Subsequent Spontaneous Preterm Birth Research Articles

Maternal serum alpha-1 antitrypsin levels in spontaneous preterm and term pregnancies

Currently, there are no accurate means to predict spontaneous preterm birth (SPTB). Recently, we observed low expression of alpha-1 antitrypsin (AAT) in SPTB placentas. Present aim was to compare the concentrations of maternal serum AAT in pregnancies with preterm and term deliveries. Serum C-reactive protein (CRP) was used as a reference inflammatory marker. Two populations were studied. The first population comprised women who eventually gave birth spontaneously preterm (SPTB group) or term (control group). The second population included pregnant women shortly before delivery and nonpregnant women. We observed that serum AAT levels were higher in the SPTB group than in the controls, and a similar difference was observed when serum CRP was considered in multivariable analysis. However, the overlap in the AAT concentrations was considerable. No statistical significance was observed in serum AAT levels between preterm and term pregnancies at delivery. However, AAT levels were higher at delivery compared to nonpregnant controls. We did not observe a strong correlation between serum AAT and CRP in early pregnancy samples and at labor. We propose that during early pregnancy, complicated by subsequent SPTB, modest elevation of serum AAT associates with SPTB.

Placental histology for targeted risk assessment of recurrent spontaneous preterm birth

Spontaneous preterm birth significantly increases the risk for a recurrent preterm birth (rPTB). Few identifiable clinical risk factors exist in counseling of rPTB. Furthermore, treatment with progesterone supplementation has not consistently prevented preterm birth in high-risk patients, but may be effective in a subset of such patients. Placental pathology from a prior pregnancy may be used to predict which patients will experience rPTB, or to identify a subset more likely to respond to treatment with antenatal progesterone. To determine if histologic patterns are associated with rPTB among patients with an index spontaneous preterm birth. A secondary objective was to determine if placental histologic types and/or progesterone receptor density in the decidua is associated with response to progesterone supplementation with intramuscular 17 hydroxyprogesterone caproate (17-OHPC). This was a retrospective cohort study at a single institution of singleton pregnancies with an index spontaneous preterm birth and subsequent birth within the same hospital system between 2009 and 2019. Patients were included if placental pathology was available in the index spontaneous preterm birth. Logistic regression was utilized to determine independent association of four histologic types (acute inflammation (AI), maternal vascular malperfusion (MVM), fetal vascular malperfusion, chronic inflammation (CI)) with rPTB. For the secondary endpoint, 17-OHPC response was defined as achievement of > 3 weeks beyond the gestational age at delivery in the index pregnancy. Patients who delivered < 3 weeks from index pregnancy but > 39 weeks were excluded. Logistic regression was used to assess the independent association of placental histology with 17-OHPC response. Sensitivity analyses were completed utilizing only patients with an index birth < 36 weeks, and then excluding those with medically indicated preterm birth in a subsequent pregnancy. A nested case-control immunohistochemical study was done among 20 patients with a subsequent term and 20 patients with a subsequent spontaneous preterm birth. The percent of cells in the maternal decidua positive for progesterone receptor (PR) was correlated with subsequent pregnancy outcome. A total of 352 patients were included. AI was the most common histologic type seen among patients with spontaneous preterm birth (44.1%), followed by CI (40.9%) and MVM (31.3%). No histologic type was independently associated with rPTB. 155 patients received 17-OHPC in a second pregnancy. Low grade AI was significantly associated with decreased likelihood of 17-OHPC response. Low grade MVM in those with index pregnancy delivered at < 36 weeks was significantly associated with over 4 times increased likelihood of 17-OHPC response when excluding those with an iatrogenic subsequent preterm birth. Progesterone receptor staining was not associated with recurrent preterm birth. While AI was prevalent among spontaneous preterm births, over half of spontaneous preterm births were not associated with AI. Low grade AI was associated with significantly decreased response to 17-OHPC supplementation. Low grade MVM was associated with 4 fold increase likelihood of 17-OHPC response among those with index deliveries < 36 weeks. Further work is needed to determine whether placental pathological examination can be utilized to target treatment in subsequent pregnancies to prevent rPTB.

