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PubMed1996

The effects of early and late preterm birth on brainstem and middle-latency auditory evoked responses in children with normal neurodevelopment.

In preterm and term infants, brainstem and middle latency auditory evoked responses (ABR and MLR) were obtained at 40 and 52 weeks conceptional age (CA) and at 5 years of age. A neurological and neuropsychological evaluation was performed at 5 years of age. To study the effect of preterm birth on the maturation of the ABR and MLR, the preterm infants were divided into early and late preterm groups. Only children with a normal neurodevelopmental outcome at 5 years of age were entered into the study. For ABR, the late preterm group showed significantly longer mean latencies IIc, III, V, and Vc when compared with the term group at 52 weeks CA. There was a trend to longer ABR latencies I in the early preterm group compared with the term group. At 52 weeks CA, the late preterm group showed longer mean interpeak latencies III-I and V-I when compared with the term as well as the early preterm group. At 5 years, the late preterm group showed significantly longer mean ABR latencies IIc and III when compared to the early preterm group. For MLR, the early preterm group showed significantly longer mean latencies of MLR component PO when compared with the term group at 40 weeks CA. At 52 weeks, the late preterm group also had longer mean MLR latencies P0 than the term group. At 5 years of age, the term group showed higher mean peak-to-peak amplitudes Na-P0 than the early as well as the late preterm group. To a large extent, the ABR results support the hypothesis that middle ear effusions in combination with retarded myelination of the central auditory pathway are responsible for the ABR differences found between term and preterm infants with a normal neurodevelopmental outcome at 5 years of age. The longer latencies and interpeak latencies found in late preterm infants when compared with early preterm infants might be explained by an augmented vulnerability of the auditory pathway between 30 and 34 weeks CA. The MLR differences found between term and preterm infants might be explained by a difference in the maturation of primary and nonprimary MLR components.

Auditory Cortex↗

PubMed2005

Trends in preterm birth and perinatal mortality among singletons: United States, 1989 through 2000.

OBJECTIVE: Despite the recent increase in preterm birth in the United States, trends in preterm birth subtypes have not been adequately examined. We examined trends in preterm birth among singletons following ruptured membranes, medical indications, and spontaneous preterm birth and evaluated the impact of these trends on perinatal mortality. METHODS: A population-based, retrospective cohort study comprising 46,375,578 women (16% blacks) who delivered singleton births in the United States, 1989 through 2000, was performed. Rates of preterm birth (< 37 weeks), their subtypes, and associated perinatal mortality (stillbirths at >/= 22 weeks plus neonatal deaths within 28 days), before and after adjustment for potential confounders, were derived from ecological logistic regression models. RESULTS: Preterm birth rates increased by 14% (95% confidence interval 13-15%) among whites from 8.3% to 9.4% and decreased by 15% (95% confidence interval 14-16%) among blacks from 18.5% to 16.2% between 1989 and 2000. Among whites, preterm birth following ruptured membranes declined by 23%, medically indicated preterm birth increased by 55%, and spontaneous preterm birth increased by 3%. Among blacks, preterm birth following ruptured membranes declined by 37%, medically indicated preterm birth increased by 32%, and spontaneous preterm birth decreased by 27%. The largest decline in perinatal mortality among whites was associated with increases in medically indicated preterm birth, whereas the largest decline in perinatal mortality among blacks was associated with declines in preterm birth following ruptured membranes and spontaneous preterm birth. CONCLUSION: Temporal trends in preterm birth varied substantially based on underlying subtype and maternal race. The recent increase in medically indicated preterm birth was associated with a favorable reduction in perinatal mortality.

Adolescent↗

PubMed2005

Evaluation and validation of a new risk score (CLEOPATRA score) to predict the probability of premature delivery for patients with threatened preterm labor.

OBJECTIVE: To develop a clinically useful tool to predict the probability of preterm delivery in patients with threatened preterm labor. METHODS: One hundred and seventy patients with preterm labor between 24 and 34 weeks of gestation were included. Preterm delivery < 37 weeks of gestation was the main endpoint of the study. The data were randomized and split into an evaluation set (n = 85) and a validation set (n = 85). The evaluation set was subjected to stepwise backward logistic regression analysis to quantify the relative impact of four potential risk factors, including individual patient factors, results of a rapid fetal fibronectin assay, and sonographic measurement of cervical length. Using the constant of the logistic regression analysis and the beta-coefficients for the identified risk factors the individual probability of preterm delivery for each woman of the validation dataset was calculated. The area under a receiver-operating characteristics curve (AUC) was used to evaluate the discriminating power of the score. RESULTS: The overall rate of preterm delivery was 27.1%. The logistic regression analysis was performed for the potential predictors of spontaneous preterm delivery, identified by univariate analysis. These were positive fetal fibronectin, cervical length, previous preterm delivery and maternal age. Two risk factors were independent predictors of preterm delivery and were included in the CLEOPATRA I (clinical evaluation of preterm delivery and theoretical risk assessment) score: cervical length measurement and previous preterm delivery were associated with a higher risk of preterm delivery (odds ratio, 7.65 and 6.74, respectively). Since fetal fibronectin assay is not available at all institutions worldwide, it was excluded from the initial model. In the CLEOPATRA II model the risk factors fetal fibronectin and previous preterm delivery were associated with higher risk of preterm delivery, with odds ratios of 17.9 and 4.56, respectively. The discrimination power (AUC) obtained from the models were: CLEOPATRA I, 0.69 (95% CI, 0.56-0.82); CLEOPATRA II, 0.81 (95% CI, 0.69-0.93). CONCLUSION: In symptomatic women the risk for preterm delivery can be predicted best with the CLEOPATRA II score based on fetal fibronectin and previous preterm delivery.

