disparities. To develop and validate a predictive algorithm for all-cause preterm birth using clinical, demographic, and laboratory data using machine learning. We performed a cohort study of pregnant individuals delivering at a single institution using prospectively collected information on clinical conditions, patient demographics, laboratory data, and health care utilization. Our primary outcome was all-cause preterm birth before 37 weeks. The dataset was randomly divided into a derivation cohort (70%) and a separate validation cohort (30%). Predictor variables were selected amongst 33 that had been previously identified in the literature (directed machine learning). In the derivation cohort, both statistical (logistic regression) and machine learning (XG-Boost) models were used to derive the best fit (C-Statistic) and then validated using the validation cohort. We measured model discrimination with the C-Statistic and assessed the model performance and calibration of the model to determine whether the model provided clinical decision-making benefits. The cohort includes a total of 12,440 deliveries among 12,071 individuals. Preterm birth occurred in 2,037 births (16.4%). The derivation cohort consisted of 8,708 (70%) and the validation cohort consisted of 3,732 (30%). XG-Boost was chosen due to the robustness of the model and the ability to deal with missing data and collinearity between predictor variables. The top five predictor variables identified as drivers of preterm birth, by feature importance metric, were multiple gestation, number of emergency department visits in the year prior to the index pregnancy, initial unknown body mass index, gravidity, and prior preterm delivery. Test performance characteristics were similar between the two populations (derivation cohort area under the curve [AUC] = 0.70 vs. validation cohort AUC = 0.63). Clinical, demographic, and laboratory information can be useful to predict all-cause preterm birth with moderate precision. · Machine learning can be used to create models to predict preterm birth.. · In our model, all-cause preterm birth can be predicted with moderate precision.. · Clinical, demographic, and laboratory information can be useful to predict all-cause preterm birth..

Predicting preterm birth using machine learning techniques in oral microbiome

Preterm birth prediction is essential for improving neonatal outcomes. While many machine learning techniques have been applied to predict preterm birth using health records, inflammatory markers, and vaginal microbiome data, the role of prenatal oral microbiome remains unclear. This study aimed to compare oral microbiome compositions between a preterm and a full-term birth group, identify oral microbiome associated with preterm birth, and develop a preterm birth prediction model using machine learning of oral microbiome compositions. Participants included singleton pregnant women admitted to Jeonbuk National University Hospital between 2019 and 2021. Subjects were divided into a preterm and a full-term birth group based on pregnancy outcomes. Oral microbiome samples were collected using mouthwash within 24 h before delivery and 16S ribosomal RNA sequencing was performed to analyze taxonomy. Differentially abundant taxa were identified using DESeq2. A random forest classifier was applied to predict preterm birth based on the oral microbiome. A total of 59 women participated in this study, with 30 in the preterm birth group and 29 in the full-term birth group. There was no significant difference in maternal clinical characteristics between the preterm and the full-birth group. Twenty-five differentially abundant taxa were identified, including 22 full-term birth-enriched taxa and 3 preterm birth-enriched taxa. The random forest classifier achieved high balanced accuracies (0.765 ± 0.071) using the 9 most important taxa. Our study identified 25 differentially abundant taxa that could differentiate preterm and full-term birth groups. A preterm birth prediction model was developed using machine learning of oral microbiome compositions in mouthwash samples. Findings of this study suggest the potential of using oral microbiome for predicting preterm birth. Further multi-center and larger studies are required to validate our results before clinical applications.

A genome-wide and candidate gene association study of preterm birth in Korean pregnant women.

Preterm birth (PTB) refers to delivery before 37 weeks of gestation. Premature neonates exhibit higher neonatal morbidity and mortality rates than term neonates; therefore, it is crucial to predict and prevent PTB. Advancements enable the prediction and prevention of PTB using genetic approaches, especially by investigating its correlation with single nucleotide polymorphisms (SNPs). We aimed to identify impactive and relevant SNPs for the prediction of PTB via whole-genome sequencing analyses of the blood of 31 pregnant women with PTB (n = 13) and term birth (n = 18) who visited the Ewha Womans University Mokdong Hospital from November 1, 2018 to February 29, 2020. A genome-wide association study was performed using PLINK 1.9 software and 256 SNPs were selected and traced through protein-protein interactions. Moreover, a validation study by genotyping was performed on 60 other participants (preterm birth, n = 30; term birth, n = 30) for 25 SNPs related to ion channel binding and receptor complex pathways. Odds ratios were calculated using additive, dominant, and recessive genetic models. The risk of PTB in women with the AG allele of rs2485579 (gene name: RYR2) was significantly 4.82-fold increase, and the risk of PTB in women with the AG allele of rs7903957 (gene name: TBX5) was significantly 0.25-fold reduce. Our results suggest that rs2485579 (in RYR2) can be a genetic marker of PTB, which is considered through the association with abnormal cytoplasmic Ca2+ concentration and dysfunctional uterine contraction due to differences of RYR2 in the sarcoplasmic reticulum.

Risk factors associated with preterm birth among mothers delivered at Lira Regional Referral Hospital

BackgroundThe World Health Organization (WHO) defines Preterm Birth (PTB) as “a live birth taking place before the expected 37 weeks of gestation”. Annually, approximately 15 million infants are born prematurely, constituting significantly to infant mortality during the initial four weeks of life, responsible for 40% of deaths among children under the age of five. Evidently, preterm deliveries have contributed to 46% of admissions to the neonatal intensive care unit (NICU) at Lira Regional Referral Hospital (LRRH) over the past three years. Paradoxically, while the prevalence of preterm births remains high, there is a lack of documented information regarding the underlying risk factors. Consequently, the primary objective of this study was to assess the potential risk factors associated with preterm birth at LRRH.MethodsAn analytical cross-sectional research was undertaken at LRRH, employing a quantitative methodology. The study utilized secondary data obtained from a total of 590 comprehensive maternal medical records, of deliveries that occurred at the facility between April 2020 and July 2021. The collected data underwent analysis using STATA version 17 software. To identify predictors of preterm birth, a Logistic regression model was applied, yielding adjusted odds ratios (AOR) alongside 95% confidence intervals (CI). The significance level was set at p < 0.05 to establish statistical significance. Furthermore, assessments for multicollinearity and model fitness were conducted using the Variance Inflation Factor (VIF) and linktest, respectively.ResultsThe prevalence of preterm delivery among mothers who gave birth at LRRH stood at 35.8%. The outcomes of logistic regression analysis revealed that maternal employment status had a statistically significant association with preterm birth (AOR = 0.657, p = 0.037, 95%CI: 0.443–0.975); having a baby with low birth weight (AOR = 0.228, p < 0.001, 95% CI: 0.099–0.527) and experiencing preeclampsia (AOR = 0.142, p < 0.001, 95% CI: 0.088–0.229) were also identified as significant predictors of preterm birth in the study.Conclusions and recommendationsThe occurrence of preterm delivery is significantly higher (35.8%) among mothers who gave birth at LRRH when compared to the national average (13.6%). The prevalence of preterm birth among mothers was linked to factors such as employment status, delivery of low birth weight infants, and the presence of preeclampsia. Consequently, the research proposes a set of recommendations. Firstly, the Ministry of Health (MoH) should evaluate the present state of readiness within the healthcare system to effectively handle cases of preterm birth both within medical facilities and the community. Secondly, the Ministry of Gender, Labour, and Social Development should leverage Labor Officers to implement and uphold the regulations stipulated in the Employment Act and Labor Laws.