Differences in environmental factors contributing to preterm labor and PPROM - Population based study.

BACKGROUND: Previous reports indicate an association between ambient temperature (Ta) and air pollution exposure during pregnancy and preterm birth (PTB). Nevertheless, information regarding the association between environmental factors and specific precursors of spontaneous preterm birth is lacking. We aimed to determine the association between Ta and air pollution during gestation and the precursors of spontaneous preterm parturition, i.e. preterm labor (PTL) and preterm prelabor rupture of membranes (PPROM). METHODS: From 2003 to 2013 there were 84,476 deliveries of singleton gestation that comprised the study cohort. Exposure data during pregnancy included daily measurements of temperature and particulate matter <2.5 µm and <10 µm, PM2.5 and PM10, respectively. Deliveries were grouped into PPROM, PTL and non-spontaneous preterm and term deliveries. Exposure effect was tested in windows of a week and two days prior to admission for delivery and adjusted to gestational age and socio-economic status. Poisson regression models were used for analyses. RESULTS: There is an association of environmental exposure with the precursors of spontaneous preterm parturition; PPROM was more sensitive to Ta fluctuations than PTL. This effect was modified by the ethnicity, Bedouin-Arabs were susceptible to elevated Ta, especially within the last day prior to admission with PPROM (Relative Risk (RR) =1.19 [95% CI, 1.03; 1.37]). Jews, on the other hand, were susceptible to ambient pollutants, two (RR=1.025 [1.010; 1.040]) and one (RR= 1.017 [1.002; 1.033]) days prior to spontaneous PTL with intact membranes resulting in preterm birth. CONCLUSION: High temperature is an independent risk factor for PPROM among Bedouin-Arabs; ambient pollution is an independent risk factor for spontaneous PTL resulting in preterm birth. Thus, the precursors of spontaneous preterm parturition differ in their association with environmental factors.

Postpartum plasma metabolomic profile among women with preeclampsia and preterm delivery: implications for long-term health.

BACKGROUND: Preeclampsia and preterm delivery (PTD) are believed to affect women's long-term health including cardiovascular disease (CVD), but the biological underpinnings are largely unknown. We aimed to test whether maternal postpartum metabolomic profiles, especially CVD-related metabolites, varied according to PTD subtypes with and without preeclampsia, in a US urban, low-income multi-ethnic population. METHODS: This study, from the Boston Birth Cohort, included 980 women with term delivery, 79 with medically indicated PTD (mPTD) and preeclampsia, 52 with mPTD only, and 219 with spontaneous PTD (sPTD). Metabolomic profiling in postpartum plasma was conducted by liquid chromatography-mass spectrometry. Linear regression models were used to assess the associations of each metabolite with mPTD with preeclampsia, mPTD only, and sPTD, respectively, adjusting for pertinent covariates. Weighted gene coexpression network analysis was applied to investigate interconnected metabolites associated with the PTD/preeclampsia subgroups. Bonferroni correction was applied to account for multiple testing. RESULTS: A total of 380 known metabolites were analyzed. Compared to term controls, women with mPTD and preeclampsia showed a significant increase in 36 metabolites, mainly representing acylcarnitines and multiple classes of lipids (diacylglycerols, triacylglycerols, phosphocholines, and lysophosphocholines), as well as a decrease in 11 metabolites including nucleotides, steroids, and cholesteryl esters (CEs) (P < 1.3 × 10-4). Alterations of diacylglycerols, triacylglycerols, and CEs in women with mPTD and preeclampsia remained significant when compared to women with mPTD only. In contrast, the metabolite differences between women with mPTD only and term controls were only seen in phosphatidylethanolamine class. Women with sPTD had significantly different levels of 16 metabolites mainly in amino acid, nucleotide, and steroid classes compared to term controls, of which, anthranilic acid, bilirubin, and steroids also had shared associations in women with mPTD and preeclampsia. CONCLUSION: In this sample of US high-risk women, PTD/preeclampsia subgroups each showed some unique and shared associations with maternal postpartum plasma metabolites, including those known to be predictors of future CVD. These findings, if validated, may provide new insight into metabolomic alterations underlying clinically observed PTD/preeclampsia subgroups and implications for women's future cardiometabolic health.

Predictors of vaginal delivery in medically indicated early preterm induction of labor.

