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The incidence of preterm labor and specific risk factors.

A retrospective review of patients at high risk for preterm delivery because of twin gestation, uterine malformation, incompetent cervix, or previous preterm delivery was carried out to assess the rates of preterm labor and spontaneous preterm birth. Among the 119 patients with multifetal gestation, 46% had preterm labor and 36% delivered before 37 weeks' gestation. In the 58 patients with an anomalous uterus, the rate of preterm labor was 19%, and 14% had early deliveries. Of those with incompetent cervices (115), one-fourth had preterm labor and 17% had an early birth. When a history of one or more preterm deliveries was present, the preterm labor rate ranged from 41-68%, with an early delivery rate of 30-47%. Prophylactic tocolytic therapy did not prolong gestations significantly. Maternal smoking did not have an adverse effect on the incidence of preterm labor except in twin pregnancies, for which early delivery was more likely. The percentages for preterm delivery are slightly lower than those found in the literature; this may be attributable to improvement in preterm birth prevention efforts including patient education, more frequent examinations, home uterine activity monitoring, and daily nursing contact.

Female↗

Preterm labor: emerging role of genital tract infections.

Preterm birth complicates 8-10% of all pregnancies in the United States and is the leading cause of infant morbidity and mortality. Neonatal morbidity and mortality is concentrated among very low-birthweight and extremely premature infants, particularly those delivered prior to 30 weeks' gestational age. In addition to the contribution of preterm birth to neonatal morbidity and mortality, the economic costs associated with this pregnancy complication are staggering. Efforts to reduce the preterm birth rate have been largely focused on prevention and early intervention with treatment for preterm labor. Mixed results regarding the success of prematurity prevention programs have been reported, and controversy continues to surround the efficacy of tocolytic therapy in the treatment of preterm labor. Although neonatal survival for infants born at early gestational ages has steadily improved in recent years, survival of infants delivered prior to 24 weeks' gestation remains very poor. Additionally, despite this decline in neonatal mortality, the United States still lags behind most industrialized nations in infant mortality, and no change in the rate of low birthweight has occurred in recent decades. Multiple lines of evidence support a role for infection as an etiologic factor in preterm labor. Although this association has been well known for many years, a wealth of new data is emerging, linking subclinical genital tract infection with spontaneous preterm birth, particularly among pregnancies that result in birth prior to 30 weeks' gestational age as a result of spontaneous preterm labor or preterm, premature rupture of membranes. Conversely, preterm birth that occurs closer to term is less likely to be associated with genital tract infection. Improved understanding of the link between genital tract infection and preterm birth now provides an exciting potential for the development of sensitive new markers to identify women at risk and effective interventions to prevent preterm birth. A review and comment on this growing literature is provided.

Biomarkers↗

Bed rest in singleton pregnancies for preventing preterm birth.

BACKGROUND: Bed rest in hospital or at home is widely recommended for the prevention of preterm birth. This advice is based on the observation that hard work and hard physical activity during pregnancy could be associated with preterm birth and with the idea that bed rest could reduce uterine activity. However, bed rest may have some adverse effects on other outcomes. OBJECTIVES: To evaluate the effect of prescription of bed rest in hospital or at home for preventing preterm birth in pregnant women at high risk of preterm birth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (July 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003), MEDLINE (July 2003), LILACS (July 2003), EMBASE (July 2003), POPLINE (July 2003) and bibliographies of relevant papers. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials with reported data that assess clinical outcomes in women at high risk of spontaneous preterm birth who were prescribed bed rest in hospital or at home for preventing preterm birth, and their babies. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed eligibility, trial quality and extracted data. MAIN RESULTS: One study met the inclusion criteria (1266 women). This trial has uncertain methodological quality due to lack of reporting. Four hundred and thirty-two women were prescribed bed rest at home and a total of 834 women received a placebo (412) or no intervention (422). Preterm birth before 37 weeks was similar in both groups (7.9% in the intervention group versus 8.5% in the control group), and the relative risk was 0.92 with a 95% confidence interval from 0.62 to 1.37. No other results were available. REVIEWER'S CONCLUSIONS: There is no evidence, either supporting or refuting the use of bed rest at home or in hospital, to prevent preterm birth. Although bed rest in hospital or at home is widely used as the first step of treatment, there is no evidence that this practice could be beneficial. Due to the potential adverse effects that bed rest could have on women and their families, and the increased costs for the healthcare system, clinicians should not routinely advise women to rest in bed to prevent preterm birth. Potential benefits and harms should be discussed with women facing an increased risk of preterm birth. Appropriate research is mandatory. Future trials should evaluate both the effectiveness of bed rest, and the effectiveness of the prescription of bed rest, to prevent preterm birth.