Risk of spontaneous preterm birth elevated after first cesarean delivery at full dilatation: a retrospective cohort study of over 30,000 women

Having a cesarean delivery at full dilatation has been associated with increased subsequent risk of spontaneous preterm birth. The Aberdeen Maternity and Neonatal Databank provides a rare opportunity to study subsequent pregnancy outcomes after a previous cesarean delivery at full dilatation over 40 years, with an ability to include a detailed evaluation of potential confounding factors. This study aimed to investigate if having an initial cesarean delivery at full dilatation is associated with spontaneous preterm birth or other adverse pregnancy outcomes in the subsequent pregnancy. A retrospective cohort study was conducted including women with a first and second pregnancy recorded within the Aberdeen Maternity and Neonatal Databank between 1976 and 2017, where previous cesarean delivery at full dilatation at term in the first birth was the exposure. The primary outcome was spontaneous preterm birth (defined as spontaneous birth <37 weeks). Multivariate logistic regression was used to investigate any association between cesarean delivery at full dilatation and the odds of spontaneous preterm birth. Cesarean delivery at full dilatation in previous pregnancy was compared with: (1) any other mode of birth, and (2) individual modes of birth, including planned cesarean delivery, cesarean delivery in first stage of labor (<10-cm dilatation), and vaginal birth (including spontaneous vaginal birth, nonrotational forceps, Kielland forceps, vacuum-assisted birth, breech vaginal birth). Other outcomes such as antepartum hemorrhage and mode of second birth were also compared. Of the 30,253 women included, 900 had a previous cesarean delivery at full dilatation in the first pregnancy. Women with previous cesarean delivery at full dilatation had a 3-fold increased risk of spontaneous preterm birth in a second pregnancy (unadjusted odds ratio, 2.63; 95% confidence interval, 1.82-3.81; adjusted odds ratio, 3.31; 95% confidence interval, 2.17-5.05) compared with those with all other modes of first birth, adjusted for maternal age, diabetes mellitus, body mass index, smoking, preeclampsia, antepartum hemorrhage, socioeconomic deprivation (Scottish Index of Multiple Deprivation 2016), year of birth, and interpregnancy interval (in second pregnancy). When compared with women with vaginal births only, women with cesarean delivery at full dilatation had 5-fold increased odds of spontaneous preterm birth (adjusted odds ratio, 5.37; 95% confidence interval, 3.40-8.48). Compared with first spontaneous vaginal birth, first instrumental births (nonrotational forceps, Kielland forceps, and vacuum births) were not associated with increased risk of spontaneous preterm birth in the second birth. After an initial cesarean delivery at full dilatation, 3.7% of women had a repeated cesarean delivery at full dilatation and 48% had a planned cesarean delivery in the second birth. This study is a substantial addition to the body of evidence on the risk of subsequent spontaneous preterm birth after cesarean delivery at full dilatation, and demonstrates a strong association between cesarean delivery at full dilatation in the first birth and spontaneous preterm birth in subsequent pregnancy, although the absolute risk remains small. This is a large retrospective cohort and includes a comprehensive assessment of potential confounding factors, including preeclampsia, antepartum hemorrhage, and lengths of first and second stage of labor. Future research should focus on understanding possible causality and developing primary and secondary preventative measures.

PROMPT: Prospective Meta-analysis for Pessary Trials Study Protocol.

Preterm birth, defined as birth before 37 weeks of gestation, is a leading cause of perinatal and infant mortality throughout the world. Preterm birth is also associated with long-term neurological disabilities and other significant health issues in children. A short cervix in the second trimester has been noted to be one of the strongest predictors of subsequent spontaneous preterm birth in both singleton and multiple pregnancies. Some studies have shown that cervical support in the form of an Arabin pessary lowers the risk of preterm birth in women with a singleton gestation and short cervical length; however, other studies have conflicting results. Our objective was to form an international collaborative of planned or ongoing randomized trials of pessary in singleton and twin gestations with a short cervix. In November 2014, an international group of investigators, who had initiated or were planning randomized trials of pessary for pregnant people with a short cervix and singleton or twin gestation to prevent preterm birth, formed a collaboration to plan a prospective individual patient data (IPD) meta-analysis of randomized trials (PROspective Meta-analysis of Pessary Trials [PROMPT]). The PROMPT investigators agreed on meta-analysis IPD hypotheses for singletons and twins, eligibility criteria, and a set of core baseline and outcome measures. The primary outcome is a composite of fetal death or preterm delivery before 32 weeks' gestation. Secondary outcomes include maternal and neonatal morbidities. The PROMPT protocol may be viewed as a written agreement among the study investigators who make up the PROMPT consortium (PROSPERO ID# CRD42018067740). Results will be published in phases as the individual participating studies are concluded and published. Results of the first phase of singleton and twin pessary trials are expected to be available in late 2022. Updates are planned as participating trials are completed and published. · Short cervical length predicts preterm birth.. · Results of prior cervical pessary trials are mixed.. · Meta-analysis of pessary trials protocol..