Adult↗

PubMed2005

Rates of recurrent preterm birth by obstetrical history and cervical length.

OBJECTIVE: This study was undertaken to determine rates of recurrent preterm birth according to number of prior preterm births, 1 versus 2 or more and cervical length by endovaginal ultrasound at 22(0) to 24(6) weeks, less than 25 mm versus more than 25 mm. STUDY DESIGN: We retrospectively analyzed data from charts of women with prior spontaneous preterm birth seen in a Prematurity Prevention Clinic from 1998 through 2004. Women with a history of 1 or more spontaneous preterm births (18(0)-36(6) weeks) were included. Women with multiple gestations, uterine anomalies, and prior cervical surgery were excluded. Transvaginal sonography was used to evaluate each woman's cervical length at 22(0) to 24(6) weeks. Cerclage, bed rest, tocolysis, and steroids were used when clinically appropriate. Primary outcome was gestational age at delivery less than 32 and less than 35 weeks. Data were analyzed according to number of prior preterm births (1 vs > or = 2) and sonographic cervical length at 22(0) to 24(6) weeks (<25 mm vs > or = 25 mm). RESULTS: A total of 188 eligible women were evaluated. Median gestational age of earliest preterm birth was 26.3 weeks. Of the total 188, 118 (62.8%) women had 1 prior and 70 (37.2%) had 2 or more preterm births. Thirty-eight (20.2%) of the women had a cervical length less than 25 mm and 150 (79.8%) had a cervical length 25 mm or greater. A higher percentage of women with a cervical length less than 25 mm and 2 or more preterm births delivered less than 32 weeks compared with women with 1 prior preterm birth, although this did not reach statistical significance (21.5% vs 12.5%, P = .47). Rates of delivery less than 35 weeks in women with a cervical length less than 25 mm were similar in those with a history of 1 and 2 or more preterm births. Women who had 2 or more prior preterm births were analyzed separately to identify if a cervical length greater than 30 mm or greater than 35 mm could be reassuring for decreasing the risk of recurrent preterm birth. CONCLUSION: Rates of preterm birth less than 32 and less than 35 weeks were similar in women whose cervical length was less than 25 mm at 22(0) to 24(6) weeks, regardless of number of prior preterm births. Women with 2 prior preterm births and a cervix greater than 35 mm were at low risk for subsequent preterm birth less than 35 weeks.

Adult↗

PubMed1999

Cervical dimensions and risk of preterm birth: a prospective cohort study.

OBJECTIVE: To examine the relation between cervical dilatation and length and the risk of spontaneous preterm birth, including its subtypes preterm labor and preterm premature rupture of membranes (PROM). METHODS: Cervical dimensions assessed by clinical examination were recorded prospectively at 24-29 weeks' gestation in 871 subjects with singleton pregnancies who were followed to delivery. Relative risks (RRs) of preterm birth, preterm labor, and preterm PROM were calculated for clinically distinguishable categories of cervical dilatation and length and for cervical score (length minus dilatation). Regression analysis was used to adjust for confounding. Time to delivery from baseline examination was summarized using survival analysis. RESULTS: There were 73 spontaneous preterm births (8.3%), 46 preterm labors and 27 cases of preterm PROM. All cervical measurements were associated with increased risks of preterm birth, with increasing abnormality more strongly predictive of risk. The adjusted RR for preterm birth with dilatation of at least 0.5 cm was 2.9 (95% confidence interval [CI] 1.2, 7.3); for length of 1.5 cm or less, the RR was 2.1 (95% CI 1.0, 4.5), and for cervical score less than 2.0, the RR was 2.8 (95% CI 1.4, 5.6). The association with cervical measurements was stronger for preterm PROM than for preterm labor, although precision was limited. These measurements had high specificity (93-99%) and low sensitivity (8-20%) for predicting preterm birth. CONCLUSION: In asymptomatic women at 24-29 weeks' gestation, greater cervical dilatation and shorter length were associated with increased risk of spontaneous preterm delivery, particularly preterm PROM.