Bed Rest↗

Intellectual outcome, speech and school performance in high risk preterm children with birth weight appropriate for gestational age.

Intellectual development, speech and school performance of preterm infants with birth weight appropriate for gestational age are reported in two separate investigations: a longitudinal study of 97 preterm children and 93 term children as a control group, and a cross-sectional study of 249 preterm children. Both preterm groups were regarded as high risk groups with respect to number of outborns, distribution of gestational age and perinatal risk factors. Intellectual outcome at 5 and 7 years of age in the majority of the preterm children was comparable to that of the term children. However, 8% of the preterm boys and 2% of the preterm girls achieved lower IQ scores than any of the term children. Between 15% and 17% of the preterm boys and 9%-12% of the preterm girls did not attend school at grade level, compared to 4% and 2% in the term group, respectively. Intellectual and neurological development and school performance were higher interrelated in the preterm than in the term children. Articulation defects, stuttering and dysgrammatism occurred more frequently in the preterm than in the term children and in boys more so than in girls.

Achievement↗

Prediction of risk for preterm delivery by ultrasonographic measurement of cervical length.

Risk assessment for preterm delivery remains difficult, particularly among women with no prior history of preterm birth. We hypothesized that accurate assessment of cervical length by endovaginal ultrasonography could predict preterm delivery risk. A total of 178 patients with singleton gestations and without cervical incompetence were studied with transabdominal ultrasonography and endovaginal ultrasonographic cervical length measurement and manual vaginal examination of cervical length. A total of 113 patients who were evaluated by 30 weeks' gestation (excluding four induced preterm deliveries) were analyzed. Preterm delivery risk was compared between women with cervical lengths equal to or greater than the median and those with cervical lengths less than the median. An endovaginal ultrasonographic cervical measurement less than 39 mm was associated with a significantly increased risk of preterm delivery (25.0% versus 6.7%) and detected 76% of preterm births. Manual examination of cervical effacement detected 71% of preterm births, but transabdominal ultrasonographic measurement of cervical length was not preditive. Endovaginal ultrasonographic cervical measurement predicted increased preterm delivery risk regardless of parity or obstetric history. Endovaginal ultrasonography is a promising method for the prediction of risk of preterm birth. Because it has the potential to be an objective measure of cervical length, endovaginal ultrasonography may be superior to manual digital examination for preterm delivery risk assessment.

Cervix Uteri↗

The presence of cervical and vaginal fetal fibronectin predicts preterm delivery in an inner-city obstetric population.

