Long-term childhood outcomes for babies born at term who were exposed to antenatal corticosteroids.

BACKGROUND: Antenatal corticosteroids improve neonatal outcomes when administered to infants who are at risk of preterm delivery. Many women who receive antenatal corticosteroids for threatened preterm labor proceed to deliver at term. Thus, long-term outcomes should be evaluated for term-born infants who were exposed to antenatal corticosteroids in utero. OBJECTIVE: This study aimed to compare long-term outcomes between term-born children aged ≥5 years who were born to women who received antenatal corticosteroids for threatened preterm labor and children whose mothers were also evaluated for threatened preterm labor but did not receive antenatal corticosteroids. STUDY DESIGN: We performed a retrospective cohort study of children born at ≥37 weeks' gestation, aged ≥5 years, and born to mothers diagnosed with threatened preterm labor during pregnancy. The primary exposure of interest was receiving antenatal corticosteroids. Among the collected childhood medical conditions, the primary outcome of interest was a diagnosis of asthma. RESULTS: Of the 3556 term-born children aged ≥5 years, 629 (17.6%) were exposed to antenatal corticosteroids (all betamethasone), and 2927 (82.3%) were controls whose mothers were evaluated for threatened preterm birth but did not get antenatal corticosteroid injections. Women receiving antenatal corticosteroids had higher rates of maternal comorbidities (diabetes mellitus, hypertension; P≤.01). Antenatal corticosteroid-exposed children had no difference in diagnosis of asthma (12.6% vs 11.6%), attention deficit disorder, or developmental delay (P=.47, .54, and .10, respectively). Controlling for maternal and neonatal characteristics, asthma was not different between those exposed to antenatal corticosteroids and controls (odds ratio, 1.05; 95% confidence interval, 0.79-1.39). The odds of the child's weight percentile being <10% were increased for antenatal corticosteroid-exposed children born at term (odds ratio, 2.00; 95% confidence interval, 1.22-3.25). CONCLUSION: Children born at term who were exposed to antenatal corticosteroids may have increased odds of being in a lower growth percentile than those not exposed. However, rates of diagnoses such as asthma, developmental delay, and attention deficit disorders were not different.

Progestogen maintenance therapy for prolongation of pregnancy after an episode of preterm labour: A systematic review and meta-analysis.

BACKGROUND: Evidence for progestogen maintenance therapy after an episode of preterm labour (PTL) is contradictory. OBJECTIVES: To assess effectiveness of progestogen maintenance therapy after an episode of PTL. SEARCH STRATEGY: An electronic search in Central Cochrane, Ovid Embase, Ovid Medline and clinical trial databases was performed. SELECTION CRITERIA: Randomised controlled trials (RCT) investigating women between 16+0 and 37+0 weeks of gestation with an episode of PTL who were treated with progestogen maintenance therapy compared with a control group. DATA COLLECTION AND ANALYSIS: Systematic review and meta-analysis were conducted. The primary outcome was latency time in days. Secondary neonatal and maternal outcomes are consistent with the core outcome set for preterm birth studies. Studies were extensively assessed for data trustworthiness (integrity) and risk of bias. MAIN RESULTS: Thirteen RCT (1722 women) were included. Progestogen maintenance therapy demonstrated a longer latency time of 4.32 days compared with controls (mean difference [MD] 4.32, 95% CI 0.40-8.24) and neonates were born with a higher birthweight (MD 124.25 g, 95% CI 8.99-239.51). No differences were found for other perinatal outcomes. However, when analysing studies with low risk of bias only (five RCT, 591 women), a significantly longer latency time could not be shown (MD 2.44 days; 95% CI -4.55 to 9.42). CONCLUSIONS: Progestogen maintenance therapy after PTL might have a modest effect on prolongation of latency time. When analysing low risk of bias studies only, this effect was not demonstrated. Validation through further research, preferably by an individual patient data meta-analysis is highly recommended.

Inappropriate use of ritodrine hydrochloride for threatened preterm birth in Japan: a retrospective cohort study using a national inpatient database.