Adult↗

PubMed2003

History of fetal loss and other adverse pregnancy outcomes in relation to subsequent risk of preterm delivery.

OBJECTIVE: To evaluate the association between maternal reproductive history 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, moderate preterm delivery [gestational age at delivery 34-36 weeks], and very preterm delivery [gestational age at delivery <34 weeks]), were compared with 424 randomly selected women who delivered at term. Maternal medical records provided information on maternal reproductive history, pregnancy outcome, as well as sociodemographic characteristics. Using multivariate logistic regression, we derived maximum likelihood estimates of adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: A history of 2+ miscarriages was (OR = 2.2; 95% CI 1.2-3.9), but a history of 2+ prior induced abortions (OR = 1.2; 95% CI 0.7-2.0) was not, associated with preterm delivery in the index pregnancy. Analyses of preterm delivery subgroups indicated that a history of 2+ miscarriages was associated with an increased risk of spontaneous preterm labor (OR = 2.6; 95% CI 1.2-2.8), preterm premature rupture of membrane (OR = 1.8; 95% 0.7-4.4), and medically induced preterm delivery (OR = 1.9; 95% CI 0.8-4.2), though only the former approached statistical significance. Excess risk of preterm delivery was associated with maternal prior history of delivering a stillborn infant (OR = 10.7), a prior history of delivering a newborn that later died during the neonatal period (OR = 3.2), and a prior history of having a pregnancy complicated by spontaneous preterm delivery (OR = 6.0). Generally these associations were evident for each subgroup of preterm delivery, though inferences were often hindered by our relatively small sample size. CONCLUSIONS: These results support the hypothesis that maternal adverse reproductive history is associated with an increased risk of preterm labor and delivery.

Abortion, Induced↗

PubMed2005

Macrophage migration inhibitory factor in patients with preterm parturition and microbial invasion of the amniotic cavity.

OBJECTIVE: Macrophage migration inhibitory factor (MIF) has emerged as an important mediator of septic shock. The administration of MIF increases lethality during endotoxemia, whereas neutralization of this cytokine prevents endotoxic shock and death associated with bacterial infection. The objective of this study was to determine whether there is a change in the amniotic fluid concentration of MIF in intra-amniotic infection and human parturition. STUDY DESIGN: A cross-sectional study was conducted in women in the following categories: (1) mid-trimester (n = 84); (2) preterm labor and intact membranes who delivered at term (n = 33), who delivered preterm (n = 53) and preterm labor with intra-amniotic infection (n = 23); (3) preterm premature rupture of membranes (PROM) with (n = 25) and without intra-amniotic infection (n = 26); and (4) term with intact membranes, in labor (n = 52) and not in labor (n = 31). MIF concentrations in amniotic fluid were determined using a sensitive and specific immunoassay. MIF concentrations in maternal plasma were also determined in patients with preterm labor and intact membranes. Immunohistochemistry was conducted in chorioamniotic membranes obtained from a different set of patients presenting with preterm labor with (n = 18) and without (n = 20) histologic chorioamnionitis. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure MIF mRNA expression in chorioamniotic membranes of patients with preterm labor with (n = 13) and without (n = 13) histologic chorioamnionitis. Parametric and non-parametric, receiver-operating characteristic (ROC) curve, survival analysis, and Cox regression model were used for analysis. RESULTS: Immunoreactive MIF was detectable in 96% (313/327) of amniotic fluid samples. The concentration of amniotic fluid MIF at term was higher than that in the mid-trimester (p = 0.004). Intra-amniotic infection in women with preterm labor and preterm PROM was associated with a significant increase in median amniotic fluid MIF concentration (p < 0.001 and 0.004, respectively). Patients with preterm labor with sterile amniotic fluid who delivered preterm had a significantly higher median amniotic fluid MIF concentration than those who delivered at term (p = 0.007). Among patients with preterm labor with intact membranes, survival analysis indicated that the median amniocentesis-to-delivery interval was significantly shorter in patients whose amniotic fluid concentrations of MIF were above 302 ng/ml than those below this cutoff value (p < 0.001). Human parturition at term was not associated with changes in the amniotic fluid MIF concentrations (p > 0.05). There was no significant difference in median maternal plasma MIF concentrations among patients with preterm labor and intact membranes who delivered at term, those who delivered preterm, and those who had intra-amniotic infection (p > 0.05 for all comparisons). Immunohistochemistry demonstrated that MIF protein was present in amniotic epithelial cells, and the mean percentage of immunoreactive MIF-staining cells was higher in patients with histologic chorioamnionitis than in those without this lesion (p = 0.03). Similarly, the mean MIF mRNA expression was higher in chorioamniotic membranes obtained from patients with histologic chorioamnionitis than in those without this lesion (p = 0.03). CONCLUSIONS: Intra-amniotic infection and preterm parturition, but not term parturition, are associated with a significant increase in amniotic fluid MIF concentrations. Among patients with preterm labor with intact membranes, elevated amniotic fluid concentrations of MIF are associated with intra-amniotic inflammation, histologic chorioamnionitis, and shorter amniocentesis-to-delivery interval. These changes in amniotic fluid were not reflected in maternal plasma. An increased expression of MIF protein and mRNA in chorioamniotic membranes was observed in patients with histologic choricamnionitis.