OBJECTIVE: It has previously been shown that fibronectin bearing a specific oncofetal domain is present at the chorionic-decidual interface and that its release into cervical and vaginal secretions accurately predicts preterm delivery in patients with uterine contractions. This study examines whether serial assessment of cervical and vaginal fetal fibronectin allows for the prediction of preterm delivery in symptom-free patients derived from an inner-city, general obstetric population. STUDY DESIGN: Cervical and vaginal samples were obtained from 429 consenting patients who received routine prenatal care between 24 and 37 weeks' gestation. A sensitive immunoassay was used to quantitate cervical and vaginal fetal fibronectin levels, and clinicians were blinded to fetal fibronectin results. Post hoc receiver operating characteristic curve analysis was used to determine which sample site (cervical or vaginal), fetal fibronectin concentration, and number of consecutive positive samples optimized screening efficacy. Logistic regression was employed to determine whether fetal fibronectin was an independent predictor of preterm delivery. RESULTS: The spontaneous preterm delivery rate was 11% (49/429). Among the 326 patients sampled within 28 days of delivery, receiver operating characteristic curve analysis indicated that the presence of a single cervical fetal fibronectin value > 60 ng/ml between 24 and 36 weeks' gestation predicted preterm delivery with a sensitivity of 73%, a specificity of 72%, and positive and negative predictive values of 25% and 95%, respectively. A vaginal fetal fibronectin value > 50 ng/ml predicted preterm delivery with a sensitivity of 68%, a specificity of 80%, and positive and negative predictive values of 30% and 95%, respectively. Cervical and vaginal fetal fibronectin predicted preterm deliveries resulting from both membrane rupture and preterm labor with intact membranes. A positive fetal fibronectin result preceded preterm delivery by 3.4 (+/- 3.2) weeks. Stepwise logistic regression demonstrated that cervical and vaginal fetal fibronectin levels were independent predictors of preterm delivery with adjusted odds ratios of 8.9 (95% confidence interval 3.6 to 22.1) and 6.0 (95% confidence interval 2.6 to 13.7), respectively. CONCLUSIONS: Among patients undergoing monthly cervical and vaginal sampling between 24 and 36 weeks' gestation, the presence of fetal fibronectin is a sensitive and specific predictor of preterm delivery.

Cervix Uteri↗

Previous pregnancy loss: risks related to severity of preterm delivery.

OBJECTIVES: The purpose of this study was to examine the association between previous pregnancy losses and subsequent risk of preterm delivery. STUDY DESIGN: A population-based Swedish study including information on all births and women's hospital admissions for pregnancy loss (n = 601,883) in Sweden between 1987 and 2000 was performed. The risk of preterm delivery after a previous pregnancy loss was estimated using logistic regression models. The risk of preterm premature ruptures of the membranes (PROM), preterm labor, and other reasons for preterm delivery was also assessed. RESULTS: Previous spontaneous abortions and missed abortions were associated with increased risks of preterm delivery, and the risks increased with severity of preterm delivery. Previous pregnancy loss increased the risk of preterm PROM and preterm labor foremost in deliveries before 32 weeks, but was not associated with other reasons of very preterm delivery. CONCLUSION: Our results support the hypothesis that pregnancy loss and early preterm delivery may share etiologic causes.

Abortion, Spontaneous↗

High levels of fetal cell-free DNA in maternal serum: a risk factor for spontaneous preterm delivery.

OBJECTIVE: This study was conducted to determine whether there is a relationship between the concentration of fetal cell-free DNA in maternal serum and the duration of pregnancy in women who are at high risk for preterm delivery because of either preterm labor or preterm premature rupture of the membranes. STUDY DESIGN: Sera were collected and frozen from 71 women with a male fetus. Maternal serum fetal cell-free DNA concentration was measured with the use of real-time polymerase chain reaction amplification of DYS1. Fetal cell-free DNA concentrations were converted to multiples of the median. The following groups were studied: group 1: women with preterm labor and intact membranes who were delivered at > or = 36 weeks of gestation (n = 21); group 2: women with preterm labor who were delivered at <36 weeks of gestation (n = 29); and group 3: women with preterm premature rupture of the membranes in labor (n = 20) or not in labor (n = 1) who were delivered prematurely (<36 weeks of gestation). Kaplan-Meier and Cox regression analyses were used to analyze the relationship between fetal cell-free DNA concentrations and the likelihood of preterm delivery. RESULTS: A cut-off value for fetal cell-free DNA of 1.82 multiples of the median was chosen for analysis. The cumulative rate of early preterm delivery (<30 weeks of gestation) was significantly higher for women with fetal cell-free DNA concentrations of > or = 1.82 multiples of the median than those with fetal cell-free DNA concentrations below this cut-off (45% [95% CI, 36%-74%] vs 18% [95% CI, 11%-25%]; P = .008]. The cumulative rate of preterm delivery (<36 weeks of gestation) was also significantly higher at > or = 1.82 multiples of the median (73% [95% CI, 52%-93%] vs 66% [95% CI, 54%-79%]; P = .02). After adjustment for covariates, Cox analysis showed that fetal cell-free DNA at > or = 1.82 multiples of the mechanisms of disease that are associated with a mean hazard rate of delivery of 1.57 (P = .005). CONCLUSION: High concentrations of fetal cell-free DNA in maternal serum are associated with an increased risk of spontaneous preterm delivery. This observation may have implications for the understanding of the mechanisms of disease that is associated with preterm labor.