BACKGROUND: No study has revealed the effectiveness of long-term tocolysis for patients diagnosed with threatened preterm birth, and the use of betamimetics in these patients has not been recommended in the United States or Europe because of the potential for severe maternal adverse effects. However, long-term tocolysis with intravenous infusion of ritodrine hydrochloride, a betamimetic, can be selected as the first-line tocolytic treatment in Japan. This study was performed to (i) examine the current status of long-term tocolytic treatment, particularly with intravenous infusion of betamimetics, for threatened preterm birth in Japan and (ii) clarify the association between long-term tocolytic treatment and maternal adverse effects. METHODS: This retrospective cohort study was conducted using a national inpatient database for acute-care inpatients in Japan. Among all pregnant women who were diagnosed with threatened preterm birth and admitted to the hospital from July 2010 to March 2016, we identified 134,959 eligible patients. The primary outcome was maternal serious adverse effects during hospitalization. A multivariable logistic regression analysis was performed to evaluate factors associated with maternal adverse effects. RESULTS: Among all patients, 17.2% received intravenous infusion of ritodrine hydrochloride for ≤48 h and 28.7% received this treatment for ≥28 days. The proportion of maternal adverse effects was significantly higher among patients treated for ≥28 days than ≤48 h. A longer duration of tocolysis was significantly associated with increased maternal adverse effects. CONCLUSIONS: Long-term tocolysis was associated with an increased incidence of maternal adverse effects in the current study using real-world data. Japanese clinicians should adjust their tocolytic treatment practices in accordance with the latest scientific evidence or make efforts to verify the effectiveness and safety of long-term tocolysis.

Maintenance tocolysis: a reappraisal of clinical evidence.

INTRODUCTION: Maintenance tocolysis, mostly defined as the continuation of tocolytic treatment beyond 48 h, remains a matter of debate. There is no sufficient evidence from randomized controlled trials, that maintenance tocolysis is able to prolong pregnancy significantly and to reduce severe neonatal morbidity and mortality. Hence, it is not recommended in current guidelines. On the contrary, maintenance tocolysis is commonly used in clinical practice and subject of current clinical-scientific investigations. TOCOLYTICS FOR MAINTENANCE TREATMENT: None of the conventional tocolytics (beta-sympathomimetics, calcium-channel blockers, magnesium, cyclooxygenase inhibitors, and oxytocin receptor antagonists) have proven to be appropriate for maintenance treatment. Progesterone and 17-α-hydroxyprogesterone caproate have shown promising results in low-quality randomized trials, but not in high-quality studies. DISCUSSION: Basically, the value of studies regarding maintenance tocolysis is limited by a considerable heterogeneity, its mostly low quality, significant differences in methodology as well as the inadequate statistical power due to the small number of women studied. So far, maintenance tocolysis is a case-by-case decision outweighing the benefits and harms of tocolytic treatment.

Effectiveness of a cervical pessary for women who did not deliver 48 h after threatened preterm labor (Assessment of perinatal outcome after specific treatment in early labor: Apostel VI trial).

BACKGROUND: Preterm birth is a major cause of neonatal mortality and morbidity. As preventive strategies are largely ineffective, threatened preterm labor is a frequent problem that affects approximately 10 % of pregnancies. In recent years, risk assessment in these women has incorporated cervical length measurement and fetal fibronectin testing, and this has improved the capacity to identify women at increased risk for delivery within 14 days. Despite these improvements, risk for preterm birth continues to be increased in women who did not deliver after an episode of threatened preterm labor, as indicated by a preterm birth rate between 30 to 60 % in this group of women. Currently no effective treatment is available. Studies on maintenance tocolysis and progesterone have shown ambiguous results. The pessary has not been evaluated in women with threatened preterm labor, however studies in asymptomatic women with a short cervix show reduced rates of preterm birth rates as well as perinatal complications. The APOSTEL VI trial aims to assess the effectiveness of a cervical pessary in women who did not deliver within 48 h after an episode of threatened preterm labor. METHODS/DESIGN: This is a nationwide multicenter open-label randomized clinical trial. Women with a singleton or twin gestation with intact membranes, who were admitted for threatened preterm labor, at a gestational age between 24 and 34 weeks, a cervical length between 15 and 30 mm and a positive fibronectin test or a cervical length below 15 mm, who did not deliver after 48 h will be eligible for inclusion. Women will be allocated to a pessary or no intervention (usual care). Primary outcome is preterm delivery < 37 weeks. Secondary outcomes are amongst others a composite of perinatal morbidity and mortality. Sample size is based on an expected 50 % reduction of preterm birth before 37 weeks (two-sided test, α 0.05 and ß 0.2). Two hundred women with a singleton pregnancy need to be randomized. Analysis will be done by intention to treat. DISCUSSION: The APOSTEL VI trial will provide evidence whether a pessary is effective in preventing preterm birth in women who did not deliver 48 h after admission for threatened preterm labor and who remain at high risk for preterm birth. TRIAL REGISTRATION: Trial is registered at the Dutch Trial Register: http://www.trialregister.nl , NTR4210, date of registration: October 16th 2013.

