Risk Of Recurrent Preterm Birth Research Articles

Trends and risk of recurrent preterm birth in pregnancy cohorts in rural Bangladesh, 1990–2019

IntroductionA history of preterm birth reportedly increases the risk of subsequent preterm birth. This association has primarily been studied in high-income countries and not in low-income settings in transition with...

Obstetric Indications for Progestin Therapy

Specifically, meta-analyses of randomized trials demonstrate that vaginal progesterone reduces the risk of preterm birth in selected high-risk singleton pregnancies. 17-OHPC may also reduce the risk of recurrent preterm birth in singletons. Finally, one trial suggests that vaginal progesterone may also be beneficial in improving live birth rates in singletons with prior miscarriages and early pregnancy bleeding.

Effectiveness of 17-Alpha-Hydroxyprogesterone in the Prevention of Preterm Labour

Objective: To compare the effectiveness of 17-Alpha- Hydroxyprogesterone in preventing preterm labour.
 Study Design: Prospective longitudinal study.
 Place and Duration of Study: Department of Obstetrics and Gynecology, Combined Military Hospital, Sakardu Pakistan, from Jun to Dec 2019.
 Methodology: A total of 208 patients (104 in each group) were recruited in this study. Group-A 17-alpha-hydroxyprogesterone (250mg) intramuscular injection was given weekly from 20-36 weeks of gestation or delivery, whichever occurred first. GroupB (Control Group) received no treatment except routine antenatal care but was treated actively with tocolytic drugs and corticosteroids if they presented with preterm labour.
 Results: Mean age of the patients was 26.1±4.9 and 25.7±4.5 in Group-A and B, respectively. In Group-A (17-alphahydroxyprogesterone), the mean gestational age at delivery was 36.8±3.8; in Group-B (control), the mean gestational age was 35.7±1.3. Treatment was efficacious in 82 patients (78.8%) in Group-A and 65(62.5%) in Group-B. The difference was statistically significant between the two groups (p=0.009).
 Conclusion: 17 Alpha-Hydroxyprogesterone caproate preventive therapy likely plays an important role in reducing the risk of recurrent preterm birth.

Risk of recurrent preterm birth following spontaneous immature and extreme preterm birth in the Netherlands

Spontaneous preterm birth (sPTB) has proven to be an important risk factor for recurrent sPTB, yet the lower limit of gestational age of prior birth is not well defined. In this study, we assessed the risk of recurrent sPTB following immature and extreme preterm birth between 16+0 - 27+6 weeks and we assessed the relationship between the interpregnancy interval and the recurrent risk.

Outcomes of immediate subsequent pregnancy following previable preterm premature rupture of membranes

The risk of recurrent preterm birth (PTB) or premature rupture of membranes (PPROM) in subsequent pregnancy after spontaneous PTB or PPROM is well-described. Less is known about outcomes in subsequent pregnancy after previable PPROM (pPPROM). This study describes outcomes in a single health system over 10 years.

Low-dose aspirin use in pregnancy and the risk of preterm birth: a Swedish register-based cohort study