Cross-Sectional Studies↗

Prognostic significance of prior preterm twin delivery on subsequent singleton pregnancy.

OBJECTIVE: Our purpose was to determine whether preterm birth of twins is associated with an increased risk of preterm birth in a subsequent singleton pregnancy. STUDY DESIGN: The Medical University of South Carolina perinatal database was accessed to identify a cohort of patients who were delivered of twins followed by a singleton gestation (1981 to 1993). Maternal transports were excluded to minimize referral bias. Preterm birth was defined as < 37 weeks' gestation. Relative risks with 95% confidence intervals were calculated. RESULTS: One hundred forty-four patients were identified who were delivered of twins followed by a singleton gestation. Preterm delivery occurred in 86 (59.7%) of the twins and 21 (14.6%) of the subsequent singletons. Preterm birth of twins was associated with a significantly increased risk of preterm delivery in a subsequent singleton pregnancy (relative risk 2.87, 95% confidence interval 1.02 to 8.09). In the subset of women who were delivered of twins at < 30 weeks' gestation, 42% of the subsequent singletons were delivered preterm (relative risk 6.11, 95% confidence interval 2.07 to 18.02). The relative risk of preterm birth of a singleton after delivery of twins between 30 and 34 weeks' gestation was 3.63 (95% confidence interval 1.02 to 12.92). However, if the preceding twins delivered between 34 and 37 weeks' gestation, the relative risk of preterm birth of the subsequent singleton was not significantly increased (relative risk 1.42, 95% confidence interval 0.40 to 5.01). CONCLUSIONS: Preterm birth of twins before 34 weeks' gestation is associated with a significant risk for preterm delivery in a subsequent singleton pregnancy. The magnitude of risk increases with decreasing gestational age of the preceding twin delivery.

Adult↗

Cervical ultrasonography compared with manual examination as a predictor of preterm delivery.

OBJECTIVE: Our purpose was to compare the accuracy of ultrasonographic and manual cervical examinations for the prediction of preterm delivery. STUDY DESIGN: One hundred two singleton pregnancies at high risk for preterm delivery were followed up prospectively from 14 to 30 weeks with both serial cervical ultrasonography measurements and manual examinations of the length of the cervix. The primary outcome studied was preterm (< 35 weeks) delivery. RESULTS: Excluding six induced preterm deliveries, 96 pregnancies were analyzed. The mean cervical length measured by ultrasonography was 20.6 mm in pregnancies delivered preterm (n = 17) and 31.3 mm in pregnancies delivered at term (n = 79) (p = 0.003); the mean cervical lengths measured by manual examination were 16.1 mm and 18.6 mm in the same preterm and term pregnancies, respectively (not significant). The sixteenth- and twentieth-week ultrasonographic cervical lengths predicted preterm delivery most accurately (p < 0.0005). The 25th percentiles of ultrasonographic (25 mm) and manual (16 mm) cervical lengths showed relative risks for preterm delivery of 4.8 (95% confidence interval 2.1 to 11.1, p = 0.0004) and 2.0 (95% confidence interval 0.5 to 4.7, p = 0.1), respectively; sensitivity, specificity, and positive and negative predictive values were 59%, 85%, 45%, 91%, and 41%, 77%, 28%, and 86%, respectively. CONCLUSION: Cervical length measured by ultrasonography is a better predictor of preterm delivery than is cervical length measured by manual examination. Cervical ultrasonography in patients at high risk for preterm birth seems to be most predictive of preterm delivery when it is performed between 14 and 22 weeks' gestation.