Association between the first and second trimester cell free DNA fetal fraction and spontaneous preterm birth

ABSTRACT Objective To evaluate whether the fetal fraction of cell-free DNA at the first and second trimesters is associated with spontaneous preterm birth. Methods This was a retrospective cohort study with singleton pregnancies who underwent noninvasive prenatal testing. According to pregnancy outcome, eligible patients were divided into a delivery group ≥37 weeks of pregnancy (term group) and <37 weeks of pregnancy (spontaneous preterm group). Stepwise linear regression was used to identify maternal characteristics associated with the fetal fraction of cell‐free DNA. Logistic regression analysis was performed to evaluate the association between the fetal fraction of cell-free DNA and spontaneous preterm birth, adjusted for confounding factors. Results 14,020 cases were included in the study, 13292 cases (94.81%) in the term group and 728 cases (5.19%) in the spontaneous preterm group. The cell-free fraction of fetal DNA was inversely correlated with maternal age and body mass index. Positively correlated with gestational age, fertility, and assisted reproductive technology. After adjusting for the covariates, logistic regression analysis revealed no statistically significant association between the fetal fraction of cell-free DNA and spontaneous preterm birth. Conclusion In our original study, we found no association between the fetal fraction on NIPT and subsequent spontaneous preterm birth.

Second stage cesarean and subsequent spontaneous preterm birth risk

Second stage cesarean and subsequent spontaneous preterm birth risk

Interventions to Prevent Spontaneous Preterm Birth in Women With Singleton Pregnancy Who Are at High Risk: Systematic Review and Network Meta-Analysis

(BMJ. 2022;376:e064547. doi: https://doi.org/10.1136/bmj-2021-064547) Two-thirds of preterm births (&lt;37 wk gestation) occur spontaneously, while one-third are intentionally induced. Patients at risk of spontaneous preterm birth may or may not exhibit symptoms. Among high-risk patients without symptoms, cervical length &lt;25 mm and history of spontaneous preterm birth are the 2 strongest predictors of a subsequent spontaneous preterm birth. In the United Kingdom, vaginal progesterone or cervical cerclage are the recommended interventions for preventing spontaneous preterm birth in patients with those 2 predictors, though only 16% of preterm birth clinics in the UK routinely administer vaginal progesterone in this setting. This study used network meta-analysis estimates and compares the effectiveness of vaginal progesterone and cervical cerclage in preventing spontaneous preterm birth in at-risk patients.

Cervical microRNA expression and spontaneous preterm birth

Preterm birth remains a major public health issue affecting 10% of all pregnancies and increases risks of neonatal morbidity and mortality. Approximately 50% to 60% of preterm births are spontaneous, resulting from preterm premature rupture of membranes or preterm labor. The pathogenesis of spontaneous preterm birth is incompletely understood, and prediction of preterm birth remains elusive. Accurate prediction of preterm birth would reduce infant morbidity and mortality through targeted patient referral to hospitals equipped to care for preterm infants. Two previous studies have analyzed cervical microRNAs in association with spontaneous preterm birth and the length of gestation, but the extent to which microRNAs serve as predictive biomarkers remains unknown. This study aimed to examine associations between cervical microRNA expression and spontaneous preterm birth, with the specific goal of identifying a subset of microRNAs that predict spontaneous preterm birth. We performed a prospective, nested, case-control study of 25 cases with spontaneous preterm birth and 49 term controls. Controls were matched to cases in a 2:1 ratio on the basis of age, parity, and self-identified race. Cervical swabs were collected at a mean gestational age of 17.1 (4.8) weeks of gestation, and microRNAs were analyzed using a quantitative polymerase chain reaction array. Normalized microRNA expression was compared between cases and controls, and a false discovery rate of 0.2 was applied to account for multiple comparisons. Histopathologic analysis of slides of cervical swab samples was performed to quantify leukocyte burden for adjustment in conditional regression models. We explored the use of Relief-based unsupervised identification of top microRNAs and support vector machines to predict spontaneous preterm birth. We performed microRNA enrichment analysis to explore potential biologic targets and pathways in which up-regulated microRNAs might be involved. Of the 754 microRNAs on the polymerase chain reaction array, 346 were detected in ≥75% of participants' cervical swabs. Average cervical microRNA expression was significantly higher in cases of spontaneous preterm birth than in controls (P=.01). There were 95 significantly up-regulated individual microRNAs (>2-fold change) in cases of subsequent spontaneous preterm birth compared with term controls (P<.05; q<0.2). Notably, miR-143, miR-30e-3p, and miR-199b were all significantly up-regulated, which is consistent with the 1 previous study of cervical microRNA and spontaneous preterm birth. A Relief-based, novel variable (feature) selection machine learning approach had low-to-moderate prediction accuracy, with an area under the receiver operating curve of 0.71. Enrichment analysis revealed that identified microRNAs may modulate inflammatory cell signaling. In this prospective nested case-control study of cervical microRNA expression and spontaneous preterm birth, we identified a global increase in microRNA expression and up-regulation of 95 distinct microRNAs in association with subsequent spontaneous preterm birth. Larger and more diverse studies are required to determine the ability of microRNAs to accurately predict spontaneous preterm birth, and mechanistic work to facilitate development of novel therapeutic interventions to prevent spontaneous preterm birth is warranted.

