Immune Modifications in Fetal Membranes Overlying the Cervix Precede Parturition in Humans.

In humans, parturition is currently viewed as an intrauterine outbreak of inflammation, accompanied by a massive release of proinflammatory cytokines at the maternal-fetal interface that comprises the maternal decidua, placenta, and fetal membranes. At term, fetal membranes overlying the cervix, the future site of rupture, show altered morphology and are termed the zone of altered morphology (ZAM). These alterations occur in normal fetal membranes during late pregnancy, in preparation for labor. In this study, transcriptome, flow cytometry, electron microscopy, and immunohistochemistry analyses collectively highlight a local shift in gene expression and lymphocyte activation in the ZAM. Just before labor, we show that highly polymorphic HLA-A, -B, and -C determinants of fetal origin are selectively exposed in the ZAM to the maternal immune system. A graft rejection-like program occurs in the ZAM, which involves 1) the activation of cytotoxic decidual NK cells, and 2) the decline of decidual immunotolerant M2-like macrophages. Comparison with a prior cohort of fetal membranes shows that acute inflammation only takes place after these first steps of immune modifications. Our results therefore strongly argue in favor of local immune remodeling at the onset of parturition.

Impact of routine transvaginal ultrasound monitoring of cervical length in twins on administration of antenatal corticosteroids.

OBJECTIVE: To evaluate whether routine measurement of cervical length (CL) by transvaginal ultrasound (TVU) in twin pregnancies can enable identification of women who will give birth before 34 weeks and require antenatal corticosteroids (ACSs), and whether it can limit their administration to women who will give birth later. STUDY DESIGN: Retrospective comparative study in two tertiary referral centers in France. Women with twin gestations followed in two tertiary university hospital maternity units and who delivered from January 1, 2007 to December 31, 2009 were included. In one center, TVU was targeted to women with cases of suspected preterm labor, while the other center used it monthly for all twin pregnancies. The main outcome measure was the administration of a full course of ACS to twins delivered before 34 weeks. RESULTS: Two hundred and seventy women were eligible in the "targeted use" group, and 296 women in the "routine use" group. The rate of administration of at least one full course of ACS for twins born before 34 weeks did not differ between the two groups (85.0% in the targeted use group and 90.0% in the routine use group, P=0.40), but the rate of such administration for those born after 34 weeks was lower in the targeted use group (25.7% vs. 81.2%, P<0.01). On adjusting for confounders using logistic regression modeling, no significant difference in ACS administration before 34 weeks was found between the two groups [adjusted odds ratio (aOR), 0.71, 95% confidence interval (CI), 0.39-1.30]. CONCLUSION: Routine monitoring performed every month of CL with TVU does not affect the rate of administration of ACS to twins born before 34 weeks, but is associated with a higher rate of such administration for those born later in the specific center of the study.

Neural correlates of infant accent discrimination: an fNIRS study.

The present study investigated the neural correlates of infant discrimination of very similar linguistic varieties (Quebecois and Parisian French) using functional Near InfraRed Spectroscopy. In line with previous behavioral and electrophysiological data, there was no evidence that 3-month-olds discriminated the two regional accents, whereas 5-month-olds did, with the locus of discrimination in left anterior perisylvian regions. These neuroimaging results suggest that a developing language network relying crucially on left perisylvian cortices sustains infants' discrimination of similar linguistic varieties within this early period of infancy.

Vertical and horizontal smooth pursuit eye movements in children with developmental coordination disorder.

AIM: Our aim was to study horizontal and vertical smooth pursuit eye movements in children with developmental coordination disorder (DCD). METHOD: Horizontal and vertical smooth pursuit eye movements of 91 children were studied using electro-oculography: 27 children with DCD (23 males, four females), according to the DSM-IV-TR criteria, and 64 comparison children (26 males, 38 females). All children were 7 to 12 years old (mean 9y, SD 1.5y). Among the group of children with DCD, eight had received intervention. Intervention exercised static and dynamic fixation, saccades, visual strategies, visuospatial abilities, and eye-hand coordination. A smooth pursuit gain index was calculated and statistical comparisons were made between the two groups of children. RESULTS: Horizontal pursuit gain was similar in both populations, but vertical pursuit gain was significantly impaired (p<0.001, after adjusting for age as covariate), i.e. more saccadic in children with DCD (18-99%; n=27, mean 51.6%, median 48.5%, SD 23.2%) than in comparison participants (35-97%; n=63, mean 66.4%, median 65.0%, SD 15.4%). Among the DCD group, the vertical pursuit index was also significantly higher (p=0.009) in the intervention subgroup (29-99%; n=8, mean 69.4%, median 75.5%, SD 28.7%) than in the non-intervention subgroup (18-74%; n=19, mean 44.1%, median 42.5%, SD 15.9%). INTERPRETATION: These results suggest a delay in the maturation of the pursuit system in children with DCD.