Preterm birth is the leading cause of neonatal mortality and morbidity. Women who have had a previous preterm birth are at increased risk for preterm birth in their subsequent pregnancies. Low-dose aspirin use reduces the risk for preterm birth among women at risk of developing preeclampsia, however, it is unclear whether low-dose aspirin may reduce the risk of recurrent preterm birth. This study aimed to investigate the association between low-dose aspirin use and preterm birth among women with a previous preterm birth. We conducted a Swedish register-based cohort study and included women who had a first and second pregnancy between 2006 and 2019, with the first pregnancy ending in preterm birth (medically indicated or with spontaneous onset <37 weeks of gestation). The association between low-dose aspirin use and preterm birth in the second pregnancy was estimated via logistic regression via standardization and expressed as marginal relative risks with the 95% confidence interval. Among the study cohort (N=22,127), 3057 women (14%) were prescribed low-dose aspirin during their second pregnancy and 3703 women (17%) gave birth prematurely. Low-dose aspirin use was associated with a reduced risk for preterm birth, (marginal relative risk, 0.87; 95% confidence interval, 0.77-0.99). There were no statistically significant associations between low-dose aspirin use and an altered risk for moderate preterm birth, defined as birth between 32 and 36 weeks' gestation (marginal relative risk, 0.90; 95% confidence interval, 0.78-1.03), or very preterm birth, defined as birth <32 weeks' gestation (marginal relative risk, 0.75; 95% confidence interval, 0.54-1.04). Regarding the onset of preterm birth, low-dose aspirin use was associated with a reduced risk for spontaneous preterm birth (marginal relative risk, 0.70; 95% confidence interval, 0.57-0.86) but no reduction in the risk for medically indicated preterm birth (marginal relative risk, 1.09; 95% confidence interval, 0.91-1.30) was observed. Among women with a previous preterm birth, low-dose aspirin use was associated with a reduced risk for preterm birth. When investigating preterm birth by onset in the second pregnancy, low-dose aspirin use was associated with a reduced risk for spontaneous preterm birth. Our results suggest that low-dose aspirin may be an effective prophylaxis for recurrent preterm birth.

A comprehensive analysis of the association between placental pathology and recurrent preterm birth

Histologic examination of the placenta is often performed after preterm birth. Although placental examination cannot change the index pregnancy outcome, it may inform the risk of adverse outcomes in a subsequent pregnancy. Previous research has examined the association between individual histologic lesions and pregnancy outcomes without consistent results. This study aimed to determine the independent contributions of the major placental pathology histologic types to recurrent preterm birth. This was a retrospective cohort study of deliveries at a tertiary care center from January 2009 to March 2018. Individuals with ≥2 births, an index birth of <37 weeks of gestation, and a placental pathology report from the index pregnancy were included. The presence of maternal vascular malperfusion, fetal vascular malperfusion, acute inflammation, and chronic inflammation was extracted from the pathology reports for each index placenta and classified as none, low grade, or high grade. A log-binomial model incorporating all 4 placental pathology histologic types, index gestational age, race, and maternal age was used to estimate the associations between each placental histologic type and risk of recurrent preterm birth. Moreover, 2-way interaction terms were studied among placental histologic types. In addition, 2 stratified analyses were completed on the basis of characteristics of the index preterm birth: (1) by late preterm (gestational age of 34-36 weeks) vs early-to-moderate preterm birth (<34 weeks) and (2) a subgroup analysis of those with spontaneous preterm birth. A total of 924 pregnancy pairs met the inclusion criteria. Only high-grade chronic inflammation was independently associated with an increased risk of recurrent preterm birth (adjusted risk ratio, 1.37; 95% confidence interval, 1.03-1.81). Stratified analysis by gestational age group demonstrated maternal vascular malperfusion was associated with recurrent preterm birth only among those with early preterm birth (adjusted risk ratio, 1.40; 95% confidence interval, 1.01-1.93). Among participants with spontaneous preterm labor, no association was found between pathology histologic types and risk of preterm birth. Among index preterm pregnancies, high-grade chronic placental inflammation was associated with recurrent preterm birth. Low-grade maternal vascular malperfusion was associated with recurrent preterm birth only among those with an early or moderate index preterm birth (<34 weeks of gestation). These findings may be useful in determining the risk profile for individual patients and may generate hypotheses as to the pathogenesis of recurrent preterm birth.

Vaginal progesterone vs intramuscular 17-hydroxyprogesterone caproate for prevention of recurrent preterm birth: a randomized controlled trial