Postpartum cervical length as a predictor of subsequent preterm birth—novel insights on an old enigma

Preterm birth poses one of the biggest challenge in modern obstetrics. Prediction of preterm birth has previously been based on patient history of preterm birth, short cervical length around midtrimester, and additional maternal risk factors. Little is known about cervical length and physiology during the postpartum period and any associations between postpartum cervical features and subsequent preterm birth. This study aimed to determine the feasibility and utility of postpartum cervical length measurements in prediction of subsequent spontaneous preterm birth. This was a prospective cohort study in a single tertiary center, conducted during a 5-year period (2017-2021). We evaluated the mean postpartum cervical length in patients after both preterm birth and term deliveries at 4 time periods: 8, 24, and 48 hours, and 6 weeks postpartum, with follow-up in their subsequent pregnancies to evaluate gestational age at delivery. The mean postpartum cervical length in different populations stratified by gestational age at delivery was assessed in phase 1 of the study, and the gestational age at subsequent delivery was assessed in phase2. A total of 1384 patients participated in phase 1. Mean postpartum cervical length was significantly shorter in the preterm birth (<34 weeks' gestation) group than in the term group at 8 hours (8.4±4.2 vs 22.3±3.5 mm; P<.0001), 24 hours (13.2±3.8 vs 33.2±3.1 mm; P<.0001), and 48 hours (17.9±4.4 vs 40.2±4.2 mm; P<.0001) postpartum. There was no significant difference in mean postpartum cervical length between the preterm birth group and the term group at 8, 24, and 48 hours postpartum. Cervical length was similar between the groups at 6 weeks postpartum. A total of 891 patients participated in phase 2. The area under the curve was higher for preterm birth screening based on a history of a short postpartum cervix alone than for a history of spontaneous preterm birth alone (0.66 [95% confidence interval, 0.63-0.69] vs 0.57 [95% confidence interval, 0.54-0.61]; P<.0001). Combining both a history of spontaneous preterm birth and a short postpartum cervix resulted in additional benefit, with an area under the curve of 0.74 (95% confidence interval, 0.73-0.84; P<.0001). Postpartum cervical length measurements may assist in detecting the group of patients at higher risk of subsequent spontaneous preterm birth. It may be beneficial to consider an increased follow-up regimen and earlier interventions in this group to reduce adverse perinatal outcomes.

Fetal station at caesarean section and risk of subsequent preterm birth - A cohort study

ObjectivesAn increased risk of preterm birth (PTB) following a caesarean section (CS) in the second stage of labor has been demonstrated. We aimed to investigate the relationship between the station of the presenting fetal part and the surgical technique at first CS, and the risk of subsequent PTB. Study designThis was a cohort study of 11,850 women in Sweden, delivered by CS in 2001–2007 at any of 23 birth units, with a second delivery in 2001–2009. Clinical information was retrieved from electronic birth records linked to national health registers. The risk of subsequent PTB was analyzed by fetal station, defined as low (at or below the ischial spines) or high (above the ischial spines), and aspects of the surgical technique at index CS. Associations were explored with logistic regression and results are presented as odds ratios (ORs) with 95% confidence intervals (CIs), by type and severity (very early < 32 gestational weeks and moderate preterm 32–36 gestational weeks) of PTB. Multiple logistic regression included adjustments for maternal age, gestational age at first delivery, and inter-delivery interval. ResultsOut of 11,850 women delivered by CS, 1,016 (8.6%) delivered preterm in their subsequent pregnancy. There was an increased likelihood of spontaneous PTB, but not with medically indicated PTB, after an index CS with the fetal presenting part at a low station (aOR 1.61, 95% CI 1.23–2.11). CS performed at a low station was associated with birth < 32 gestational weeks (aOR 1.73, 95% CI 1.05–2.84) and birth at 32–36 gestational weeks (aOR 1.29, 95% CI 1.00–1.65), compared with high fetal station. Thickness of the uterine wall, incision type, and closure of the uterus at index CS did not affect the risk. ConclusionA primary CS at a low station was associated with a subsequent spontaneous PTB, but not medically indicated PTB. Surgical technique at index CS did not alter the risk.