Air stepping in response to optic flows that move Toward and Away from the neonate.

To shed further light on the perceptual regulation of newborn stepping, we compared neonatal air stepping in response to optic flows simulating forward or backward displacement with stepping forward on a surface. Twenty-two 3-day-olds performed four 60 s trials in which they stepped forward on a table (Tactile) or in the air in response to a pattern that moved toward (Toward) or away (Away) from them or was static (Static). Significantly more steps were taken in the Tactile and Toward conditions than the Static condition. The Away condition was intermediate to the other conditions. The knee joint activity across the entire trial was significantly greater in the Toward than the Away condition. Within-limb kinematics and between-limb coordination were very similar for steps taken in the air and on the table, particularly in the Toward and Tactile conditions. These findings highlight that visual and tactile stimulation can equally elicit neonatal stepping.

(Non)words, (non)words, (non)words: evidence for a protolexicon during the first year of life.

Previous research with artificial language learning paradigms has shown that infants are sensitive to statistical cues to word boundaries (Saffran, Aslin & Newport, 1996) and that they can use these cues to extract word-like units (Saffran, 2001). However, it is unknown whether infants use statistical information to construct a receptive lexicon when acquiring their native language. In order to investigate this issue, we rely on the fact that besides real words a statistical algorithm extracts sound sequences that are highly frequent in infant-directed speech but constitute nonwords. In three experiments, we use a preferential listening paradigm to test French-learning 11-month-old infants' recognition of highly frequent disyllabic sequences from their native language. In Experiments 1 and 2, we use nonword stimuli and find that infants listen longer to high-frequency than to low-frequency sequences. In Experiment 3, we compare high-frequency nonwords to real words in the same frequency range, and find that infants show no preference. Thus, at 11 months, French-learning infants recognize highly frequent sound sequences from their native language and fail to differentiate between words and nonwords among these sequences. These results are evidence that they have used statistical information to extract word candidates from their input and stored them in a 'protolexicon', containing both words and nonwords.

Functional screening of TLRs in human amniotic epithelial cells.

Intrauterine infection is a major cause of spontaneous preterm birth. Amniotic epithelial cells represent the first line of defense against intra-amniotic bacteria. We hypothesize that this epithelial cell barrier is able to recognize and respond to pathogens through the function of TLRs, which are crucial regulators of the innate immune system. In this study, we describe the expression of transcripts for TLR1-TLR10 in human amniotic epithelial cells. We show that amniotic epithelial cells express functional TLR5, TLR6/2, and TLR4. Activation by TLR5 and TLR6/2 agonists produces IL-6 and IL-8, concomitantly with the activation of NF-κB signaling pathway, matrix metalloproteinase-9 induction, and PTGS2 expression. In contrast, TLR4 activation reduced amniotic epithelial cell viability and induced cell apoptosis evidenced by an elevated Bax/Bcl-2 ratio and cleavage of caspase-3. These data suggest specific TLR-mediated functions in human amniotic epithelial cells for initiating different immune responses, which ultimately may lead to preterm birth.

Secreted surfactant protein A from fetal membranes induces stress fibers in cultured human myometrial cells.

In the present study, we investigated the ability of human fetal membranes (amnion and choriodecidua) to regulate human maternal uterine cell functions through the secretion of surfactant protein (SP)-A and SP-D at the end of pregnancy. We detected the expression of both SP-A (SP-A1 and SP-A2) and SP-D by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry revealed that human fetal membranes expressed both SP-A and SP-D. By Western blot analysis, we demonstrated that SP-A protein expression was predominant in choriodecidua, whereas the amnion predominantly expressed SP-D. Only the secretion of SP-A was evidenced in the culture supernatants of amnion and choriodecidua explants by immunodot blot and confirmed by Western blot. Exogenous human purified SP-A induced stress fiber formation in cultured human myometrial cells via a pathway involving Rho-kinase. Conditioned medium from choriodecidua and amnion explants mimicked the SP-A effect. Treatment of myometrial cells with SP-A-depleted conditioned medium from choriodecidua or amnion explants failed to change the actin dynamic. These data indicate that SP-A released by human fetal membranes is able to exert a paracrine regulation of F-actin filament organization in myometrial cells.