Cervix Uteri↗

Prediction of preterm delivery with transvaginal ultrasonography of the cervix in patients with high-risk pregnancies: does cerclage prevent prematurity?

OBJECTIVES: We sought to determine the predictive accuracy for preterm delivery of transvaginal ultrasonography of the cervix between 14 and 24 weeks' gestation in high-risk patients and to determine whether cerclage prevents preterm delivery in patients with ultrasonographic cervical changes. STUDY DESIGN: Patients with asymptomatic singleton pregnancies at high risk for preterm delivery were followed prospectively from 14 weeks' to 23 weeks 6 days' gestation with transvaginal ultrasonography of the cervix. The subgroup of patients with either a cervical length of <25 mm or funneling of >25% or both was offered McDonald salvage cerclage, which was performed at the discretion of the patient and the obstetrician. The 2 groups (with and without cerclage) were compared for the primary outcome of preterm delivery at <35 weeks' gestation. RESULTS: One hundred sixty-eight women were followed, including 97 (58%) with >/=1 prior 14- to 34-week preterm deliveries. Of 63 (37. 5%) patients identified as having cervical changes, 23 (37%) had preterm delivery; of 105 patients with no cervical changes, 8 (8%) had preterm delivery (relative risk, 4.8; 95% confidence interval, 2. 3-10.1). The sensitivity, specificity, and positive and negative predictive values of either a short cervix of <25 mm or funneling of >25% or both were 74%, 70%, 37%, and 92%, respectively. Of 63 pregnancies in which there were cervical changes, 39 underwent cerclage and 24 did not. These 2 groups were similar for demographic characteristics, risk factors, and transvaginal ultrasonographic cervical length and funneling but dissimilar for gestational age at identification of cervical changes (18.3 vs 21.2 weeks' gestation in the groups with and without cerclage, respectively; P <.001). Multivariate logistic regression analysis after adjustment for gestational age at cervical changes showed no difference in the rate of preterm delivery between the groups with and without cerclage (odds ratio, 1.1; 95% confidence interval, 0.3-4.6). Stratified analysis of patients identified between 18 and 24 weeks revealed 22 pregnancies with cerclage and 22 pregnancies without cerclage, which was similar for all characteristics studied. The incidence of preterm delivery remained similar (27% vs 23%, respectively; P =.7), as did days from cervical changes to delivery (111 vs 96, respectively; P =.2). CONCLUSIONS: Transvaginal ultrasonography of the cervix between 14 and 24 weeks' gestation is a good predictor of preterm delivery in high-risk pregnancies. Cerclage may not prevent preterm delivery in patients identified to be at high risk for this outcome by transvaginal ultrasonography.

Cervix Uteri↗

Maternal serum interleukin-6 during pregnancy and during term and preterm labor.

OBJECTIVE: To determine the normal concentrations of maternal serum interleukin-6 during the second and third trimesters of pregnancy and the different stages of term and preterm labor, and to examine the clinical usefulness of measuring this cytokine in the serum of women in preterm labor to diagnose asymptomatic intrauterine infections. METHODS: Maternal serum interleukin-6 concentrations were measured cross-sectionally in 315 gravidas in their second and third trimesters and during term and preterm labor. Placentas from women who delivered preterm were examined for histologic chorioamnionitis. RESULTS: At term, women in labor had significantly elevated median maternal serum interleukin-6 concentrations compared with those at term not in labor (4.7 pg/mL versus 2.2 pg/mL, P < .001). Women admitted in preterm labor who delivered had significantly higher median interleukin-6 concentrations than did those in preterm labor who responded to tocolysis (9.3 pg/mL versus 1.9 pg/mL, P < .001). Women in preterm labor who delivered preterm with evidence of chorioamnionitis had significantly higher serum concentrations of interleukin-6 than did those in preterm labor who delivered in the absence of chorioamnionitis (15.9 pg/mL versus 4.6 pg/mL, P = .006). CONCLUSION: Compared with antepartum gravidas, those in term or preterm labor had significantly higher concentrations of maternal serum interleukin-6 concentrations; extremely elevated levels were found in patients whose preterm labor was associated with intrauterine infection.