Preterm birth is the leading cause of neonatal morbidity and mortality, and previous preterm birth is one of the strongest risk factors for preterm birth. National and international obstetrical societies have different recommendations regarding progesterone formulation for the prevention of recurrent preterm birth. This study aimed to determine whether vaginal progesterone is superior to 17-hydroxyprogesterone caproate in the prevention of recurrent preterm birth in patients with singleton pregnancies who had a previous spontaneous preterm birth. This was an open-label multicenter pragmatic randomized controlled trial at 5 US centers of patients with singleton pregnancies at <24 weeks of gestation who had a previous spontaneous preterm birth randomized 1:1 to either 200 mg vaginal progesterone suppository nightly or 250 mg intramuscular 17-hydroxyprogesterone caproate weekly from 16 to 36 weeks of gestation. Based on the estimated recurrent preterm birth rate of 36% with 17-hydroxyprogesterone caproate, 95 participants were needed in each arm to detect a 50% reduction in preterm birth rate with vaginal progesterone, with 80% power and 2-sided alpha of 0.05. The primary outcome was preterm birth at <37 weeks of gestation. Prespecified secondary outcomes included preterm birth at <34 and <28 weeks of gestation, mean gestational age at delivery, neonatal morbidity and mortality, and measures of adherence. Analysis was by intention to treat. The chi-square test and Student t test were used as appropriate. P<.05 was considered significant. Overall, 205 participants were randomized; 94 participants in the vaginal progesterone group and 94 participants in 17-hydroxyprogesterone caproate group were included. Although gestational age at enrollment was similar, those assigned to vaginal progesterone initiated therapy earlier (16.9±1.4 vs 17.8±2.5 weeks; P=.001). Overall continuation of assigned formulation until delivery was similar (73% vs 69%; P=.61). There was no significant difference in preterm birth at <37 (31% vs 38%; P=.28; relative risk, 0.81 [95% confidence interval, 0.54-1.20]), <34 (9.6% vs 14.9%; P=.26; relative risk, 0.64 [95% confidence interval, 0.29-1.41]), or <28 (1.1% vs 4.3%; P=.37; relative risk, 0.25 [95% confidence interval, 0.03-2.20]) weeks of gestation. Participants in the vaginal progesterone group had a later mean gestational age at delivery than participants in the 17-hydroxyprogesterone caproate group (37.36±2.72 vs 36.34±4.10 weeks; mean difference, 1.02 [95% confidence interval, 0.01-2.01]; P=.047). Vaginal progesterone did not reduce the risk of recurrent preterm birth by 50% compared with 17-OHPC; however, vaginal progesterone may lead to increased latency to delivery. This trial was underpowered to detect a smaller, but still clinically significant, difference in the efficacy of preterm birth prevention. Patient factors that impact adherence and ability to obtain medication in a timely fashion should be included in counseling on progesterone selection.

Eligibility, Utilization, and Effectiveness of 17-Alpha Hydroxyprogesterone Caproate in a Statewide Population-Based Cohort of Medicaid Enrollees.

The primary objective was to estimate the initiation and adherence rates of 17 α-hydroxyprogesterone caproate (17OHPC) among eligible mothers in a statewide population-based cohort of Medicaid enrollees. The secondary objectives were to (1) determine the association of maternal sociodemographic and clinical characteristics with 17OHPC utilization and (2) assess the real-world effectiveness of 17OHPC on recurrent preterm birth prevention and admission to neonatal intensive care unit (NICU). This is a retrospective cohort study using a linked, longitudinal administrative dataset of birth certificates and medical assistance claims. Medicaid-enrolled mothers in Pennsylvania were included in this study if they had at least one singleton live birth from 2014 to 2016 following at least one spontaneous preterm birth. Maternal Medicaid claims were used to ascertain the use of 17OHPC from various manufacturers, including compounded formulations. Propensity score matching was used to create a covariate balance between 17OHPC treatment and comparison groups. We identified 4,781 Medicaid-covered 17OHPC-eligible pregnancies from 2014 to 2016 in Pennsylvania, 3.4% of all Medicaid-covered singleton live births. The population-based initiation rate was 28.5% among eligible pregnancies. Among initiators, 50% received ≥16 doses as recommended, while 10% received a single dose only. The severity of previous spontaneous preterm birth was the strongest predictor for the initiation and adherence of 17OHPC. In the matched treatment (n = 1,210) and comparison groups (n = 1,210), we found no evidence of 17OHPC effectiveness. The risks of recurrent preterm birth (relative risk [RR] 1.10, 95% confidence interval [CI] 0.97-1.24) and births admitted to NICU (RR 1.00, 95% CI 0.84-1.18) were similar in treated and comparison mothers. The 17OHPC-eligible population represented 3.4% of singleton live births. Less than one-third of eligible mothers initiated treatment. Among initiators, 50% were treatment adherent. We found no difference in the risk of recurrent preterm birth or admission to NICU between treatment and comparison groups. · About 3.4% of singleton live births were eligible for 17OHPC.. · About 30% of eligible mothers initiated treatment.. · We found no association of 17OHPC with recurrent preterm birth..