The PDE4 inhibitor rolipram prevents NF-kappaB binding activity and proinflammatory cytokine release in human chorionic cells.

Spontaneous preterm delivery is linked to intrauterine inflammation. Fetal membranes are involved in the inflammatory process as an important source of mediators, and the chorion leave produces high levels of the proinflammatory cytokine TNF-alpha when stimulated by LPS. The transcription factor NF-kappaB is the main regulator of this inflammatory process and controls the production of cytokines by the chorion leave. Phosphodiesterase 4 inhibitors are recognized for their anti-inflammatory and myorelaxant effects. The purpose of this study was to investigate whether PDE4 inhibition affects the LPS signaling in human cultured chorionic cells. We showed that these cells express TLR4, the main LPS receptor, and exhibit a predominant PDE4 activity. Upon LPS challenge, PDE4 activity increases concomitantly to the induction of the specific isoform PDE4B2 and chorionic cells secrete TNF-alpha. LPS induces the nuclear translocation of the NF-kappaB p65 subunit and the activation of three different NF-kappaB complexes in chorionic cells. The presence of the PDE4 inhibitor rolipram reduces the TNF-alpha production and the activation of the three NF-kappaB complexes. These data indicate that the PDE4 family interacts with the LPS signaling pathway during the inflammatory response of chorionic cells. PDE4 selective inhibitors may thus represent a new therapeutic approach in the management of inflammation-induced preterm delivery.

Active versus expectant management for preterm prelabor rupture of membranes at 34-36 weeks of completed gestation: comparison of maternal and neonatal outcomes.

OBJECTIVE: To compare maternal and neonatal outcomes in deliveries managed by a policy of expectant management and active management of women with preterm prelabor rupture of membranes (pPROM), at 34-36 completed weeks of gestation. DESIGN: Retrospective multicenter cohort study. SETTING: Three tertiary care teaching hospitals in France. POPULATION: Women with pPROM were identified from the databases of three perinatal centers. METHODS: Maternal and neonatal complications were compared according to the hospital policy in effect at pPROM--expectant or active management. MAIN OUTCOME MEASURES: Clinical chorioamnionitis, neonatal morbidity including neonatal infection, respiratory problems, and metabolic disorders. RESULTS: During the seven-year study period, 634 women were admitted for pPROM at 34-36 completed weeks of gestation, 241 of whom were included in the study: 126 in the group with a policy of expectant management and 115 in the active management group. The incidence of clinical chorioamnionitis was 4.8% in the former and 0.9% in the latter (p = 0.07). Neonatal oxygen was still needed at 24 hours significantly more often in the active than in the expectant management group (7.0 vs. 1.6%, p = 0.05). However, after adjustment for gestational age at birth, only delivery at 34 weeks of gestation remained associated with the need for neonatal oxygen at 24 hours. The rate of hypoglycemia or hypocalcemia was 5.6% in the expectant management group versus 12.3% in the active management group (p = 0.07). There were no neonatal deaths. CONCLUSION: A policy of active management, especially at 34 weeks of gestation, was associated with greater neonatal morbidity, whereas an expectant management policy tended to be associated with an increased rate of clinical chorioamnionitis.

Pregnancy outcomes in women with HIV type-1 receiving a lopinavir/ritonavir-containing regimen.