Female↗

Risk factors for preterm birth in an upper middle class Chinese population.

OBJECTIVE: To examine the risk factors associated with preterm birth in an upper middle class Chinese population. STUDY DESIGN: From March 1994 to February 1995, a total of 301 cases (gestational age between 20 and 37 weeks) and 656 controls (gestational age at or greater than 37 weeks) were recruited at Mackay Memorial Hospital, Taipei, Taiwan. Using a case-control study design, logistic regression was used to examine the relative significance of various risk factors associated with preterm birth. RESULTS: Age and educational level were identified as significant risk factors for preterm birth. Multiple pregnancies, fetal congenital anomalies, placenta previa or abruptio placentae, and preeclampsia were found to be strongly associated with preterm birth (crude odds ratios between 6.37 and 25.89); vaginal bleeding during or after the first trimester, prior history of preterm delivery, and two or more previous first trimester abortions were associated with preterm birth to a lesser extent (crude odds ratios between 1.67 and 2.9). The magnitude of the increased risk associated with these variables in preterm birth did not show change to any great extent after age and educational level were adjusted for. Further stratification of these cases into groups with and without premature rupture of the membranes (PROM), showed that a multiple pregnancy was still the leading risk factor of preterm birth in both groups. Carrying an abnormal fetus was the next important risk factor for preterm birth in cases with PROM, but was less important in the group without PROM. However, placenta previa or abruptio placentae and preeclampsia were the next most important factors in the group without PROM. CONCLUSIONS: Unfavorable current obstetric conditions and a history of more than two prior abortions and preterm delivery were positively associated with preterm birth.

Abruptio Placentae↗

Maternal plasma fibronectin: a predictor of preterm delivery.

OBJECTIVE: Current opinion holds that there are several distinct groups among patients with preterm labour: one of them is characterized by bacterial infection, another one by the presence of placental vascular abnormalities with endothelial damage. The aim of this study was to investigate plasma fibronectin, a suspected biochemical marker of endothelial damage, as an indicator for pregnancies with a high risk of preterm delivery. METHODS: Plasma fibronectin levels were measured in patients with preterm labour (n = 80) and in healthy pregnant women with uncomplicated (control) pregnancies (n = 64) between the 22nd and 36th week of gestation. Furthermore, the plasma concentrations of fibronectin in 15 newborns at term and ten babies born preterm were measured to study the relationship between preterm delivery and plasma fibronectin concentration in newborns. Fibronectin was measured by nephelometry. RESULTS: The mean concentration of fibronectin in patients with preterm labour was 0.44 g/l (S.D., 0.15) vs. 0.25 g/l (S.D., 0.12) in uncomplicated control pregnancies matched for gestational age. In control patients who actually delivered at term, fibronectin values were found to be lower than in control patients who underwent preterm delivery (0.25 g/l; S.D., 0.05; vs. 0.46 g/l; S.D., 0.15; P < 0.05). Particularly high values were detected in patients with preterm labour delivering before 32 weeks of gestation (0.60 g/l; S.D., 0.16). There was no significant difference between fibronectin concentrations in the umbilical arterial and venous blood of premature infants and mature infants. Leucocyte concentration, bacteriological smear and cervical dilatation did not correlate with fibronectin concentrations in patients with preterm delivery or controls. CONCLUSION: We conclude that the higher plasma concentrations of fibronectin in women with preterm labour may be a biochemical marker and a predictor of preterm delivery.

Adolescent↗

Maternal asthma and risk of preterm delivery.