Amniocentesis↗

PubMed2005

Genetic factors in preterm birth--the future.

The genetic regulation of common biological functions has redundant control mechanisms, and it is unlikely that a single marker will ever be identified that will be both highly sensitive and specific. It is more likely that combinations of gene and/or protein markers, perhaps also combined with obstetric family histories, will be required to achieve the goal of a truly sensitive and specific screening profile for spontaneous preterm labour and preterm birth. The rapidly evolving disciplines of genomics and proteomics are now beginning to be applied to the study of spontaneous preterm labour and preterm birth. These techniques are able to measure multiple markers (in the thousands) in a biological sample and, given the likely presence of biological changes that precede by weeks or even months the clinical manifestations of the disease, are ideally suited to the evaluation of spontaneous preterm labour and preterm birth. Over the next few years, these technologies will hasten a deeper understanding of the pathophysiology of spontaneous preterm labour, discover novel target molecules and diagnostic biomarkers and ultimately aid in formulating more effective interventions to prevent preterm birth. Pharmacogenomics is another rapidly evolving discipline that holds great promise for the treatment and prevention of spontaneous preterm labour and preterm birth. Because spontaneous preterm labour is a final common pathway for multiple aetiologies, there remains no reason why any single therapy will work optimally for all women. As patient-specific pharmacogenomic profiles are developed, it will be possible to develop patient-specific treatment regimens. Beyond that, it may become possible to identify those women who are, or are not, destined to labour spontaneously and give birth remote from term and to institute patient-specific preventive measures. Spontaneous preterm labour and preterm birth remains a syndrome, with a final common pathway for multiple aetiologies. As a result, no single explanation, marker or treatment is likely to be 100% sensitive, specific or successful. It is also clear, however, that there is a genetic predisposition in many cases of spontaneous preterm labour. Over the next few years, several recently developed diagnostic mechanisms, and others that have yet to evolve, will hold a greater potential than ever before to unlock the secrets of the genetic predisposition to spontaneous preterm labour and its underlying causes. An improved understanding of these mechanisms will allow clinicians to employ therapies that will be optimally effective for individual women and their unborn babies. Eventually, these advances could be applied to the presymptomatic prevention of spontaneous preterm labour. It is the intent of this manuscript to review the current status of these new technologies and disciplines and to speculate on their applications in the intermediate future.

Biomedical Research↗

PubMed1996

Preterm delivery and perinatal death among black and white infants in a Chicago-area perinatal registry.

OBJECTIVE: To explore associations between race, preterm delivery, etiologic classification of preterm delivery, and perinatal mortality. METHODS: The study population consisted of 13,010 black and 19,007 white mother-infant pairs delivered at Chicago-area hospitals in 1988-1989 categorized as term or preterm births. Preterm births were further divided by severity and etiology. Black-white differences in perinatal mortality within groups were calculated and adjusted for birth weight and other potential confounding variables. RESULTS: Black women were nearly twice as likely as whites to experience preterm (before 37 weeks' gestation) and very preterm (before 32 weeks' gestation) delivery associated with premature rupture of membranes (PROM) or classified as idiopathic. Although black infants were also found to have twice the perinatal mortality risk of white infants (relative risk [RR] 2.1, 95% confidence interval [CI] 1.7-2.5), the overall preterm perinatal mortality rates did not differ between black and white women (RR 1.0, 95% CI 0.8-1.2). However, among preterm births, perinatal mortality was not uniform within categories of medical etiology. The mortality risk was the same for black and white infants born preterm following polyhydramnios or placental complications (RR 1.1, 95% CI 0.6-1.9), the same for black and white infants born preterm after labor induction (RR 1.1, 95% CI 0.6-1.9), and higher for black infants classified as idiopathic preterm deliveries (RR 1.6, 95% CI 1.1-2.3). In contrast, mortality rates tended to be lower for black infants born preterm following PROM-amnionitis (RR 0.8, 95% CI 0.5-1.2). The idiopathic disparity was explained by a differential birth weight distribution (adjusted RR 1.1, 95% CI 0.7-1.9); however, the apparent survival benefit among black infants born preterm following PROM increased even further after adjustment for birth weight (adjusted RR 0.4, 95% CI 0.2-0.7). CONCLUSION: Black infants born preterm after PROM appear to have a survival advantage compared with their white counterparts, an effect not observed within other etiologic categories of preterm delivery.