The association between induction of labour in nulliparous women at term and subsequent spontaneous preterm birth: a retrospective cohort study.

To evaluate the rate of subsequent spontaneous preterm birth in patients with previous induction of labour at term compared to women with previous spontaneous labour at term. This was a retrospective cohort study of all women with consecutive births at the Royal Brisbane and Women's Hospital between 2014 and 2018. All nulliparous women with a singleton pregnancy and induction of labour at term or in spontaneous labour at term in the index pregnancy were included. Data was extracted from electronic medical records. The outcome of spontaneous preterm birth in the subsequent pregnancy was compared between patients with previous term induction of labour and in previous term spontaneous labour. A total of 907 patients with consecutive births met the inclusion criteria; of which 269 (29.7%) had a term induction of labour and 638 (70.3%) had a term spontaneous labour in the index pregnancy. The overall subsequent spontaneous preterm birth rate was 2.3%. Nulliparous women who underwent term induction of labour were less likely to have a subsequent preterm birth compared to nulliparous women in term spontaneous labour (0.74 vs. 2.98%; odds ratio [OR], 0.25; 95% confidence interval, 0.06-1.07; p=0.0496) in the index pregnancy. This however was not significant once adjusted for confounders (adjusted OR, 0.29; p=0.10). Spontaneous preterm birth was associated with a previous spontaneous labour compared to induction of labour between 37 to 37+6 and 38 to 38+6 weeks (adjusted OR 0.18 and 0.21; p=0.02 and 0.004 respectively). Term induction of labour does not increase the risk of subsequent spontaneous preterm birth compared to spontaneous labour at term in nulliparous women. Further research is needed to validate these findings in a larger cohort of women and to evaluate the effect of elective IOL among low-risk nulliparous women.

Prior term delivery increases risk of subsequent recurrent preterm birth: An unexpected finding.

BackgroundWomen with a prior pregnancy at term are generally considered to be at reduced risk for subsequent spontaneous preterm birth (sPTB), whereas a previous sPTB is a major predictor for a future sPTB.AimsThe objective of this study was to investigate the risk of recurrent sPTB in women with a prior term birth and a subsequent sPTB.Materials and MethodsThis is a retrospective cohort study conducted at St Thomas’ Hospital in London, UK. There were 430 women included: 230 with a term birth (caesarean section or vaginal delivery) preceding a sPTB (term + sPTB group) and 200 with a prior sPTB only (sPTB only group). The primary outcome was sPTB, <37 weeks gestation.ResultsOf the term + sPTB group, 38.7% (89/230) had a recurrent sPTB compared to 20% (40/200) in the sPTB only group (P < 0.0001), with a relative risk (RR) of 1.9. Of women who had a term caesarean section and a subsequent PTB, 50% (30/60) had a further sPTB (RR 2.5 compared to the sPTB only group), while 34.7% (59/170) of women who had a term vaginal birth and subsequent sPTB, had a further sPTB (RR 1.7 compared to the sPTB only group).ConclusionIn women who have had a previous sPTB, the risk of a recurrence is much higher than in women with a prior term birth. The aetiology of PTB may be different in this subgroup of women and needs to be further elucidated to determine how best to identify and treat them.

Duration of the second stage of labour and risk of subsequent spontaneous preterm birth.