A Possible Mechanism of Action of 17α-Hydroxyprogesterone Caproate: Enhanced IL-10 Production.

The rate of recurrent spontaneous preterm birth (PTB) was reduced by 33% in the Maternal-Fetal Medicine Unit (MFMU) Network trial of 17α-hydroxyprogesterone caproate (17-OHPC), but the mechanism of action, 17 years later, remains elusive. The robustness of the interleukin-10 (IL-10) response to lipopolysaccharide (LPS) stimulation of leukocytes in pregnant women with a prior PTB correlates with gestational age at delivery. This study sought to determine if there is a relationship between the concentration of 17-OHPC and response to LPS stimulation. We performed a secondary analysis of data from the Omega-3 MFMU trial which evaluated the effectiveness of omega-3 fatty acid supplementation in reducing recurrent PTB. We utilized previously characterized data from a subanalyses of the Omega-3 trial of IL-10 and tumor necrosis factor alpha (TNF-α) levels from peripheral blood mononuclear cells stimulated with LPS. Blood was obtained from enrolled women at 16 to 22 weeks' gestation (baseline) and 25 to 28 weeks' gestation (posttreatment). All women received 17-OHPC and plasma 17-OHPC concentrations were measured at 25 to 28 weeks' gestation. We analyzed these data to determine if there was a relationship between 17-OHPC concentration and cytokine production. We then performed an in vitro study to determine if 17-OHPC could directly alter cytokine production by THP-1-derived macrophages. In the clinical samples, we found that 17-OHPC plasma concentrations were correlated with the quantity of the LPS-stimulated production of IL-10. TNF-α production after LPS stimulation was unrelated to 17-OHPC concentration. In the in vitro study, we demonstrate a 17-OHPC concentration dependent increase in IL-10 production. In women receiving 17-OHPC for PTB prevention, we demonstrate a relationship between plasma 17-OHPC and LPS-stimulated IL-10 production by circulating leukocytes. We also demonstrate that, in vitro, 17-OHPC treatment affects IL-10 production by LPS-stimulated macrophages. Collectively, these findings support an immunomodulatory mechanism of action of 17-OHPC in the prevention of recurrent PTB. · 17-OHPC plasma concentrations and LPS-stimulated IL-10 levels correlate in clinical samples in women at risk for recurrent preterm birth.. · 17-OHPC can modulate the response of LPS-stimulated macrophages to increase IL-10 production.. · There was no relationship between TNF-α and plasma concentration of 17-OHPC in clinical samples or in vitro..

Recurrent preterm birth risk assessment for two delivery subtypes: A multivariable analysis.

The study sought to develop and apply a framework that uses a clinical phenotyping tool to assess risk for recurrent preterm birth. We extended an existing clinical phenotyping tool and applied a 4-step framework for our retrospective cohort study. The study was based on data collected in the Genomic and Proteomic Network for Preterm Birth Research Longitudinal Cohort Study (GPN-PBR LS). A total of 52 sociodemographic, clinical and obstetric history-related risk factors were selected for the analysis. Spontaneous and indicated delivery subtypes were analyzed both individually and in combination. Chi-square analysis and Kaplan-Meier estimate were used for univariate analysis. A Cox proportional hazards model was used for multivariable analysis. : A total of 428 women with a history of spontaneous preterm birth qualified for our analysis. The predictors of preterm delivery used in multivariable model were maternal age, maternal race, household income, marital status, previous caesarean section, number of previous deliveries, number of previous abortions, previous birth weight, cervical insufficiency, decidual hemorrhage, and placental dysfunction. The models stratified by delivery subtype performed better than the naïve model (concordance 0.76 for the spontaneous model, 0.87 for the indicated model, and 0.72 for the naïve model). The proposed 4-step framework is effective to analyze risk factors for recurrent preterm birth in a retrospective cohort and possesses practical features for future analyses with other data sources (eg, electronic health record data). We developed an analytical framework that utilizes a clinical phenotyping tool and performed a survival analysis to analyze risk for recurrent preterm birth.