BACKGROUND: The pregnancy-related adverse effects of antiretroviral therapy (ART) have yielded discordant results, which could be explained in part by the heterogeneity of ART protocols. The objective of our study was to explore whether lopinavir/ritonavir (LPV/r) exposure during pregnancy is associated with adverse outcomes. METHODS: Data on 100 consecutive HIV type-1 (HIV-1)-infected women receiving LPV/r during pregnancy and who delivered after 15 weeks gestational age (GA) between January 2003 and June 2007 in a single centre were analysed. For each HIV-1-infected woman, two uninfected women matched by age, parity and geographical origin were selected among patients delivering during the same period. Preterm delivery (PTD), vasculoplacental complications, gestational glucose intolerance and post-partum complication rates were compared between cases and controls. Factors associated with PTD and post-partum complications were assessed in HIV-1-infected women by a logistic regression model. RESULTS: Rates of vasculoplacental complication and gestational glucose intolerance were not higher among HIV-1-infected women than in controls. PTD was higher in HIV-1-infected women (21%) than in controls (10%; P<0.01). In HIV-1-infected women, PTD was associated with HIV-1 RNA level > or =50 copies/ml at delivery (adjusted odds ratio 6.15, 95% confidence interval 1.83-20.63; P=0.003). No association was found between occurrence of PTD and LPV/r exposure before 14 weeks GA. CONCLUSIONS: In this population of HIV-1-infected pregnant women receiving LPV/r, the risk of PTD was higher than in HIV-1-uninfected controls. As PTD risk was not associated with early exposure to LPV/r, these data support current guidelines to initiate ART earlier in pregnancy.

Neonatal stepping in relation to terrestrial optic flow.

This experiment examined whether newborn stepping, a primitive form of bipedal locomotion, could be modulated by optical flow. Forty-eight 3-day-old infants were exposed to optical flows that were projected onto a horizontal surface above which the infants were suspended. Significantly more air steps were elicited by exposure to a terrestrial optical flow specifying forward translation than by a rotating optical flow or a static optical pattern. Thus, a rudimentary coupling between optical flow and stepping is present at birth, suggesting a precocious capacity in the newborn to perceive and utilize visual information specifying self-motion. The findings may help the early diagnosis of infants with visual or visual-motor deficits and the development of visually based interventions for disabled infants.

History of cesarean before 32 weeks' gestation and trial of labor: what is the risk of uterine rupture?

OBJECTIVES: To estimate the risk of uterine rupture in women with a previous cesarean delivery before 32 weeks' gestation and a trial of labor. DESIGN: Retrospective case control study. Setting. Level III maternity center. METHODS: Among women with trial of labor, the case and control groups were women with previous cesarean section before and after 32 weeks, respectively. The main outcome was uterine rupture, defined as rupture of the three layers of the uterine wall. RESULTS: The study compared 108 trials of labor in patients with a previous cesarean delivery at a mean gestation of 29.8 weeks+/-2.0 SD and 137 trials of labor in patients with a previous cesarean delivery at a mean gestation of 39.2 weeks+/-2.3 SD. Mode of delivery did not differ between groups. Two uterine ruptures (1.9%, 95% CI: 0.0-4.4) occurred in the case group and none in the control group (p=0.16). Uterine ruptures caused no serious maternal or neonatal complications. The condition of the neonates was similar in the two groups. CONCLUSION: In view of the small number of uterine ruptures and the absence of severe maternal and fetal consequences over an 8-year period, a trial of labor may be proposed to women with a history of cesarean delivery before 32 weeks, when obstetrical conditions are optimal.

[Perineal consequences according to obstetric practices: A comparative study here and elsewhere, Canada and France]. / Conséquences périnéales selon les pratiques obstétricales: une étude comparative "ici-ailleurs" Canada-France.

OBJECTIVE: To study how differences in birth management can influence the frequency and types of perineal lesions. MATERIAL AND METHODS: We compared outcomes and obstetric practices during labour and birth in low-risk primiparous women in two maternity units: one Canadian (maternitA Sainte-Justine, Montreal, Quebec), one French (maternité Cochin-Port-Royal, Paris). We compared the occurrence of perineal lesions--episiotomy and severe perineal tear--in these two maternity units according to delivery method. Furthermore, we studied risk factors for perineal lesions using univariate and multivariate analyses. RESULTS: Among the 1044 births in Montreal and the 1154 births in Paris, the Caesarian-section rate, about 19%, was comparable in both maternity units. Among primiparous women who had a vaginal delivery, the rate of instrumental extraction was higher in the French unit than in the Canadian one (28.2% vs. 21.5%, P < 0.001). The rate of episiotomy was significantly higher in the French unit (65.9%) than in the Canadian one (23.2%), whether the vaginal delivery was spontaneous (OR adjusted = 5.8 [4.4-7.7]) or assisted (OR adjusted = 120.2 [61.0-23.1]). The rate of severe perineal tear was significantly higher in the Canadian maternity unit (11.1%) than in the French one (1.3%), whether the vaginal delivery was spontaneous (OR adjusted = 17.4 [2.4-128.7]) or assisted (OR adjusted = 45.7 [6.1-343.4]). CONCLUSION: The significant differences in episiotomy and severe perineal tear rates observed in low-risk primiparous women are in part due to the different methods used to manage delivery in these two maternity units, particularly with regard to the angle of incision during episiotomy: median in Canada and median-lateral in France.