To determine the risk of spontaneous preterm birth (sPTB) associated with the length of second stage of labour in the first term delivery. Retrospective cohort study. University hospital. Women with first two consecutive singleton births and the first birth at term. Those who did not reach the second stage of labour in the first delivery were excluded. Charts from 2007 to 2019 were reviewed. Rate of sPTB (<37weeks of gestation) in the second delivery. Of 13958 women who met study inclusion criteria, 1464 (10.5%) parturients had a prolonged second stage (≥180min) in their first term delivery. The rate of sPTB in the second delivery was similar in those with and without a prolonged second stage in first delivery (2.8% versus 2.8%; adjusted odds ratio [aOR] 1.35, 95% CI 0.96-1.90). After adjustment for mode of delivery, prolonged second stage was also not associated with subsequent sPTB in those who delivered by spontaneous and operative vaginal delivery. Those delivered by second-stage caesarean section in the first delivery had a higher risk of sPTB in the second delivery (25/526, 4.8%; aOR 2.66, 95% CI 1.71-4.12; p<0.001), with a more pronounced risk in those with second-stage caesarean following a prolonged second stage of labour (15/259, 5.8%; aOR 3.40, 95% CI 1.94-5.94; p<0.001). Second-stage duration in a first term vaginal delivery is not associated with subsequent sPTB. The risk of sPTB is increased following second-stage caesarean section, particularly if performed after a prolonged second stage. Second-stage caesarean delivery, particularly after prolonged second stage, increases the risk of preterm birth.

618Is mode of first birth a risk factor for subsequent preterm birth?

Abstract Background Previous preterm birth is a strong predictor of subsequent preterm birth but less is known about the causes of preterm birth following a full-term pregnancy. Recent research highlighted previous caesarean as a potential risk factor and we aimed to further explore this risk. Methods This population-based record linkage study included all women in NSW, Australia who had a live singleton first birth at ≥ 37 weeks gestation, followed by a singleton second birth between 2005–2017. Relative risk (RR) and 95%CI of having a subsequent preterm birth, spontaneous preterm birth or preterm pre-labour caesarean was calculated using individual modified Poisson regression models, with mode of first birth as the exposure. Results Women who had an intrapartum (RR:1.26, 95%CI 1.19–1.32) or prelabour caesarean (RR:1.26,95%CI 1.18–1.35) first birth had a higher risk of subsequent preterm birth, than those who birthed vaginally. Those who had a pre-labour caesarean (RR:0.74, 95%CI 0.67–0.82) had a lower risk of subsequent spontaneous preterm birth. However, prior pre-labour caesarean also greatly increased the risk of subsequent preterm prelabour caesarean (RR:5.25, 95%CI 4.65–5.93). Conclusions Pre-labour and intrapartum caesareans have differing effects on the risk of subsequent spontaneous preterm birth and preterm pre-labour caesarean. Key messages The risk of subsequent preterm birth following a first birth caesarean depends on whether the caesarean occurred before or after the onset of labour and whether the subsequent preterm birth is spontaneous or a pre-labour caesarean.

Is mode of first birth a risk factor for subsequent preterm birth?

Previous preterm birth is a strong predictor of subsequent preterm birth, but less is known about the causes of preterm birth following a full-term first pregnancy. Recent research has highlighted previous caesarean section as a potential risk factor. To examine the relationship between mode of first birth and the risk of subsequent preterm birth in New South Wales (NSW), Australia. A population-based record-linkage study of NSW women who had a live singleton first birth at ≥37weeks gestation, followed by a singleton second birth between 2005 and 2017. Relative risk (RR) and 95% CI of preterm birth in the subsequent pregnancy was calculated using modified Poisson regression, with mode of first birth as the exposure. Spontaneous preterm birth and preterm prelabour caesarean were secondary outcomes. Women who had either an intrapartum (RR: 1.26, 95% CI 1.19-1.32) or prelabour caesarean (RR: 1.26, 95% CI 1.18-1.35) first birth had a higher risk of subsequent preterm birth (any birth <37weeks gestation), than those who birthed vaginally. Women who had a previous instrumental birth (RR: 0.85, 95% CI 0.79-0.91) or prelabour caesarean (RR: 0.74, 95% CI 0.67-0.82) had lower risks of subsequent spontaneous preterm birth. However, prior prelabour caesarean also greatly increased risk of subsequent preterm prelabour caesarean (RR: 5.25, 95% CI 4.65-5.93). The mode of first birth has differing effects on the risk of subsequent spontaneous preterm birth and preterm prelabour caesarean. Awareness of the risk of subsequent preterm birth following caesarean section may help inform clinical decisions around mode of first birth.