Preventing recurrent preterm birth with 125 mg of 17-alpha-hydroxyprogesterone caproate.

There is strong evidence that weekly intramuscular (IM) injections of 250 mg of 17-alpha-hydroxyprogesterone caproate (17-OHPC) reduce the risk of recurrent preterm birth (PTB); however, whether a lower dose of 17-OHPC could reduce the risk of recurrent PTB remains unclear. This study aimed to assess whether 125 mg of 17-OHPC reduces recurrent PTB among women with a prior singleton spontaneous PTB and cervical length >25 mm. This retrospective cohort study at a tertiary-care medical center in Japan included women with a prior singleton spontaneous PTB between 20 and 36 weeks' gestation and cervical length >25 mm, between 2008 and 2018. Primary outcomes were PTB <37 and <34 weeks' gestation. We calculated the adjusted odds ratio (aOR) and 95% confidence interval (CI) using a multiple logistic regression model. Gestational age at delivery was compared using the Kaplan-Meier survival curve and log-rank test. Overall, 173 women met the inclusion criteria. Eighty-four women received weekly injections of 125 mg of 17-OHPC, and 89 did not. Treatment with 125 mg of 17-OHPC significantly reduced the risk of recurrent spontaneous PTB <37 (aOR: 0.156 [95% CI: 0.049-0.497]) and <34 weeks' gestation (aOR: 0.156 [95% CI: 0.049-0.497]). The mean delivery gestational age was also significantly longer in the 17-OHPC group (log-rank p= 0.005). In this study population, weekly IM injections of 125 mg of 17-OHPC reduced the risk of recurrent PTB <37 and <34 weeks' gestation.

823 African-American race and subsequent pregnancy outcomes after a prior preterm birth

Whether African American (AA) race is a true causal risk factor for recurrent preterm birth (PTB) versus reflective of socioeconomic factors is debated. We investigate if AA race is a risk factor for recurrent PTB and adverse outcomes in the subsequent pregnancy after the first PTB, accounting for select social factors. Retrospective cohort study of nulliparas whose first delivery was between 16-37 weeks gestational age (GA) and had a subsequent pregnancy between 2013-2018. Multiple gestations in the index PTB were excluded. Women were grouped by self-identified race/ethnicity: AA, non-AA. The primary outcome was any recurrent PTB. Secondary outcomes were early PTB <34 weeks, delivery GA, cesarean delivery (CD), and perinatal outcomes. Outcomes were compared between groups; multivariable logistic regression calculated adjusted odds ratios (95% CI) with non-AA women as reference. Of 1744 women with singleton PTBs 16-37 weeks, 257 (15%) had a subsequent delivery in our study period –140 (54%) were AA. AA women were younger, more likely unmarried, used government insurance, and delivered vaginally in the index PTB (all p<0.05). Index PTB GA was similar (30 weeks AA vs 31 non-AA, p=0.12); AA women had a shorter interpregnancy interval (IPI: 11 months [IQR 5-22] vs 15 [9-25], p=0.003). In the subsequent pregnancy, there were no significant differences (crude or adjusted) in PTB <37 weeks, delivery GA, early PTB, preeclampsia, or perinatal outcomes between groups (Table). In fact, there were no subsequent PTBs <28 weeks. Of note, AA women had significantly higher odds of blood transfusion, and lower neonatal birthweights. Outcomes were unchanged when stratifying non-AA women into individual racial/ethnic groups. AA race was not significantly associated with risk for recurrent PTB, even when accounting for select socioeconomic factors – suggesting a role for race perhaps in the index PTB. While AA women had shorter IPIs, IPI was within appropriate ranges. Larger studies of race, recurrent PTB, and availability of immediate long-acting postpartum contraception are needed.