BACKGROUND: When delivery is indicated prior to 34 weeks, many providers perform a cesarean delivery rather than induce labor based on perceptions of a high failure rate. Given the morbidity of cesarean delivery, an accurate estimate of the success rate and factors associated with success in preterm induction of labor is important in management decisions. OBJECTIVE: We sought to develop a prediction model for successful induction of labor in preterm patients using factors known at the time the decision is made to deliver. STUDY DESIGN: A retrospective cohort study of all live singletons undergoing an indicated induction of labor between 23 and 34 0/7 weeks from 2011 through 2015. Pregnancies with major fetal anomalies or no intrapartum fetal monitoring were excluded. Successful induction of labor was defined as vaginal delivery. The cohort was randomly split into a training cohort to develop a prediction model for vaginal delivery and a validation cohort to test the model. Factors significantly associated with vaginal delivery were identified using univariate analyses, and candidate factors were used in the multivariate logistic regression model. Only factors known at the start of the induction of labor were used in the model. Receiver-operating characteristic curves were created to estimate the predictive value of the model. Sensitivity and specificity of the model were assessed. RESULTS: Of 331 patients who underwent induction of labor, 208 (62.8%) delivered vaginally and 123 (37.1%) by cesarean delivery. Of the factors significantly associated with cesarean delivery, the final model included gestational age, simplified Bishop score, suspected intrauterine growth retardation, chronic hypertension, and body mass index. In the training cohort, the model correctly classified 72.3% of subjects with a sensitivity (cesarean delivery predicted/cesarean delivery performed) of 56.7% and a specificity (vaginal delivery predicted/vaginal delivery performed) of 84.1%. When applied to the validation cohort, 73.9% of subjects were correctly classified, with a sensitivity of 44.6% and specificity of 89.0%. Receiver-operating characteristic curves had an area under the curve of 0.75 for the training cohort and 0.77 for the validation cohort. CONCLUSION: More than 60% of women undergoing induction of labor at <34 0/7 weeks deliver vaginally. For women undergoing induction of labor at <34 0/7 weeks, this prediction model rarely classifies individuals who can have a vaginal delivery as needing a cesarean delivery. This model may provide an accurate assessment tool to evaluate which patients will likely deliver vaginally to avoid the morbidity of cesarean delivery while conversely identifying subjects at high risk of cesarean delivery <34 0/7 weeks.

Maternal bereavement and the risk of preterm delivery: the importance of gestational age and of the precursor of preterm birth.

BACKGROUND: Maternal stress during pregnancy may increase the risk of preterm delivery (PD), but the associations between stress and subtypes of PD are not clear. We investigated maternal loss of a close relative and risks of very and moderately PD (<32 and 32-36 weeks, respectively) and spontaneous and medically indicated PD. METHOD: We studied 4 940 764 live singleton births in Denmark (1978-2008) and Sweden (1973-2006). We retrieved information on death of women's family members (children, partner, siblings, parents), birth outcomes and maternal characteristics from nationwide registries. RESULTS: Overall, the death of a close family member the year before pregnancy or in the first 36 weeks of pregnancy was associated with a 7% increased risk of PD [95% confidence interval (CI) 1.04-1.10]. The highest hazard ratios (HR) for PD were found for death of an older child [HR (95% CI) 1.20 (1.10-1.31)] and for death of a partner [HR (95% CI) 1.31 (1.03-1.66)]. These losses were associated with higher risks of very preterm [HR (95% CI) 1.61 (1.29-2.01) and 2.07 (1.15-3.74), respectively] than of moderately preterm [HR (95% CI) 1.14 (1.03-1.26) and 1.22 (0.94-1.58), respectively] delivery. There were no substantial differences in the association between death of a child or partner and the risk of spontaneous v. medically indicated PD. CONCLUSIONS: Death of a close family member the year before or during pregnancy was associated with an increased risk of PD, especially very PD. Possible mechanisms include both spontaneous and medically indicated preterm birth.

Neonatal outcomes by delivery indication after administration of antenatal late preterm corticosteroids.