Neonatal outcomes of twin pregnancy according to the planned mode of delivery.

OBJECTIVES: To assess neonatal morbidity in twin pregnancy according to the planned mode of delivery. METHODS: A retrospective cohort study of 758 consecutive sets of twins born after 35 weeks of gestation with a cephalic-presenting first twin was undertaken in a level III maternity unit in which active management of the second twin delivery is performed routinely. The primary outcome was a composite measure of neonatal mortality and morbidity, including pH less than 7.0, 5-minute Apgar score less than 4, neonatal intensive care unit transfer more than 4 days, pneumothorax, and fracture. Control for potential confounders was performed by excluding from the analysis women who experienced pregnancy complications and by using logistic regression models. RESULTS: Vaginal or cesarean delivery was planned for 657 (86.7%) and 101 (13.3%) women, respectively. Among planned vaginal deliveries, 515 (78.4%) patients delivered both twins vaginally, 139 (21.1%) had a cesarean delivery during labor, and 3 (0.5%) had cesarean delivery for the second twin. After vaginal birth of the first twin, the mean intertwin delivery interval was 4.9+/-3.2 minutes. When patients who experienced pregnancy complications were excluded (n=202), the neonatal composite morbidity for the second twin did not differ between planned cesarean and planned vaginal delivery (5.0% compared with 4.7%, adjusted odds ratio 1.5, 95% confidence interval 0.3-7.4, P=.63). Neonatal composite morbidity of first twins did not differ between groups. CONCLUSION: For twin gestations with a cephalic-presenting first twin, planned vaginal delivery after 35 weeks of gestation in selected women remains a safe option in centers used to active management of the second twin delivery.

Early preterm breech delivery: is a policy of planned vaginal delivery associated with increased risk of neonatal death?

OBJECTIVE: The purpose of this study was to compare neonatal death rates in preterm singleton breech deliveries from 26 weeks to 29 weeks 6 days of gestation in centers with either a policy of planned vaginal delivery (PVD) or planned cesarean delivery (PCD). STUDY DESIGN: Women with preterm singleton breech deliveries were identified from the databases of 3 perinatal centers and classified as PVD or PCD according to the center's management policy. RESULTS: The study included 84 women in the PVD group and 85 women in the PCD group. Incidence of neonatal death was similar in both (10.7% vs 7.1%; P = .40). Head entrapment (adjusted odds ratio, 7.2; 95% CI, 1.7-29.8), preterm premature rupture of membranes at <24 weeks of gestation (adjusted odds ratio, 13.3; 95% CI, 2.8-63.0), and gestational age between 26 weeks and 27 weeks 6 days of gestation (adjusted odds ratio, 4.7; 95% CI, 1.2-18.5) were associated independently with neonatal death. CONCLUSION: Risk of neonatal death was not associated with any particular policy of mode of delivery.

Manual rotation in occiput posterior or transverse positions: risk factors and consequences on the cesarean delivery rate.

OBJECTIVE: To identify the risk factors for failure of manual rotation in patients with occiput posterior or transverse positions during labor and to study the cesarean rate according to the success of the rotation. METHODS: Case-control study comparing failure and success of manual rotation. Cases were all fetuses for whom rotation failed. We used computerized randomization (without matching) to select one control with a successful rotation during the same period for each case with a failed rotation. Maternal, neonatal, and obstetric risk factors for failed rotation were studied with bivariable and multivariable analyses. Mode of delivery was analyzed according to success of the rotation. RESULTS: During the study period, manual rotations were performed in 796 patients. The procedure failed in 77 (9.7%) women. Attempted rotation before full dilatation tripled the risk of failure in comparison with rotation at full dilatation (adjusted odds ratio 3.4, 95% confidence interval 1.3-8.6), and rotation for failure to progress quadrupled that risk in comparison with prophylactic rotation (adjusted odds ratio 3.3, 95% confidence interval 1.2-8.5). Failure of manual rotation was associated with a higher cesarean delivery rate than was success (58.8% compared with 3.8%, P<.001). All women with unsuccessful manual rotations who delivered vaginally delivered in the occiput posterior position, and all women with successful manual rotation delivering vaginally delivered in the occiput anterior position. CONCLUSION: Manual rotation may be an effective technique for reducing the cesarean delivery rate in patients with an occiput posterior or transverse position during labor. The success or failure of attempted manual rotation depends upon obstetric conditions, including the indication for rotation and cervical dilatation.