Adult↗

PubMed1996

The preterm prediction study: risk factors in twin gestations. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: Our purpose was to determine the association between the presence of bacterial vaginosis, fetal fibronectin, and a short cervix and the risk of spontaneous preterm birth of twins. STUDY DESIGN: We prospectively screened 147 women with twins at 24 and 28 weeks' gestation for more than 50 potential risk factors for spontaneous preterm birth. We also measured cervical length with ultrasound scans and tested for the presence of bacterial vaginosis. Fetal fibronectin level was evaluated every 2 weeks from 24 to 30 weeks' gestation. Outcomes included spontaneous preterm birth at < 32 weeks, < 35 weeks, and < 37 weeks. RESULTS: Among twin as compared with singleton pregnancies, a cervical length < or = 25 mm was more common at both 24 and 28 weeks, a statistically significant difference. There were no significant differences in most other risk factors. Of the factors evaluated by means of univariate analysis at 24 weeks, only a short cervix (< or = 25 mm) was consistently associated with spontaneous preterm birth. The odds ratio and 95% confidence interval for spontaneous preterm birth at < 32 weeks, < 35 weeks, and < 37 weeks were 6.9 (2.0 to 24.2), 3.2 (1.3 to 7.9), and 2.8 (1.1 to 7.7). At 28 weeks, a cervical length < or = 25 mm was not a strong predictor of spontaneous preterm birth. At both 28 weeks (odds ratio, 9.4; confidence interval, 1.0 to 67.7) and 30 weeks (odds ratio 46.1; confidence interval, 4.2 to 1381), a positive fetal fibronectin result was significantly associated with spontaneous preterm birth at < 32 weeks. Bacterial vaginosis at 24 or 28 weeks was not associated with spontaneous preterm birth of twins. Multivariate analysis confirmed the association between cervical length < or = 25 mm at the 24-week visit and spontaneous preterm birth and also confirmed that at 24 weeks the other risk factors were less consistently and often not statistically significantly associated with spontaneous preterm birth. Of the risk factors evaluated at 28 weeks, only a positive fetal fibronectin was associated with a significantly increased risk for spontaneous preterm birth. CONCLUSIONS: Most known risk factors for spontaneous preterm birth were not significantly associated with spontaneous preterm birth of twins. At 24 weeks, cervical length < or = 25 mm was the best predictor of spontaneous preterm birth at < 32 weeks, < 35 weeks, and < 37 weeks. Of the risk factors evaluated at 28 weeks, fetal fibronectin was the only statistically significant predictor of spontaneous preterm birth at < 32 weeks.

Adolescent↗

PubMed1999

Association of polymorphism within the promoter of the tumor necrosis factor alpha gene with increased risk of preterm premature rupture of the fetal membranes.

OBJECTIVE: The rarer allele of a polymorphism within the promoter region at position -308 of the gene for tumor necrosis factor alpha is associated with increased gene transcription. In this study we tested the hypothesis that this rarer allele is associated with spontaneous preterm birth. STUDY DESIGN: We conducted a case-control study of women admitted to our labor and delivery unit. To assess data from a single racial group with a high incidence of preterm birth we restricted our analysis to African American women, who contributed 73.6% of the samples collected during the study period. Case patients (n = 55) were defined as women who were delivered before 37 weeks' gestation after idiopathic preterm labor or preterm premature rupture of membranes. Control subjects (n = 110) included women who were delivered after 37 weeks' gestation and had no history of preterm delivery. We also performed subgroup analyses of women with idiopathic preterm labor and delivery (n = 29) and women who were delivered preterm after preterm premature rupture of the fetal membranes (n = 26). RESULTS: Although carriers (homozygotes plus heterozygotes) of the rarer allele of the polymorphism at position -308 in the gene for tumor necrosis factor alpha were not significantly more common among women who were delivered preterm (n = 24/55, 44%) than among control subjects (n = 33/110, 30%, P =.08, odds ratio 1.81, 95% confidence interval 0.92-3.54), carriers of the rarer allele were more common among women who were delivered preterm after preterm premature rupture of membranes (n = 15/26, 58%) than among control subjects (P =.008, odds ratio 3.18, 95% confidence interval 1.33-7.83). CONCLUSIONS: Our results demonstrate an association between allelic variants of the polymorphism at position -308 in the gene for tumor necrosis factor alpha and preterm birth after preterm premature rupture of the fetal membranes. We hypothesize that host susceptibility to environmental factors, such as hyperresponsiveness of the gene for tumor necrosis factor alpha to genital tract infection, may promote preterm premature rupture of the fetal membranes and subsequent preterm delivery.