PURPOSE: We studied the relation between maternal history of asthma and preterm delivery. METHODS: The 312 preterm delivery cases, studied in aggregate, and in subgroups (spontaneous preterm labor, preterm premature rupture of membranes, medically induced preterm delivery), were compared with 424 randomly selected women who delivered at term. Maternal medical records provided information on maternal lifetime asthma status, pregnancy outcome, and sociodemographic characteristics. Using multivariate logistic regression, we derived maximum likelihood estimates of adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Maternal history of asthma was associated with an increased risk of preterm delivery overall (OR = 2.37; 95% CI 1.15-4.88). Analyses of preterm delivery sub-groups indicated that maternal history of asthma was associated with at least a doubling in risk of spontaneous preterm labor (OR = 2.35; 95% CI 0.84-6.58) and medically induced preterm delivery (OR = 2.69; 95% CI 1.11-6.53), though only the latter approached statistical significance. There was some evidence of a modest association between maternal asthma and risk of preterm premature rupture of membranes (OR = 1.63; 95% CI 0.50-5.33). CONCLUSIONS: These results support the hypothesis that maternal asthma is associated with an increased risk of preterm labor and delivery.

Adult↗

Stress, infection and preterm birth: a biobehavioural perspective.

Preterm birth is currently the most important problem in maternal-child health in the United States. Epidemiological studies have suggested that two factors, maternal stress and maternal urogenital tract infection, are significantly and independently associated with an increased risk of spontaneous preterm birth. These factors are also more prevalent in the population of sociodemographically disadvantaged women who are at increased risk for preterm birth. Studies of the physiology of parturition suggest that neuroendocrine and immune processes play important roles in the physiology and pathophysiology of normal and preterm parturition. However, not all women with high levels of stress and/or infection deliver preterm, and little is understood about factors that modulate susceptibility to pathophysiological events of the endocrine and immune systems in pregnancy. We present here a comprehensive, biobehavioural model of maternal stress and spontaneous preterm delivery. According to this model, chronic maternal stress is a significant and independent risk factor for preterm birth. The effects of maternal stress on preterm birth may be mediated through biological and/or behavioural mechanisms. We propose that maternal stress may act via one or both of two physiological pathways: (a) a neuroendocrine pathway, wherein maternal stress may ultimately result in premature and/or greater degree of activation of the maternal-placental-fetal endocrine systems that promote parturition; and (b) an immune/inflammatory pathway, wherein maternal stress may modulate characteristics of systemic and local (placental-decidual) immunity to increase susceptibility to intrauterine and fetal infectious-inflammatory processes and thereby promote parturition through pro-inflammatory mechanisms. We suggest that placental corticotropin-releasing hormone may play a key role in orchestrating the effects of endocrine and inflammatory/immune processes on preterm birth. Moreover, because neuroendocrine and immune processes extensively cross-regulate one another, we further posit that exposure to both high levels of chronic stress and infectious pathogens in pregnancy may produce an interaction and multiplicative effect in terms of their combined risk for preterm birth. Finally, we hypothesise that the effects of maternal stress are modulated by the nature, duration and timing of occurrence of stress during gestation. A discussion of the components of this model, including a theoretical rationale and review of the available empirical evidence, is presented. A major strength of this biobehavioural perspective is the ability to explore new questions and to do so in a manner that is more comprehensive than has been previously attempted. We expect findings from this line of proposed research to improve our present state of knowledge about obstetric risk assessment for preterm birth by determining the characteristics of pregnant women who are especially susceptible to stress and/or infection, and to broaden our understanding of biological (endocrine, immune, and endocrine-immune interactions) mechanisms that may translate social adversity during pregnancy into pathophysiology, thereby suggesting intervention strategies.

Female↗

Ontogeny of autonomic regulation in late preterm infants born at 34-37 weeks postmenstrual age.