964 Prior spontaneous preterm birth: subsequent pregnancy outcomes among women with PPROM vs spontaneous preterm labor

Women with a history of spontaneous preterm birth (sPTB) are at an increased risk for recurrent preterm birth. Preterm premature rupture of membranes (PPROM) and spontaneous preterm labor (sPTL) have potentially varying mechanisms and etiopathogenesis. The objective of our study was to evaluate the differential impact of history of PPROM vs sPTL on subsequent pregnancy management and perinatal outcomes. Retrospective review of women delivering at a single hospital from July 2018- November 2019 to identify women with a history of sPTB of singleton gestations. The cohort was divided into two groups based on a history of sPTL vs PPROM. Demographic data, pregnancy management, and perinatal outcomes were abstracted through a review of electronic medical records and compared across the 2 groups using student’s t test and chi squared/Fischer’s exact test for continuous and categorical data respectively. Out of 2,803 women, 168 women had a history of sPTB: 125 (74%) with a history of sPTL and 43 (23%) with a history of PPROM. Demographic characteristics were similar across groups. We found no significant differences in the pregnancy interventions (Table 1) and perinatal outcomes (Table 2) among study groups. Subgroup analyses were performed evaluating the impact of vaginal vs IM progesterone. While there were no significant differences noted in women with a history of PPROM, differences were noted among women with a history of sPTL. Women who received IM progesterone had longer cervical lengths (mean ± SD) [36.3mm ± 4.4; N=21 vs 20.5 ± 12.2; N=18 p<0.001] and delivered at a later gestational age (mean ± SD) (37.2 ± 1.6 weeks; N=28 vs 34.7 ± 5.6 weeks; N = 23) as compared to women receiving vaginal progesterone. In our cohort, similar outcomes were noted in subsequent pregnancies among women with history of PPROM and sPTL. However, subgroup analyses in women with a history of sPTL suggest a potential benefit of IM progesterone. Further research in a larger cohort is warranted to delineate the differential impact of the history of sPTB in the context of PPROM vs sPTL.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

337 High grade chronic placental inflammation is independently associated with increased risk of recurrent preterm birth

Histologic examination of the placenta is often performed following delivery. Although placental examination cannot change the index pregnancy outcome, it may inform risk assessment for subsequent pregnancy. Prior research has examined the association between individual histologic lesions and pregnancy outcomes. The purpose of this study is to determine the association of combinations of histologic findings and risk of subsequent preterm birth (PTB). This was a retrospective cohort study of deliveries at a tertiary care center from January 2009 to March 2018. Individuals with two births and an index placental pathology report during the study period were included. The presence of maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM), maternal and/or fetal acute inflammation (AI) and chronic inflammation (CI) was extracted from the pathology report for each index placenta, classified as none, low, or high grade. A logistic model incorporating all four placental components was used to estimate associations between each histologic lesion category and risk of subsequent preterm birth, while controlling for the other lesion categories. Analysis was repeated restricting the sample only to those with an index PTB. 3926 women were included. Among all index pregnancies, presence of high grade CI and low grade MVM were associated with increased odds of subsequent PTB. AI (both low- and high-grade) and low grade FVM were associated with lower odds of subsequent PTB (Table). Among 924 index pregnancies delivering preterm, only high grade CI was independently associated with recurrent PTB (OR 1.57, 95% CI 1.02- 2.41, Figure). High-grade chronic placental inflammation in an index pregnancy is the only pathology independently associated with an increased risk of subsequent PTB, regardless of whether the index delivery is preterm or term. Decreased odds of PTB with AI and FVM in the full sample were not replicated when evaluating recurrent PTB.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The Risk of Preterm Birth in Women with Three Consecutive Deliveries—The Effect of Number and Type of Prior Preterm Births

Background: We aimed to explore the association of the number, order, gestational age and type of prior PTB and the risk of preterm birth (PTB) in the third delivery in women who had three consecutive singleton deliveries. Methods: A retrospective cohort study of all women who had three consecutive singleton births at a single medical center over a 20-year period (1994–2013). The primary outcome was PTB (<37 weeks) in the third delivery. Results: 4472 women met inclusion criteria. The rate of PTB in the third delivery was 4.9%. In the adjusted analysis, the risk of PTB was 3.5% in women with no prior PTBs; 10.9% in women with prior one PTB only in the first pregnancy; 16.2% in women with prior one PTB only in the second pregnancy; and 56.5% in women with prior two PTBs. A similar trend was observed when the outcome of interest was spontaneous PTB and when the exposure was limited to prior spontaneous or indicated PTB. Conclusions: In women with a history of PTB, the risk of recurrent PTB in subsequent pregnancies is related to the number and order of prior PTBs. These factors should be taken into account when stratifying the risk of PTB.