Adolescent↗

PubMed2004

The complex relationship between smoking in pregnancy and very preterm delivery. Results of the Epipage study.

OBJECTIVE: To assess the relationship between cigarette smoking during pregnancy and very preterm births, according to the main mechanisms of preterm birth. DESIGN: Case-control study (the French Epipage study). SETTING: Regionally defined population of births in France. POPULATION: Eight hundred and sixty-four very preterm live-born singletons (between 27 and 32 completed weeks of gestation) and 567 unmatched full-term controls. METHODS: Data from the French Epipage study were analysed using a polytomous logistic regression model to control for social and demographic characteristics, pre-pregnancy body mass index and obstetric history. The main mechanisms of preterm delivery were classified as gestational hypertension, antepartum haemorrhage, premature rupture of membranes, spontaneous preterm labour and other miscellaneous mechanisms. MAIN OUTCOME MEASURES: Odds ratios for very preterm birth for low to moderate (1-9 cigarettes/day) and heavy (>/=10 cigarettes/day) maternal smoking in pregnancy, estimated according to the main mechanisms leading to preterm birth. RESULTS: Smokers were more likely to give birth to very preterm infants than non-smokers [adjusted odds ratio (aOR) 1.7, 95% confidence interval (CI) 1.3-2.2]. Heavy smoking significantly reduced the risk of very preterm birth due to gestational hypertension (aOR 0.5, 95% CI 0.3-1.0), whereas both low to moderate and heavy smoking increased the risk of very preterm birth due to all other mechanisms (aOR between 1.6 and 2.8). CONCLUSION: These data from the Epipage study show that maternal smoking during pregnancy is a risk factor for very preterm birth. The impact of maternal smoking on very preterm birth appears to be complex: it lowers the risk of very preterm birth due to gestational hypertension, but increases the risk of very preterm birth due to other mechanisms. These findings might explain why maternal smoking is more closely related to preterm birth among multiparous women than among nulliparous women.

Age Factors↗

PubMed2000

Placental transfer and decay of varicella-zoster virus antibodies in preterm infants.

OBJECTIVES: To compare the placental transfer of maternal varicella-zoster (VZV) antibodies to preterm and term infants and to investigate antibody decay during the first 6 months of life in the preterm infants. STUDY DESIGN: Maternal and umbilical cord blood samples were taken from 113 healthy mother-newborn pairs: 64 term (gestational age > or =37 weeks) and 49 preterm (gestational age < or =35 weeks). Premature infants were further tested at 1, 2, and 6 months. Anti-VZV antibody to membrane antigen was measured with the immunofluorescent technique. RESULTS: Preterm infants of gestational age < or =28 weeks had positive cord antibody and a geometric mean titer significantly lower than those in preterm infants of gestational age 29 to 35 weeks and term infants (25% vs 95% and 95%, respectively, P <.001 for each, and 2.5 +/- 2.2 vs 10.5 +/- 2.4 and 12.6 +/- 2.4, respectively, P <.001 for each). There was no difference between the preterm 29 to 35 weeks of gestation and term groups. Fetal-maternal ratios for both preterm groups were <1 and were significantly less than the fetal-maternal ratio in the term infants. The transfer of maternal antibodies to term infants was significantly greater than to the 29- to 35-week preterm infants (P =.01). At 2 months of age, 25% of 29- to 35-week preterm infants and no preterm infant < or =28 weeks had a positive titer. At 6 months of age, all preterm infants were seronegative, and the geometric mean titer in both groups declined to undetectable levels. CONCLUSION: Transplacental transfer of maternal VZV antibodies is diminished in preterm infants. VZV antibody levels are significantly lower in preterm infants born at < or =28 weeks' gestational age compared with those in preterm infants 29 to 35 weeks' gestational age and term infants. Anti-VZV titers decrease to undetectable levels in preterm infants by 6 months of age or earlier; thus these infants appear to be susceptible to chickenpox before the scheduled 12-month vaccination.

Antibodies, Viral↗

PubMed2005

Monocyte chemotactic protein-1 is increased in the amniotic fluid of women who deliver preterm in the presence or absence of intra-amniotic infection.