Background: Antenatal corticosteroids, specifically betamethasone, administered to patients at risk for late preterm delivery have been associated with reduced rates of neonatal respiratory complications. However, whether these risks vary by delivery indication among betamethasone-exposed, late-preterm infants is not known. Objective: This study aimed to evaluate if spontaneous preterm labor or preterm prelabor rupture of membranes, compared with indicated late preterm delivery, is associated with better neonatal respiratory outcomes after accounting for betamethasone administration in the late preterm period. Study Design: This was a secondary analysis of the Antenatal Late Preterm Steroids trial, a multicenter, placebo-controlled trial in which patients with singleton pregnancies at risk for delivery at 34 0/7 to 36 5/7 weeks of gestation were randomized to a single course of antenatal corticosteroids (betamethasone) or placebo. Patients were eligible if they had spontaneous preterm labor, preterm prelabor rupture of membranes, or if they were undergoing indicated late preterm delivery. The primary outcome was a composite of need for respiratory support, stillbirth, or neonatal death within 72 hours after delivery. Secondary outcomes included individual neonatal morbidities. Bivariate analyses were performed, and multivariable logistic regression models were used to control for potential confounders. Using the indicated preterm delivery group as the reference group, adjusted odds ratios and 95% confidence intervals were calculated for the outcomes by delivery indication. Subgroup analyses separately examined the treatment and placebo groups to determine the odds of the primary outcome by delivery indication. Results: Of 2827 participants at high risk for late preterm delivery, 1427 (50.5%) received betamethasone. There were 790 (27.9%) infants born after preterm labor, 620 (21.9%) born after preterm prelabor rupture of membranes, and 1417 (50.1%) born after indicated preterm delivery. Compared with indicated preterm delivery, the odds of the primary outcome were lower among those born after preterm labor (7.3% vs 16.4%; adjusted odds ratio, 0.57; 95% confidence interval, 0.40-0.82) and among those born after preterm prelabor rupture of membranes (12.4% vs 16.4%; adjusted odds ratio, 0.49; 95% confidence interval, 0.35-0.69). Preterm labor had lower odds of all neonatal complications except feeding problems, and preterm prelabor rupture of membranes had lower odds of all neonatal complications except newborn intensive care unit admission for ≥3 days when compared with indicated preterm delivery. For the placebo group, the odds of the primary outcome were lower for the preterm labor group (8.2% vs 18.5%; adjusted odds ratio, 0.55; 95% confidence interval, 0.34-0.91) and the preterm prelabor rupture of membranes group (13.2% vs 18.5%; adjusted odds ratio, 0.46; 95% confidence interval, 0.29-0.73) than for the indicated preterm delivery group. For those exposed to betamethasone, the odds of the primary outcome remained lower for the preterm labor group (6.5% vs 14.3%; adjusted odds ratio, 0.58; 95% confidence interval, 0.34-0.99) and the preterm prelabor rupture of membranes group (11.7% vs 14.3%, adjusted odds ratio, 0.56; 95% confidence interval, 0.34-0.91) than for the indicated preterm delivery group. Conclusion: Compared with indicated preterm delivery, preterm labor and preterm prelabor rupture of membranes were associated with reduced odds of neonatal respiratory complications irrespective of betamethasone exposure in the late preterm period.

Missed opportunities for optimal antenatal corticosteroid timing in medically indicated preterm births.

OBJECTIVE: Although delivery timing is physician dictated in indicated preterm births, suboptimal antenatal corticosteroids (ACS) administration occurs in most cases. We aimed to characterize the patterns of use of ACS in indicated preterm births and identify missed opportunities of optimal ACS administration. METHODS: We reviewed the records of women who received ACS and were delivered due to maternal or fetal indications at 24-34 weeks of gestation during 2015-2017 at a university hospital. Optimal ACS timing was defined as delivery ≥24 h ≤7 d from the previous ACS course. RESULTS: Overall, 188 pregnancies were included. The median gestational age at delivery was 32 weeks. Considering only the initial ACS course, the rate of optimal timing was 32.4%. Of 105 (55.8%) women eligible (delivery >7 d since the initial ACS course), only a third (n = 38) received a rescue ACS course. Among women who did not receive rescue ACS course despite their eligibility (n = 67), the decision-to-delivery was ≥3 h in 36 (53.7%), and ≥24 h in 20 (29.9%), representing 19.1 and 10.6% of the entire cohort, respectively. The urgency of the decision to deliver (i.e. in the upcoming 24 h and later) and allowing a trial of labor, were both positively associated with decision-to-delivery interval ≥3 h and ≥24 h. The rate of delivery within any optimal window (either initial or rescue course) was 40.4%, with gestational hypertensive disorders (OR [95% CI]: 2.40 (1.23, 4.72), p = .01) and decision to deliver made at first hospitalization (OR [95% CI]: 2.27 (1.04, 4.76), p = .04) as independent positive predictors of optimal ACS timing. The rate of composite adverse neonatal outcome was significantly lower in those with optimal ACS administration as compared to those with suboptimal timing (32.9 versus 50.9%, OR [95% CI]: 0.47 (0.26, 0.87), p = .02). CONCLUSIONS: Suboptimal ACS administration occurred in most indicated preterm births. Underutilization of rescue ACS course and a substantial rate of missed opportunities for optimal ACS administration were identified as potentially modifiable contributors to improve ACS timing.

Maternal obesity is associated with chorioamnionitis and earlier indicated preterm delivery among expectantly managed women with preterm premature rupture of membranes.