A historical narrative review through the field of tocolysis in threatened preterm birth.

Preterm birth presents a significant challenge in clinical obstetrics, requiring effective strategies to reduce associated mortality and morbidity risks. Tocolytic drugs, aimed at inhibiting uterine contractions, are a key aspect of addressing this challenge. Despite extensive research over many years, determining the most effective tocolytic agents remains a complex task, prompting better understanding of the underlying mechanisms of spontaneous preterm birth and recording meaningful outcome measures. This paper provides a comprehensive review of various obsolete and current tocolytic drug regimens that were instituted over the past century, examining both historical contexts and contemporary challenges in their development and adoption. The examination of historical debates and advancements highlights the complexity of introducing new therapies. While the search for effective tocolytics continues, questions arise regarding their actual benefits in obstetric care and the necessity for ongoing exploration. The presence of methodological limitations in current research emphasizes the importance of well-designed randomized controlled trials with robust endpoints and extended follow-up periods.In response to these complexities, the consideration of shifting towards prevention strategies aimed at addressing the root causes of preterm labor becomes more and more evident. This potential shift may offer a more effective approach than relying solely on tocolytics to delay labor initiation.Ultimately, effectively managing threatened preterm birth necessitates ongoing investigation, innovation, and a willingness to reassess strategies in pursuit of optimal outcomes for mothers, neonates, and long-term child health.

Efficacy of atosiban combined with ritodrine on spontaneous threatened preterm birth and its effect on PAF and fFN levels.

OBJECTIVE: To explore the efficacy of Atosiban combined with Ritodrine treatment on spontaneous threatened preterm birth and its effect on platelet-activating factor (PAF) and fetal fibronectin levels. METHODS: Medical records from 120 patients with threatened preterm birth admitted to Baoji Maternal and Child Health Hospital from October 2020 to December 2021 were collected for this retrospective analysis. A total of 56 patients treated with Ritodrine alone were taken as the control group (CG), and the other 64 patients given combined treatment of Atosiban and Ritodrine were seen as the observation group (OG). Indexes of uterine contraction inhibition rate, pregnancy prolongation time, onset time, adverse reactions and pregnancy outcomes were compared between the two groups; in addition, the levels of inflammatory factors as well as PAF and fFN before and after treatment were detected and compared between two groups. RESULTS: Compared with the CG, the uterine contraction inhibition rate as well as the pregnancy prolongation time in the OG were evidently higher (all P<0.05); the time of the disappearance of uterine contraction in the OG was significantly shorter (P<0.05); the rate of full-term delivery and neonatal 1-min Apgar score in the OG were obviously higher (P<0.05); and the incidence of total adverse reactions in the OG was markedly lower (P<0.05). However, there was no significant difference observed in the neonatal asphyxia rate and the number of fetuses between the two groups (P>0.05). After treatment, the OG was observed with markedly lower level of inflammatory factors C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) than the CG (P<0.05); levels of PAF and fFN decreased significantly in both two groups (P<0.05), and the levels in the OG were comparatively lower as compared to the CG (P<0.05). The areas under the ROC curve for PAF and fFN to predict pregnancy outcome were 0.766 and 0.757, respectively. CONCLUSION: Atosiban combined with Ritodrine evidently improves the therapeutic efficacy in patients with threatened preterm labor, reduces the occurrence of adverse pregnancy outcomes as well as the levels of PAF and fFN.

Tocolysis compared with no tocolysis in women with threatened preterm birth and ruptured membranes: A propensity score analysis.