OBJECTIVE: Pro-inflammatory chemokines have been associated with preterm parturition. Monocyte chemotactic protein-1 (MCP-1) is a chemokine capable of recruiting monocytes/macrophages into sites of inflammation, as well as stimulating the respiratory burst required for macrophage activation. MCP-1 transcripts and immuno-reactivity are expressed by uterine tissues (i.e., decidual cells and myometrium) and, thus, may participate in the process of labor. This study was conducted to determine if preterm labor leading to preterm delivery and intra-amniotic infection (IAI) are associated with changes in the amniotic fluid concentrations of MCP-1. STUDY DESIGN: A cross-sectional study was designed to examine the amniotic fluid concentrations of MCP-1 in women in two groups: 1) those presenting with preterm labor with intact membranes; and 2) those with preterm prelabor rupture of membranes (PROM). Amniotic fluid was obtained by transabdominal amniocentesis from 131 women in preterm labor with intact membranes and 105 women with preterm PROM. IAI was defined by a positive amniotic fluid culture for microorganisms. Group 1 included women with preterm labor and intact membranes (n=131), and was subdivided into the following groups: a) delivery at term in the absence of IAI (n=42); b) preterm delivery (< 37 weeks) in the absence of IAI (n=58); and c) preterm delivery in the presence of IAI (n=31). Group 2 consisted of women with PROM (n=105), and was subdivided into women with (n=51) and without (n=54) IAI. Non-parametric statistics were used for data analysis. RESULTS: 1) Immuno-reactive MCP-1 was detected in all amniotic fluid samples; 2) IAI, regardless of the membrane status, was associated with a significantly higher median amniotic fluid concentration of immuno-reactive MCP-1 than those without IAI (p<0.001 for both comparisons); 3) women in preterm labor who delivered preterm without IAI had a significantly higher median amniotic fluid concentration of immuno-reactive MCP-1 than those who delivered at term (p<0.001); 4) histological chorioamnionitis was associated with increased amniotic fluid concentrations of immuno-reactive MCP-1; and 5) a significant relationship existed between the amniotic fluid concentrations of immuno-reactive MCP-1 and the interval from amniocentesis to delivery. CONCLUSIONS: Amniotic fluid concentrations of immuno-reactive MCP-1 were increased in women in preterm labor with IAI, those without IAI who delivered preterm, and those who displayed acute inflammatory lesions in the extra-placental membranes. These findings suggest that MCP-1 may play a role in preterm labor regardless of the presence of IAI.

Adolescent↗

PubMed2006

Epidemiology of preterm birth and its clinical subtypes.

Preterm birth (<37 weeks) complicates 12.5% of all deliveries in the USA, and remains the leading cause of perinatal mortality and morbidity, accounting for as many as 75% of perinatal deaths. Despite the recent temporal increase in preterm birth, efforts to understand the problem of prematurity have met with little success. This may be attributable to the under-appreciation of the etiologic heterogeneity of preterm birth as well as the heterogeneity in its underlying clinical presentations--spontaneous onset of labor, preterm premature rupture of membranes, and medically indicated preterm birth. In this paper, we review data regarding preterm births with particular focus on its incidence, temporal trends, and recurrence. Studies of births from the USA indicate that the recent temporal increase in the overall preterm birth rate is driven by an impressive concomitant increase in medically indicated preterm birth. However, the largest temporal decline in perinatal mortality has also occurred among medically indicated preterm births (relative to other clinical subtypes), suggesting that these obstetric interventions at preterm gestational ages are associated with a reduction in perinatal mortality. Recent data indicate that spontaneous preterm birth is not only associated with increased recurrence of spontaneous, but also medically indicated, preterm birth, and vice versa. This suggests that the clinical subtypes may share common underlying etiologies. Since medically indicated preterm birth accounts for as many as 40% of all preterm births, efforts to understand the reasons for such interventions and their impact on short- and long-term morbidity in newborns is compelling. Further research is necessary in order to understand the mechanisms and etiology of preterm birth, thus leading to the possibility of effective preventive or therapeutic strategies.

Black or African American↗

PubMed2004

Vaginal bleeding during pregnancy and preterm birth.

This study investigated the relation between self-reported vaginal bleeding during pregnancy and preterm birth in a prospective cohort of 2,829 pregnant women enrolled from prenatal clinics between 1995 and 2000 in central North Carolina. The overall association between vaginal bleeding and preterm birth was modest (risk ratio (RR) = 1.3, 95% confidence interval (CI): 1.1, 1.6). Bleeding in the first trimester only was associated with earlier preterm birth (< or =34 weeks' gestation) (RR = 1.6, 95% CI: 1.1, 2.4) and preterm birth due to preterm premature rupture of the membranes (PPROM) (RR = 1.9, 95% CI: 1.1, 3.3). Bleeding in both trimesters was associated with preterm birth due to preterm labor (RR = 3.6, 95% CI: 1.9, 6.8). Bleeding of multiple episodes, on multiple days, and with more total blood loss was associated with an approximate twofold increased risk of earlier preterm birth, PPROM, and preterm labor. In contrast, bleeding in the second trimester only, of a single episode, on a single day, and with less total blood loss was not associated with any category of preterm birth. Vaginal bleeding was not associated with preterm birth among African Amercians (RR = 1.2, 95% CI: 0.9, 1.7). This study indicates that more intense but not less intense bleeding is associated with earlier preterm birth and spontaneous preterm birth presenting as PPROM or preterm labor, and it suggests that bleeding is less predictive of preterm birth among African-American compared with White women.