OBJECTIVE: To determine the association between maternal obesity and delivery due to chorioamnionitis prior to labor onset, among expectantly managed women with preterm premature rupture of membranes (pPROM). METHODS: This was a secondary analysis of a multicenter randomized trial of magnesium sulfate versus placebo to prevent cerebral palsy or death among offspring of women with anticipated delivery at 24-31-week gestation. After univariable analysis, Cox proportional hazard evaluated the association between maternal obesity and chorioamnionitis, while Laplace regression investigated how obesity affects the gestational age at delivery of the first 20% of women developing the outcome of interest. RESULTS: A total of 164 of the 1942 women with pPROM developed chorioamnionitis prior to labor onset. Obese women had a 60% increased hazard of developing such complication (adjusted HR 1.6, 95%CI 1.1-2.1, p = .008), prompting delivery 1.5 weeks earlier, as the 20th survival percentile was 27.2-week gestation (95%CI 26-28.6) among obese as opposed to 28.8 weeks (95%CI 27.4-30.1) (p = .002) among nonobese women. CONCLUSIONS: Maternal obesity is a risk factor for chorioamnionitis prior to labor onset. Future studies will determine if obesity is important enough to change the management of latency after pPROM according to maternal BMI.

Placenta accreta in the department of gynaecology and obstetrics in Rabat, Morocco: case series and review of the literature.

Placenta accreta spectrum disorders is a rare pathology but the incidence has not stopped to increase in recent years. The purpose of our work was the analysis of the epidemiological profile of our patients, the circumstances of diagnosis, the interest of paraclinical explorations in antenatal diagnosis and the evaluation of the evolutionary profile. We hereby report a case series spread over a period of one year from 01/01/2015 to 01/01/2016 at the Gynaecology-Obstetrics department of the University Hospital Center IBN SINA of Rabat where we identified six cases of placenta accreta. We selected patients whose diagnosis was confirmed clinically and histologically. The major risk factors identified were a history of placenta previa, previous caesarean section, advanced maternal age, multiparity. 2D ultrasound and magnetic resonance imaging (MRI) allowed us to strongly suspect the presence of a placenta accreta in a pregnant woman with risk factor(s) but the diagnosis of certainty was always histological. Placenta accreta spectrum disorders were associated with a high risk of severe postpartum hemorrhage, serious comorbidities, and maternal death. Leaving the placenta in situ was an option for women who desire to preserve their fertility and agree to continuous long-term monitoring in centers with adequate expertise but a primary elective caesarean hysterectomy was the safest and most practical option. Placenta accreta spectrum disorders is an uncommon pathology that must be systematically sought in a parturient with risk factors, to avoid serious complications. In light of the latest International Federation of Gynecology and Obstetrics (FIGO) recommendations of 2018, a review of the literature and finally the experience of our center, we propose a course of action according to whether the diagnosis of the placenta is antenatal or perpartum.

Elevated maternal serum-free ß-human chorionic gonadotropin (ß-hCG) and reduced risk of spontaneous preterm delivery.

Objective: To evaluate the relationship between first and second trimester maternal serum-free ß-hCG and the risk of spontaneous preterm delivery (PTD). Study design: This was a case-control study of women evaluated and delivered at our institution from 2011 to 2015. Spontaneous PTD was defined as delivery before 37 weeks due to spontaneous preterm labor or premature rupture of membranes. Patient with multifetal gestation and those with medically indicated term or PTD were excluded. Results: Of 877 women meeting the inclusion criteria, 173 delivered preterm and 704 delivered at term, and 8.1% had high free ß-hCG in one or both trimesters. High maternal first and/or second trimester free ß-hCG (≥95th percentile) was associated with lower rates of PTD. Thirty-two women with high free ß-hCG in both first and second trimesters delivered at term. Gestational age at delivery and birth weights were lower in women who did not have high free ß-hCG in any trimester. Low free ß-hCG (≤5th percentile) in either trimester was not associated with an increased or decreased likelihood of PTD. Logistic regression demonstrated an independent association of high free ß-hCG (≥95th percentile) with a reduced likelihood of PTD. Stratified analysis revealed a stronger impact of this association in women with no prior history of PTD. Conclusions: High free ß-hCG, in the absence of risk factors for medically indicated PTD, is associated with a reduced likelihood of spontaneous PTD and may represent a marker indicating lower risk.

Placenta accreta spectrum: accreta, increta, and percreta.

Placenta accreta can lead to hemorrhage, resulting in hysterectomy, blood transfusion, multiple organ failure, and death. Accreta has been increasing steadily in incidence owing to an increase in the cesarean delivery rate. Major risk factors are placenta previa in women with prior cesarean deliveries. Obstetric ultrasonography can be used to diagnose placenta accreta antenatally, which allows for scheduled delivery in a multidisciplinary center of excellence for accreta. Controversies exist regarding optimal management, including optimal timing of delivery, surgical approach, use of adjunctive measures, and conservative (uterine-sparing) therapy. We review the definition, risk factors, diagnosis, management, and controversies regarding placenta accreta.