PDE4 as a target in preterm labour.

Cyclic nucleotide phosphodiesterases (PDE) are the enzymes catalyzing the hydrolysis and inactivation of the second messengers, cAMP and cGMP. Eleven PDE families are described to date, and selective inhibitors of some PDEs families are currently used in clinic for treating cardiovascular disorders, erectile dysfunction, and pulmonary hypertension. Isoforms of the PDE4 family are involved in smooth muscle contraction and inflammation. PDE4 selective inhibitors are currently in clinical trials for the treatment of diseases related to inflammatory disorders. Because of their myorelaxant properties, we first examined their expression in human myometrium and uncover an increased expression of one specific isoform, PDE4B2, in the near-term myometrium as compared to myometrium in the nonpregnant state. Using human myometrial cells in culture, we demonstrated that PDE4B2 can be induced by its own substrate, under the control of one of the major utero-contractile agonists, PGE2, itself upregulated by the proinflammatory cytokine IL-1beta. Functionally, augmentation of global PDE4 activity decreases the ability of beta-adrenergic agonists (the most commonly used tocolytic drugs) to inhibit myometrial contraction at the end of pregnancy and during pathophysiological situations, such as persistent intrauterine inflammation which is a major cause of very preterm delivery. Currently exploring the anti-inflammatory properties of PDE4 inhibitors in gestational tissues, we recently demonstrated the ability of these drugs to block a persistent inflammatory response of the foetal membranes in Humans and to prevent inflammation-driven preterm delivery and foetal demise in mice. These data open up a new therapeutical strategy to prevent inflammation-induced preterm delivery and its sequelae in very preterm infants.

Should phosphodiesterase 5 selective inhibitors be used for uterine relaxation?

Sildenafil citrate is a phosphodiesterase 5-selective inhibitor used successfully in treating erectile dysfunction. High doses of sildenafil can inhibit myometrial contractions. However, no study has demonstrated a role for phosphodiesterase 5 in myometrial contractility. No clinical trial using sildenafil to promote uterine relaxation should be initiated based on the currently available data.

Selective use of fetal fibronectin detection after cervical length measurement to predict spontaneous preterm delivery in women with preterm labor.

OBJECTIVE: The purpose of this study was to determine whether selective use of fetal fibronectin detection after ultrasound measurement of cervical length predicts preterm delivery in symptomatic patients better than either indicator alone. STUDY DESIGN: This prospective blinded study performed both tests on 359 women hospitalized for preterm labor between 18 and 34 completed weeks' gestation. The primary outcome was preterm delivery before 35 weeks'gestation. RESULTS: Among the 359 women included, 48 (13.4%) delivered before 35 weeks' gestation. The sensitivity, specificity, and positive and negative predictive values of cervical length < or = 25 mm were 75%, 63%, 24%, and 94%, respectively, and of fetal fibronectin > or = 50 ng/mL, 63%, 81%, 33%, and 93%. Fetal fibronectin detection was significantly (P < .001) more specific than cervical length measurement. For selective use of fetal fibronectin detection after cervical length measurement, the test was considered positive if cervical length was < or = 15 mm or if cervical length was between 16 and 30 mm with fetal fibronectin > or = 50 ng/mL. The predictive values of this test were not significantly different from those of fetal fibronectin detection (67%, 81%, 36%, and 94%). This strategy could have avoided 200 fibronectin tests. CONCLUSION: Selective use of fetal fibronectin detection after cervical length measurement is more specific than cervical length and as effective as fetal fibronectin assays in the entire population of women in preterm labor for predicting preterm birth.