Adult↗

PubMed1998

Nutritional and antimicrobial interventions to prevent preterm birth: an overview of randomized controlled trials.

The study was conducted to assess the effectiveness of interventions for the prevention or treatment of nutritional and infectious disorders during pregnancy on preterm birth rates. Cochrane systematic reviews or any other more up-to-date systematic review of antimicrobial and nutritional interventions were sought. Electronic searches of the Cochrane Controlled Trials Register were carried out to identify any trials published since the most recent update of the systematic review. Also, authors of Cochrane systematic reviews, which have not been updated recently, were contacted regarding new information. Systematic reviews of nutritional and antimicrobial interventions during pregnancy, reporting preterm delivery rates (delivery before 37 weeks) and "prematurity" (including low birth weight) either as primary or secondary outcomes, were included. General interventions without a specific nutritional supplementation or antimicrobial component were not considered for inclusion. Interventions to stop labor or prolong pregnancy after a diagnosis of preterm labor were excluded. For each systematic review, data on preterm delivery rate by intervention group was obtained. The total number of trials in the review, number of trials reporting preterm birth as an outcome, number of participants and events have been systematically extracted. Eighteen systematic reviews (10 nutritional and 8 antimicrobial) were considered. Our results indicated that, overall, the treatment of asymptomatic bacteriuria reduces the incidence of preterm birth or low birth weight (< 2500 gm) (typical relative risk (RR): 0.67; 95 percent confidence interval (CI): 0.52-0.85). The protective effect of treating asymptomatic bacteriuria for preterm delivery persisted when only the three trials reporting preterm delivery (< 37 weeks) were included in the meta-analysis (typical RR: 0.53, 95 percent CI: 0.33-0.86). Routine iron supplementation prevents maternal anemia and one trial comparing routine versus selective iron supplementation showed a statistically nonsignificant reduction in preterm birth. Zinc, magnesium, and fish oil supplementations show promising results in reducing preterm birth, but the evidence is not strong. Calcium supplementation remains controversial, although there was a statistically significant reduction in preterm delivery in the subgroup of women at high risk of developing hypertension during pregnancy. Two trials with use of metronidazole (alone or with erythromycin) showed a reduction in preterm delivery in women who were at a high risk of preterm delivery and had bacterial vaginosis at screening. We have concluded that asymptomatic bacteriuria should be screened and treated in all settings that offer antenatal care. Single dose treatment seems to be as effective as longer (4-7 days) treatment, although this needs to be confirmed by a large, methodologically rigorous trial. There are a number of promising interventions such as calcium supplementation in women with low calcium intake, iron, zinc, magnesium, and fish oil supplementation, and treatment of bacterial vaginosis in women at high risk of preterm delivery that need additional research to determine a possible role for prevention of preterm delivery.

Anti-Infective Agents↗

PubMed2005

Preterm birth in Sweden 1973-2001: rate, subgroups, and effect of changing patterns in multiple births, maternal age, and smoking.

BACKGROUND: The objectives of this report are to evaluate changes in the preterm birth rate in Sweden 1973-2001. Furthermore, describe the proportion of spontaneous and indicated preterm births and assess risk factors for the subgroups of preterm birth during the period from 1991 to 2001. METHODS: A population-based register study of all births occurring in Sweden from 1973 to 2001 registered in the Swedish Medical Birth Register was designed. The analysis of subgroups was restricted to the period 1991-2001. Gestational age was calculated using last menstrual period and best estimate. Odds ratio for preterm birth related to risk factors was calculated for the subgroups' spontaneous and indicated preterm birth. RESULTS: After an increase in the beginning of the 1980s, the preterm birth rate has decreased from 6.3% in 1984 to 5.6% in 2001 (P < 0.0001). The proportion of multiple births born preterm of the total birth rate increased from 0.34% in 1973 to 0.71% in 2001 (P < 0.0001). Spontaneous preterm births account for 55.2% and iatrogenic preterm births for 20.2% of all preterm births. The strongest association with maternal smoking in early pregnancy was found at gestational age <28 weeks and spontaneous preterm birth [odds ratio (OR) smoking versus no smoking: 1.55, 95% confidence intervals (CI): 1.42-1.69]. The strongest association for maternal age was found between gestational age <28 weeks and indicated preterm birth (OR 5-year increase: 1.34, 95% CI: 1.21-1.47). CONCLUSIONS: The preterm birth rate in Sweden has decreased since the mid 1980s. The composition of different subtypes of preterm birth in a Scandinavian low-risk population seems to be similar to populations with higher incidence of preterm birth and perinatal infections.

Adult↗