Pregnancy duration with use of 17-α-hydroxyprogesterone caproate in a retrospective cohort at high risk of recurrent preterm birth

The use of 17-α-hydroxyprogesterone caproate for the prevention of recurrent spontaneous preterm birth has become widespread, yet there are conflicting data regarding its efficacy. We sought to determine whether administration of 17-α-hydroxyprogesterone caproate was associated with pregnancy prolongation in women at a high risk of recurrent spontaneous preterm birth. This is a retrospective cohort study of women with singleton pregnancies and a history of spontaneous preterm birth at <37 weeks' gestation who received care at our academic tertiary care center between 2009 and 2019. We included women with gestations that progressed beyond 16 weeks. We excluded those who underwent history-indicated cerclage placement. We first examined the characteristics of women who received 17-α-hydroxyprogesterone caproate and those who did not. Covariates with a P value of ≤.2 on this univariate analysis were considered for incorporation into a Cox proportional hazards model to assess the association between 17-α-hydroxyprogesterone caproate use and pregnancy prolongation up to 35 weeks. Of 861 women included in the study, 570 (66.2%) reported non-Hispanic black racial identity, 237 (27.5%) lived in zip codes with a high infant mortality rate (≥12.1/1000 infants), 287 (33.3%) had more than 1 previous spontaneous preterm birth, 372 (43.2%) had previous spontaneous preterm birth at ≤32 weeks' gestation, and 242 (28.1%) were smokers. Here, 152 pregnancies (17.6%) were complicated by spontaneous preterm birth at <35 weeks' gestation. Factors independently associated with pregnancy duration up to 35 weeks included weight gain of <0.2 kg (0.5 lb) per week, first recorded weight of <98 kg (215 lb), obstetrical history, non-Hispanic white racial identity, lack of prenatal care, and vaginal bleeding. Gestational age at delivery was also independently associated with interventions typically employed for midtrimester cervical shortening and/or dilation, including ultrasound- and examination-indicated cerclage, pessary placement, and vaginal progesterone administration. The use of 17-α-hydroxyprogesterone caproate was not associated with pregnancy prolongation (adjusted hazard ratio, 0.83; 95% confidence interval, 0.60-1.15). The risk profile of our cohort is similar to that of women enrolled in the landmark trial that led to the Food and Drug Administration's approval of 17-α-hydroxyprogesterone caproate. Despite the high-risk nature of the pregnancies examined, we found no association between use of the medication in daily clinical practice and pregnancy prolongation up to 35 weeks. This finding adds to the mounting evidence that calls into question the drug's efficacy in reducing the risk of recurrent spontaneous preterm birth.

Retrospective study of the recurrence risk of preterm birth in Japan

Background A history of preterm birth is a risk factor for preterm birth in a future pregnancy, and there are some reports of prevention methods, such as the administration of progesterone. However, the rate of recurrence of preterm birth in Japan has not been clarified, and there is no data for judging whether these preventive methods are effective. Objective To clarify the risk of recurrence of preterm birth and preterm prelabor rupture of membranes (pPROM) in Japan. Materials and methods A retrospective study was conducted using the perinatal registration database of the Japan Obstetrics and Gynecology Society for the Perinatal Center from 2014 to 2016. There were 704,418 subjects, of which 190,990 were excluded those with unknown maternal information, those under the age of 20 years, those with perinatal disease related to preterm birth, and first-time mothers. Results Logistic model unavailable and multivariate analysis were performed. An analysis of the preterm birth history indicated the risk of preterm birth in the current pregnancy, and the odds ratio for preterm birth recurrence once, twice, and three times or more was 3.3, 6.6, and 7.8, respectively. As a secondary analysis, we analyzed whether the history of pPROM is a risk factor of recurrence of pPROM and found a significant association with an odds ratio of 3.4. Conclusion Having a preterm birth history increases the risk of recurrence of preterm birth, and the risk of recurrent preterm birth increases as the number of preterm births increases. Although this report is intended for high-risk pregnancies wherein the rate of preterm birth is high, as previously reported, our data indicate that in Japan, preterm birth is a risk factor of recurrent preterm birth.