Prolonged second stage of labor and risk of subsequent spontaneous preterm birth

Preterm birth is the leading cause of neonatal morbidity and death in the United States. Although many risk factors for spontaneous preterm birth have been elucidated, some women with a previous term delivery experience spontaneous preterm birth in the absence of any identifiable risk factors. Cervical trauma during a prolonged second stage of labor has been postulated as a potential contributor to subsequent spontaneous preterm birth. This study was designed to examine the relationship between the length of the second stage of labor in the first pregnancy and the risk of spontaneous preterm birth in the subsequent pregnancy. This was a retrospective cohort study of all women with 2 consecutive singleton deliveries at a single institution between July 2012 and June 2018, with the first delivery occurring ≥37 weeks of gestation. Multiparous women and those women who did not reach the second stage of labor in the first pregnancy were excluded. Prolonged second stage of labor was defined as ≥4 hours, based on the 75th percentile for this cohort and on recommendations from the National Institute of Child Health and Human Development. Very prolonged second stage of labor was defined as ≥7 hours, based on the 95th percentile for this cohort. The primary outcome was spontaneous preterm birth <37 weeks of gestation in the subsequent pregnancy. The Kruskal-Wallis test compared median values for nonparametric continuous variables; Fisher's exact tests compared proportions for categoric variables, and logistic regression generated odds ratios. A total of 1032 women met criteria for study inclusion, with an overall subsequent spontaneous preterm birth rate of 3.1%. Prolonged second stage of labor of ≥4 hours was identified in 24.4% (252/1032 women) of the cohort, with 70.6% (178/252 women) of this group delivering vaginally. There was no statistically significant difference in rate of spontaneous preterm birth in those with and without prolonged second stage of labor (4.4% [11/252 women] with prolonged labor vs 2.7% [21/780 women] without prolonged labor; P=.21; odds ratio, 1.6; 95% confidence interval, 0.8-3.5). Very prolonged second stage of labor of ≥7 hours was identified in 4.3% (44/1032 women) of the cohort, with 45.4% (20/44 women) of this group delivering vaginally. There was a significantly higher rate of spontaneous preterm birth in those with very prolonged second stage of labor compared with those without prolonged labor (9.1% [4/44 women] with prolonged labor vs 2.8% [28/988 women] without prolonged labor; P=.04; odds ratio, 3.4; 95% confidence interval, 1.1-10.2), although this finding did not persist after we controlled for the mode of first delivery (adjusted odds ratio, 1.55; 95% confidence interval, 0.65-3.73). Spontaneous preterm birth after very prolonged second stage of labor was identified in only 4 patients, all of whom had a cesarean delivery with the first pregnancy. A second stage of labor of ≥4 hours in the first pregnancy was not associated with an increased risk of subsequent spontaneous preterm birth and was associated with a high rate (>70%) of vaginal birth. A second stage of labor of ≥7 hours did not appear to be associated with an increased risk of preterm birth, when we adjusted for mode of first delivery. There was a nonsignificant increase in the risk of preterm birth in those who delivered via cesarean section after a second stage of labor of ≥7 hours.

Recurrence risk of preterm births: a retrospective Indian study

Preterm birth (PTB) is the leading cause of neonatal deaths and India is the biggest contributor to the global burden of PTBs. This study aimed to determine the risk of recurrence of PTBs and factors associated with recurrence among mothers delivered at a tertiary care perinatal centre in India. This retrospective study comprised women who had delivered singleton preterm babies (24–37 weeks of gestation and weighing ≥500 g) in 2009 and 2010, and had subsequent deliveries beyond 24 weeks of gestation by the end of March 2016. Preterm births were stratified as spontaneous and those with an indication for delivery. Information on demographic data and maternal and neonatal outcomes was accessed from the case records or enquired over telephone. Among 291 eligible women, the recurrence rate of PTB was 31.6%; 29.1% for prior spontaneous and 34.0% for indicated preterm deliveries. This recurrence risk is similar to that in the western populations. In 75.0% of the cases, the type of recurrent PTB corresponded to the index PTB. Preeclampsia (PE) was significantly associated with recurrence (OR 7.10; 95% CI: 3.33, 15.11; p < .001); thus, prevention of PE is a key component in the prevention of PTB. Impact Statement What is already known on this subject? Preventing preterm birth (PTB) remains a challenge because the causes of PTBs are numerous, complex and poorly understood. Spontaneous PTB before 34 weeks of gestation is a strong predictor of subsequent spontaneous PTB. Spontaneous PTB is not only associated with increased recurrence of spontaneous but also medically indicated PTB and vice versa. Risk factors may vary by the clinical subtype of the most recent PTB. What the results of this study add? Despite the highest reported number of PTBs, there are no data on recurrence from India. This study reveals that the recurrence rate of PTBs in an Indian population appears to mirror the rates in the developed nations and preeclampsia (PE) is strongly associated with recurrence. What the implications are of these findings for clinical practice and/or future research? The results of this study are useful for counselling women who had previous PTBs regarding their future obstetric outcomes. Focussed research on prediction and prevention of PE is an essential element in the algorithm for prevention of PTBs.