INTRODUCTION: In women with preterm ruptured membranes and contractions, the administration of tocolysis is controversial. This study compares tocolysis with no tocolysis in women with threatened preterm birth and ruptured membranes. OBJECTIVE: To compare tocolysis with no tocolysis in women with threatened preterm birth and ruptured membranes. STUDY DESIGN: Data from the APOSTEL III RCT was combined with data from the National Maternity Hospital, Dublin. In the APOSTEL III trial, women with threatened preterm birth were randomized to atosiban or nifedipine. Patient data from Ireland were obtained from a cohort of women with threatened preterm birth with ruptured membranes. The Irish women received no tocolytic treatment. Only women with ruptured membranes and contractions were selected. We studied women with singleton or twin pregnancies and a gestational age between 25+0 and 33+6 weeks. Propensity score matching was performed to create comparable groups. Primary outcome was a composite adverse neonatal outcome. Secondary outcomes were individual components of the primary outcome, as well as neonatal intensive care unit (NICU) admission, gestational age at delivery, prolongation of pregnancy and mode of delivery. RESULTS: 153 women from the Apostel III trial were compared with 51 eligible women of the Irish cohort. We could match 46 women who received tocolysis and 46 women who received no tocolysis. All women had ruptured membranes. Maternal age, BMI, parity and gestational age at study entry were comparable between the groups after matching. There were no statistically significant differences in neonatal composite outcome (9.6 % in the tocolysis group versus 18 % in the control group, OR 0.46, 95 % CI 0.13-1.63). We found a lower incidence of NICU admission in the tocolysis group (63 %) than in the control group (94 %; OR 0.11, 95 % CI 0.03-0.41), which could be explained by differences in national admission policies. There were no statistically significant differences between tocolysis and no tocolysis in any of the other outcomes including sepsis, gestational age at delivery and time to delivery. CONCLUSION: In this propensity score analysis of women with threatened preterm birth and ruptured membranes, tocolytic therapy did not alter composite adverse neonatal outcome or time to delivery.

Ultrasound measurement of cervical length as predictor of threatened preterm birth: a predictive model.

INTRODUCTION: The incidence of preterm delivery has been increasing even in developed countries and remains a serious problem for fetuses and neonates. Although many predictors for preterm delivery have been proposed, complete prediction and prevention have not yet been established. AIMS: To examine the potential association between sonographic measurement of cervical length and threatened preterm birth (TPTB) in pregnant woman at 24-36 weeks of gestation. MATERIALS AND METHODS: A cross-sectional study included a total of 360 pregnant woman at 24-36 weeks of gestation categorized in two groups: TPTB group (n=160) and non TPTB group (n=200). The study was carried out at the Department of Obstetrics and Gynecology of the Clinical Center University of Sarajevo (KCUS). Sociodemographic and clinical characteristics of patients were obtained from medical records and physical examination by gynecologist. Transvaginal sonography was carried out by GE Voluson 730. RESULTS: There was a significant association between TPTB and sonographic measurement of cervical length <25 mm (P<0.001). The logistic regression model was statistically significant, x(2)(7) = 281.530, P<0. 001. The model explained 72.6% of the variance in TPTB and correctly classified 88.1% of cases. Sensitivity was 83.8%, specificity was 91.5%, positive predictive value was 88.7% and negative predictive value was 87.6%. Out of the 7 predictor variables only 5 were statistically significant: cervical length, cervical consistency, rupture of membranes, uterine contractions and amine odor test. CONCLUSION: The findings of this study suggest association between sonographic measurement of cervical length and TPTB.

[Pronostic risk assessment of delivery, in patients admitted for threatened preterm birth, in a tertiary care maternity center]. / Étude pronostique du risque d'accouchement, des patientes hospitalisées pour menace d'accouchement prématuré, dans une maternité de niveau III.

OBJECTIVES: To assess preterm birth rate, in patients admitted for threatened preterm birth (TPB) in a tertiary care maternity center and evaluate our diagnostic and therapeutic tools. MATERIALS AND METHODS: A retrospective cohort study, in a tertiary care maternity center (Marseille, France), reviewed all admissions for TPB from January 1 to December 31, 2009. RESULTS: We recorded 224 admissions for TPB (181 single pregnancies and 43 twin pregnancies), 43.8% of TPB admissions were from materno-fetal transfer. Preterm birth rate was 44.9% (n=89), 39% (n=66) for single pregnancy and 76.6% (n=23) for twins. The 15 mm threshold for transvaginal sonography cervical length (CL) was the most relevant to predict the risk of preterm delivery, 77.3% (85/110) of patients with CL>15 mm having full term delivery. CONCLUSION: For single pregnancy, most of the patients with cervical length>15 mm have full term delivery. It seems important to us to develop the use of more efficient predictive markers of risk-premature labor in order to improve the diagnosis and management of TPB.