Recurrence risk of preterm birth in a subsequent singleton pregnancy after a spontaneous preterm triplet delivery

ObjectiveHistory of prior preterm birth (PTB) represents one of the strongest risk factors for recurrent PTB. Nevertheless, whether the occurrence of PTB in multifetal gestation is associated with increased risk of PTB in subsequent pregnancies remains unclear. We aimed to determine the recurrence risk of PTB in a subsequent singleton pregnancy after a previous spontaneous preterm triplet delivery. Study designA retrospective matched case-control study. The study group comprised all women with spontaneous preterm trichorionic triplet delivery who had a subsequent singleton pregnancy during 2006–2017 at two university hospitals. A control group of women with spontaneous preterm dichorionic twin delivery and a subsequent singleton pregnancy, was established by matching, four-to-one, according to maternal age, parity, gestational age at delivery, and delivery year. ResultsData from 170 women were analyzed, 34 with preterm triplet delivery and 136 matched control women with preterm twin delivery. Gestational age at the subsequent singleton delivery was higher in those with preterm triplet delivery than in those with preterm twin delivery (median 39 vs 38 weeks, P = 0.02). Women with prior triplet PTB had a significantly lower rate of recurrent PTB as compared with women with prior twin PTB (5.9 % vs. 25.0 %; OR [95 % CI]: 0.19 (0.04, 0.82), P = 0.02) with lower proportions of low-birth weight infants (<2500 g) (0 % vs. 11.8 %, P = 0.04). ConclusionsThe risk of recurrent PTB following spontaneous PTB in triplet pregnancy was low compared to preterm twin delivery. These data provide reassurance for those who experienced preterm triplet delivery and suggest the need for further studies to understand the mechanisms contributing to PTB in multifetal pregnancies.

Effect of Cervical Cerclage on the Risk of Recurrent Preterm Birth after a Twin Spontaneous Preterm Birth.

BackgroundThis study aimed to evaluate the effect of cervical cerclage on the recurrence risk for preterm birth in singleton pregnant women after a twin spontaneous preterm birth (sPTB).MethodsThis multicenter retrospective cohort study included women who had a singleton pregnancy from January 2009 to December 2018 at 10 referral hospitals and a twin sPTB before the current pregnancy. We compared the cervical lengths during pregnancy and pregnancy outcomes, according to the placement of prophylactic or emergency cerclage. We evaluated the independent risk factors for sPTB (< 37 weeks of gestation) in a subsequent singleton pregnancy.ResultsFor the index singleton pregnancy, preterm birth occurred in seven (11.1%) of 63 women. There was no significant difference in the cervical lengths during pregnancy in women with and without cerclage. In a multivariate logistic regression analysis, the placement of emergency cerclage was an independent risk factor for subsequent singleton preterm birth (odds ratio [OR], 93.188; 95% confidence interval [CI], 1.633–5,316.628; P = 0.027); however, the placement of prophylactic cerclage (OR, 19.264; 95% CI, 0.915–405.786; P = 0.057) was not a factor. None of the women who received prophylactic cerclage delivered before 35 weeks' gestation in the index singleton pregnancy.ConclusionCerclage did not lower the risk of preterm birth in a subsequent singleton pregnancy after a twin sPTB. However, emergency cerclage was an independent risk factor for preterm birth and there was no preterm birth before 35 weeks' gestation in the prophylactic cerclage group. Therefore, close monitoring of the cervical length and prophylactic cerclage might be considered in women who have experienced a twin sPTB at extreme gestation.