Late preterm infants (34-37 weeks postmenstrual age at birth) are intermediate between less mature preterm infants and infants born at 38 weeks or more in regard to autonomic brain stem maturation. Ventilatory responses to CO(2) in preterm infants born at 33 to 36 week are significantly higher than in infants born at 29 to 32 weeks both at 3 to 4 and 10 to 14 days postnatal age, but do not differ from full-term reference levels. The ventilatory response to hypoxia in preterm infants is biphasic; initial transient hyperventilation is followed by a return to baseline and then a decrease below baseline. In infants born at 32 to 37 weeks, parasympathetic maturation appears significantly less than in full-term infants based on diminished increases in high frequency heart rate variability in quiet sleep, suggesting that late preterm infants are still more susceptible to bradycardia than full-term infants. Both the presence and severity of apnea of prematurity progressively decrease the higher the postmenstrual age. Late preterm infants, however, are still at risk, with prevalence rates as high as 10% compared with about 60% in infants born at <1500 g. The incidence of apparent life-threatening events is more common in preterm infants (8-10%) than full-term infants (1% or less). In the Collaborative Home Infant Monitoring Evaluation studies, the frequency of conventional and extreme events in near term infants is intermediate between preterm infants <34 weeks at birth and full-term infants. The relative risk for at least one extreme event in late preterm infants is increased (5.6 and 7.6, respectively, P < 0.008) compared with full-term infants and remains higher until 43 weeks postmenstrual age. The rate for Sudden Infant Death Syndrome in preterm infants born at 33 to 36 weeks is 1.37/1000 live births compared with 0.69 in infants born full term. Affected late preterm infants die at a older mean postmenstrual age compared with less mature infants (48 and 46 weeks, respectively), but die at a younger postmenstrual age than full-term infants (53 weeks, P < 0.05).

Apnea↗

[Cerebral hemorrhage and periventricular leucomalacia in preterm neonates after intravenous tocolysis with fenoterol: results of postnatal ultrasound examination].

BACKGROUND: This study tested whether tocolysis with beta-adrenergic agonists (Fenoterol) had an effect on the frequency of cerebral lesions in preterm neonates. PATIENTS AND METHODS: Head ultrasound scans of preterm neonates who were born after long-term (> 24 h) tocolysis were compared with scans of preterm neonates without preceding tocolysis. The gestational and neonatal data were analyzed retrospectively. RESULTS: Preterm neonates after (n = 102) and without (n = 101) tocolysis were subdivided into three groups according to their gestational age (23 - 28 wk: n = 41; 29 - 33 wk: n = 66; 34 - 36 wk: n = 96). Within these groups, no significant differences were found with respect to birth weight, rate of cesarean section, or pulmonary morbidity. Preterm babies < 28 weeks of gestation from the control group had lower Apgar scores (after 1 and 5 minutes, respectively) and arterial umbilical cord pH values. Intravenous tocolysis did not lead to an increase in pseudocystic periventricular leucomalacia (PVL) or intracerebral hemorrhage (ICH) in any of the subgroups studies. However, cerebral lesions were found in preterm neonates after tocolysis who exhibited signs of infection (29 - 33 wk: PVL n = 2; 23 - 28 wk: ICH n = 1) and in preterm neonates without tocolysis who had undergone fetal hypoxia or abruptio placentae (29 - 33 wk: PVL n = 4; antenatal terminal vein bleeding n = 1; 23 - 28 wk: PVL n = 2; terminal vein bleeding n = 5; posterior cerebral artery bleeding n = 1). When compared to preterm neonates of 34 - 36 weeks of gestation, the risk of infection was increased 4-fold in neonates of 29 - 33 weeks of gestation (odds ratio 5.43, 1.10 - 26.83) and 10-fold in neonates of 23 - 28 weeks of gestation (odds ratio 20.50, 3.65 - 115.03). Chorioamnionitis also was a more common finding in preterm neonates < 28 weeks of gestation. CONCLUSION: Preterm neonates who were born after intravenous long-term (> 24 h) tocolysis with Fenoterol do not exhibit an increase in periventricular leucomalacia or intracranial hemorrhage. The occurrence of cerebral lesions in these patients merely depends on their degree of immaturity and on the presence or absence of perinatal infection. In preterm neonates without tocolysis, brain lesions are mainly associated with hypoxic events.

Cerebral Hemorrhage↗