Association between fetal fraction at the second trimester and subsequent spontaneous preterm birth.

To evaluate the association between the fetal fraction of cell-free DNA at the second trimester and subsequent spontaneous preterm birth. In this retrospective cohort study, data were collected from women with singleton pregnancies who underwent noninvasive prenatal testing at 14 to 25weeks of gestation. The eligible patients were classified into three groups according to pregnancy outcome: birth at ≥37weeks of gestation (term group), delivery at <34weeks of gestation (early spontaneous preterm), and delivery at 34+0 to 36+6 weeks of gestation (late spontaneous preterm). Stepwise linear regression was performed to determine the maternal characteristics associated with the fetal fraction of cell-free DNA. Logistic regression was used to determine the relationship between the fetal fraction of cell-free DNA and pregnancy outcomes by adjusting for history of preterm birth. A total of 8129 singleton pregnancies met the recruitment criteria. Among them, 7790 (95.83%) were in the term group, 284 (3.49%) were in the late spontaneous preterm group, and 55 (0.68%) were in the early spontaneous preterm group. The fetal fraction of cell-free DNA was negatively correlated with body mass index, maternal age, nulliparity, and history of spontaneous preterm birth; positively correlated with gestational age; and not correlated with assisted reproduction or surface antigen of hepatitis B virus (HBsAg) positivity. After adjusting for history of preterm birth, a logistic regression analysis demonstrated no statistically significant associations between the fetal fraction of cell-free DNA and spontaneous preterm birth in any of the preterm groups (<34weeks, 34+0 to 36+6 weeks, and <37weeks). Our preliminary study found no relationship between the fetal fraction on NIPT at the second trimester and subsequent spontaneous preterm birth.

Prolonged Second Stage in the First Pregnancy and Risk of Subsequent Spontaneous Preterm Birth [30R

INTRODUCTION: Preterm birth (PTB) is the leading cause of neonatal morbidity/mortality. Although some risk factors for spontaneous PTB (sPTB) are known, sPTB often occurs without identifiable risk factors. A prolonged second stage may increase sPTB risk via mechanical trauma that disrupts cervical integrity. This study examines the association between second stage length and subsequent sPTB. METHODS: This retrospective study included women with two consecutive singleton deliveries at one institution from 07/2012-06/2018, with the first delivery occurring at term. Prolonged second stage (PSS) was defined as 4 hours or more, based on this cohort's 75th percentile and on national recommendations. Very prolonged second stage (VPSS) was defined as 7 hours or more, based on this cohort's 95th percentile. The primary outcome was subsequent sPTB before 37 weeks. Fisher exact test, Kruskal-Wallis test, and logistic regression were used for statistical analysis. RESULTS: Among 1,032 included women, the overall subsequent sPTB rate was 3.1%. Identified in 24.4%, PSS was not associated with increased rate of sPTB (4.4% with PSS vs 2.7% without PSS, p=0.21). Identified in 4.3%, VPSS was associated with a higher rate of sPTB (9.1% with VPSS vs 2.8% without VPSS, p=0.04, OR 3.4, 95% CI 1.1-10.2). CONCLUSION: When dichotomized using the nationally-accepted cutoff of 4 hours, prior second stage length was not associated with subsequent sPTB. However, there was an association between increased risk of sPTB and second stage length when using a higher cutoff of 7 hours. Because that population's sample size was small, larger studies are required to confirm this association.

Management of a woman with a previous spontaneous preterm birth

Preterm birth is an important cause of neonatal morbidity and mortality and has long term adverse health consequences. Worldwide, close to 15 million babies are born preterm each year, and there is no sign that the rate of preterm birth is slowing. A history of a previous spontaneous preterm birth is a significant risk factor for a subsequent spontaneous preterm birth; identifying these women provides an opportunity to optimise care in future pregnancies. Antenatal identification of women at the highest risk of preterm birth is challenging, as tests that accurately identify asymptomatic women who go on to deliver preterm are lacking. Furthermore, the short- and long-term benefits of interventions such as cerclage and progesterone remain unclear. Research is underway to develop biomarkers that can accurately predict women who will deliver preterm. However, without effective strategies that diminish rates of preterm birth and improve perinatal outcomes, the clinical role of these tests is less well defined.